manual vitros dtii

CAT No. 8040883

Operator's Manual

VITRO

' Ortho:Clinical Diagnosticsa ^o&wton^flo^HiOH company

Export authorized under general license GTDA (General Technical Data Available)

IMPORTANT

The information contained herein is based on the experience and knowledge relating to the subjectmatter gained by Ortho-Clinical Diagnostics, Inc. prior to publication.

No patent license is granted by the information.

Ortho-Clinical Diagnostics, Inc. reserves the right to change this information without notice, andmakes no warranty, express or implied, with respect to the information.. The company shall not beliable for any loss or damage including consequential or special damages, resulting from the use of thisinformation, even if loss or damage is caused by its negligence or other fault.

VITROS is a trademark of Ortho-Clinical Diagnostics.

©2004 Ortho-Clinical Diagnostics, Inc. All rights reserved. 2004-03-30

About the VITROS DT II System Binder

Operator's Manual

This binder contains all you need to know to analyze samples on theVITROS DT60 II Chemisty System and the accompanyingVITROS DTSC II and VITROS DTE II Modules.

This section provides general information about how to operate andmaintain the VITROS DT II System. Topics covered are:

• Operating Instructions

• Coronary Risk Classification (CRC) and Derived Tests

• Calibration

• Instrument Care and Cleaning

• Quality Control

• Options

• Troubleshooting

• Instrument Status Messages

• Coded Warning Messages

• Installation and Site Specifications

• Warranty

In writing the Operator's Manual we strove to achieve multiple goalsin meeting your needs. The Operator's Manual has some sections (1,6, and 7-12) that are primarily informative. These are formattedvertically, making it easier to read these sitting down or at a desk.

Sections 2-5 and 1 3 are considered functional, for daily use whileyou are operating the analyzer, and are oriented horizontally.

VITROS DT II System BinderRev. 2004-03-30 VITROS DT II System

I VITROS Chemistry Products DT Instructions for Use Manual

| This separate manual provides information on the specificchemistries that the DT II System analyzes. It includes the followinginformation for each chemistry:

• Intended Use

• Summary and Explanation of the Test

• Principles of the Procedure

• Test Type and Conditions

• Warnings and Precautions

• Reagents

• Specimen Requirements

• Testing Procedure

• Calibration

• Quality Control

• Expected Values and Reporting Units

• Limitations of the Procedure

• Performance Characteristics

iv VITROS DT II System BinderVITROS DT l| System Rev. 2004-03-30

Revision History

Revision Date Description

2004-03-30 About the VITROS DT II System Binder iii-iv, updated to reflect movingInstructions for Use to separate manualRevision History v-viii, updated to reflect current documentationList of Revised Pages ix-x, updated to reflect current documentationTable of Contents xi-xiv, updated to reflect current documentationChapter 1, page 1 - 1 , removed reference to HbChapter 2, page 2-19, 2-23 and 2-25, inserted text for tracking errorChapter 4, page 4-3, updated "When to Calibrate" sectionChapter 4, page 4-3, removed reference to HbChapter 4, page 4-11, removed section "Preparing DT Hb Calibrators"Chapter 4, page 4-13 and 4-15, inserted text for tracking errorChapter 6, page 6-3, removed section "Preparing DT Hb controls"Chapter 8, page 8-3, added "Unexpected Results" to section title, added bulletfor calibration failuresChapter 8, page 8-4, In 'Possible Causes" extracted text from third bullet toemphasize importance, added bullet for overfilled slide disposal boxChapter 8, page 8-4, In "if You Suspect a Tracking Error" added text to reviewand confirm previous resultsChapter 8, page 8-4, In "Important Points to Remember" underlined text foremphasisChapter 9, page 9-8, added Important note to prevent tracking errorChapter 1 0, page 10-1 and 10-3, added tracking error textChapter 1 0, page 10-2 and 10-20, removed reference to HbChapter 10, page 10-10, added tracking error text

Rev. 2004-03-30Operator's Manual

VITROS DT II System

Revision Date Description

2003-10-01 Note: Formatting has changed but only pages with content changes are labeled2003-10-01.Added "For in vitro Diagnostic Use"Replaced "Methodology Sheets" with "Instructions for Use"About, pages iii-iv, edited to reflect current documentationRevision History, v-vii, added update informationList of Revised Pages, viii, updated to include all pagesTable of Contents, xi-xii, updatedIntroduction, page 1-1Introduction, pages 1-7-1-8Introduction, pages 1 -7 and 1 -9; removed DT from VITROS Micro TipsSection 2.2.1, page 2-5Section 2.2.1, page 2-7, updated the power socket illustrationSection 2.2.1, page 2-27, changed J&JCD to OCDSe tion 6.10, page 6-13Section 7.2, page 7-3, changed J&JCD to OCDSection 7.2, page 7-7, changed J&JCD to OCDSection 8.2, page 8-3-8-6, replaced information with a reference; changed

paging to 8-3-8-4Section 9.1, page 9-5Section 10.1.8, page 10-19

Revised Instructions for Use:• ALB DT• ALT DT• AST DT• BUN DT• CHE DT• CKDT• Cl- DT• CREA DT• FeDT• LAC DT• LDH DT• Mg DT• Na+ DT• NBIL DT• NH, DT• THEO DT• TBIL DT• TPDT• UrCr DT

VI Operator's ManualVITROS DT II System Rev. 2004-03-30

Revision Date

2003-08-11

2003-04-30

2OO3FEB

10/01

11/00

1/99

4/96

DescriptionRevised Instructions for Use for:• AMYL DT• CO2 DT• GGT DT• GLU DT• HDLC DT (Using the VITROS DT HDL Cholesterol Kit)• HDLC DT (Using the VITROS DT Micro HDL Cholesterol Kit)• Li DT• URIC DTRemoved:• Anion Gap Calculation Supplement, C-363• Coronary Risk Classification Supplement, C-359• Globulin and Albumin_Globulin Calculations Supplement, C-360• VLDL, LDL, and CHOLJHDLC Ratio Calculations Supplement, C-362

New Format.New organization and sections consistent with IVD Directive.Revised Instructions for Use:• ALKP DT• Ca DT• CHOL DT• CKMB DT• CRSC DT• K+ DT• LI PA DT• PHOS DT• TRIG DT

Update the Methodology Section to include revision to Test Methodology:CK2003FEB01

Revised Table of Contents to include Test Methodology Sheets.Revised Section 5, pages 1-46, deleted all references to cleaning and chargingthe VITROS DT Pipette. Refer to the VITROS DT Pipette User's Guide forinformation on cleaning and charging the DT Pipette.• Section 5, pages 1-10, minor text and format changes.• Section 5.1, page 3, deleted reference to the daily cleaning of the DT Pipette.• Section 5.3, pages 19-26, removed.• Section 5.4, pages 27-34, removed.• Updated Methodology Section to include Test Methodologies: NBIL

2001 SEP24, TBIL 2001 SEP24.

Updated Methodology Section to include Test Methodologies: GGT 8/99, CK2000SEP21, CREA 2000SEP21.

Reflects company name change to Ortho-Clinical Diagnostics, a Johnson &Johnson Company.

Reprinted for the introduction of J&JCD VITROS Chemistry Systems trademarknomenclature.


VITROS DT II SystemVII

Revision Date

5/95

9/93

2/92

1/92

9/91

DescriptionReprint of all pages.Trade dress changes.Style changes for consistency.Section 2.2.1, pages 7-1 7, changes made to reflect new pipette information.Section 2.2.2, page 23, item 6, new information added.Section 4.2, minor text changes.Section 4.4, page 13, pipette graphic updated.Section 4.4, page 15, step 4, minor text changes.Section 5.3, pages 19-25, new information on cleaning the DT Pipette.Section 5.4, pages 27-33, heading changed to Charging the DT Pipette andnew information added.Section 5.5, page 35, clean cloth changed to cotton swab.Section 8.2, page 3, new pipette troubleshooting information added.Section 8.3, Analyzer Tracking Errors section added.Section 11.1, page 2, item 3, reference to Electrical Requirements added.Section 11.2.3, page 5, rewrite.Section 11.3, page 6, changes in headings and rewrite of item 2 under 11.3.1and 11.3.2.

Reprint of all pages.

Table of Contents undated to reflect derived tests in Section 3 and switch ofsubheads in Section 11.Section 2, page 13, second bullet under Ektachem DTE pipette removed.Section 3, style changes to comply with other subheads.Section 3, pages 11 and 13, md/dl changed to mg/dl.Section 3, pages 18-36, new pages added as per derived test development.Section 4.3.2, page 11, second bullet changed.Section 4, page 1 7, IMPORTANT NOTE changed.Section 6.4.2, page 3, second bullet changed.Section 7, pages 4-10, new pages added as per derived test development.Section 11.3.1 and 11.3.2, heading corrections.

Updated Sections 3 & 7 to include new features.Revised tab for Section 3 to include both CRC and Derived Tests.Revised Section 3 in Table of Contents to reflect additions.

First release.

Operator's ManualVITROS DT II System Rev. 2004-03-30

List of Revised Pages

Each page in your manual should be at the date listed below:

Chapter or Section

Title Page/Copyright

AboutRevision HistoryList of Revised PagesTable of Contents (book)

Introduction

Operating Instructions

CRC

Calibration

Instrument Care & Cleaning

Quality Control

Options

Troubleshooting

Page Number(s)/Portrait (P)or Landscape (L)

P

iii-iv Pv-viii Pix-x Pxi-xiv P

1-1 P1-2-1-6 P1-7-1-9 P1-10 P

2-1-2-4 L2-5 L2-6 L2-7 L2-8-2-18 L2-19 L2-20-2-22 LL2-23 L2-24 L2-25 L2-26 L2-27 L2-28-2-34 L

3-1-3-36 L

4-1-4-2 L4-3 L4-4-4-10 L4-11 L4-12 L4-13 L4-14 L4-15 L4-16-4-22 L

5-1-5-30 L

6-1-6-2 P6-3 P6-4-6-12 P6-136-14

7-1-7-2 P7-3 P7-4-7-6 P1-7 P7-8-7-10 P

8-1-8-2 P8-3-8-4 P

Revision Date

Rev. 2004-03-30

Rev. 2004-03-30Rev. 2004-03-30Rev. 2004-03-30Rev. 2004-03-30

Rev. 2004-03-305/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99

5/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99

5/95. Reprinted 1/99

5/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99

Rev. 10/01

5/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99

5/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99

5/95. Reprinted 1/99Rev. 2004-03-30


VITROS DT II SystemIX

Chapter or Section

Status Messages

Coded Warning Messages

Installation and Site Spec

Warranty

Log Sheets

Page Number(s)/Portrait (P)

or Landscape (L)

9-1-9-4 P9-5 P9-6-9-7 P9-8 P

10-1-10-3 P10-4-10-9 P10-10 P10-11-10-18 P10-19 P10-20 P10-21-10-22 P

11-1-11-6 P

12-1-12-2 P

13-1-13-3 L13-4-13-8 P

Revision Date

5/95. Reprinted 1/99Rev. 2003-10-015/95. Reprinted 1/99Rev. 2004-03-30

Rev. 2004-03-305/95. Reprinted 1/99Rev. 2004-03-305/95. Reprinted 1/99Rev. 2003-10-01Rev. 2004-03-305/95. Reprinted 1/99



5/95. Reprinted 1/99.5/95. Reprinted 1/99

Operator's ManualVITROS DT II System Rev. 2004-03-30

Table of ContentsAbout the VITROS DT II System Binder iii

Operator's Manual iiiVITROS Chemistry Products DT Instructions

for Use Manual ivRevision History vList of Revised Pages ixTable of Contents xi

1.1 General Description 1-11.2 Equipment Features 1-2

1.2.1 Keyboard and Functions 1-21.2.2 Display Panel 1-31.2.3 Printer and Results Printout 1-3

1.3 Principles of Operation:VITROS DT60 II Chemistry System 1-31.3.1 Slide Identification 1-31.3.2 Slide Spotting 1-31.3.3 Incubation and Readout 1-4

1.4 Principles of Operation: VITROS DTE II Module 1-51.4.1 Slide Identification 1-51.4.2 Slide Spotting 1-51.4.3 Incubation and Readout 1-5

1.5 Principles of Operation VITROS DTSC II Module 1-61.5.1 Slide Identification 1-61.5.2 Slide Spotting 1-61.5.3 Incubation and Readout 1-6

1.6 Supplies and Supply Handling and Storage 1-71.6.1 Storage Temperature Requirements 1-71.6.2 VITROS DT Slides 1-71.6.3 VITROS DT and DTE Pipettes and Micro Tips 1-71.6.4 VITROS DT Calibrator Kits 1-71.6.5 ViTROS DT Control I and DT Control II 1-81.6.6 VITROS DT Reference Fluid 1-81.6.7 VITROS DTE Dual-Sample Cups.. 1-81.6.8 Printer Paper 1-81.6.9 VITROS DT Accessory Kit* 1-9

2.1 Start-up Procedure 2-12.2 Testing Procedure 2-5

2.2.1 Pipetting Techniques 2-52.2.2 Steps for Analysis on the VITROS DT II System .... 2-19

2.3 Calibration Data Module andChemistry Language Module 2-272.3.1 Description of Calibration Data Module 2-27

Section 1Getting To Know YourVITROS DT II System

Section 2Operating Instructions


VITROS DT II Systemxi

2.3.2 Description of Calibration Language Module 2-272.3.3 How to Install a New Calibration Data Module

(CDM) and a Chemistry Language Module (CLM) .2-292.4 Normal Shutdown Procedure 2-332.5 Emergency Shutdown 2-33

3.1 CRC Overview 3-13.2 Entering Data for Coronary Risk Classification 3-33.3 Printing CRC Results 3-13Derived Tests 3-213.4 Overview 3-213.5 GLOB and A/G 3-233.6 Lipid Calculation (VLDL, LDL and CHOL/HDLC Ratio) 3-273.7 Anion Gap (AGP) 3-33

4.1 Why You Need to Calibrate 4-14.2 When to Calibrate 4-34.3 How to Calibrate 4-5

4.3.1 Preparing VITROS DT Calibrators 4-74.3.2 Entering the Calibration Mode 4-11

4.4 Calibration 4-13

5.1 Daily Cleaning 5-35.2 Weekly Cleaning 5-55.3 Other Cleaning: VITROS DT60 II Chemistry System

FORSHead '... .. 5-195.4 Paper Loading ,;;: 5-21

5.4.1 Removing the Paper 5-215.4.2 Inserting Paper '. 5-23

6.1 What Is Quality Control? 6-16.2 What Are Controls? 6-16.3 How Often Should Controls Be Run? 6-16.4 How to perform a quality control test 6-2

6.4.1 Preparing Lyophilized Controls 6-26.5 Analyzing the Controls 6-36.6 How to Record the Results 6-4

6.6.1 Recording Quality Control Results on a Log 6-46.6.2 Recording Quality Control Results on a Graph 6-5

6.7 Interpreting Control Results 6-66.7.1 Interpreting the Control Results from the Log 6-66.7.2 Interpreting the Control Results from the Graph 6-6

6.8 Establishing Your Own Control Ranges 6-76.8.1 How to Calculate the Mean 6-86.8.2 Variables to Consider in Establishing the Mean 6-9

Section 3Coronary RiskClassification (CRC)

Section 4Calibration

Section 5Instrument Care andCleaning

Section 6Quality Control

XII Operator's ManualVITROS DT II System Rev. 2004-03-30

6.8.3 Calculating the Standard Deviation 6-96.8.4 How to Calculate a Standard Deviation 6-10

6.9 Quality Control Troubleshooting Chart 6-126.10 Factors to Consider When Your Results Are Out of Range 6-13

7.1 How to Run Options 7-17.2 Options for the VITROS DT60 II Chemistry System 7-1

7.2.1 Serial Communication Options for theDT60 II System 7-8

7.3 Options for the VITROS DTE II Module 7-97.4 Options for the VITROS DTSC II Module 7-10

8.1 General Troubleshooting 8-18.2 Pipette Troubleshooting 8-38.3 Unexpected Results (Analyzer Tracking Errors) 8-3

9.1 Status Messages 9-1

10.1 Coded Warning Messages 10-110.1.1 Calibration (C) 10-110.1.2 Data Storage (D) 10-410.1.3 Electrometer (E) 10-610.1.4 Instrument Function (F) 10-1010.1.5 Temperature (H) 10-1410.1.6 Communications (N) 10-1610.1.7 Reflectometer (R) DT60 II System 10-1810.1.8 Reflectometer (L) DTSC II Module 10-19

11.1 Installation 11-111.2 Site Specifications 11-3

11.2.1 Space Requirements 11-311.2.2 Environmental Requirements

(Temperature, Humidity, and Altitude) 11-411.2.3 Electrical Requirements 11-511.2.4 Refrigerator and Freezer Space 11-6

11.3 Moving the Analyzer 11-611.3.1 Relocation Outside the Office 11-611.3.2 Relocation Within the Office 11-6

12.1 New Equipment Warranty VITROS DT II System 12-112.2 New Accessory Warranty VITROS DT Pipette and

VITROS DTE Pipette 12-2

Section 7Options

Section 8Troubleshooting

Section 9Instrument Status Messages

Section 10Coded Warning Messages

Section 11Installation and SiteSpecifications

Section 12Warranty


VITROS DT II SystemXIII

Section 13 CALIBRATION LOG 13-1Log Sheets SERVICE LOG 13-2

TEST/REAGENT LOG 13-3VITROS DT II System Maintenance Log 13-4VITROS DT II System Quality Control Log 13-5Levey-Jennings Quality Control Chart for VITROS DT II System.13-6

Section 14Instructions For Use

xiv Operator's ManualVITROS DT II System Rev. 2004-03-30

Getting To Know Your VITROS DT II System

1.1 General Description

This manual is designed to familiarize you with the operation of yourVITROS DT60 II Chemistry System and, if applicable, your ViTROSDTE II and VITROS DTSC II Modules. We suggest that the operatorbecome familiar with the information in this manual prior tooperating the analyzer and the associated modules.

Intended Use

For in vitro diagnostic use.

The VITROS DT60 II System uses VITROS DT Slides to perform anumber of discrete clinical tests on serum or plasma specimens. Allreactions needed for a single quantitative measurement take placewithin the multilayered analytical element of the slide. A slide isused once for a single patient test and is then discarded. The uniqueproperties of these slides eliminate the need to store, mix, anddispose of liquid reagent chemicals and permit reliable analyses witha very small patient sample.

All processes performed by the analyzer are controlled by a self-contained microcomputer. You communicate with themicrocomputer through the keyboard; it communicates with youthrough messages that appear on the display screen and printouts.

TABLE 1 Summary of System Characteristics

.and y ^mîM^MstC: h. ::! I l l : :Jhr:: the specific Instructions;for Use^ta;rrrore: infofrrfaiti(Jinr;

'Specimen Sample: - : : : m : "•" :v •;: )•:'!':: •••""% N#i::::;:;; :

:. n •; C i i H JSerum or|p)asma* ; : ';S.f-wi:;H-|Vi; i -^XM^/

Sample Size: : ; • -^r^ •: y '• -^ ^'•un^&S^, ;:1 ^'^; 1 ; Q ( J L p e r t e s t r T " ; ^ : : ; : ; / : :: » : :

: • L - v i i J ••••••• J J i i n i i . . M ;

per -lest JResutfcVITR(3iS:PT60 II ChemistryVlTRQfilpE II Module: A

d J f c iModule:

^fKW|>Mghput Rate:" • •" '^îW^Bttlu; I ^"••'•1DTOpli :l-i|eni^try:Systern: i;: ApproximiSlf.feS tests per hour0 IE i rMo | (u ]e : i'Approxiniately 15 testsêrihour -M :

y' : : ' ^^Ml^= ^^fflGscJWlijt^tiK" -t 5 f^M-1^!^1^ -hour••:|-:i:':.:. : . •

* Appropriate anticoagulants for plasma specimens are suggested in the testInstructions for Use


VITROS DT II System1-1

1.2 Equipment Features

1.2.1 Keyboard and Functions

The keyboard is used to issue commands to the analyzer'smicrocomputer and to enter necessary data. Instructions for using thekeyboard are provided in this section.

To protect the analyzer against damage from spills and to make theequipment easier to clean, the keyboard consists of a pressure-sensitive pad rather than actual keys. An audible tone sounds shortlyafter a key is pressed. If no tone sounds, you have to apply morepressure to the center of the key. A double tone sounds if you attemptto enter information that is incorrect.

1 patient ID

in progresscomplete

' clear

.shift

SHIFT:Used to perform all functions shown in red onyour keyboard—test in progress, servicemode, and delete test. Use the shift key first,then proceed with your second key selection.

CLEAR:Erases data from the display panel.

TEST IN PROGRESS/COMPLETE:Test in Progress: (Press SHIFT key.) Used todisplay tests that are currently in the incubatorof the DT60 II System and any active tests inthe DTE II or DTSC II Module.Test Complete: Used to display the results ofthe last 20 tests that were completed.

PATIENT ID:Used to assign the patient identificationnumber to a sample. Test results are thenprinted with the appropriate patient

print

service modecal mode

delete testchemistry

select

enter

NUMERIC KEYS:Used in entering numeric data, such as patientidentification numbers, and in identifyingcalibrators used in the calibration procedure.

ENTER:Enters the information input via the keyboard intothe microcomputer.

DELETE TEST/CHEMISTRY SELECT: —Delete Test: (Press SHIFT key.) Used to delete a testafter a slide has been entered, identified andspotted. When a test is deleted, the slide mustcontinue through the analyzer, DTE II Module, orDTSC II Module. The printout indicates that the testwas deleted. Do not remove a slide manually oncedeleted.Chemistry Select: Used to identify a test if theanalyzer is unable to read the informationcontained in the barcode. Press the CHEMISTRY

SERVICE MODE/CAL MODE:Service Mode: (Press SHIFT key.) Used to enter andexit the service mode and to access variousequipment options.Cal Mode: Used to enter and exit the calibrationmode. Signals to the microcomputer that theanalyzer is about to be calibrated and registers the

PRINT:Advances paper in the printer when pressed duringnormal analyzer operation.

1-2 Operator's ManualVITROS DT II System 5/95. Reprinted 1/99.

1.2.2 Display Panel

The liquid crystal display panel is located above the keyboard anddisplays messages of up to two 40-character lines. In general, the firstline of the display message tells you the status of the function you arein the process of performing, and the second line providesinstructions on what to do next.

1.2.3 Printer and Results Printout

The printer is located to the left of the keyboard and is used to printout test results and other information. It provides a paper record.

1.3 Principles of Operation: VITROS DT60 II Chemistry System

1.3.1 Slide Identification

Place the VITROS DT Slide into the loading station of the analyzer.After loading a slide for the DT60 II System into the loading station,push the slide advance lever steadily and smoothly to move the slideinto the spotting station.

As the slide enters the spotting station, a bar code reader reads thelaser bar code on the slide to identify the test and the slidegeneration number for the microcomputer. The test identificationthen appears on the display panel.

1.3.2 Slide Spotting

When the display says SPOT SLIDE WITH FLUID, insert theVITROS DT Pipette into the pipette locator and press down on thepipette button to dispense 10 uL of sample fluid onto the slide in thespotting station.

An optical drop detector starts the analyzer's built-in timer andverifies that the slide has been spotted. Then, the analyzerautomatically transports the slide into the incubator.

Operator's Manual 1-35/95. Reprinted 1/99. VITROS DT II System

1.3.3 Incubation and Readout

The incubator can hold a maximum of six slides stacked one on topof the other. Each slide enters the incubator at the top of the stackand exits from the bottom. The slides are incubated forapproximately 5 minutes at 37°C (98.6°F).

At the completion of the incubation period, the lower rack assemblyautomatically moves the slide from the bottom of the slide stack inthe incubator to the read station. White and black reference readingsare automatically taken. These readings, together with the slidereading, are used to determine the density of the color formed by thechemical reactions in the slide. As the lower rack assembly isretracted, the slide falls on top of the fiber-optics reflection system(FORS) head in the read station. The FORS head contains red, green,and yellow light-emitting diodes (LEDs). The appropriate LED isenergized depending upon the type of slide present in the readstation.

The light is transmitted to the slide by fiber optics, and the lightreflected off the slide is conducted to a photodetector within theFORS head. The microcomputer uses this reflectance reading,together with the white and black reference readings, a calibrationmodel, and the stored calibration parameters, to calculate theconcentration of the sample.

This concentration is printed out by the analyzer's printer. The slideremains in the read station until the next slide pushes it into the slidedisposal box at the rear of the analyzer.


1.4 Principles of Operation: VITROS DTE II Module


Place the DT Slide in the loading station on the moduleand use theslide advance lever to move the slide to the spotting station. As theslide enters the spotting station, a bar code reader in the moduleidentifies the test and the slide generation number by reading the barcode on the slide. The test identification then appears on theanalyzer's display panel.


The VITROS DTE Pipette, a dual pipette designed for use with theDTE II Module, allows you to simultaneously aspirate sample fluidand electrolyte reference fluid from the VITROS DTE Dual-SampleCup. After the fluid is aspirated, you position the pipette over theslide in the spotting station. When you press down on the pipettebutton to dispense the fluids on the slide, a 3-minute timer isactivated. When the slide is spotted, the indicator on the modulelights up and begins flashing to alert you to wait before loadinganother slide.


The electrometer assembly moves over the slide. The slide is thenincubated in place for 3 minutes at 25°C (77°F). The electrometerhas two contact points: one penetrates the contact area on the half ofthe slide where the reference fluid was dispensed, the otherpenetrates the contact area on the half where the sample fluid wasdispensed.

At the completion of the 3-minute incubation period, a tone soundsand the electrometer measures the potential difference between thetwo ion-selective electrodes in the slide. This potential difference isrelated to the difference in ionic concentration between thereference fluid and the sample fluid. This reading is used by theanalyzer's microcomputer, together with the calibration parameters,to calculate the concentration of the electrolyte in the sample.

The slide remains in this position until the next slide pushes it intothe slide disposal box in the left side of the module.


1.5 Principles of Operation VITROS DTSC II Module


Place the DT Slide for the DTSC II into the pick-up station of theDTSC II Module. After the slide enters the slide pickup station, it isautomatically moved to the bar code reader in the module. The barcode scanner identifies the test and the slide generation number onthe slide. This information is then transmitted to the DT60 II System,where the test identification is displayed on its display panel.


The DT Pipette is designed for use with the DTSC II Module. A greenindicator light on the DTSC II Module, and a message on the DT60 IISystem, signal you that you may spot the slide. You then insert thepipette into the pipette locator and press down on the pipette buttonto dispense 10 uL of sample fluid onto the slide in the spottingstation.

The spotting of the slide is automatically detected by an optical dropdetector and the slide is transported to the preheat station.


The slide is transported to the preheat station and then to theincubator where it is incubated in place at approximately 37°C(98.6°F) for a time specified by the tes-t. After incubation, while theslide is being transported to the read station, it momentarily stops toallow the system to take a white reference reading, a dark referencereading, and a voltage reference reading, and then transmits thesereadings to the DT60 II System for later use.

At the completion of the reference readings, the slide is transportedto the reflectometer read station where it is illuminated with lightfrom a xenon flash lamp. At this point several readings are takendepending on the test. The light reflected from the analysis slidepasses through an interference filter of the proper wavelength andonto a silicon photodetector. The electrical signals from thephotodetector are fed to an analog-to-digital converter and theresulting data is sent to the DT60 II System. The microcomputer usesthe reflectance readings, reference readings, and the calibrationparameters to determine the concentration of the sample.

When the slide readings are completed, the slide is automaticallymoved to the disposal station and into the slide disposal box.


1.6 Supplies and Supply Handling and Storage

1.6.1 Storage Temperature Requirements

VITROS slide and fluid boxes are color coded in order to indicate thestorage temperature of the slides and fluids.• Light blue indicates the product must be frozen at temperatures

less than -18°CorO°F.• Purple indicates storage in refrigerator or freezer (<8°C or 46°F).• Yellow indicates storage in a refrigerator at temperatures between

2° an.d 8°C or 36° and 46°F.

1.6.2 VITROS DT Slides

The DT60 II System, DTE II Module, and DTSC II Module each use adifferent type of DT Slide for analysis. The slides are individuallywrapped for their protection during storage. The slide wrapperidentifies the test and the slide lot number. The laser bar code on theslide is used by the analyzer and the associated modules to identifythe slide and the generation number.

1.6.3 VITROS DT and DTE Pipettes and Micro Tips

The DT Pipette (a battery operated pipette) is supplied for use withyour DT60 II System and DTSC II Module. The DTE Pipette issupplied with the DTE II Module. It is a dual sample pipette designedto permit you to simultaneously aspirate and dispense sample fluidand VITROS DT Reference Fluid.

Disposable VITROS Micro Tips are used with these pipettes. Thesemicro tips are designed to meet the specific metering requirements ofthe VITROS DT II System. A tip is used once to spot a single slide andis then discarded.

1.6.4 VITROS DT Calibrator Kits

Calibration of the analyzer requires the use of calibrator fluids whichare provided in sets.

Storage and stability requirements of calibrators are provided in theinstruction sheet packaged with the fluids. The instruction sheetshould be read prior to using the calibrators. Refer to the specific testInstructions for Use for special calibration precautions.

Operator's Manual 1-7Rev. 2003-10-01 VITROS DT II System

1.6.5 VITROS DT Control I and DT Control II

VITROS DT Control I and DT Control II contain known amounts ofthe same analytes that the analyzer measures in actual patientsamples. Use these to compare analyzer results with known valueswhich are provided with the control fluid. Quality control verifies thesuccess of a calibration and allows you to monitor the long-termperformance of the equipment.

Refer to the specific test Instructions for Use for information on DTControls I and II.

Storage and stability requirements of unreconstituted andreconstituted fluids are provided in the instruction sheet packagedwith the fluids and should be read prior to using controls. Forspecific analyte stability information, handling precautions and assaycontrol values, refer to the assay sheet.

1.6.6 VITROS DT Reference Fluid

DT Reference Fluid is required for use with slides that are tested onthe DTE II Module. Reference fluid is supplied in 10 mL squeezebottles with a dropper-like tip that permits dispensing fluid into theDTE Dual-Sample Cup. The fluid is colored to permit you to easilyview the amount aspirated.

The bottle label identifies the fluid generation number, the lotnumber, and the expiration date. Storage and stability requirementsare provided in the instruction sheet packaged with fluids and shouldbe read prior to using reference fluids.

1.6.7 VITROS DTE Dual-Sample Cups

1.6.8 Printer Paper

Single-use, disposable dual-sample cups are used in the sampleholder of the DTE II Module. The sample cups contain two wells. Asindicated on the sample carrier in the module, the sample to beanalyzed is placed in the large well, and DT Reference Fluid isplaced in the small well. The wells are positioned in the cup so thatthe DTE Pipette will aspirate both fluids simultaneously.

Thermal printer paper is used in the analyzer's data printer. Thepaper is supplied in rolls 57 mm (2.25-inches) wide and 44mm(1.75-inches) in diameter.

1-8 Operator's ManualVITROS DT II System Rev. 2003-10-01

1.6.9 VITROS DT Accessory Kit51

The VITROS DT Accessory Kit is supplied with each new system.The kit contains:• One 3 mL pipette• One package of 75 pipette tips for the 3 mL pipette• One package of 100 2 mL plastic sample cups• One package of 100 plastic sample cup caps• One package of 100 transfer pipettes• One box microwipes• One package of 250 ViTROS Micro Tips• One package of 1 60 VITROS DTE Dual-Sample Cups• One VITROS DT Pipette battery recharger

• U.S. customers only

Operator's Manual 1-cRev. 2003-10-01 VITROS DT II System

1 -10 Operator's ManualVITROS DT II System 5/95. Reprinted 1/99.

Operating Instructions

The previous section gave you an overview of your equipment's operating features. By following theoperating instructions and illustrations in this section, you will discover how easy it is to make yourVITROS DT60 II Chemistry System work for you. As you become more familiar with your DT60 II System,many of the frequently performed operating procedures explained in this section will become secondnature.

2.1 Start-up Procedure

STEP

1. Prepare materials for use.

2. Check power cord connections.

ACTION TO TAKE

Allow the controls, slides, and reference fluids tocome to room temperature (15-30 minutes). Unlessotherwise noted on the control sheet packed withthe control, reconstitute a new vial after 7 days.Write the date on the control and reference fluidwhen first opened.

Allow patient samples to come to roomtemperature if refrigerated or frozen.

Mix all fluids before using (gently invert severaltimes).

Check that all power cords are securely pluggedinto the proper outlets.

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This page has been left blank intentionally.

2-2 Operator's ManualVITROS 'I System 5/95. Repr' •< 1/99.

2.1 Start-up Procedure (continued)

STEP

3. Turn DT60 II System on.

4. Turn DTSC II Module on.

5. Do daily maintenance.

6. Enter date.

7. Run control materials.

ACTION TO TAKE

The On/Off switch is on the back of the analyzer.

Requires a 20-minute warm-up period.

The On/Off switch is on the back of the module.

Requires a 5-minute warm-up period.

Turning the DTSC II Module off and on every 24hours will allow it to adjust for changes in lampoutput.

Empty all slide disposal boxes.

Check the end of the.pipettes for residue and cleanif necessary. See the Cleaning the DT Pipettessection of this Operator's Manual

Press SHIFT and SERVICE keys.

Key in option 1 7 and ENTER.

Key in month, day, and year (NN-NN-NN) andENTER. Press SHIFT and SERVICE to exit.

Run the controls on those tests that you will beusing that day. See the How to Perform a QualityControl Test section of this manual.




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2.2 Testing Procedure

2.2.1 Pipetting Techniques

Samples to be analyzed require accurate fluid dispensing through pipetting. The importance of accuratepipetting procedures cannot be over-emphasized. Before attempting to analyze patient samples orperforming routine calibration procedures, you should become thoroughly familiar with the pipettingprocedures recommended for the DT Pipette and the DTE Pipette. Follow the simple instructions outlinedon the next page.

Collect and handle the patient sample according to standard laboratory procedures, centrifuging it toseparate the serum or plasma. Place a cap on the container to avoid sample evaporation andcontamination. Refer to Instructions for Use for proper storage of samples if analysis cannot be performedthe same day that the sample is drawn.



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2.2.1 Pipetting Techniques (continued)

COMMENT OR ACTION TO TAKE

STEPS DT Pipette DTE Pipette

1. Place disposable tips in the holder.

2. Check pipette(s). 2a. If the message I* R5P] appears in thedisplay proceed to step 3.

IMPORTANT: When the message appears inthe display the DT P pette may be used toaspirate samples as long as the displayindicates the presence of at least oneaspiration |* Lo (]. The DT Pipette shouldremain plugged into the charger until it isfully charged.

2b. Plug the recharge unit into a wall outlet.

NOTE: The DT Pipette only charges when theLong Term Storage switch is in the Onposition.

2c. Plug the power cord of the recharge unitinto the power socket on the top of the DTPipette.

PowerSocket




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2d. Make sure the message \jh . [ appearsin the display. If it does not, check thepower cord and make sure it is attached

2e. The message Lo will appear in the displaywhen the DT Pipette is ready to aspirate a10 uL drop of fluid.

3. Insert tip(s). Attach a disposable tip by pressing the tipcone of the DT Pipette into one of the tipsin the tip holder. The tip will click intoplace when it is seated correctly.

i

• • • • ?

1

To attach disposable tips, press the DTEPipette firmly into two of the tips in theholder. The tips will click into place whenseated correctly.

Visually inspect tips to make sure that thetips project equally from the pipette.

\ //

' !

T r

\j y7




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4. Insert and fill dual-sample cup. Swing the sample holder into the loadingposition. Place a dual-sample cup into theholder so that the small well fits into thesmall depression in the holder and the largewell fits into the large depression in theholder.

• Gently invert the bottle of VITROS DTReference Fluid to mix the fluid, and thensqueeze at least 4 drops into the small wellof the cup. Using a transfer pipette, pipette4 drops (need at least 50 uL) of sample to beanalyzed into the large well of the cup.

IMPORTANT: Avoid bubbles in the fluid.

• Gently swing the sample holder back intoplace.




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5. Aspirate fluids. • Hold pipette in vertical position.

• Insert the tip below the surface of the fluid,but not to the bottom of the fluid container.

• Press the Start button to aspirate 10 uL offluid.

NOTE: The start button must be pressed twiceto aspirate a sampje just before the messagesf Ltff l ] and f LoG] appear. This is anindication that the pipette needs to becharged.

• Remove the DT Pipette from the fluidwithin two seconds.

IMPORTANT: A dotted line wi l l appear in thedisplay for two seconds while the DT Pipetteis waiting. The pipette must be removed fromthe fluid before the dotted line disappears toprevent accidental aspiration of additionalfluid.

After the two second pause, the DT Pipettewil l aspirate 2 uL of air. Upon completionof the 2 uL pullback, the message j< d5P|wil l appear in the display.

Hold pipette in vertical position.

Depress button and continue to hold buttondown as you insert pipette into pipettelocator at the aspiration station.

Slowly release pipette button and wait onesecond before removing pipette from thepipette locator in the aspiration station.

Hold the pipette vertically whenever thereis fluid in the.tips. If you tilt the pipette orlay it on its side, fluid might enter themechanism, causing it to become clogged.If this occurs, clean the pipette immediately.




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6. Remove excess fluid. Remove any droplets which may beclinging to the outside of the tip by taking alaboratory tissue and wiping the outside ofthe tip in a light, quick, downward motion.Do not wipe across the bottom of the tip.

IMPORTANT: If the tip is not wiped,results may not be accurate.

test

To remove any droplets which may beclinging to the outside of the tips, take alaboratory tissue and wipe the outside ofthe tips in a light, quick, downward motion.Do not wipe across the bottom of the tip. Ifthe tips are not wiped, test results may beinaccurate.

7. Check fluid volume. Visually check the fluid level inside the tip.

If fluid volume is not as shown, dispensesample, eject tip, and repeat steps 1-6.

Fluid Level

Check for AirSpace at Tip

NOTE: Inadequate fluid in tip can lead toerrors in test results.

• Visually check fluid level in both tips asshown in the illustration.

• Both tips should have approximately equalfluid levels.

• If fluid level is not as shown, dispensesample, eject tips, and repeat steps 1 -6.

NOTE: Inadequate fluid in tip(s) can lead toerrors in test results.




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8. Spot the slide. For procedures on slide spotting refer toSection 2.2.2.

For procedures on slide spotting refer toSection 2.2.2.

9. Check pipette tips. Visually check the tip to assure that the fluidwas completely dispensed from the tip. Iffluid is still visible, dispense the fluid into atissue and repeat the test with a fresh tip.

Check that the fluid was completelydispensed from the tips. If fluid is stillvisible, press the button to dispense thefluid into a tissue.

1O.Ejecttip(s) IMPORTANT: Never eject a tip that has fluidin it. Always dispense the fluid completelybefore ejecting the tip.

• Press the tip eject lever to eject the used tip.

• Dispose of tip.

NOTE: Use tips only once. Always use a newtip for each aspiration, even if it is drawn fromthe same fluid.

• Press the latch button to eject the used tips.

• Dispose of tips.

NOTE: Fluid should not be used if it has beenin the dual-sample cup for more than 5minutes. If so, take a clean dual-sample cupand pipette fresh fluid.




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2.2.2 Steps for Analysis on the VITROS DT II System


STEPSGENERAL

INFORMATION DT60 II System DTSC II Module DTE II Module

1. Warm slides to roomtemperature.

This takes approximately15 minutes

2. Load slides. Position the slide into theloading station.

IMPORTANT: Insertingor removing a slide withoutfollowing the analyzerprompts can causeunexpected results:

• Wait until the"ANALYZER READY"message appears beforeinserting a slide.

• DO NOT remove slidefrom spotting station afterinsertion unless directedby the analyzer.

Manually push the slideadvance lever to moveslide into spottingstation.

Manually insert theslide. It is automaticallycarried to the spottingstation.

Manually push the slideadvance lever to moveslide into the spottingstation.

U

cm •0 O j

See illustrations forproper insertion of slide.

• Notch in first

• Bar code up

• Notch to right

• Bar code up

• Notch in first

• Bar code down




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2.2.2 Steps for Analysis on the VITROS DT II System (continued)


STEPSGENERAL

INFORMATIONDT60 II System DTSC II Module DTE II Module

3. Enter patient • Analyzer wi l l displayidentification the message (optional)(optional). to enter information

with "1D=".

• To enter any patientidentification numberup to 10 characters,press the PATIENT IDkey and the numbers orcharacters you wish toenter, then press theENTER key.

• If you do not wish an IDto printout, press thePATIENT ID and CLEARkey and then press theENTER key.

4. Insert tips onto the Press tips firmly intoDT Pipette or DTE place.Pipette.

5. Aspirate the fluid.

• Use 1 new tip. • Use 1 new tip. • Use 2 new tips.




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STEPSGENERAL


6. Spot the slide. • Gently insert pipette(s)into locator. The pipettemust be fully seated inthe pipette locator.

• Press the Start button todispense 10 uL of fluidonto the slide.

• A dotted line willappear in the displayafter which the message(* R5P] or the messagela will appear in thedisplay indicating thatthe DT Pipette is readyfor the next aspiration/dispense cycle.

IMPORTANT: DO NOTremove slide from spottingstation after insertion unlessdirected by the analyzer.

An audible toneindicates that the slidehas been spotted.Remove the DT pipettefrom the pipette locatorwithin one second ofthe tone.

Green flashing lightindicates "ready-to-spot" status.

At the sound of the tonepromptly remove thepipette from the locator.Delay in the removal ofthe pipette may result ininaccuracy andimprecision.

• Depress the pipettebutton and continue tohold it depressed. Withthe button stilldepressed, promptly butslowly, remove thepipette from the locator.

• An audible tone will tellyou when the slide hasbeen spotted.

IMPORTANT: Do notrelease the pipette buttonuntil you have removed itfrom the pipette locator.Reaspiration of fluid thathas already beendispensed on the slidemay occur.

• Red indicator light willflash while slide isincubating.

7. Eject tip(s). Always use a new tip(s)for each sampleanalyzed.

Dispose of tip. Dispose of tip. Dispose of tips.




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STEPSGENERAL


8. Repeat for othertests.

Repeat steps 1 -7 foradditional sampleanalysis once analyzeris ready to acceptanother slide.

Display wi l l readANALYZER READY.

Display wi l l read DTSCMODULE READY.

Display wi l l read DTEMODULE READY.

IMPORTANT TIPS

Allow the slides to reach room temperature before use.

Press tip(s) firmly onto pipette.

Check fluid level in tip(s).

Wipe excess fluid from Ihe oulside of tips.

Handle pipette carefully while aspirating fluid and spotting slide.

Orient slides as shown in illustrations.

Enter the patient ID when prompted by the analyzer. If an ID is nol enlered, [he previous ID thatwas entered will print out.

When DT60 il System is turned on, the number 1 is an analyzer-assigned ID number for yourfirst sample until the operator changes it.

Always follow the analyzer prompts. Wait until the "ANALYZER READY" message appearsbefore inserting a slide.




2-26 Operator's ManualVITROS M System 5/95. Repr < 1/99.

2.3 Calibration Data Module and Chemistry Language Module

2.3.1 Description of Calibration Data Module

The calibration data module (CDM) is an electronic device contained in a protective carrier. The CDMcontains several different types of data required to perform various tests on the DT60 II System and the DTEII and DTSC II Modules (for example, the generation number and the calibration kit number).

OCD will issue a new CDM when:

1. You receive slides with a new generation number that is not supported in your current CDM. (Thegeneration number appears on the individual slide wrapper and slide cartons, and on the bottle labels forReference Fluid to define a formulation and process of manufacture.)

2. You receive calibrators having a new kit number which is not supported in your current CDM. The CDM mustbe installed before you use the new calibrators in order for the instrument to use the correct calibration data.

CAUTION: A CDM is a delicate electronic device. Handle with care.

2.3.2 Description of Calibration Language Module

Like the calibration data module, the chemistry language module (CLM) is an electronic device containedin a protective carrier. The CLM contains data on the messages that appear on the screen display andinformation needed to perform all tests available on the analyzer. Like the CDM, the CLM is designed toplug into back of the analyzer.

CAUTION: The CLM is a delicate electronic device. Damage can occur. Handle with care.

A new CLM is provided whenever an additional test becomes available unless your current CLM alreadycontains the test. French, German, and Italian language CLMs are available to non-U. S. customers uponrequest.



2-28 Operator's ManualVITROS " " II System 5/95. Repr" ' 1/99.

2.3.3 How to Install a New Calibration Data Module (CDM) and a Chemistry Language Module (CLM)

Follow the steps outlined below for simple installation instructions for both the CDM and CLM.

STEP ACTION TO TAKE

1. Turn the analyzer off.

2. Remove the old CDM or CLM.

The analyzer must be turned off before installingeither a new CDM or CLM.

Begin removing the old CDM or CLM byopening the door on the back of the analyzer togain access to the compartment that houses theCLM and CDM.

Read the labeling on the side of the compartmentto make sure that you are unplugging the correctcomponent.

Unplug the old CLM or CDM as shown in theillustration.


. VITROS DT II System2-29


2-30 Operator's ManualVITROS I! System 5/95. Repr \ 1/99.

2.3.3 How to Install a New Calibration Data Module (CDM) and a Chemistry Language Module (CLM) (Continued)

STEP ACTION TO TAKE

3. Install the new CLM or CDM. • Hold either component by the side edges andcarefully remove it from its packaging.

• Position the new CLM or CDM as shown on thebody of the analyzer. Note the positioning of thetabs.

• Check the alignment of the carrier to thereceptacle before inserting the CLM or CDM.

• Check the labeling to make sure that you haveinserted the correct component into the correctreceptacle.

• For CLM installation: Calibrate the analyzer forthe new test if you received the CLM with thematerials for the test. If you changed the CLMonly to change the language on the displayscreen then there is no need to recalibrate.

NOTE: If the print is jumbled on the printer, theCLM and CDM may be in the wrong positions.




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2.4 Normal Shutdown Procedure

The analyzer can be left on at the end of each day, however, the DTSC II Module should be turned off at theend of each day. Turning the analyzer off results in the loss of tests that may remain in the incubator and testresults that have not been printed. Turning the analyzer off has no effect on the instrument's memory, anddoes not result in loss of calibration values or loss of other information stored in the memory. Do not havethe DTSC II Module on if the DT60 II System is turned off. When turning the analyzer off, follow the stepsoutlined here.

1. Check incubator for tests in progress.

First, check that there are no unread slides in the analyzer through use of the TEST IN PROGRESS/TESTCOMPLETE key.

If the analyzer is connected to a VITROS DTE II Module, check the red indicator on the module. If theindicator is flashing, wait until the test result is reported and the indicator stops flashing.

2. Turn analyzer off.

2.5 Emergency Shutdown

When you are sure that all tests are complete, turn off the DTSC II Module. Then turn the DT60 II System offby moving the main power switch to the OFF position.

In case of an emergency, simply turn the main power switch on the DTSC II Module to OFF, then turn offthe DT60 II System. When you turn the analyzer on again, you will have to repeat the analysis for all teststhat remained in the incubator at the time of the shutdown.



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Coronary Risk Classification (CRC)

3.1 CRC Overview

The analyzer's microcomputer has the ability to perform Coronary Risk Classification (CRC) analysis for thepurpose of determining five- and ten-year coronary risk probabilities. The American Heart Association(AHA) recognizes this analysis which is based on an update of the coronary risk assessment methodology ofthe Framingham Heart Study conducted by the National Heart, Lung and Blood Institute (Anderson, K. M.,Wilson, P. W. R, Odell, P. M., and Kannell, W. B., "An Updated Coronary Risk Profile," Circulation: Vol. 83,No. 1Jan. 1991).

This section provides you with instructions for accessing the CRC program, entering the appropriate dataneeded to calculate coronary risk probabilities, and printing the five- and ten-year risk probabilities.

To develop a coronary risk profile, the AHA recognizes various risk factors including sex, age, cigarettesmoking, high blood pressure, high levels of serum cholesterol, low HDL-cholesterol, diabetes and ECGabnormalities. Although these are not the only accepted risk factors, they represent information which iseasily available from a doctor's office and is without patient discomfort. Values assigned for each risk factorare awarded points, based on the relative degree of risk. The sum of all points then determines the CRC five-and ten-year risk probabilities.

CRC five- and ten-year risk probabilities take into account eight risk factors and should be used as a guideonly. The test does not take into account other risk factors, e.g., obesity, x-ray cardiac enlargement, lack ofphysical activity, heredity etc. Furthermore, the probabilities represent average values over a givenpopulation and not necessarily the experience of any one person.

Coronary Risk Classification should be used with other information and parameters available from clinicalpatient evaluation. The CRC predictions provide a diagnostic tool, but are not a substitute for thephysician's judgment.




3-2 Operator's ManualVITROS "" '1 System 5/95. Repri ' 1/99.

The CRC program allows the user to input "what if?" values for a given profile in order to determine theoverall effect of that change on the five- and ten-year risk probability. For example, a 55-year-old malesmoker who has a five-year CRC of 22% may see that he can reduce his risk probability to 1 6% if he givesup smoking. Of course, there is no assurance that lowering any given risk factor wil l in reality reduceoverall risk. Clinical trials of risk-factor alteration, however, provide positive evidence that improving therisk-factor profile wil l lower the risk of coronary disease.

3.2 Entering Data for Coronary Risk Classification

1 . Access the CRC option

Press SHIFT, then SERVICE/CAL MODE. When the display prompts you to ENTER OPTION NO., key inoption 24 and press ENTER to create, enter and modify CRC records.

You may only enter this option if there are no samples processing. If samples are processing, the analyzerwill beep and display WAIT - TESTS IN PROGRESS until it completes the test.

2. Enter Patient ID

At the CRC ENTER PATIENT ID prompt, the current CRC record in memory will be displayed if one exists.You have three choices:

• Press ENTER if you wish to use the patient ID currently displayed.

• Key in up to 1 0 characters and press ENTER if you wish to enter a new patient ID. You cannot change thepatient ID, once it has been entered.

• Press the PATIENT ID key if you wish to use a patient ID in memory other than the patient ID currentlydisplayed.



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3.2 Entering Data for Coronary Risk Classification (continued)

3. Enter Sex

The CRC program allows you to maintain CRC records for up to three different patient IDs at one time. If afourth record is created, it replaces the oldest of the three existing CRC records. When you attempt to createa fourth record, the analyzer wil l tell you if the oldest record has not been reported.

CRCxxxxxxxxxNOT REPORTEDDELETE TEST TO REPLACE

It wil l identify the patient ID that wil l be replaced and will give you two options.

1. Replace the oldest record with the new patient ID by pressing SHIFT and DELETE TEST.

2. Return to the CRC ENTER PATIENT ID prompt with no replacement. To do this press ENTER.

You may also print from the patient ID screen. Touch PRINT for a printout of the CRC report. The analyzerwil l indicate which, if any, data is missing. It wil l not generate a coronary risk classification until allinformation needed to calculate the test has been entered.

Key in 0 for female or 1 for male, as appropriate. Press ENTER.

If you are working with an established record and do not wish to make a change, press ENTER to continue.




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4. Enter Age

Enter the current age of the patient and press ENTER.

The program is based on an age range of 30 to 74 years. If an age is entered that is less than 30, the programwill accept the value but wil l automatically set that age value to 30; similarly, if an age is entered that isgreater than 74, the program will set that age value to 74. Any data modified by CRC program in this waywill be noted with both a plus sign (+) next to the age and by the words "DATA SET TO AHA CHARTLIMITS" on the printed CRC report.


5. Enter Systolic Blood Pressure

Enter the systolic blood pressure of the patient and press ENTER.

If an SBP value is less than 98 or greater than 185, the program will accept the value but will automaticallyset that value to 98 or 185, respectively. When the SBP field is modified this way, a plus sign (+) and thewords "DATA SET TO AHA CHART LIMITS" will appear on the printed CRC report.

SBP measurements should be taken with the patient seated. The average of at least two readings ispreferred.

If you are working with an established record and do not wish to make a change press ENTER to continue.



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6. Enter Smoker or Nonsmoker

Enter 0 if the patient is not a smoker and has not smoked for the past 12 months. Enter 1 if the patient is asmoker or has quit smoking within the past 12 months. Once your selection is made, press ENTER.

NOTE: The program is based on data which does not address the "degree" of smoking, i.e., heavy smokersand light smokers. A distinction is made only between smokers and nonsmokers.


7. Enter Diabetic or Nondiabetic

Enter 0 for nondiabetic or 1 for diabetic, whichever is appropriate, and press ENTER.

For purposes of coronary risk assessment, the program defines a diabetic patient as one who is currentlyunder treatment with insulin or oral hypoglycemic agents OR who has a fasting glucose level of 140 mg/dLor greater.


8. Enter ECG-LVH

Enter 0 if the patient tests negative for left-ventricular hypertrophy by ECG. Press 1 if the patient testspositive. Press ENTER to continue.

LVH-ECG consists of finding tall R-waves in leads reflecting potentials from the left ventricle. The R-wavesare accompanied by nonspecific S-T or T-wave abnormalities.

Enter 0 for ECG-LVH to get a rough estimate of a person's coronary risk classification, when ECG data areunavailable. It should be recognized, however, that in a small fraction of people the CRC assessment willbe inappropriately low since ECG-LVH is a strong risk factor when it is reported as positive. See the CRCSupplement for further information.




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9. Enter CHOL value

There are 3 approaches to entering the CHOL and HDLC values.

1. You may run up to 10 CHOL tests and 10 HDLC tests (the analyzer has the capacity to remember theresults for 20 tests) and then enter the corresponding CRC data for those 10 patients. After a complete setof data is stored for a patient, you may successfully request a printout of the Coronary Risk Classificationresults.

2. You may enter the CRC data for up to three patients at a time, then run the CHOL and HDLC tests. Theanalyzer will automatically printout the CRC results after printing the results for the chemistry tests.

3. You may run the CHOL and HDLC tests and keep a record of the test results for input into the CRC optionat a later time. This allows you to run the CRC tests at your convenience and not worry about the 20-result capacity in the buffer.

Assuming the CHOL test was run on the patient sample previous to entering CRC data, the cholesterolvalue will automatically be displayed on the analyzer screen. If the screen is blank, the CHOL value needsto be entered. Once the data has been computed and printed, you may enter a new CHOL value replacingthe current value or alter other risk parameters, permitting you to conduct "what if?" tests.

NOTE: Values that printout GREATER THAN ANALYZER RANGE will not be included in the 20 reportbuffer. Once the sample has been diluted it will not be considered multiple. The analyzer willautomatically print a result based on the diluted sample. The CHOL value must be multiplied by two andentered into the data to replace the current (diluted) value. You will receive an incorrect CRC result if thedata is not modified.

Both CHOL and HDLC require manual entry if either was multiple within the last 20 results. In this case,the word MULTIPLE will be displayed on the screen. Enter the appropriate CHOL value. The printed CRCreport will be marked with an asterisk (*) next to the value indicating that the value was manually enteredor "User Modified" and with a pound sign (#) indicating multiple results. Both CHOL and HDLC will bemarked as multiple if either was multiple.

If a CHOL value is less than 139 mg/dL or greater than 330 mg/dL, the program will accept the value butwill automatically setthat value to 139 mg/dL or 330 mg/dL, respectively. When the CHOL field is modifiedin this manner, a plus sign (+) and the words "DATA SET TO AHA CHART LIMITS" will appear on theprinted CRC report.

Operator's Manual 3-115/95. Reprinted 1/99. . VITROS DT II System


10. Enter HDLC value

As mentioned in step 9, there are 3 approaches to entering HDLC values.

If the screen is blank, the HDLC needs to be run or the value entered manually.

If an HDLC value is less than 25 mg/dL or greater than 96 mg/dL, the program automatically sets that valueto 25 mg/dL or 96 mg/dL, respectively. When the HDLC field is modified in this manner an asterisk (+) andthe words "DATA SET TO AHA CHART LIMITS" will appear on the printed CRC report.

NOTE: If all other criteria are in the analyzer memory and the HDLC has been pre-diluted, the analyzer wil lautomatically print a result based on the diluted sample. The HDLC value must be multiplied by two andentered into the data to replace the current (diluted) value. You will receive an incorrect CRC result if thedata is not modified.

If you tend to manually enter your results, make sure you multiply the diluted value by two when enteringthe number. If you enter the CRC data after running the tests, make sure you modify the HDLC data beforerequesting a CRC report.

3.3 Printing CRC Results

Press PRINT if you wish to have the keyed-in values computed and a coronary risk classification reportprinted. The printed report lists the CRC values you entered for each field along with the five- and ten-yearrisk factors and it prints the peer average for 10-year risk within the appropriate gender.

If all CRC data is available but the computed CRC total point value exceeds the American Heart Associationchart maximum of 32, the following message will be printed to finish the CRC printout:

************************

AHA CHART EXCEEDED**** ********** **********

Press ENTER if you wish to return to the PATIENT ID prompt to add missing data or modify data beforeprinting.

The program will be unable to calculate the five- and ten-year risk probability if any field of information ismissing. Note the meaning of certain indicators that may precede entered data (see sample CRC reports onnext two pages):




3-14 Operator's Manual- VITROS 'I System 5/95. Repr ' 1/99.

3.3 Printing CRC Results (continued)

plus sign (+) DATA SET TO AHA CHART LIMITS.

Indicates that the entered value was not within the limits set by the program.Subsequently, the program modified the entered value.

asterisk (*) USER MODIFIED.

• Data was modified after the CRC report was printed, e.g. smoker vs. nonsmoker.

• It also indicates a CHOL or HDLC value was entered manually AND the manualentry was made prior to printing the CRC report.

pound (#) MULTIPLE RESULTS.

Indicates that multiple results were found for either CHOL and/or HDLC prior toprinting the CRC report. Both are marked a multiple if either had multiple results priorto printing.

12. Press SHIFT, then SERVICE/CAL MODE to exit option 24.

13. Press SHIFT, then SERVICE/CAL MODE again to exit the service mode.



3-16 Operator's ManualVITROS " 'I System 5/95. Repr" ' 1/99.


1. CHOL & HDLC report, followed by CRC prediction and user-modifiedCRC prediction.

2. Age and SBP were set to AHA chart limits

*"*** ** *%*~¥**Ni*y<***y

*******************

I.D:99-04-91*******************CHOL

HDLC46 MG/DL

**•••******•***•***CRC

- ^ - ^ V V V V V ™ ^ ^ ^ ^ p

PT ID 190FEMALE45 VEARS118 MM HQ SBPSMOKERNON-DIABETICECG-LVH NEGATIVECHOL 239 MG/DL

HDLC 46 MG/DL

5 VR RISK 3"-:

10 VR RISK 6":AVERAGE 19 VEARRISK FOR FEMALE45-49 VEARS: 5>.**************************************

*******************MODIFIED CRC

*******************PT ID 190FEMALE45 VEARS113 MM HS SBP

* NON-SMOKERNON-DIABETICECG-LVH NEGATIVE

* CHOL 189 MG/DLHDLC 46 MG/DL

* USER MODIFIED

5 VR RISK IS

19 VR RISK 2m<

AUERAGE 10 VEARRISK FOR FEMALE45-49 VEARS: 5'<**************************************

I.D: 589-04-91******** ***********CHOL

HDLC45 MG/DL

*******************CRC

*******************PT ID =FEMALE

+ 74 VEARS •+ 185 MM HG SBP

NON-SMOKERNON-DIABETICECG-L'JH NEGATIVECHOL 163 MG/DLHDLC 45 MG/DL

+ DATA SET TOCHART LIMITS

5 VR RISK b'-i

19 VR RISK 13'-.

AVERAGE 10 VEARRISK FOR FEMALE76-74 VEARS: 12X**************************************




3-18 Operator's ManualVITROf II System 5/95. Rep' i 1/99.


3. Multiple reports for CHOL and/or HDLCfollowed by CRC report with manualentry of CHOL and HDLC.

*******************CRC

*******************PT ID 19FEMALE37 VEARS12@ MM HG SBPSMOKERNON-DIABETICECG-LVH NEGATIUE

#CH0L MULTIPLE#HDLC MULTIPLE

# MULTIPLE RESULT

MISSING CRC DATA* * * * * * * * * * * * * * * * * * ** * * * * * * * * * * * * * * * * * *

* * * * * * * * * * * * * * * * * * *MODIFIED CRC

*******************PT ID 10FEMALEZ7 VEARS120 MM HG SBPSMOKERNON-DIABETICEC6-LUH NEGATIUE

*#CH0L 174 MG/DL*#HDLC 59 M6/-DL

* USER MODIFIED# MULTIPLE RESULT

5 VR RISK

10 VR RISK <2'/.

AVERAGE 10 VEARRISK FOR FEMALE35-39 VEARS: <i\**************************************

4. CHOL and HDLC followed by CRCreport indicating risk factors weregreater than AHA Chart Limits.

* * * * * * * * * * * * * * * * * * *1.0: 1509-94-91* * * * * * * * * * * * * * * * * * *CHOL

231 ItQ/DL

5. CRC report requested without allinformation needed to make prediction.

HDLC45 MQ/DL

*******************CRC

*******************PT ID ItFEMALE72 YEARS131 MM HG SBPSMOKERDIABETICECS-LUH POSITIUECHOL 231 MG/DLHDLC 45 MQ/DL

*******************AHA CHART EXCEEDED**************************************

*******************CRC

*******************PT ID 2?MALE48 VEARS119 MM HG SBPNON-SMOKERDIABETICECG-LUH NEGATIUECHOL MISSINGHDLC MISSING

MISSING CRC DATA**************************************




3-20 Operator's ManualVITROS H T II System 5/95. Repn -I 1/99.

Derived Tests

The VITROS DT II System has the ability to calculate derived tests based on the results of related chemistrycomponents.

This section describes how to access the options for derived tests, how to process derived tests, and how toprint derived test results.

3.4 Overview

Derived test processing is available for:

1. Globulin (GLOB) and the Albumin-Globulin Ratio (A/G). Calculations are derived from ALB and TP testresults.

2. Very low density lipoproteins (VLDL), low density lipoproteins (LDL) and the cholesterol/high densitylipoprotein cholesterol ratio (CHOL/HDLC Ratio). These tests are collectively called the LipidCalculation. Calculations are derived from CHOL, HDLC and TRIG test results.

3. Anion gap (AGP). This calculation is derived from Na+, Cl" and CO2 test results.

For derived test processing to occur, the following conditions must be met:

• The derived test must be turned on by selecting the appropriate Option number prior to running tests onthe component chemistries.

• Ajj of the components required to calculate the derived test result must be within the last 20 testsreported.

• There must be no more than one test result stored in the analyzer for the component and patient ID justtested. No multiple results are allowed.

IMPORTANT

To assure completion and accuracy of derived test processing:

• Component chemistry values must not be based on a dilution factor.

• A 1-10 character patient ID must be entered for the component tests prior to spotting the necessaryslides with fluid.




3-22 Operator's ManualVITROS M System 5/95. Repr" < 1/99.

3.5 GLOB and A/G

These derived tests are calculated from ALB and TP test results as follows:

GLOBA/C

TP-ALBALB/GLOB

To access globulin and the albumin/globulin processing:

• Press SHIFT, then SERVICE/CAL MODE to enter the service mode.

You may only enter this option if there are no samples processing. If samples are processing, the analyzerwill beep and display - WAIT - TESTS IN PROGRESS until it completes all tests.

• When the display prompts you to ENTER OPTION NO., key in 25 and press ENTER.

• Press 1, then ENTER to turn on GLOB and A/G Ratio derived test processing.

• Press SHIFT, then SERVICE/CAL MODE again to exit the service mode.

Now you are ready to run the component tests as outlined in section 2 of this manual, OperatingInstructions.

Once the patient ID is entered and both the ALB and TP slides are analyzed, GLOB and A/G test results wil lautomatically be calculated and printed along with the ALB and TP test results.

If more than one value for ALB or TP for a given patient ID appears in the last 20 results buffer, the testname and MULTIPLE RESULTS Will appear on the printout followed by the name of the derived test and NORESULT-COMPUTE MANUALLY.




3-24 Operator's Manual• VITROS 'I System 5/95. Repr '1 /99.

3.5 GLOB and A/G (continued)

To turn globulin and the albumin/globulin processing off:

• Press SHIFT, then SERVICE/CAL MODE.


• Press 0 to turn off GLOB and A/G derived test processing.


1. Results from component tests, ALB andTP, followed by GLOB and A/G results.

*******************I.D: 515481-20-92*******************ALB3.0 8/DL

TP4.5 G/DL

*******************I.D: 5i5dTP 4.5 G---DLALB 3.0 G/DL

GLOB 1.5 6/-DLA/G 2 . 0* * * * * * * * * * * * * * * * * * *

2. A 1-10 character patient ID was notentered prior to running ALB or TP tests.

6 1 - 2 8 - 9 2* ft************** ***ALB

Z.B

TP3.6

*******************I.D!TPBLANK PATIENT ID

HQ RESULTCOHPUTE HAHUALLV*******************

3. The analyzer cannot calculate results forGLOB or A/G if there are multiple resultsfor either of the component tests.

1,1 1*.***,-, * : : • . * * * * * * • * * * * *

8..: •j-'DL

TP

ALB5. i

j,'DL

j/DL

* * * * x * »: * * * * * * * * * * * *

I.D: 1Tp

HL'-'.PLE RESULTS

GLOB,A,G HO RESULTCOMP.Ti MANUALLV* * * * : / * : y t * * * * * * * * * * * *

Operator's ManualV1TROS DT II System

3-25

3.6 Lipid Calculation (VLDL, LDL and CHOL/HDLC Ratio)

These derived tests are calculated from TRIG, CHOL and HDLC test results as follows:

VLDL = TRIG/5.0 (Conventional units)

TRIG/2.2 (SI units)

LDL = C H O L - H D L C - V L D L

CHOL/HDLC ratio = CHOL/HDLC

To access VLDL, LDL and CHOL/HDL Ratio processing:


You may only enter this option if there are no samples processing. If samples are processing, the analyzerwill beep and display - WAIT - TESTS IN PROGRESS until it completes all tests.


• Press 1, then ENTER to turn on the lipid calculation derived test processing.



Once the patient ID is entered and CHOL, HDLC and TRIG slides are analyzed, VLDL, LDL AND CHOL/HDLC ratio results wil l automatically be calculated and printed along with the CHOL, HDLC, and TRIGtest results.

If more than one value for CHOL, HDLC or TRIG for a given patient ID appears in the last 20 results buffer,the test name and MULTIPLE RESULTS wil l appear on the printout followed by the name of the derived testand NO RESULT-COMPUTE MANUALLY.



3-28 Operator's ManualVITRO II System 5/95. Rep d 1/99.

3.6 Lipid Calculation (VLDL, LDL and CHOL/HDLC Ratio) (continued)

VLDL and LDL will not be calculated if the TRIG value is greater than or equal to 400 mg/dL (4.52 mmol/L).In this case, the error message NO RESULT TRIG TOO HIGH wil l be printed.

To turn the lipid calculation derived test processing off:



• Press 0, then ENTER to turn off the lipid calculation derived test processing.




3-30 Operator's ManualVITROS M System 5/95. Repr ' 1/99.

3.6 Lipid Calculation (VLDL, LDL and CHOL/HDLC Ratio) (continued)

1. Results from component test, TRIG,followed by the VLDL result.

Results from component tests, CHOL andHDLC, followed by LDL, VLDL andCHOL/HDLC results.

*******************I . D : 7881601-28-92* * * * * * * * * * * * * * * * * * *TRIQ

125 MG-'DL

* * * * * * * * * * * * * * * * * * *I .D: 78916TRIG 125 MQ/DL

ULDL 25 PfG/DL* * * * * * * * * * * * * * * * * * *

2. A 1-10 character patient ID was notentered prior to running CHOL, HDLC,or TRIG.

3. The analyzer cannot calculate results forLDL, VLDL, or CHOL/HDLC if there aremultiple results for any of the componenttests.

*******************

CHOL163

HDLC65

MQ/DL

MG.'DL

*******************I.D:TRIGCHOLHDLC

70816125 MS/DL163 MG/DL65 WG/DL

LDL 73 MQ^DLULDL 25 MG/DLCHOL-'HDL RATIO 2.5*******************

*******************I. o;01-20-92* * * * ******** * * * * * * *CHOL

160 CIG-'DL

HDLC66 riG.-'DL

*******************I.D:HDLC

BLANK PATIENT ID

Cv-H,LDL HO RESUL T

COMPUTE MANUALLV***•***********+***

TRIG128 TIQ/OL

*******************

I. D :TRIG

BLANK PATIENT ID

ULDL,LDL NO RESULTCOMPUTE MANUALLV*******************

* * * * * * * :f * **********I.D: 2 "561-24--92*******************CHOL232

CHOL234

TRIG255

MG.'DL

Mi

MG/DL

*******************I.D: 25TRIG 255 MS/DL

ULDL 51 MG-'DL•fc************************************

HDLC52 f1G-'0L

*******************I.D: 25CHOL

MULTIPLE RESULTS

C/H,LDL HO RESULTCOMPUTE MANIJALLV* * * * * * * * * * * * * * * * * * *


VITROS DT I! System3-31


3-32 Operator's ManualVITROS '! System 5/95. Repr< ' 1/99.

3.7 Anion Gap (AGP)

This derived test is calculated from Na+, CI" and CO2 test results as follows:

AGP = N a + - ( C r

To access AGP processing:


You may only enter this option if there are no samples processing. If samples are processing, the analyzerwil l beep and display - WAIT - TESTS IN PROGRESS until it completes all tests.


• Press 1, then ENTER to turn on AGP derived test processing.



Once the patient ID is entered and Na+, CI" and CO2 slides are analyzed, the AGP result wil l automaticallybe calculated and printed along with the Na+, CI" and CO2 test results.

If more than one value for Na+, CI" or CO2 for a given patient ID appears in the last 20 results buffer, the testname and MULTIPLE RESULTS will appear on the printout followed by the name of the derived test and NORESULT-COMPUTE MANUALLY.


. VITROS DT II System3-33


3-34 Operator's ManualVITROS M System 5/95. Repr '1/99.

3.7 Anion Gap (AGP) (continued)

To turn anion gap processing off:



• Press 0, then ENTER to turn off the AGP derived test processing.


1 . Results from component test, Cl", CO2 ,and Na+, followed by AGP result.

01-29-92* * * * * * * * * * * * * * * * * * *

CL-Sl

C0225

HA+119

MMOL-'L

riMOL/L

MMOL/L

*******************I.D: 484243NA+ 119 MMOL-'LCL- 81 MMOL.-'LC02 25 PHIOL-'L

A8P 13 MMOL-'LH e * * * * * * * * * * * * * * * * * *

2. A 1-10 character patient ID was notentered prior to running Cl", CO2, andNa+ tests.

*******************I.D:61-20-92*******************

UL-32 MMOL/L

C0222

NA+119 MMOL/L

*******************I.D:NA+BLANK PATIENT ID

AGP NO RESULTCOMPUTE MANUALLV*******************

3. The analyzer cannot calculate results forAGP if there are multiple results for anyof the component tests.

* f * -i- .«•• i- ,: * * * * * * * * * * . * *

I .D: 2* :f * f •-: • * * * * * * * * * * * *

CL-12: .iMOL-'L

121

COX

NA +

***y- i . . * * * * * * * * * * * *

I.D: 2CL-

Ml'-'-PLE RESULTS

AGP ..: RESULTCOM?W

T£ MHNUALLV* * • * . . * . • , • : * * * * * * * * * * * *

:M0L/L




3-36 Operator's Manual.VITROS 'I System 5/95. Repr '1/99.

Calibration

Calibration of blood-chemistry analysis equipment is an extremely important part of good laboratoryprocedure, since calibration helps to ensure the accuracy of test results. Faulty calibration — or failure tocalibrate the VITROS DT60 II System when recommended — can lead to erroneous test results.

When you calibrate the DT60 II System, you are programming new information into the software thattranslates data gathered during a slide reading into test results. Thus, during calibration, you are establishingnew parameters for this translation process.

The actual calibration procedure involves the analysis of VITROS calibrators — fluids with known analyteconcentrations — in much the same manner as you analyze patient samples. Unlike sample analysis,however, the entire calibration procedure takes place with the System in the calibration mode, rather thanthe run mode.

This procedure has been designed with ease and flexibility in mind. For instance, while it is suggested thatyou calibrate the tests in a certain order to make sure you do not miss any of them, you are free to calibratein any order you wish. Thus, you can rearrange this procedure to meet your special needs.

4.1 Why You Need to Calibrate

Periodic calibration of the DT60 II System is required to maintain instrument reliability.

As you calibrate, the analyzer establishes calibration parameters used to translate the response of theanalyzer into concentrations of a desired analyte. These parameters, which are printed out at thecompletion of the calibration process, are stored in the analyzer's microcomputer memory.



4-2 Operator's ManualVITROS 'I System 5/95. Repr '1/99.

4.2 When to Calibrate

Calibration is crucial to the ongoing reliability of your test results. CALIBRATE THE ANALYZER FOR ALLTESTS:

1. When the analyzer is initially installed.

2. When government regulations require.

- For example, in the USA, CLIA regulations require calibration or calibration verification at least once everysix months.

3. When your Field Engineer indicates that calibration is necessary because servicing procedures mighthave affected the validity of the stored calibration parameters.

Calibrate the analyzer for individual tests:

1. When the lot number of the ViTROS DT Slides change.

2. When the results of a quality control test using VITROS DT Controls or VITROS DT Isoenzyme Controlsare consistently outside an acceptable range.

3. When a new lot of VITROS DT Reference Fluid is used. (This requires recalibration of tests run on theDTE II Module only.)

NOTE: Refer to Section 13, "Log Sheets," for a sample of calibration log sheets to record data.




4-4 Operator's ManualVITROS 'I System 5/95. Repr M/99.

4.3 How to Calibrate

The major steps in the calibration procedure are: preparing the calibrators, analyzing them on theinstrument, and assaying quality control fluids. Refer to the chart provided in this section for proceduralsteps on calibration.

The procedure for analyzing the calibrators is designed to be simple and straightforward. In fact, it is verysimilar to the procedure used to analyze patient samples. However, the analyzer operates in the calibration(CAL) mode and analyzes the concentration of VITROS DT calibrators rather than patient samples.



4-6 Operator's Manual. VITROS 'I System 5/95. Repr '1/99.

4.3.1 Preparing VITROS DT Calibrators

Calibrators needed for the DT60 II System are generally lyophilized materials that need to be reconstitutedand used as soon as possible. Refer to the instruction sheet packaged with the product for reconstitutionprocedures and storage and stability requirements.

STEP

1. Allow calibrators to warm to roomtemperature.

2. Open bottles.

3. Reconstitute the calibrators.

ACTION TO TAKE

• Allow at least 30 minutes for frozen calibratorsand diluents.

• Remove metal seal from each bottle just beforeyou intend to use them.

IMPORTANT: DO NOT allow the diluents to standwithout the stoppers.

• Tap the top of each bottle so that any lyophilizedmaterials adhering to the inside of the rubberstopper drop down into the bottle.

• Add exactly 3.0 mL of the appropriate diluent toeach vial of lyophilized calibrator.

• Use a new 3.0 mL pipette tip for each diluent.

• Discard any remaining diluent.

IMPORTANT: DO NOT interchange calibratorsand diluents.




4-8 Operator's ManualVITROS 'I System 5/95. Repr' i 1/99.

4.3.1 Preparing VITROS DT Calibrators (continued)

STEP ACTION TO TAKE

4. Dissolve all lyophilized particles. Allow calibrators to stand for 30 minutes.

Slowly invert the diluent bottles several times tomix the contents thoroughly. Swirl bottlesperiodically, but DO NOT SHAKE the bottles.

Invert the bottles slowly to dissolve thelyophilized particles.

• All particles must be dissolved before using.




4-10 Operator's ManualVITRO!" II System 5/95. Rep i 1/99.

4.3.2 Entering the Calibration Mode

STEP

1. Allow the slide to warm to roomtemperature.

2. Enter the calibration mode.

ACTION TO TAKE

This takes approximately 1 5 minutes.

Press the CAL key. The word CAL wil l appear in theupper right hand corner of the display.

3. Enter the calibrator kit number. • The display will prompt you ENTERCALIBRATOR KIT NUMBER.

• Enter the kit number that is printed on the cartoncontaining the calibrators, then press the ENTERkey.

4. Enter the generation number of theReference Fluid.

• Enter the generation number found on the labelof Reference Fluid, then press the ENTER key.

• If you do not have reference fluid, then enter 01and press the ENTER key.




4-12 Operator's ManualVITROS 'I System 5/95. Repr M/99.

4.4 Calibration

STEPS FOR CALIBRATION ON THE VITROS DT II SYSTEM

STEP GENERAL INFORMATION

1. Push slide into spotting station. • Run bottles in sequence.

• The display will prompt you which bottlenumbers to use.

• Enter calibrator bottle number by pressing thebottle number and ENTER key.

IMPORTANT: DO NOT insert slide until DT60indicates "ANALYZER READY".

IMPORTANT: DO NOT remove slide from spottingstation after insertion unless directed by the analyzer.

2. Insert and fill dual-sample cup. DTE II Module only.

See Section 2 for specific instructions.

3. Aspirate calibrator fluid.

DT60 IIand

DTSC II

Fluid Level

Check for AirSpace at Tip

• For specific instructions on proper pipettingtechniques see Section 2.

• Carefully place pipette into calibrator bottle.

• Aspirate fluid.

• Check fluid volume as shown in illustrations.




4-14 Operator's ManualVITROS 'I System 5/95. Repr < 1/99.

4.4 Calibration (continued)

STEPS FOR CALIBRATION O N THE VITROS DT II SYSTEM


4. Spot slide.

IMPORTANT: DO NOT remove slide fromspotting station after insertion unless directed by theanalyzer.

Carefully position pipette in locator.

DT60 I I System

• With the pipette in the locator, depress andrelease the start button.

• An audible tone indicates that slide is spottedand you should then remove the pipette fromlocator.

DTSC II Module

• A green flashing light and an audible toneindicate a "ready-to-spot" status.

• When spotting is completed the green light willgo off.

DTE II Module

• Depress the pipette button and continue to holdit depressed. With the button still depressed,slowly remove the pipette from the locator.

• An audible tone will tell you when the slide hasbeen spotted.

• A flashing red light appears to indicateincubation has begun.

5. Eject tips. DTE II Module

• Discard dual-sample cup after each bottle.




4-16 Operator's Manual.VITROS' '[System 5/95. Repr '1/99.




6. Repeat steps 1-5 for the same test using thenext bottle.

Flashing numbers on the display indicate thebottles which have been run for a particular test.

7. Examine test results. • Printout should read as follows:

* 1 REP # 1

• The number after the * is the bottle number, andthe number after the # is the successful replicatecompleted.

IMPORTANT: if a slide is not processedsuccessfully on the first rep during calibration, azero is reported instead of a valid replicate number(for example, * 1 REP # 0). If this happens, runanother slide for the same test using the bottlenumber indicated on the display screen.

8. Repeat steps 1 through 7 for other tests. Before exiting the calibration mode, be sure thereare no printout messages which report a zero (0)instead of a valid replicate number.






9. Exit calibration mode. • Press CAL key.

• If you accidentally forgot to run a bottle (forexample, * 1 REP # 0), the display wil l read:

TEST MISSING BOTTLESLOAD "TEST" OR PRESSCAL TO EXIT.

• Rerun missing bottle if indicated.

• If you do not run the bottle indicated, the testwil l not be calibrated.

• Press CAL key a second time to exit cal mode.

• Date and save calibration printout, label with 12-digit slide lot #.

***************CALIBROTIONGLUCP*1-5.6943CP#2 106.9SCP#3 2.3413******************************CALIBRATIONURICCPK1-1.8474CP#2 12.551CP#3 1.581S******************************CALIBRATIONK +CFB1 1.2825CP#2 .016945***************




4-20 Operator's ManualVITRO? II System 5/95. Repr 11/99.




10. Run a quality control test. • Refer to Section 6.

IMPORTANT TIPS

Warm slides and calibrator fluids to room temperature.

Do not interchange calibrators and diluents.

For tests run on the DTE II Module, it is recommended that you run each bottle twice.

Examine printout results.

Run a quality control test to verify calibration.




4-22 Operator's ManualVITRO? II System 5/95. Rep' 11/99.

Instrument Care and Cleaning

Your VITROS DT60 II Chemistry System is designed to keep routine care and cleaning to a minimum. Sinceall analyses take place within VITROS DT Slides, there are no liquid reagents to mix or dispose of andfewer opportunities for messy spills. The self-contained nature of the analysis method also minimizes theneed to clean the internal parts of the equipment.

In short, the analyzer is not a demanding piece of equipment, but it does require some simple care to keepit operating reliably.

The dry chemistry technology employed by DT Slides and the design of the DT60 II System, DTE II Module,and the DTSC II Module combine to minimize the need for care and cleaning. However, attention to dailyand weekly cleaning, along with good housekeeping practices (keeping the analyzer and surrounding workareas as clean as possible, wiping up spills on the analyzer surface as soon as they occur) arerecommended to provide for the continued optimum performance of your equipment.

CAUTION: Routine cleaning does not necessitate opening the analyzer's main cover.

Do not remove main cover or clean analyzer, DTE II Module or the DTSC II Module with ammonia orammonia-containing compounds.

Operator's Manual 5-1Rev. 10/01 VITROS DT II System


Operator's Manual 5-2Rev. 1^""T VITROS r M System

5.1 Daily Cleaning

WHAT TO CLEAN HOW TO CLEAN

1. Slide disposal box(es). • Lift out box(es) from analyzer and modules.

• Wash box(es) in a dilute solution of sodiumhypochlorite — for example, a 10% solution ofliquid household bleach, or autoclave thebox(es).

• Replace box(es) after cleaning.

NOTE: Please refer to the VITROS DT Pipette User's Guide for information on cleaning and charging theDT Pipette.

Operator's Manual 5-3Rev. 10/01 VITROS DT II System


Operator's Manual 5-4Rev. 1 r "M VITROS ^ " M System

5.2 Weekly Cleaning

Clean the analyzer and modules as outlined here. You may use these same procedures when you detectaccumulated dust or serum contaminants on the equipment during normal operation.

Cleaning the DT60 II System


1. Pipette locator and visible slide track area. Clean the pipette locator and all visible slidetrack areas with a cotton swab moistened withwater.

PipetteLocator

SlideTrack

Rev. 10/01Operator's Manual



Operator's Manual 5-6Rev. T" n VITROS' 'I System

Cleaning the DT60 II System (continued)


2. Bar code reader and drop detector surfaces. • Put your thumb in the hole at the front of theanalyzer spotting station cover and lift up toexpose the internal assemblies.

• Use lukewarm water and a clean, dry cottonswab to clean the surfaces. When cleaning iscomplete close the spotting station cover.

Bar CodeReader

DropDetectorSensor




Operator's Manual 5-8Rev. VITRO? 'I System

Cleaning the DTE II Module


1. Pipette locator and visible slide track area. Clean the pipette locators at the aspiration andspotting stations and the visible slide track areas,with a clean, cotton swab moistened with water.After cleaning, dry the area with another swab.

PipetteLocator

Slide Track

PipetteLocator




Operator's Manual 5-10Rev. 1 ' . VITROS 'I System

Cleaning the DTE II Module (continued)


2. Rubber boot on the front of the electrometer.

Screw

Electrometer 'Assembly

Remove the pipette locator by placing your handon the module and your thumb under the pipettelocator slot. Lift the pipette holder up and out.

Remove the nose assembly by turning the screwcounterclockwise.

Inspect and clean nose assembly and rubberboot with distilled water, then dry with lintlesstissue. Place back into position and tightenscrews clockwise.

1 Replace the pipette locator by placing the locatorat an angle and placing the tabs on the squareholes. Pull up slightly and push in anddownward at the same time.

ElectrometerNose Assembly,Removed

Top View

Bottom View

Rubber Boot




Operator's Manual 5-12Rev. 1 VITROS 1 System

Cleaning the DTSC II Module


1. Pickup and slide spotting stations.

2. Slide track.

• Clean these stations with a clean, absorbentcloth moistened with water. Dry them with acloth after cleaning.

• Raise the access cover of the module to exposethe internal parts.

• Remove the pipette locator.

• Use water and a clean absorbent cloth to cleanthe length of the slide track. Dry the slide trackafter cleaning.

SlideSpottingStation

Pickup Station




Operator's Manual 5-14Rev. 1 ' VITROS '! System

Cleaning the DTSC II Module (continued)


3. Pipette locator. • Use water and a swab to clean the hard-to-reachareas.

• Carefully replace the pipette locator.

Disassembled PipetteLocator




;. Operator's Manual 5-16Rev. ' 1 VITROS II System

Cleaning the DTSC II Module (continued)


4. White reference cap and sapphire readwindow.

The white reference cap is located on theunderside of the read station preheater arm. Usewarm water and a clean, absorbent cloth.

The sapphire read window is directly beneaththe read station arm. Use warm water and aclean, absorbent cloth to clean the window.

WhiteReferenceCap

Sapphire Read Window




Operator's Manual 5-18Rev. 1 • VITROS 'I System

5.3 Other Cleaning: VITROS DT60 II Chemistry System FORS Head

Cleaning of the fiber optics reflectance system (FORS) head in the analyzer is recommended prior torecalibration and when dust is present. The analyzer wil l prompt you with one of the error codes R11-R1 7to notify you of the necessity to clean.


FORS HEAD

WeightCoveringFORS Head

Put your thumb in the hole at the front of theanalyzer's spotting station cover, and lift it toexpose the internal assemblies. To expose theFORS head, lift up on the weight that covers thehead and rotate it out of the way.

Clean with a cotton swab moistened with water.Dry with a fresh cotton swab. Remove all lint.Return the weight into position over the FORShead and close the spotting station cover.

FORS Head




Operator's Manual 5-20Rev. ' ' . VITROS 'I System

5.4 Paper Loading

5.4.1 Removing the Paper

STEP

1. Remove printer cover.

2. Remove paper core.

ACTION TO TAKE

• Position your thumb on the top of the cover andyour fingers along the bottom edge of the coverwhere it joins the left side of the analyzer. Pull itup firmly and away from the analyzer.

• Slide the paper core out of the printer cradle andcut the paper tape at any point between the coreand the slot where the paper enters the printer.

• After the tape is cut away from the core, removethe remaining tape by pulling it out through theprint head.

CAUTION: Remove the paper with a forwardmotion only. Reverse motion can damage thefeeder.




Operator's Manual 5-22Rev. 1 ' VITROS II System

5.4.2 Inserting Paper

STEP ACTION TO TAKE

1. Load new roll. Cut both corners of the edge.

Position paper roll as shown in illustration.

Load paper into the printer cradle keeping thepaper in the same position so that it feeds fromthe bottom of the roll.


VITROS DT il System5-23


Operator's Manual 5-24Rev. 1 ^ 1 VITROS '—II System

5.4.2 Inserting Paper (continued)

STEP ACTION TO TAKE

2. Feed paper into print head.

3. Advance paper.

Feed paper over the roller and through the slot inthe back of the print head.

Feed the paper until you feel resistance, a signthat the paper has engaged in the pressure rollerof the print head.

Press the PRINT key to feed the paper throughthe print head.

If the paper does not feed through the print head,try feeding it through the slot in the back of theprint head again, or it may be necessary to turnthe DT60 II System off and back on again to resetthe printer.




Operator's Manual 5-26Rev. 1 ' VITROS II System


STEP ACTION TO TAKE

4. Replace printer cover. • Make sure that the paper feeds out through theslot between the printer cover and the rest of theanalyzer surface.

• Manually feed the paper through the tear bar andpaper cover.




Operator's Manual 5-28Rev. 1 VITROS 'I System


STEP ACTION TO TAKE

5. Check printer operation. Press the SHIFT key and then the SERVICEMODE key to enter the service mode.

When the display prompts you to enter anoption, enter Option 4.

When the character set has printed out, press theSHIFT and SERVICE MODE key again to exit theservice mode. The analyzer then returns to runmode.

Rev. 1 0/01Operator's Manual



Operator's Manual 5-30Rev. 1 ^ 1 VITROS^' II System

Quality ControlReporting reliable patient test results can be assured through acomprehensive quality control program. Like calibration, regularquality control testing is an important part of laboratory procedures,playing a vital role in maintaining the accuracy of test results.

6.1 What Is Quality Control?

6.2 What Are Controls?

Quality control is a means of monitoring the precision and accuracyof the performance of an analytical system. In a clinical laboratory,an analytical system consists of: operators' techniques, theinstrument, the reagents (for example, the slides), the calibrators andthe environment of the laboratory, (for example, temperature andhumidity). Precision is the reproducibility of a test and accuracy is adescription of how closely your test results agree with the true valueof the analyte being tested.

Quality control verifies the success of a calibration and allows you tomonitor the long-term performance of the equipment.

There are two primary elements in maintaining quality control (QC).• Monitoring of the control results• Following generally accepted lab procedures

Controls contain known amounts of the same analytes that theanalyzer measures in actual patient samples. This allows you tocompare the results the analyzer delivers with known values.

If controls fall within an acceptable range, patient samples may beanalyzed with confidence.

6.3 How Often Should Controls Be Run?

Local regulations may indicate both the number of and frequencywith which you are required to run controls. Analyzing controls dailywill assist you in identifying changes in the system and taking actionpromptly. We recommend that, at a minimum, you perform a qualitycontrol test:• Once a day for all tests being performed in your office that day• After completing calibration• When you suspect patient results are inaccurate• After any major repairs performed on the analyzer

In addition to these, your lab may establish its own requirements. It isimportant that the time interval between control tests satisfies bothyour needs and the requirements of local regulations.


6.4 How to perform a quality control test

6.4.1 Preparing Lyophilized Controls

Most tests performed on the VITROS DT II System are lyophilized,(freeze-dried) material, although some are in liquid form. These areprepared from human and bovine serum and should be handled withthe same precautions that you would with any other serum sample.The lyophilized controls must be reconstituted before use.

Avoid ingesting any material and wipe up any spills immediately.Refer to the instruction sheet packaged with the product for storageand stability requirements.

1. Allow the controls to reach room temperature.

• Materials should be at room temperature before reconstitution.Vials should sit out approximately 30 minutes if stored inrefrigerator or approximately 60 minutes if stored in the freezer.

2. Open the bottle.

• Remove the metal seal from the bottle. IMPORTANT: DO NOTallow the control or diluent to stand open without the stopper.

3. Reconstitute the control.

• Tap the top of the bottle to dislodge any particles before opening.

• Invert the diluent bottles several times to mix the contentsthoroughly, but DO NOT SHAKE.

• Use a new pipette tip for each vial.

• Add exactly 3 ml_ of the appropriate diluent to the vial of thelyophilized control.

• Discard any remaining diluent.

4. Dissolve all lyophilized particles.

• Allow controls to stand for 30 minutes with occasional inversion,or place on a rotator or rocker for 10 minutes.

• Invert the bottles gently, but do not shake. Check that noundissolved particles remain before using.

• When not in use, cover the vial tightly, label with the date, andrefrigerate.

• To best realize the keeping stability of the control, transfer theamount needed for the day's use from the vial into anothercontainer, and return the vial to the refrigerator. Seal the workingcontainer to prevent evaporation.


I 6.5 Analyzing the Controls

1. Run the controls.• Use the same procedure that you use when analyzing a patient

sample, substituting the control for the patient sample. SeeSection 2, "Operating Instructions".

• When the display prompts you to enter the patient I.D., substitutethe lot number on the bottle of the control fluid.


6.6 How to Record the Results

It is important to record the results of your control tests in order tomonitor trends and patterns over a period of time. Data can betracked on either of two forms: on a quality control log or on a graph.

6.6.1 Recording Quality Control Results on a Log

If you are using VITROS DT Controls you may find the necessaryinformation on the yellow assay sheets or you may enter the valuesestablished by your lab.

VITROS CheratSTfysProducts DT Control I Assay SheetLot Number (T1317)Expiration Dale: Auquft3i, 1997 /

CAT 842 0317VITROS DT Systama

mrnmmAnalytt GEN

AMVL 62/63

TBIL 16Bf>((,'67

BUWJREA V

CHOL 5354

CREA

GLU

Vi lu *

129140

1.10.9

0.6

18

aa"1" i •Bang* Qp||» |v»1u.

104-154115=165

' o . e - T 60.4-1.4

15-21

152-178148 174

0.6-!.?

74-96

\ / L

mfl/dtt

mutiny

mfl/dL1

ma/dLmgrtL

mg/dl

mg/dL

\

2940

IS15

10

AN"\• o \

4.7 '

Rang*

104-154115-165

10-277-24

2-19

S.4-7.5

53-106S

U . 1-5.3

Units

IM.U/L

j*mo1/i_LJTIOL'1

mmDlA.

mmol/1.

sPmofL

Ftafaranea Fluid Ganarallon 01

Anaiyta G«n

CO?

cr

K*

Na+

Value

24.2

80

2.9

119

Ranga Unlla

19.2-29.2 mmoi/L

75-B5 rwr.oi/L

2.6-3.2 mmol/L

114 124 mmoK.

Control Log

Slwet

317iot no. changes, use the new comrot aooay find acceplabie ranges and begin e new

ol Value Acceptable? Corrective Action/Comments

12/1212/1312/1412/15

0.91.01.81.0

'Jes'Jes9{oJes

Repeat test-1.4-0.%

TECTECTECTEC

1. Record the control lot number, test name and range on the logsheet. Confirm that the control lot number on the assay sheet is thesame as on the bottle of control you are using.

2. Record the date and result on the log sheet.

3. Compare the control value with the assay range on the log sheet.

4. If the control value is within range, it is acceptable. If it is notacceptable, see the "Quality Control Checklist". Record yourcorrective actions as indicated in the example.

5. Write your initials in the space provided.

6. Start a new log sheet when the control lot number changes.Record the new assay values on the control sheet.


6.6.2 Recording Quality Control Results on a Graph

Charting quality control information on a graph such as the Levey-Jennings is a simple way to present data for interpretation because itprovides a visual representation of control results. The chart is basedon the mean and standard deviation values which are calculatedfrom a minimum of 20 control results for a given laboratory test. Themean is simply another term for the calculated average and is drawnas the center on the control chart; standard deviation (SD) is astatistical method for measuring dispersion. In terms of qualitycontrol, SD is used to evaluate how far quality control results fallfrom the mean. The acceptable range for control results is usually2SD or 3SD. Because results may fall above or below the mean, SDis expressed as both a positive and a negative value.

A blank Levey-Jennings chart is included in Section 13 of thismanual. We have provided two charts so that you may monitor yournormal and abnormal control results on a single sheet. If you areusing VITROS DT Controls, you may use the mean (value) and rangepublished on the control assay sheets. Confirm that the control lotnumber on the assay sheet is the same as the lot number on thebottle of control you are using. Using this information, fill in theLevey-Jennings chart.

VITROS Chemistry Products DT Control I Assay SheetLotNumbe<jri317Expi ra t ion Da le : A u g u s T 3 T r r e 3 7 ~ " " > y

CAT 842 0317VITiflOS DT Systems

Analyte GEN

AMYL 62/6361/64/65

TBIl. 6866/67

NBIL

BUN/UREA

CHOI 53S4

Value

129140

1.10.9

0.6

(""is""1

Ms(M61

ConventionsRange

104-154115-165

0.6-1.60.4-1.4

0.1-1.1

) C ^152-148-

7874

Units

U/lU.t

mg/dlmg/dL

mg/dL

mg/dL

mg/dLmg/dL

\Value^

129140

1915

10

6.4

4.34.2

SIRange

iWiS4115-SfE

10-277-24

2-19

5.4-7.5

3.9-4.63.8-4.5

Units

U/LU/L

\mtol /L(tfhoM.

(imolO

mmoi/L

m mo I/Lmmo!/f

DTE Modules ••

\

Analyte

CO,

c r

K*

SNa+

Reference Fluid Generation 01Gen Value

24.2

80

2.9

119

Range

19.2-29.2

75-85

2.6-3.2

114-124

Units

mmol/L

mmol/L

mmol/L

mmol/L

Obtain from the side panelof your box of slides.

Limit

Observed r

Value



1. Write the test name, generation number, slide lot number, controland control lot number in the spaces indicated above theappropriate chart.

2. Fill in the mean (value), +2SD and -2SD values from the assaysheet. To determine the SDs from the published assay sheet:

+2SD = the upper range value listed on the assay sheet.-2SD = The lower range value listed on the assay sheet.

3. Fill in the +1SD and -1SD values, which must be calculatedaccordingly.

+1SD = mean value + (+2SD value)2

-1 SD = mean value + (-2SD value)2

4. You are now ready to record results. Be sure to record the date andcontrol test with each entry.

6.7 Interpreting Control Results

6.7.1 Interpreting the Control Results from the Log

If you are using VITROS DT Controls compare the printout with theresults listed on the assay sheet that is packaged with the controls.Or you can compare the printout with the values established byyour lab.

If results are within range, it is acceptable.

If results are outside the range, repeat the procedure for thatparticular test and consult the checklist at the end of this chapter.

6.7.2 Interpreting the Control Results from the Graph

Generally, a test is considered "in control" if the results fall withinthe ±2SD range on the chart. If the control result falls outside the2SD limit, there may be a problem that requires attention. Resultsmay also fall out of range clue to random chance. In either case,simply repeat the test. If the control result falls back in range, the testis considered in control and you may proceed to report patientresults.

Other conditions that the chart wil l reveal to you are trends andshifts. A trend in a control chart refers to a series of control valuesthat continue to increase or decrease over a period of severalconsecutive days. It may be indicative of an unsatisfactory laboratorycondition. When values on several consecutive days fall on one sideof the mean but remain at a constant level, the trend is referred to asa shift.

Regular use of the Levey-Jennings chart wil l not only assist you indocumenting your quality control activities, but can provide insightinto the overall performance of each test for preventive actionsbefore control values go out of range.


This control chart indicatesa trend in the observedvalue from 2/7 to 2/14,respectively.

'SUihi____ Gen # J0_Slide Lots 0153-0223-4789 Control Vitro?'PI'ControlJ Control Lot # '11317

Level 1

ObservedValue

DateUpper = 91 —-----

Limit

Mean =

Lower _Limit

Cornictive Action: 2/14/96 Level1: Cleanedpipette/repeatedtest

Reviewed: Date __2/2&/96 Signature __J&£ity_!D_ay_ _ .

This control chart indicates ashift in the observed valuefrom 3/11 to 3/14,respectively.

Test '3itJ{ Gen# S3Slidel_ot# 0_l53-0223-41S9 control Vitms•DIComroll_ controlLots T1317_

Level 1

DateUpper = 21

Limit

Mean = _

LowerLimit

= 15

corrective Action: 3/15/96 Level1: '-Reconstituted a new vial of control

Reviewed- Date 3/28/96 Signature 'Betty 'Day

6.8 Establishing Your Own Control Ranges

The determination of the target value for your laboratory is based onstatistical methods. Whenever you test a quality control fluidcontaining a known quantity of a certain analyte, your test resultswill vary slightly due to such factors as: environmental differences,how the test was performed, and the performance of the analyzer.These variations are considered normal.

However, it is important in assuring test accuracy that your resultsfall within the established range of the control, preferably close tothe target value.



6.8.1 How to Calculate the Mean

A mean (average) can be calculated on a calculator. The following isan example of how to calculate a mean for the last 10 quality controltests you have run, for example, on glucose: (For statistical analysisyou may want to collect more data points.)

llOmg/dL120mg/dLlOOmg/dL107 mg/dL112mg/dL120 mg/dL

103 mg/dL110 mg/dL104 mg/dL114 mg/dL

1. To calculate the mean, add these values. The total is 1100.

2. Divide this number by the number of values quality control testsyou obtained, in this case 10. Thus, your mean for glucose is110 mg/dL (1100 + 10 = 110).

Operator's ManualVITROS DT II System 5/95. Reprinted 1/99.

6.8.2 Variables to Consider in Establishing the Mean

The values used to calculate the mean will affect the result. Althoughmany commercially available control fluids have been tested toprovide a pre-determined mean, you should establish your ownmean target for each test.

To establish such a mean, you should run quality control tests dailyfor a number of days. In hospital laboratories, at least 20 days ofquality control results are gathered. Running QC tests for 20 daysbefore establishing a mean target value for each test may not befeasible for an in-office laboratory, therefore you should obtain amean that includes at least five to ten days of QC results.

The mean that you establish for your laboratory should take intoaccount a number of important variables so that it simulates thesituations that occur during normal patient testing as closely aspossible.

For instance, day-to-day variables are critical. The results used tocalculate the mean must have been gathered over several days toaccount for day-to-day changes in the environment and ininstrument upkeep.

If more than one person operates the analyzer, you must alsoaccount for operator-to-operator variables in establishing your mean.In other words, all the operators who run patient tests must have aportion of the QC test that you use in deriving the mean.

Your mean should also include vial-to-vial variables. The QC resultsused to calculate the mean must be run using more than one vial ofcontrol fluid.

6.8.3 Calculating the Standard Deviation

Standard deviation is a statistical method for measuring dispersion.In terms of quality control, standard deviation is used to measurehow far quality control results differ from the average that youestablished. You should establish a standard deviation for each testwhen you have established your mean. This standard deviationmeasurement can make use of the same values used in deriving themean.


6.8.4 How to Calculate a Standard Deviation

1. Calculate your mean as shown in section 6.8.1. In this case themean was 110.

2. Calculate how much each of your values deviates, or differs fromthe mean.110 mg/dL = mean, so deviation = 0120mg/dL = mean+10100 mg/dL = mean -10107 mg/dL = mean -3112 mg/dL = mean +2120 mg/dL = mean+10103 mg/dL = mean -7110 mg/dL = mean, so deviation = 0104 mg/dL = mean -6114 mg/dL = mean +4

3. Then you square each of these deviations, which means that youmultiply it by itself.

o2

102

-102

- 3 2

22

102

- 7 2

02

- 6 2

42

4. Add0

100100

94

10049

0

3616

414

= 0= 100= 100= 9= 4= 100= 49= 0= 36= 16

all of the squared values together.


5. Next, divide this sum by the total number of values minus one, inthis case, 1 0 - 1 . You would divide by nine in this example.(414-9 = 46).

6. Finally, you take a square root of this value. This step is designedto "undo" the extra step that you took earlier in which you squaredall the values. You can easily find the square root by using apocket calculator.

This square root of 46, which is written 46 equals 6.78 (approx.). Inthis example, 6.78 - one standard deviation.

Generally, a test value is considered to be acceptable from a qualitycontrol point of view, if it is within two standard deviations of themean that you have established. In the example given, then anyquality control result for glucose that was within 6.78 x 2 or 13.56mg/dL, of the mean of 110 would be considered acceptable. Thiswould include any values between 96.44 (110- 13.56 = 96.44) and123.56 (110+ 13.56 = 123.56).

NOTE: The standard deviation you obtain should be similar inmagnitude to those published by the manufacturer. A result that ismuch higher than stated by the manufacturer's figure can signal asystem problem.


6.9 Quality Control Troubleshooting Chart

If a quality control value is inaccurate follow these guidelines tocorrect the problem.

Factors to Consider

Slides

• Stored properly.

• Warmedsufficiently.

• Lot calibrated.

Control

• How old is thecontrol?If > 7 days, use anew one. Checkassay sheet forstability.

• Werereconsitutionproceduresproperlyfollowed?

• Stored accordingto requirements.

• WarmedV V CA 1 1 1 I V- v j

sufficiently.

Pipette

• Tip(s) insertedproperly.

• Tip fill sufficient.

• Pipette removedat correct timeafter spotting.

• Check battery—was battery lowindicator on?

• For DTE IIModule—leavebuttondepressed afterspotting untilyou remove fromlocator.

Reference Fluid

• DTE II Moduleonly.

• Stored according

to requirements;usable for only30 days afteropening.

• Fluid warmedsufficiently.

• Check expirationdate on carton.

• How long atroomtemperature indual-samplecup?

• New VITROSReference Fluidlot # requirescalibration ofNa+, K*, Cl", andco2.

Step

1. Rerun thecontrol.

2. If QC failsagain, call yourCustomerSupport Center.


6.10 Factors to Consider When Your Results Are Out of Range

You may find that your quality control results occasionally falloutside the acceptable range you have established, even after yourepeat the QC test; or you may become suspicious of the results youobtain when you run patient samples. Either condition should alertyou to the need to check the factors:• Instrument maintenance• Housekeeping procedures• Errors in labeling and transcription• Centrifugation• Pipetting technique• Pipette performance• Storage and handling of patient samples• Storage and handling of test fluids and supplies• Calibration• Storage and handling of patient samples

- Keep all samples tightly capped.- Frozen samples should be properly mixed when thawed.- Spin down samples before you store them and draw serum/

plasma off.- Store samples in the refrigerator (refer to Instructions for Use).- Warm refrigerated samples to room temperature before

analyzing them.


Options

7.1 How to Run Options

Keyboard options are primarily used to check the function of theequipment after it is initially installed. They are also used introubleshooting the equipment. For example, you may run a certainoption to respond to an error message on the display. Some optionsare also used to obtain data that are stored in th.e microcomputer'smemory - for instance, the type of reporting units for a test.

To access the options you must be in the service mode of operations.Follow the sequence outlined below to enter the service mode fromthe run mode, and then to return to the run mode when you havecompleted running the desired options.

To enter the service mode:• Press SHIFT then SERVICE/CAL MODE.• When the display prompts you to ENTER OPTION NO., key in the

desired option number and press ENTER.• To exit the service mode, press SHIFT then SERVICE/CAL MODE.

NOTE: You cannot enter the service mode when the DT60 II systemis processing samples. Wait until all samples are processed beforeexecuting options.

7.2 Options for the VITROS DT60 II Chemistry System

OPTION NUMBER DESCRIPTION

0 TERMINATING OPTIONS Terminates Options 1, 2, 6, 7,8, 14, and 31.

1 SLIDE TO INCUBATOR Activates the mechanism(upper rack) that transports aslide from the spotting stationto the incubator. Use Option 0to terminate.

POSITION WHITE REF ATREAD

Advances the lower slidetransfer mechanism (lowerrack) to the correct position fora white reference reading. UseOption 0 to terminate.



OPTION NUMBER

3 ENTER # OF CYCLES (1-99)

4 PRINTER TEST INPROGRESS

5 (Display lights up)

6 GREEN LED TEST

7 RED LED TEST

8 YELLOW LED TEST

9 RAM CHECK-INITIALIZEON D14

DESCRIPTION

Cycles the slide transfermechanism. This option is self-terminating. To specify numberof cycles:• Key in the desired number of

cycles.• Press ENTER.

Checks the operation of theprinter by printing out theentire set of characters from Ato Z and 0 to 9, and allpunctuation marks. This optionis self-terminating.

The two rows of 40 blackrectangles light up.

Lights the green LED in theFORS head. Run Options 0, 7,or 8 to terminate.

Lights the red LED in the FORShead. Run Options 0, 6, or 8 toterminate.

Lights the yellow LED in theFORS head. Run Options 0, 6,dr 7 to terminate.

Tests the read-write memoryON D14(RAM) in the analyzer.This option reinitializes theanalyzer. Rerun all tests for allslides that were in the analyzerat the time of the loss. Thisoption is self-terminating.


OPTION NUMBER

10 PROM MEMORY CHECK(IS VALID or ERROR INPROM or D13)

11 U.S. UNITS IN EFFECT orS.I. UNITS IN EFFECT

12 LAST 64 KEYSTROKES

13 VERSION XX.X CDMXXXX ALL RIGHTSRESERVED1995COPYRIGHT OCD

14 A/D READS TO PRINTER

DESCRIPTION

Tests the read-only memory(PROM). If the display reads:• ERROR IN PROM-the

keyboard wil l not accept anyfurther information until theproblem is resolved.

• PROM OK - the option willbe self-terminating at itscompletion.

• D13-PROM CHECKSUMERROR - call your CustomerSupport Center.

Displays current reportingunits.Run Option 63 to select U.S.Units or Option 64 to selectStandard International Units(S.I.)- This option is self-terminating.

Prints out the last 64 characters,entered. This option is self-terminating.

Displays the current version ofsoftware and the CDM numberinstalled in your system.

This test is usually performedonly at the request of servicepersonnel. Prints the analog-to-digital reading with each testresult in the run, calibration orservice mode. Run option 0 toterminate.



OPTION NUMBER

16 LED#? (GR =6, RD =7,YL =8, OFF =9)

17 ENTER DATE NN-NN-NN

18 ENABLE COUNTDOWN

22 REPORT NH3 WITHCREATININE

23 CRC PROCESSINGON/OFF

DESCRIPTION

Prints analog-to-digital readingof the light coming throughFORS. The display will promptyou to enter the followfng data:• ENTER STEP CNT - select the

number of steps to move thelower rack assembly (-255 to+255).

• ENTER # OF READS - selectthe number of analog-to-digital readings.

• Your selections will appearon the display as they aremade.

Date should be entered beforeroutine analyses begin. Use thenumeric keys to enter any 8digits. The dashes must beentered between the numbersor the date will not berecognized. Press the ENTERkey after you have entered allnumerals and dashes. Do notpress ENTER after eachindividual entry. The date willthen be printed out with everypatient ID for your recording ofrecords. See Section 2.2 forwhen you should enter thedate.

When enabled, shows theamount of time left for slides inthe incubator. Energize theanalyzer again to delete thisoption.

Prints out an ammonia resultwith a creatinine result, ifDSCREA is run.

Turns the capability to processCoronary Risk Classification onand off. Allows you to verifythe status as on or off.Touch 1 to turn on and 0 toturn off.


OPTION NUMBER

24 CRC DATA INPUTEDITING

25 GLOB AND A/G RATIOON/OFF

26 LIPIDCALC.-VLDL, LDLAND CHOL/HDLCRATIO ON/OFF

27 AGP ON/OFF

DESCRIPTION

This option automatically turnsCRC on and allows you toinput the data necessary to runCoronary Risk Classificationand to run "what if..." tests. SeeSection 3, "Coronary RiskClassification" for specificoperating instructions.

Turns the capability to processGlobulin andAlbumin/Globulin ratiocalculations on and off. Allowsyou to verify the status as on oroff.Touch 1 to turn on and 0 toturn off. Option 25 will remainon even if the analyzer ispowered off and then on again,until the option is manuallyturned off.

Turns the capability to processVLDL, LDL and CHOL/HDLCratio calculations on and off.Allows you to verify the statusas on or off.

Turns the capability toprocessAnion Gap (AGP)calculations on and off. Allowsyou to verify the status as on oroff.Touch 1 to turn on and 0 toturn off. Option 27 will remainon even if the analyzer ispowered off and then on again,until the option is manuallyturned off.



OPTION NUMBER

30 SAV UPDATE SELECTTEST AND INDEX

31 CDM DATA NOT USED:UNIT WILL USE EAPROM CAL VALUES

32 CALIBRATION UPDATESELECT CHEMISTRY ANDINDEX

DESCRIPTION

Allows you to change the SAVsand the post-prediction valuesfor any test.For SAVs:• When the display prompts

you with SELECTCHEMISTRY, press theCHEMISTRY SELECT key toadvance to the desired test.

• Press 1, 2, 3, or 4 to accessthe values for bottles 1, 2, 3,or 4.

• To change values, press theCLEAR key and enter the newvalue.

• To cancel, pressSERVICE/CAL MODE.

For post-prediction values:• Press 6 to display the post-

prediction slope.• Press 7 to display the post-

prediction intercept.• To change the values, press

the CLEAR key and enter thenew value.

• To cancel, pressSERVICE/CAL MODE.

Use this option after usingoption 30 to change SAVs andbefore calibrating. Use Option0 to terminate once calibrationis complete.

Allows you to enter and printcalibration parameters.• Press the CHEMISTRY

SELECT key to scroll to thedesired test.

• Press 1, 2, 3, and 4 forcalibration parameters.

• Press 5 for the webgeneration number.

• To update the value, press theCLEAR key then enter thenew value, and press ENTER.

• To print values, press thePRINT key.

• Press SERVICE/CAL MODE toterminate the option.


OPTION NUMBER

33 SEL-F1ELD, ENT-VALUE,PRINTSO WB BF (Accessspline values off the CDM)

34 SEL-FIELD, ENT-VALUEPRINTSO WB BF KN(Access SAV calibratorvalues off the CDM)

35 CDM LISTING O=FULL1=SHORT

36 PRINTING REFERENCEFACTORS (for DT60 II)

DESCRIPTION

This option should be usedonly when recommended bytrained OCD servicepersonnel.• This option is used in

conjunction with Option 35to print a selected group ofspline records from theCDM. For the spline records,SO number, web generation,and body fluid code are usedin the record system.

• Run Option 35 first.• Press the CHEMISTRY

SELECT key to move fromone field to another.

• Select the field and use 0-9for A-J, and SHIFT 0- SHIFT 9for K-T. The CLEAR key clearsany previous values.

• Press PRINT to obtain all t

spline records.

This option should be usedonly when recommended bytrained service personnel.• Run Option 35 first.• Press the CHEMISTRY

SELECT key to move fromone field to another.

• Select the field and use 0-9for A-J, and SHIFT 0-SHIFT9 for K-T. The CLEAR keyclears any previous values.

• Press PRINT to obtain allSAV values.

The default for the Options 33and 34 is the short form. Press0 to obtain a long form.

Prints the correction factorsand reference slidereflectances.

NOTE: Use Option 50 to obtainthe data for the DTSC II Module.



7.2.1 Serial Communication Options for the DT60 II System

OPTION NUMBER

19 SERIALCOMMUNICATIONSTEST

20 DATA INTERFACELOOPBACK TEST

21 INTERNAL LOOPBACKTEST

DESCRIPTION

This option is used to check thedata transfer from the DT60 IISystem to an attachedcomputer system.• TEST OK - A record was

successfully sent out and anacknowledgment wasreceived by the external PC.

• UNABLE TO TRANSMIT -The test record was nottransmitted.

• NO RESPONSE FROM PCNo acknowledgment wasreceived from the PC.

This option runs an interfacetest.• Plug an interface connector

onto the end of the serialcommunications cable.

• TEST OK - All characters sentand received correctly.

• TEST FAILS - The charactersare not sent or receivedcorrectly.

This option runs an internalloopback test.• TEST OK - All characters are

sent and received correctly.• TEST FAILS - The characters

are not sent or receivedcorrectly.

7-£ Operator's ManualVITROS DT II System 5/95. Reprinted 1/99.

7.3 Options for the VITROS DTE II Module

OPTION NUMBER

40 DTE ELECTROMETERFORWARD orELECTROMETER AT READ

41 DTE ELECTROMETERREVERSE orELECTROMETER ATHOME

42 ENTER # OF CYCLES

43 DTE ELECTOMETERVERIFIED

44 DTE MODULE TEMP TESTSTARTED

DESCRIPTION

Advances the electrometer tothe read position. Run Option41 to terminate the option.

Returns the electrometer to thehome position. This option isself-terminating.

Cycles the drive mechanism aspecified number of times. Keyin the desired number of cyclesand press ENTER. This option isself-terminating

Verifies the electricalperformance of theelectrometer. The gain factor,reference, and offset values ofthe electrometer will be thefollowing range:GAIN FACTOR 24.0 to-21.5REFERENCE 80.22 to-83.46OFFSET 0 ± 1This option is self-terminating.

Checks the incubator in themodule. This test takes 40seconds from the time youselect the option. The followingdisplay messages may appear:•DTE MODULE TEMP OK

- temperature is within thecorrect range.

• DTE MODULE TEST FAILED- temperature is outside theproper range.



7.4 Options for the VITROS DTSC II Module

OPTION NUMBER

50 DTSC REFERENCEVALUES (prints correctionfactors for DTSC II)

52 DTSC TEMPERATURE

53 DTSC SOFTWAREVERSION XX.X

DESCRIPTION

The black and white correctionvalues and reference slidevalues are printed out. Valuesare printed only for the filtersthat are in use. Each value wil lbe labeled with itscorresponding wavelength.

Prints out the temperature indegrees Celsius.

Prints out the current softwareversion number.


Troubleshooting

The software of the VITROS DT60 II Chemistry System,VITROS DTE II Module, and VITROS DTSC II Module monitorsmany hardware functions. Information regarding most sources ofmalfunction is provided to you through the display or the paperprintout. This section provides you with instructions on what to dowhen your analyzer is not operating properly, including suggestionson the possible causes.

8.1 General Troubleshooting

Each description in this section lists one or more possible causes anda series of operator responses. Perform the steps in the orderindicated. If one step does not correct the problem, proceed to thenext one, and so forth, until all suggested responses have beencompleted. If the analyzer is not properly operating after all thesuggested responses have been completed, contact your CustomerSupport Center.

POSSIBLE CAUSE

VITROS DT60 II System • Power cord pulled fromcannot be turned on. the analyzer or from the

outlet.

• Main power switch inthe OFF position.

• Nonfunctioning outlet.

VITROS DTE II Module is not • Cable leading fromoperating. module to the analyzer is

not securely fastened.• Instrument malfunction.

OPERATOR RESPONSE

• Verify that the power cord isplugged securely into the poweroutlet and the analyzer.

• Verify that the main power switchat the back of the analyzer is in theON position.

• Verify that the outlet is functioning.• If the analyzer is still not

functioning, call your CustomerSupport Center.

• Check that the cable leading fromthe analyzer to the DTE II Moduleis securely plugged in. Turn theanalyzer off, then on again. If theproblem recurs, call yourCustomer Support Center.



POSSIBLE CAUSE

VITROS DTSC II Module is not • Cable leading fromoperating. module to the analyzer is

not securely fastened.

• Power cord is notsecurely plugged into theoutlet.

• Main power switch is.OFF.

• Nonfunctioning outlet.

Printer working but does not • Printer paper insertedprint hard copy. with heat sensitive side

on the back. The heatsensitive side of thepaper marks whenscratched with fingernail.

Complete power loss. • Main power switch inOFF position.

• Power cord pulled fromthe power outlet.

OPERATOR RESPONSE

• Check that the cable leading fromthe analyzer to the DTSC IIModule is securely plugged in.Turn the analyzer off, then onagain. If the problem recurs, callyour Customer Support Center.

• Check that the plug is pluggedsecurely into the outlet.

• Turn the switch to the ON position.

• Verify that the outlet is functioning.

• See Section 5.6.2, "PaperLoading," for correct loadingprocedures.

• If the main power switch is in theOFF position, turn it to the ONposition.

• Verify that the power cord isplugged securely into the analyzerand into the power outlet.

• Turn the main power switch to theOFF then ON again.

• Rerun tests for all slides that werein the analyzer at the time of thepower loss.

• Repeat the calibration process forall tests being calibrated at thetime of the power loss.

• If the problem recurs, call yourCustomer Support Center.


POSSIBLE CAUSE OPERATOR RESPONSE

Temporary power loss. • Line voltage droppedbelow specifications.

If the voltage temporarily dropsand then returns to normal, theunit will reinitialize. Afterreinitialization, repeat tests for allthe slides in the analyzer at thetime of the power loss.Repeat the calibration process forall tests being calibrated at thetime of the power loss.

8.2 Pipette Troubleshooting

Please refer to the VITROS DT Pipette User's Guide for informationon cleaning and charging the DT Pipette.

| 8.3 Unexpected Results (Analyzer Tracking Errors)

Tracking errors occur when the sequence of slides in the DT60 IISystem does not match the sequence the analyzer was expecting.Tracking errors are caused when display prompts are not followedexactly or when the slide disposal box is overfilled. Tracking errorscause the analyzer to report unexpected results such as:

• A series of results outside the analyzer range when runningmultiple chemistries on the DT60 II System.

• A series of highly unusual results outside the expectedphysiological range.

• Occasional slide transport malfunctions that are reported as F12 -F15 error codes - "Transfer malfunction."

• Calibration failures that are reported as C13 (EXTREMA) or C18(MONOTONICITY) error codes.

Possible Causes

• A slide is pushed into the analyzer prematurely when the displayshows a WAIT prompt. This may cause a transfer malfunction.

• A slide is not removed from the analyzer when the display promptsto do so. An example is an unreadable bar code on a slide thatcauses the analyzer to reject the slide.


• An incorrect usage of the delete test key. The delete test key deletesa test after a slide has been entered, identified, and spotted. Whena test is deleted, the slide must continue through the analyzer. Donot remove a slide manually once it has been deleted.

IMPORTANT: If a slide is removed manually after the delete test isrequested, a tracking error will occur.

• A slide disposal box that is not emptied on a daily basis. Anoverfilled slide disposal box causes the slides to backup resultingin a tracking error.

If You Suspect a Tracking Error

1. Wait until the analyzer has finished processing.

2. Empty the slide disposal box.

3. Enter the service mode by pressing SHIFT then SERVICE/CALMODE.

4. When the display prompts you to ENTER OPTION NO., press 3then press ENTER.

5. When the display prompts you to ENTER # OF CYCLES (1-99),press 6 then press ENTER.

6. After the cycles have completed, check the slide disposal box.

IMPORTANT: If the slide disposal box does not contain exactly oneslide then a tracking error has occurred.

7. Exit the service mode by pressing SHIFT then SERVICE/CALMODE.

8. The analyzer is now ready to resume routine operation.The aboveactions have cleared the tracking error. Please review and confirmprevious results.

Important Points to Remember

• Please follow the display messages.

• Insert and remove slides only when the display indicates to do so.

• Once the slide is spotted, use the SHIFT + DELETE keys to inhibitresults from printing, but do not remove the slide.


Instrument Status Messages

9.1 Status Messages

Status messages may appear on the display of the printout during thecourse of normal operation — for instance, in response toinformation that you input or in response to actions such as insertinga slide. This section includes a list of all messages along withexplanations of the messages and recommended responses to them.

The messages in this section, for the most part, do not point toequipment malfunction. Instead they are designed to "talk youthrough" various operating procedures.

MESSAGE EXPLANATION ACTION TO TAKE

ANALYZER INITIALIZATION(Display)

The DT II System is goingthrough a series of self-checks.

• Wait until the messagedisappears before attemptingto run any tests.

ANALYZER READY-CREA/NH3

ONLY (Display)An NH 3 slide is in theincubator.

You must run a creatinine orammonia slide next. To runany other tests wait until thecreatinine and ammoniaslides clear the incubator.

ANALYZER READY — NOCREA/NH3

• In the CAL mode, creatinineand ammonia cannot be runwhile a slide for BUN is in theincubator.

Run a slide other than acreatinine or ammonia slide.

ANALYZER TEMP. LOW(Display)

Instrument is still warmingup.

If the message appears whenthe analyzer is first turned on,wait until ANALYZER READYmessage is displayed(approximately 25 minutes).

COVER OPEN (Display)

COVER OPEN TESTINVALIDATED (Printout)

• Pipette locator cover on theanalyzer was left open longerthan 5 seconds.

Check to see that the pipettelocator cover is closedproperly. After it is closed, theINCUBATOR WARMING UPmessage will appear. Waituntil the display disappearsand the ANALYZER READYdisplay appears beforerunning the next test.




DISCARD PM SLIDE ANDREPEAT (Display)

Bar code reader cannot readthe bar code on slide.

Slide inserted upside down.

The patient sample andelectrolyte reference fluidwere dispensed without firstloading a slide.

• Discard slide and repeat thetest. This message will bedisplayed until the cover islifted.

• Clean the barcode reader.

• Remove pipette locator cover.Examine internal assembliesand clean any serum orelectrolyte reference fluid thatmay be present, following theinstructions in Section 5.3.

DTE ELECTROMETERCYCLING (Display)

A DTE II Module option wasrequested, and theelectrometer is still cycling.

• Wait until you hear theelectrometer stop cycling,then run the desired option.

ENTER CALIBRATOR KITNUMBER (Display)

The analyzer is promptingyou to enter the number ofthe calibrator kit. Thismessage appears after youenter the calibration mode.

Using the numeric keys onthe keyboard, enter thenumber of the calibrator kitthat you are using. Thisnumber is found on the boxof calibrator fluids.

ENTER CALIBRATOR BOTTLE(Display)

The analyzer is promptingyou to enter the bottlenumber of the calibrator.

Using the numeric keys onthe keyboard, enter the level(1, 2, 3, or 4) of calibrator thatyou are about to use.

ENTER REF FLUID GEN NO.(Display)

The analyzer is promptingyou to enter the referencefluid generation number onthe bottle of VITROS DTReference Fluid.

Enter the generation number.If you do not have the DTE IIModule, enter the number 1.

ENTER SLIDE GENERATION(Display)

The analyzer is promptingyou to enter the generationnumber of the slide. Thismessage appears after a test isselected in response to theSELECT TEST message.

Using the numeric keys onthe keyboard, enter thegeneration number of theslide that you just inserted.The generation number canbe found on the box of slidesbeing used. (The ENTER keymust be pushed twice toidentify the generation on theDTSC II Module).



EXIT SERVICE MODE FIRST(Display)

• You tried to run a test whilethe instrument is in theservice mode.

• Exit the service mode bypressing the SHIFT andSERVICE keys on thekeyboard.

GAIN CHANGES This message is for serviceuse only.

No operator response.

INCUBATOR FULL (Display) Incubator is filled to capacity. Wait until messagedisappears or until theanalyzer processes at leastone test result before enteringanother slide.

If you had already entered aslide, lift the pipette locatorcover and remove the slide toprevent a jam. Close thecover within 5 seconds or theanalyzer wil l reinitialize.

INCUBATOR WARMING UP(Display)

The incubator in the analyzerhas not yet warmed to theproper operating temperature.

Wait until the ANALYZERREADY message appearsbefore you attempt to run anytests.

INSERT NH3 SLIDE (Display) • This message is displayedafter spotting a creatinineslide to indicate that the nextslide to be run must be anNH 3 slide.

Load a slide for

OPEN COVER TO CLEAR(Printout)

Printed as a result of a slidejam. The message that followson the printout (F11-F15TRANSFER MALFUNCTION)indicates the location of thejam.

• Open the pipette locatorcover and remove thejammed slide.

• When you close the cover,the instrument wil lreinitialize. Wait for theANALYZER READY messageto appear before runninganother test.




REMOVE CM SLIDE (Displayand Printout)

You tried to spot a slide thatwas not identified.

Bar code reader cannot readbar code on slide.

You dispensed the patientsample without first loading aslide.

• Check to be sure the slide isinserted into the correctmodule.

• Open pipette cover andremove slide within 5seconds by pulling it backfrom the ends. (Do not touchcenter of slide because i t .contains the reagent).

NOTE: If the pipette cover isopen longer than 5 seconds, theanalyzer will delete all slides inthe incubator and require anincubator warm up. If a slide isbeing read at the same time thatthe cover is open, that slide resultmay be deleted.

• Reinsert the slide at a fasterrate of speed. If the bar codereads, continue processing. Ifthe bar code does not read,open the pipette locator andclean the bar code sensorwith a dry swab. After theanalyzer displays READY,reinsert the slide. If the barcode reads, continueprocessing slides. If the barcode still does not read, callyour Customer SupportCenter.



RESULTS ABOVE ANALYZERRANGE (Printout)

• In the calibration mode, thismessage informs you that theresult from the calibrator fluidis above the range of theanalyzer.

• Incorrect information wasmanually entered.

• In the run mode, the sampleconcentration is above theanalyzer range.

• Rerun the calibrator fluid inquestion.

• If message recurs, reconstitutea fresh calibrator fluid andrerun the test. If messagerecurs, call your CustomerSupport Center.

• If the CHEMISTRY SELECTkey was used, make sure thatall the information enteredwas correct.

• Dilute the sample and rerunthe test. (Be sure to adjust theresults according to thedilution factor). See theInstructions for Use for thetest you are running for moreinformation on dilutionprocedures.

• If message recurs, call yourCustomer Support Center.

RESULTS BELOW ANALYZERRANGE (Printout)

• In the calibration mode, thismessage informs you that theresult from the calibrator fluidis below the range of theanalyzer.

• In the run mode, the sampleconcentration is below theanalyzer range.

"• Rerun the calibrator fluid inquestion.

• If message recurs, reconstitutea fresh calibrator fluid andrerun the test.


• If the CHEMISTRY SELECTkey was used, make sure thatall the information enteredwas correct.

• Rerun the test.

• If message recurs, run aquality control test. If qualitycontrol results are within theproper range, report the testresults as being below theanalyzer range.




SELECTING DTSC TEST(Display)

This message is asking you toverify your test selection.

• Press ENTER to verify theselection. If the selection isincorrect, use theCHEMISTRY SELECT key toscroll to the correct test andthen press ENTER.

SLIDE NOT IDENTIFIED(DT60 II System) (Display)

• Slide was inserted backward.

• Instrument was unable toread the bar code.

• Unsteady motion whileinserting the slide.

• Instrument malfunction.

• Do not remove theunidentified slide. Leave it inthe instrument and use theCHEMISTRY SELECT key tomanually select the test thatyou have loaded into thespotting station.

• If the analyzer prompts you toremove the slide, do so asquickly as possible. If thecover is open more than 5seconds, it could result in theloss of the tests in progress.

• If any of these problems recur,call your Customer SupportCenter.



SLIDE NOT IDENTIFIED(DTE II Module) (Display)

Slide was inserted backward.

Instrument was unable toread the bar code.

Instrument malfunction.

• Visually check to see that theslide is correctly positionedbelow the pipette locator atthe spotting station. The slideshould be positioned asindicated in the diagram onthe slide track. (The two smallholes where the sample andreference fluid are depositedshould face you.)

• If the slide is positionedcorrectly, press theCHEMISTRY SELECT key tomanually identify the test.

• If the slide was insertedbackward, insert a new slide.You can do this even whilethe SLIDE NOT IDENTIFIEDmessage appears on thedisplay.

• If the message remains, callyour Customer SupportCenter.

TEST DELETED (Display andPrintout)

The test was deleted by theoperator before it wascomplete.

Leave slide in and repeat test.

TESTS INVALIDATED(Printout)

The pipette locator cover wasleft open longer than 5seconds, so the incubatortemperature dropped and thetests in progress wereinvalidated.

Check to see that the cover isclosed. Wait for theANALYZER READY messageto appear, then repeat the testin question.




TEST MISSING BOTTLESLOAD XXX OR PRESS CAL TOEXIT (DT60 II System)(Printout and Display)

• This message appears whenexiting the calibration mode.The analyzer is indicating thatyou accidentally forgot to runa bottle during the calibrationprocedure, or you had aninvalid calibration reading.

Load a slide for the testindicated to find out whichcalibrator bottle you aremissing. Any number that isnot flashing indicates thebottle that you need to run.After running the missingbottle(s) and after validreplicate numbers areprinted, press the CAL key toexit the calibration mode.

WAIT—SLIDE BEING LOADED(Display)

• The analyzer is indicating thatthe slide you just spotted withfluid on the DT60 II has notyet been transferred into theincubator.

IMPORTANT: DO NOT insertslide until the DT60 indicates"Analyzer Ready".

Wait until this message isreplaced by the ANALYZERREADY message before tryingto insert the next slide.

XXX (test name) USESBOTTLES (1,2,3,4) ENTERBOTTLE NO. (Printout andDisplay)

During the calibrationprocedure, after the bar codeon the slide is read, theanalyzer is prompting you tochoose the calibrator bottlethat you want to run.

To respond, enter the bottlenumber (press 1,2,3, 4) toindicate which calibratorbottle you have chosen torun.


Coded Warning Messages

In addition to monitoring operating procedures, the analyzer'smicrocomputer monitors several analyzer functions and alerts youby means of coded warning messages on the display panel and/orthe paper printout if there is a deviation from performancespecifications. This section lists these coded messages inalphabetical and numerical order.

10.1 Coded Warning Messages

The code number beside each message appears on the printout and/or the display along with the message. It is designed to help youlocate troubleshooting information in this manual. The code numberalso provides valuable information to your Customer Support Centerin case the instrument fails to operate properly after you have triedall the suggested responses listed here. If the problem persists, callyour Customer Support Center.

10.1.1 Calibration (C)

CODE/MESSAGE EXPLANATION/CAUSE ACTION TO TAKE

C12 INVALIDCALIBRATION(Printout)

• This message appears as aheading on the printout. Itis followed on the printoutby another coded warningmessage that specifies theproblem.

Respond as instructed for thecoded warning message thatfollows this heading.

C13 EXTREMA ERROR(Printout)

Response (DR value)obtained for a calibratorbottle is not within anacceptable range:- bottles misidentified.- drop is too small.- calibrator bottle is

reconstitutedimproperly.

- Tracking error may haveoccurred

• Exit cal mode.To clear slides out ofincubator, empty the slide disposalbox and run option 3 (6 cycles)(VITROS DT60 II Chemistry Systemonly). After the cycles havecompleted, check the slide disposalbox. If the slide disposal box doesnot contain exactly one slide then atracking error has occurred. Referto section 8.3.

• Be sure pipette is clean.

• Repeat calibration with samecalibrators.

• If the same error occurs,reconstitute new calibrators andrecalibrate.




C14 SLIDE GENERATIONERROR (Display)

Run Mode:

• Generation of slide loadedin the run mode has notyet been calibrated.

• Operator keyboard error(if number was enteredmanually).

Remove the slide and calibrate thetest.

Remove the slide and enter correctgen. #.

Calibration Mode:

• Incorrect calibrator kit forthe test being calibrated.

o

• Calibration Data Module(CDM) does not containthe information requiredfor the slide generationbeing used.

• Use the correct calibrator kit:

Calibrator to Use TestVITROS SpecialtyCalibrator Kit *Theo&CHEVITROS IsoenzymeCalibrator Kit *CKMBVITROS Calibrator Kit All Other

*L19 error code will occur on DTSCII Module.

• Replace with the most currentCDM. Install new CDMs when theyarrive.

C15 KIT NUMBER NOTIN MEMORY(Display)

Calibrator kit expired.

Calibrator kit not on CDMin the analyzer.

Check the expiration date on thecalibrator box. Obtain newcalibrator kit, if expired.

Verify that the number entered wascorrect. Re-enter if necessary.

Replace with most current CDM.Be sure to install CDMs when theyarrive.

C17 MISSING BOTTLE(Display)

• Calibration mode wasexited before all levelswere run for a given test.

Recalibrate the test in question.Follow proper procedure for allrequired levels of calibrator.

If message recurs, call yourCustomer Support Center.



C18 MONOTONICITYERROR (Print out)

Response (DR value)obtained for a calibratorbottle is not within anacceptable range:

- bottles run out of order.

- drop is too small.

- calibrator bottle isreconstitutedimproperly.

- Tracking error may haveoccurred

• Exit cal mode. To clear slides out ofincubator, empty the slide disposalbox and run option 3 (6 cycles)(VITROS DT60 II Chemistry Systemonly). After the cycles havecompleted, check the slide disposalbox. If the slide disposal box doesnot contain exactly one slide then atracking error has occurred. Referto section 8.3.

• Be sure pipette is clean.

• Repeat calibration with samecalibrators.

• If the same error occurs,reconstitute new calibrators andrecalibrate.

C19 CDM RECORDFORMAT ERROR(Display)

The computer softwarewill not accept the recordformat number of theCDM.

Damaged CDM or CDMsocket.

Software problem.

Turn analyzer off. Remove theCDM and reinsert it, or replacewith a new CDM.

Turn analyzer on and wait for it toreinitialize.


C21 INVALID REF FLUIDNO. (Display)

Calibration data module(CDM) is not programmedwith the generationnumber of reference fluidthat you entered.

Operator keyboard error.

• Check the number on the referencefluid bottle label. Either replace theCDM or the reference fluid toachieve a match.

• Check that the number entered wascorrect and reenter if necessary.

• If message recurs, all yourCustomer Support Center.

C22 NO NH3

CALIBRATION(Printout)

The analyzer is trying tocalibrate for creatinine,but cannot find theammonia result, whichshould have already beencalculated.

Recalibrate creatinine andammonia as stated in the manual.



10.1.2 Data Storage (D)


D12 EA PROM ERROR(Display and Printout)

Occurs when there is acomputer malfunction.

• Call your Customer Support Center.

D13 PROM CHECKSUMERROR (Display)

• Occurs when there is acomputer malfunction,either during initializationor while running option10.

D14 RAMMALFUNCTION(Display)

• Occurs when a memorycheck is unsuccessful.

D16 MEMORY ERROR(Printout)

The correction factors arelost.

Run option 36 (DT60 II System) oroption 50 (DTSC II Module) to seeif correction factors are in memory.If the correction factors are 0, enterthe correction factors from aprevious option 36/50 tape usingoption 81 (DT60 II System) or 101(DTSC II Module).

• The calibration data arelost.

• There was an error incalibration.

• To determine if calibration data arein memory:- enter option 32.- press CHEM SELECT until desired

chemistry appears on the display.- press PRINT.- compare the printout to the

calibration data from a previouslysaved printout.

Enter the lost calibration data againor wet calibrate the DT60 II System,DTSC II Module, or DTE II Module.

• Refer to option 32.

• Wet calibrate all chemistries ifunable to restore lost calibrationfrom saved printout.



D18 MEMORY RESET(Printout)

• Instrument malfunction. Call your Customer Support Center.

D19 MEMORY HAS BEENERASED (Printout)

The correction factors arelost.

Run option 36 (DT60 II System) oroption 50 (DTSC II Module) to seeif correction factors are in memory.If the correction factors are 0, enterthe correction factors from aprevious option 36/50 tape usingoption 81 (DT60 II System) or 101(DTSC II Module).

The calibration data arelost.

• To determine if calibration data arein memory:- enter option 32.- press CHEM SELECT until desired

chemistry appears on display.- press PRINT and compare the

printout to the calibration datafrom a previously saved printout.

• Enter the lost calibration data againor wet calibrate the DT60 IISystem, DTSC II Module, or DTE IIModule.

There was an error incalibration.

Wet calibrate all chemistries ifunable to restore lost calibration.

D25 DTSC INTERNALRAM FAILURE(Printout)

When initializing theDTSC II Module thesoftware detects that theinternal memory test hasfailed.

Turn the DTSC II Module off andthen back on again, waiting for it toreinitialize. Repeat any tests thatmay have been deleted by turningthe module off. If the problemrecurs, call your Customer SupportCenter.




D26 DTSC EXTERNALRAM FAILURE(Printout)

• When initializing theDTSC II Module, thesoftware detects that theexternal memory test hasfailed.

D27 DTSC BATTERY RAMFAILURE (Printout)

•The DTSC II Module failsto write to the batterybacked RAM as expected.This error can occur at anytime during operation.

D28 DTSC CHECKSUM. FAILURE (Printout)

• When initializing theDTSC II Module, thesoftware detects achecksum error on itsPROM.

Turn the DTSC II Module off andthen back on again. Wait for it toreinitialize. Repeat any tests thatmay have been terminated byturning the module off. If theproblem recurs, call your CustomerSupport Center.

10.1.3 Electrometer (E)


E11 RESULTS INVALID(Printout)

Instrument malfunction. Check the interface cable.

Repeat the test in question.

If message recurs, callyourCustomer Support Center.







• Improper slide placement.

Check that the interface cable andpipette locator are secure.

Repeat the test in question, makingsure that the slide is insertedcorrectly.



Sample/reference fluidlevels are not adequate indual sample cup.

Assure that patient specimen andreference fluid volumes areadequate (at least 4 drops of each)in the dual sample cup.

The DTE II Pipette is notworking properly.

Verify pipette operation and properprotocol:

- install the tips tightly.

- check fluid levels in tips (bothtips should have nearly equalfluid volumes). If fluid level is noteven, dispense sample, eject tip,and insert new tips.

- wipe outside of tips beforedispensing fluid, being carefulnot to touch ends with tissuewipes (which will absorb fluidfrom tips).

- 'keep pipette button depressedafter spotting until you removepipette from locator or fluid willbe aspirated by pipette back offslide.

The pipette locator or bootis not seated correctly.

Remove pipette locator and noseassembly and make sure rubberboot is in place. Reposition pipettelocator as it snaps into position.

•The DTE II Interface Cableis not seated correctly.

Be sure the DTE II Interface Cable(the cable that connects the DTE IIModule to the back of the DT60 IISystem) is seated correctly.





• Instrument malfunction.This message appearsduring option 43 alongwith the message: El 4RESULTS INVALID.

• Check the interface cable.



• Instrument malfunction.This message appearsduring option 43 alongwith the message: E14RESULTS INVALID.

• It may also appear whenyou are running a test.

Check interface cable.

If the message appears while youare running a test, run the testagain.



Instrument malfunction.This message appearsduring option 43 alongwith the message: E14RESULTS INVALID.

If message recurs at an excessivefrequency, call your CustomerSupport Center.


Instrument malfunction. Check the interface cable.




Instrument malfunction. Check the interface cable, thepipette and the pipette locator.





E20 A/D OUT OF RANGEOR BUSY

Sample/reference fluidlevels are not adequate indual sample cup.

Assure that patient specimen andreference fluid volumes areadequate (at least 4 drops of each)in the dual sample cup.

The DTE II Pipette is notworking properly.

Verify pipette operation and properprotocol:- install the tips tightly.- check fluid levels in tips (both

tips should have nearly equalfluid volumes). If fluid level is noteven, dispense sample, eject tip,and insert new tips.

- wipe outside of tips beforedispensing fluid, being carefulnot to touch ends with tissuewipes (which will absorb fluidfrom tips).

- after spotting, keep the pipettebutton depressed until youremove the pipette from thelocator or fluid will be aspiratedoff the slide.

The pipette locator or bootis not seated correctly.

Remove pipette locator and noseassembly and make sure rubberboot is in place. Reposition pipettelocator as it snaps into position.

The DTE II Interface Cableis not seated correctly.

Be sure the DTE II Interface Cable(the cable that connects the DTE IIModule to the back of the DT60 IISystem) is seated correctly.

Reference fluid isoutdated.

Discard any bottles open longerthan the 30 day stability period.



10.1.4 Instrument Function (F)


F12, F14, F16

DT 60 II SLIDE TRANSPORTERROR (Printout)

A slide jam has beendetected.

• Allow "tests in progress" to printout.

• Raise the pipette locator cover andcheck for slide jam. If there is ajam, remove the jammed slide.

• Check the pressure pad for bindsby moving it up and down.

• Check the heated FORS weight forbinds.

• To clear slides out of incubator,empty the slide disposal box andrun option 3 (6 cycles) (VITROSDT60 II Chemistry System only).After the cycles have completed,check the slide disposal box. If theslide disposal box does not containexactly one slide then a trackingerror has occurred. Refer to section8.3.

• Lower the pipette cover andresume testing when prompted bythe analyzer.

NOTE: When inserting slides into theDT60 II System, always insert theslide until the forward movement ofthe slide is stopped by the analyzer.

F17 LINE VOLTAGE TOOLOW (Printout)

Fluctuation in the internalpower supply.

Repeat tests that may have beendeleted by the low line voltage.



F18 PRINTERMALFUNCTION(Printout)

Paper jam occurred duringloading.

• Press PRINT on the keyboard. Thismay dislodge loose paper bits.

• Remove paper bits from top ofprinter.

• Turn the DT60 II System off andback on again.

• An easy way to load paper:

- remove printer cover by pulling itup and towards the left, awayfrom the analyzer.

- cut the remaining paper awayfrom core and pull the tapethrough top of print end.

IMPORTANT: Do not pull tapebackwards! This might damage paperfeeding mechanism.

- Cut corners of the fresh roll andposition roll so that lead edgefaces you and feeds from bottomof roll. Feed pointed end overroller and through slot in back ofprinter head until you see paper.Grab paper as it exits top ofprinter and pull a short distancethrough printer. Touch PRINT onkeyboard overlay to advancepaper.

- Test printer by running option 4.

NOTE: If the paper cannot bereloaded due to printer malfunction,test results may be obtained bypressing the TEST COMPLETE.

To prevent this code, change thepaper when a color strip appears.




F19 MECHANISM ERROR(Printout)

A slide jam has beendetected.

Allow "tests in progress" to printout.

Raise the pipette locator cover andcheck for slide jam. If there is ajam, remove the jammed slide.

Check the pressure pad for bindsby moving it up and down.

Run option 3 for three cycles.

Lower the pipette cover andresume testing when prompted bythe analyzer.

F20 ELECTROM.POSITION ERROR(Display)

• DTE II Modulemalfunction.

Repeat the test.


F30 DTSC TRANSFERMALFUNCTION(Printout)

• A slide jam has beendetected.

F31 SLIDE NOT AT READSTATION (Printout)

F32 SLIDE NOT ATBARCODE STATION(Printout)

• Remove the slide, if visible at thepickup station. Open the cover, ifnecessary, and remove the slide,then close the cover. Wait for theDTSC II Module to initialize (fiveminutes).

• Run option 108 and follow theinstructions to step the slidethrough the slide transport cycle.

• Exit options and resume normaloperation when prompted by theanalyzer.

NOTE: Does not require an operatorresponse. Respond as instructed tothe coded warning message thatfollows.

To reduce slide jams, empty slidedisposal box regularly.



F33 DTSC FILTER • DTSC II Module could not • Check to see that the arm is downPOSITION ERROR find home on the filter at the read station, or make sure(Printout) wheel, or is having that a slide is at the read station.

problems with moving the -,- ., n T c r , u , , , u ,f u . ., , & • Turn the DTSC II Module off andfilter to the correct . .x . . i. cturn it on again waiting for it top ' reinitialize. Repeat tests that may

have been deleted by turning theanalyzer off.

• Clean the opal plug and sapphirewindow.


10.1.5 Temperature (H)


H11 TEMPERATUREMALFUNCTION(Display)

Instrument malfunction. • Call your Customer Support Center.

H12 ANALYZER TEMP.HIGH (Display)

Room temperature toohigh.

• Temporary temperaturefluctuation after thepipette locator cover wasopen.


• Check that the room temperature iswithin the range. The analyzer willnot operate if the room temperatureexceeds 29°C (85°F). If necessary,adjust the room thermostat.

• If the message appeared after thepipette locator cover was openedand closed, wait until theANALYZER READY message isdisplayed.

3ms• If neither of the first two probler..-,exists, call your Customer SupportCenter.

HI 3 ANALYZER TEMP.LOW (Display)

• Room temperature toolow.

• Temporary temperaturedecrease after the pipettelocator cover was open.

Instrument is still warmingup.


Check that the room temperature iswithin the range. The analyzer willnot operate if the room temperaturefalls below 15°C(60°F). Ifnecessary, adjust the roomthermostat.

If the message appeared after thepipette locator cover was openedand closed, wait until theANALYZER READY message isdisplayed.

If the message appears when theanalyzer is first turned on, waituntil the ANALYZER READYmessage is displayed.

If none of the first three problemsexists, call your Customer SupportCenter.

10-14 Operator's ManualV1TROS DT I! System 5/95. Reprinted 1/99.


H14 ANALYZER TEMP.LOW (Display)

This is a warning that theroom temperature is toolow. This code will appearwith another, morespecific code.

Adjust the room temperature.

HI 5 TEMPMALFUNCTION(Printout)

Test results printed on theDTE II Module with thismessage were for tests inprogress when themodule's internaltemperature fluctuatedoutside its normaloperating range.

H16 DTSC PREHEAT CAPTOO LOW/TOOHIGH —THERMISTOR FAIL(Printout - only 1response will printout)

During continuousmonitoring the DTSC IIModule detects thepreheat temperature is outof specifications.

Turn the DTSC II Module off thenback on again, waiting for it toreinitialize. Repeat any tests thatmay have been deleted by turningthe analyzer off. If the problemrecurs, call your Customer SupportCenter.

H17 DTSC PREHEATBOTTOM TOO LOW/TOO HIGH —THERMISTOR FAIL(Printout - only 1response will printout)

During temperaturemonitoring, the DTSC IIModule detects that thepreheat temperature isoutside of specifications.

H18 DTSC READ CAPTOO LOW/TOOHIGH —THERMISTOR FAIL(Printout - only 1response will printout)

During temperaturemonitoring, the DTSC IIModule detects a problemwith the temperature inthe read station.

Adjust the room temperature.




H14-H19 TemperatureCodes

Inadequate space aroundthe analyzer is preventingair circulation.

Analyzer air exhaust ventsdirty.

A fan or vent is directed atthe analyzer.

• Allow air flow between themodules.

• Clean the vents with a soft-bristledbrush after the instruments arepowered off.

• Divert any direct air flow awayfrom the analyzer.

NOTE: If these actions fail to resolvethe problem, power the instrumentoff and on.

10.1.6 Communications (N)


N11 TRANSMIT QUEUEFULL (Display)

• The DT60 II Systemcannot queue any moremessages to the DTSC IIModule resulting intransmission problem.

N12 RECEIVER QUEUEFULL (Display)

The DT60 II Systemcannot receive any moremessages from the DTSC IIModule. Problem with theprocessing of messages.

N13 BAD RECEIVERCOMMAND CODE(Printout)

The message that was sentfrom the DTSC II ModuletotheDT60 II System wasundefined by the DT60 IISystem.

• Turn the DTSC II Module off then"power off" the DT60 II System.Turn the DT60 II System back onagain then turn on the DTSC IIModule, waiting for it toreinitialize. Repeat any tests thatmay have been deleted by turningthe analyzer off. If the problemrecurs, call your Customer SupportCenter.



N14 BAD RECEIVERPROTOCOL(Printout)

• The DT60 II System didnot receive theappropriate response fromtheDTSCII Module that itwas expecting.

N15 BAD RATE SLIDE ID(Printout)

• The DT60 II Systemreceived a reading about aslide that it does not havedefined.

Turn the analyzer off then on again,waiting for it to reinitialize. Repeatany tests that may have beendeleted by turning the analyzer off.If the problem recurs, call yourCustomer Support Center.

N16 DTSC READING OUTOF SYNC (Printout)

The DT60 II Systemreceived a reading that isout of sync with what wasexpected; either doublereadings or it missed areading.

N17 SEQUENCEPROTOCOL ERROR(Printout)

• There is acommunications problembetween the DT60 IISystem and DTSC IIModule.

Turn the DTSC II Module off thenpower off the DT60 II System. Turnthe DT60 II System back on again,then turn on the DTSC II Module,waiting for it to reinitialize. Repeatany tests that may have beendeleted by turning the analyzer off.If the problem recurs, call yourCustomer Support Center.



10.1.7 Reflectometer (R) DT60II System


R11-R17RESULTS INVALID (Printout)

The FORS head is dirty. • Clean the FORS Head:lift the Spotting Station cover toexpose the FORS weight. Lift upon the weight that covers thehead.clean the FORS Head with acotton swab moistened withwater. Dry with a clean absorbentcloth before returning the weightinto position over the FORSHead. Close the spotting stationcover.

The room light isexcessive.

Check for excessive room light.Light fixtures mounted directlyabove and in close proximity to theDT60 II System may affect theFORS.

• There is a light leak. Make sure the slide disposal trayand main cover for the DT60 IISystem are in place.

R18 PROTOCOL ERROR You tried to run a slide forcreatinine and ammoniaimmediately after you rana slide for BUN and theresult for BUN was > 40mg/dL.

Repeatthe creatinine and ammoniaslides to verify the test results. It isrecommended that for optimumperformance, creatinine andammonia testing should not beperformed when a slide for BUN isin the incubator.


10.1.8 Reflectometer (L) DTSC II Module


L11 INVALID RESULTS(Display)

The concentration of thesample is too high.

The calibration isincorrect.

Dilute the sample using theappropriate diluent (refer to theInstructions for Use).

If this code occurs with a highfrequency and diluted samplesproduce normal results or anothercode, call your Customer SupportCenter.

This Substrate Depletion codeindicates that the change inkinetics for the test occurred tooquickly.

L12, INVALID RESULTSL13 (Printout)

The sample has unusualkinetics, e.g., multiplemyeloma.

Calibration parameterswere entered manually.

• Dilute the sample using theappropriate diluent (refer to theInstructions for Use).

• Recalibrate.

NOTE: Enzyme activity may be low,medium or high.

These codes are designed to flagsamples that contain interferingsubstances.

L14 RESULTS INVALID • There is some mechanicalor electrical noiseinterfering with thecalculation of the testresult.

Rerun the test. If the problemrecurs, call your Customer SupportCenter.

L15 GAIN OUT OFLIMITS FILTERCHANNEL (Printout)

A gain value sent from theDTSC II Module or a valuethat was computed for anew gain is out of theprescribed limits.

Turn the analyzer off then clean thewhite reference plug and sapphirewindow. Turn the analyzer onagain, waiting for the analyzer toreinitialize. If the problem recurs,call your Customer Support Center.




L16 MATH ERROR INGAINCALCULATION —FILTER CHANNEL(Printout)

• The analyzer is unable tocalculate new gain values.

Turn the analyzer off then on again,waiting for the analyzer toreinitialize. If the problem recurs,call your Customer Support Center.

L17 GAIN READINGOSCILLATING —FILTER CHANNEL(Printout)

Gain value is out of range,either above or belowspecification.

Turn the analyzer off then on again,waiting for the analyzer toreinitialize. If the problem recurs,call your Customer Support Center.

L18 INVALID DTSC SPOT(Printout)

The DTSC II Moduledetected a spot interruptwhen unexpected. Theslide was spotted too earlybefore the green LED onthe display was flashing,or there was no slide atthe spotting station.

If a slide is at the spotting station,and an invalid spot occurs, theDTSC II Module will invalidate thetest and process the slide throughthe unit. If the slide is in the holdstation (between the pickup andspotting station), the slide will bebacked out to the pickup station.Insert a new slide and repeat thetest. If fluid was dispensed at thespotting station without a slidepresent, clean the spotting station.

L19 INVALID DTSCBARCODE (Printout)

Run Mode:

• Generation of slide loadedin the run mode has notyet been calibrated.

• Operator keyboard error(if number was enteredmanually).

Remove the slide and calibrate thetest.

Remove the slide and enter correctgen. #.

Calibration Mode:

• Incorrect calibrator kit forthe test being calibrated.

Calibration Data Module(CDM) does not containthe information requiredfor the slide generationbeing used.

• Use the correct calibrator kit:

Calibrator to Use TestVITROS SpecialtyCalibrator Kit *Theo & CHEVITROS IsoenzymeCalibrator Kit *CKMBVITROS Calibrator Kit All Other

*C14 error code will occuron DT60 II Module.

• Replace with the most currentCDM. Install new CDMs when theyarrive.



L20 RATIO WHITE OUTOF RANGE (Printout)

The read area is dirty.

L21 RATIO BLACK OUTOF RANGE (Printout)

The black offset readinghas failed its limit check.

L22 RATIO SAMPLE OUTOF RANGE (Printout)

The read area is dirty.

• Clean the opal plug and readwindow. See section 5 as areference.

Rerun the test. If the problem recurs,call your Customer Support Center.

L23 REFERENCEVOLTAGE OUT OFRANGE (Printout)

The reference voltagereading has failed its limitcheck.-

Turn the DT60 II System off then onagain, waiting for the analyzer toreinitialize. Repeat any tests thatmay have been deleted by turningthe analyzer off. If the problemrecurs, call your Customer SupportCenter.

L27 DTSC COVER OPEN(Printout)

The cover to the DTSC IIModule is open.

Check to see that the DTSC IIModule cover is properly closed.The module will then reinitialize (5minutes). Repeat any tests that mayhave been deleted by having thecover open. If the problem recurs,call your Customer Support Center



Installation and Site Specifications

The information contained in this section tells how to install theVITROS DT60 II Chemistry System, VITROS DTE II Module, and theVITROS DTSC II Module. This information will be primarily used byyour Ortho-Clinical Diagnostics representative and your DT60 IISystem dealer when your equipment is initially installed. However,should you at some time need to move the analyzer and the module,this section will tell you how to prepare the equipment for a move,what to consider in selecting a new location for the equipment, andhow to check the instrument's performance after it is reinstalled in anew site.

11.1 Installation

The DT60 II System will be unpacked and installed by an Ortho-Clinical Diagnostics representative or other trained personnel.

CAUTION: Do not attempt to install a DT60 II System, DTE IIModule, or a DTSC II Module unless properly trained.

1. Unpack equipment.

Remove the DT60 II System, the DTE II Module, and the DTSC IIModule from the shipping container. Remove packing materialsfrom the:

DT60 II System

• FORS Weight

• Pressure Pad

• Preheat Station

DTE II Module

• Electrometer Nose Section

• Sample Holder

DTSC II Module

• Operator Access Cover

• Preheat Heater Arm

• Read Station Heater Arm


2. Set up equipment.

Place the DT60 II System, the DTE I! Module, and the DTSC IIModule in the desired location. Position the DTE II Module to theright of the analyzer, and the DTSC II Module to the left. Do not plugin the analyzer yet.

If the DTSC II Module is part of the installation then remove theconnector shroud (Part No. 613871). Attach the DTE II Modulecable assembly (Part No. 351572) to the rear of the DT60 II Systemchassis, securing it to the chassis with the screws provided. Connectthe DTSC II Module to the adapter box using the DTE II Module'scable assembly(Part No. 338669) and secure it with the twoconnector screws provided.

With the cover of the analyzer up, check to make sure that the 120/240 switch is in the proper position (120 position for the UnitedStates and Canada, 240 position for Europe). Replace the cover andsecure the cable with the clamp (Part No. 338669).

Insure that the line module/voltage selector is at the proper setting forthe location. The setting may be changed by opening the snap-opencover of the module and rotating the selector drum to the propersetting. The voltage selected will appear in the window once thecover is closed.

3. Check power source and plug the analyzer in.

Please refer to Electrical Requirements, 11.2.3.

Check the line voltage. For the DT60 II System it must be between105 and 127V ac. Check that the button of the analyzer is in theOFF position. Then, plug the analyzer into the receptacle. After theanalyzer is plugged in, turn the DT60 II System on and wait while itgoes through a series of self-checks and warms up (approximately 25minutes).

The DTSC II Module has settings for nominal voltages of 100, 120,220, and 240V ac (-10% +5%). Check that the ON/OFF button onthe module is in the OFF position. Then plug the module into thereceptacle. After the module is plugged in, turn it on and wait whileit goes through a series of self-checks and warms up (approximately5 minutes).

NOTE: The DT60 II System must be turned on first before the DTSC IIModule. You do not need to wait for the analyzer to warm up beforeusing the DTSC II Module.

11 -2 Operator's ManualVITROS DT II System 5/95. Reprinted 1/99.

4. Calibrate.

Calibrate the DT60 II System, DTE II Module, and DTSC II Modulefor all tests.

5. Run a quality control test.

Run a quality control fluid for all tests to verify the calibration.

11.2 Site Specifications

11.2.1 Space Requirements

The analyzer and modules must rest upon a level bench or tablelarge enough to accommodate the dimensions shown and sturdyenough to support the equipment's weight. Additional space shouldbe provided adjacent to the analyzer, to permit easy operation andservicing.

VITROS DT60 II System:

Width = 47.6cm (18.75 inches)Depth = 34.9cm (13.75 inches)Height = 17.1cm (6.75 inches)Weight = Approximately 8.6kg (19 pounds)

VITROS DTE II Module:

Width = 14.6cm (5.75 inches)Depth = 35.4cm (13.9 inches)Height = 16.5cm (6.5 inches)Weight = Approximately 2.7kg (6 pounds)

VITROS DTSC II Module:

Width = 34.3cm (13.5 inches)Depth = 35.4cm (13.9 inches)Height = 16.5cm (6.5 inches)Weight = 7.7kg (1 7 pounds)

Operator's Manual 11 -35/95. Reprinted 1/99. VITROS DT II System

Total space required, DT60 II System alone:

Width = 78.7cm (31 inches)Depth = 55.9cm (22 inches)Height = 48.3cm (19 inches)

Total space required, DT60 II System and DTE II Module together:


Total space required, DT60 II System and DTSC II Module together:

Width = 127.8cm (50.3 inches)Depth = 55.9cm (22 inches)Height = 48.3cm (19 inches)

Total space required, DT60 II System, DTE II Module, and theDTSC II Module together:


11.2.2 Environmental Requirements (Temperature, Humidity,and Altitude)

The DT60 II System, DTE II Module, and DTSC II Module aredesigned to operate effectively within" the temperature and humidityranges typically found in physicians' offices. For effective operation,the temperature and relative humidity should be within the rangeindicated in the accompanying diagram. The figures below thediagram define the "corners" indicated in the diagram on the nextpage.


Humidity

58 : 60 I 62"1 I ] 1 I T64 | 66 ; 68 | 70 i 72 , 74

1 T

133 : 144 : 15.6 ' 16.7 ; 17.8 ' 18.9 ' 20.0 '' 21.1 ! 22.2 ' 23.3

Temperature

1 1""

289 30.0 : 31.1

15.5°C(60°F), 75% RH

15.5°C(60°F), 15%RH

29.4°C (85°F), 15% RH

© 29.4°C (85°F), 60% RH

(E) 23.9°C(78°F); 75% RH

11.2.3 Electrical Requirements

Both the DT60 II System and the DTSC II Module must be pluggedinto a properly grounded receptacle. Receptacle grounding shouldcomply with all applicable electrical safety codes. Proper groundingis essential to assure proper operation and to minimize the likelihoodof electrical damage to sensitive electronic circuits within theanalyzer and modules. If you are uncertain about your electricalservice, please consult a qualified electrician.

The receptacle should be within 2.4 meters (8 feet) of the analyzerand DTSC II Module. The receptacle should be capable of supplyingthe following current:

Nominal voltage DT60 II System DTSC II Module

120 VAC240 VAC

1 amp0.5 amp

0.5 amp0.25 amp

Appliances (refrigerators, freezers, air conditioners, etc.) and otherinstruments can affect electrical power quality. These effects may beminimized by using a separate power circuit exclusively for theDT60 II System and DTSC II Module.



11.2.4 Refrigerator and Freezer Space

Refrigerator and freezer space of 0.03 cubic meter (1 cubic foot) isrequired for storage of slides and test fluids.

11.3 Moving the Analyzer

11.3.1 Relocation Outside the Office

You may find it necessary to relocate the analyzer outside of yourcurrent office. If so, the new location must meet the same space,electrical, and environmental requirements as the original site.

1. Move the equipment carefully.

Keep the equipment upright, and transport it in the same manner thatyou would transport any other type of office equipment. Beforemoving the equipment, make sure that no slides remain in theanalyzer or module incubators, and turn the analyzer and DTSC IIModule off.

If the equipment is going to be transported a long distance, makesure that it is repacked and transported correctly.

2. Set up the equipment and run a quality control test.

After the equipment is set up in the new location, a 30-minuteenvironmental equilibration is required, followed by a qualitycontrol test for all relevant assays. When the results are within theacceptable range for your quality control system, the analyzer isready to report results.

11.3.2 Relocation Within the Office

At some point, you may find it necessary to relocate the analyzerwithin your office after it has been installed. If you do so, the newlocation must meet the same space, electrical, and environmentalrequirements as the original site.

1. Move the equipment carefully.

Before moving the equipment, make sure that there are no slides inthe incubators of the DT60 II System, DTE II Module, or DTSC IIModule. Turn the analyzer and the DTSC II Module OFF. Take carewhen moving the equipment since dropping or jarring could damagethe equipment.

2. Set up the equipment and run a quality control test.

After the equipment is set up in the new location, a 30-minuteenvironmental equilibration is required, followed by a qualitycontrol test for all relevant assays. When the results are within theacceptable range for your quality control system, the analyzer isready to report results.


Warranty

12.1 New Equipment Warranty VITROS DT II System

1. Warranty Time Period

Ortho-Clinical Diagnostics warrants the VITROS DT60 II System,VITROS DTE II Module, and VITROS DTSC II Module to functionproperly for one year from the date of initial installation, wheninstalled within one year from date of shipment. This warranty coversthe purchaser of this equipment and anyone else who owns it duringthe warranty period.

2. Warranty Repair Coverage

If this equipment does not function properly during the warrantyperiod, a Customer Technical Services representative wil l repair theequipment without charge during normal working hours (usually8:00 a.m. to 5:00 p.m. Monday through Friday). Such repair servicewill include any adjustments and/or replacement of parts required tomaintain your equipment in good working order. Supply items arebilled as required.

Off-hours service is available at overtime rates.

3. How to Obtain Services

Call your Customer Support Center to obtain service.

4. Limitations

Warranty service is limited to the contiguous United States. Thiswarranty does not cover service or parts for any attachments,accessories or alterations not marketed by Ortho-ClinicalDiagnostics, nor to correct problems resulting from their use.

Ortho-Clinical Diagnostics makes no other warranties express,implied, or of merchantability for this equipment.

Repair without charge is OCD's only obligation under this warranty.OCD will not be responsible for any consequential or incidentaldamages resulting from the sale, use, or improper functioning ofthis equipment, even if loss or damage is caused by the negligenceor other fault of OCD.

This limitation of liability will not apply to claims for injury topersons or damage to property caused by the sole negligence or faultof OCD.


12.2 New Accessory Warranty VITROS DT Pipette and VITROS DTE Pipette

1. Warranty Time Period

Ortho-Clinical Diagnostics warrants the VITROS DT Pipette and theVITROS DTE Pipette to function properly for one year from date ofpurchase. This warranty covers the purchaser of the pipette(s) andanyone else who owns it during the warranty period.

2. Warranty Repair Coverage

If this equipment does not function properly during the warrantyperiod, call your Customer Support Center.

3. Limitations

Replacement without charge is OCD's only obligation under thiswarranty. Ortho-Clinical Diagnostics will not be responsible for anyconsequential or incidental damages resulting from the sale, use, orimproper functioning of this equipment, even if loss or damage iscaused by the negligence or other fault ofOCD.

OCD makes no other warranties, express, implied, or ofmerchantability, for this equipment.


CALIBRATION LOGfor VITROS DT II System

Date Operator.

Calibrator Kit No. Exp. Date.

Serial Numbers:VitrosDT60 II System.

Vitros DTE II Module _

_ Pipette.

_ Pipette.

Reference Fluid Lot No.

CDM No..

Gen. No.

Exp. Date.

CLM No. _

Vitros DISC II Module.

SLIDESTest Lot Number

— —

- —

- —

- -

- -

- -

— —

- —

- —

— —

- -

- -

— —

— —

— —

— —

— —

- -

Exp. Date

•CALIBRATION COEFFICIENTSCP#1 CP#2 CP#3 CP#4 DL#1* DL#3* QC Remarks

Affix dated Calibration Printout or manually record values in appropriate spaces.* DTSC il only

Make a photocopy of this log sheet prior to use for additional sheets. Vitros is a trademark of Ortho-Clinical Diagnostics.



Vitros DT60 II System Serial Numbers: Analyzer.

Vitros DTE II Serial Numbers: Module _

Vitros DTSC II Serial Numbers: Module _

Pipette _

Pipette.

. Pipette.

SERVICE LOGfor VITROS DT II System

Date Problem Noted Corrective Action Taken Initial


13-2 Operator's ManualVITROS ' U System 5/95. Repr' i 1/99.

TEST/REAGENT LOGfor VITROSDT II System

SLIDES

Date PutInto Use

Test Lot Number

T

T

T

! T

LJ TT

T

1 T

LI TT

LJ T

T

T

T

T

T

T

T

T

T

T

T

T

T

T

1

1

1|

Gen.No.

ExpirationDate

Initials

REFERENCE FLUID

DateOpened

Lot Number

1

1 1 1

I

1 1

!

! 1

1

1

1 |

i

! 1

! 1

1

11

1

1I

1

I

1

1 I

1 !

1 1 1

1 i

1 1

1|

1

I

11 1

Gen.No.

Exp.Date

Initials




VITROS DT II System Maintenance Log

Maintenance Logfor the VITROS DT System

I MonthI Year

Refer to the "Instrument Care and Cleaning" section of your Operator's ManuaHor more details.

Daily Maintenance

Empty slide disposal box(es).

Inspect pipettes and clean ifnecessary.

Initials of person performingmaintenance.

Weekly Maintenance—DT60

Clean the bar code reader andthe drop detector surface.

Clean pipette locator and visibleslide track area.

Monthly cleaning of the FORShead is recommended.

Weekly Maintenance—DTE

Clean pipette locator and visibleslide track area.

Clean the rubber boot on thefront of the electrometer.

Weekly Maintenance—DTSC

Clean the pickup and slidespotting stations.

Clean the pipette locator.

Clean the slide track.

Clean the reference cap andthe sapphire read window.

Initials of person performingmaintenance.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1819

I

I

20 21 22 23 24 25 26 27 28 29 30 31

Supplies Inventory

Check expiration dates andinventory of the following supplies:• Slides• Reference fluid• Calibrators• Controls• Printer paper

Points to consider: T s t o r a 9 e

Temperature• Do you have enought for the next Guide -

month? for the next 6 months?

• Do you have more than one lotnumber for any chemistry? Storenew lot numbers separately. L o t N a "

• Are supplies being stored at thecorrect temperature?

1Lo

CAT

JIL

•11

SicOf

So>

e

0

Before using this page, please make copies for future use


VITROS DT II System Quality Control Log

CONTROL Lot No.

Note: When the control lot no. changes, use the new control assay sheet to find acceptable ranges and begin anew control log sheet.

Test name Range

Date• •• •^H

^HHH^H• •

^H• •• •^HHIIB^H^H

BH

Control Value Acceptable?

H|HH|

IHHHI^HHHIHBB

^ ^ ^BBHHIHIHHHH U HHHIHIHHHHHIHHHIHIHHUH

HH^^BîîHHiHH

^HHiHHH

i ^HH

I^^HH^HiH

IBHHII^HHII^HHIHIHI^HII

I^HHIHH^HI^HHI

II^^HI

Corrective Action/Comments Initials

HHH^HHHHIH^^H

^^BH^H^^HHBHIHHHHHHIHHHHBHHHHIHHHH^HIHHHHHH^^H^^^^^^HBBI^H^^H^^^^H^H^^^HII^^HIHI^^^HHHÎB^^HHIî^^HHi^H

^HI^^^^^^HH^^^S^ ^ ^ ^ H H ^ ^ ^ ^ ^ ^ ^ ^ ^ B_^^^^_—^_IHI^^^HHIÎ^^^HH^^^HIHIi^^B^^H^H^HI^^H^^^^^^H^Hi^^^^^^HHHH^^HHH^^^^HHHHHIH

B

BBHB

HI

HH

H I^•;

^H

^H•1

Before using this page, please make copies for future use.



Levey-Jennings Quality Control Chart forVITROS DT II System

Date. Gen#_

Slide Lot #. Control. Control Lot #.

L e v e l 1

D a t e

+ 2 S D =

+ 1 S D =

M e a n =

- 1 S D =

- 2 S D =

O b s e r v e d T . , . , . . . . . . . . . . . . . . . . . . . . . . . . . . .Value / / / / / / / / / / / / / / / / / / / / / / / / / / / / / / /

Control Lot #. Level 2

Date (_

+2 SD =

+1 SD =

Mean =

-1 SD =

-2SD =

Observed I IValue /

Corrective Action:

—

/ . / /

—-

/ . / / / / / / / . / / .

—

/ /

—

/ /

\ '

i i

/

—

/

-—

/ / / .

—

/ / / / / / / /

Reviewed: Date Signature.


Coronary Risk Classification Questionnaire

Please answer the following questions. This information will be used with the Vilros DT60 II Chemistry System.

Name: Today's Date / /

Female Male Age Date of Birth: / /_

Do you smoke or have you quit smoking within the last 12 months? Yes No

Are you diabetic? Yes No

Do you have a history of cardiovascular disease (left-ventricular hypertrophy)? Yes No Not sure

Notes:

Systolic Blood Pressure

For internal use only

CHOL HDLC

I f Ortho-Clinical Diagnosticsfif4fc company

Coronary Risk Classification QuestionnairePlease answer the following questions. This information will be used with the Vitros DT60 II Chemistry System.





Do you have a history of cardiovascular disease (left-ventricular hypertrophy)? Yes No Not sure

Notes:

Systolic Blortd Pressure


CHOL HDLC

' Ortho-Clinical Diagnosticscompany

Coronary Risk Classification Questionnaire

Please answer the following questions. This information will be used with the Vitros DT60 II Chemistry System.





Do you

Notes:

have a history

Systolic

of cardiovascular

Blood Pressure

disease (left-ventricular hypertrophy)?


CHOL

Yes No Not sure

HDLC

' Ortho:Clinical Diagnosticscompany

C hem i stry

TABLE OF CONTENTS-DT SLIDESInstructions For Use

Abbreviation

ALBDT

ALKP DT

ALTDT

AWIYL DT

ASTDT

BUN/UREA DT

CaDT

CHEDT

CHOL DT

CKDT

CKMB DT

CIDT

CO2DT

CREA DT

CRSC DT

FeDT

GGTDT

GLUDT

HDLC DT

HDLC DT

K+DT

LACDT

LDHDT

LiDT

LIPA DT

MgDT

Na+DT

NBIL DT

NH3 DT (AMON) DT

PHOS DT

Test Name

Albumin

Alkaline Phosphatase

Alanine Aminotransferase

Amylase

Aspartate Aminotransferase

Urea Nitrogen

Calcium

Cholinesterase

Cholesterol

Creatine Kinase

Creatine Kinase MB

Chloride

Carbon Dioxide

Creatinine (Blank-CorrectedMethod)

Creatinine (Single-Slide Method)

Iron

Glutamyltransferase

Glucose

HDL Cholesterol (Using theVITROS DT HDL Cholesterol Kit)

HDL Cholesterol (Using theVITROS DT Micro HDLCholesterol Kit)

Potassium

Lactate

Lactate Dehydrogenase

Lithium

Lipase

Magnesium

Sodium

Neonatal Bilirubin

Ammonia

Phosphorus

Pub. No.

C-355

C-337

C-336

C-311

C-338

C-301

C-348

C-358

C-304

C-342

C-351

C-309

C-308

C-334

C-353

C-371

C-343

C-300

C-341_EN

C-354_EN

C-306

C-357

C-344

C-372

C-356

C-349

C-307

C-364

C-333

C-350

Version

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

2.0

2.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

Date

2003-10-01

2003-04-30

2003-10-01

2003-08-11

2003-10-01

2003-10-01

2003-03-28

2003-10-01

2003-03-28

2003-10-01

2003-04-30

2003-10-01

2003-08-11

2003-10-01

2003-04-30

2003-10-01

2003-08-11

2003-08-11

2004-02-29

2004-02-29

2003-03-28

2003-10-01

2003-10-01

2003-08-11

2003-04-30

2003-10-01

2003-10-01

2003-10-01

2003-10-01

2003-04-30

Rev. 2004-03-30 Operator's ManualVITROS DT II System

14-1

Instructions for Use

TABIE OF CONTENTS--DT SHOES

Abbreviation

TBIL DT

THEO DT

TPDT

TRIG DT

urCR DT

URIC DT

DT Calibrator

DT IsoenzymeCalibrator

DT Specialty

DT Control

DT IsoenzymeControl

DT Reference Fluid

7% BSA

Test Name

Total Bilirubin

Theophylline

Total Protein

Triglycerides

Urine Creatinine (Single-SlideMethod)

Uric Acid

DT Calibrator

DT Isoenzyme Calibrator Kit

DT Specialty Calibrator Kit

DT Control

DT Isoenzyme Control

DT Reference Fluid

7% BSA

Pub. No.

C-305

C-347

C-310

C-303

C-373

C-302

J23110_EN

J23112_EN

J23115_EN

J23111_EN

J23113_EN

J23114_EN

J11460

Version

1.0

1.0

1.0

1.0

1.0

1.0

3.0

2.0

2.0

2.0

2.0

2.0

2.0

Date

2003-10-01

2003-10-01

2003-10-01

2003-04-30

2003-10-01

2003-08-11

2004-03-31

2004-02-29

2004-02-29

2004-02-29

2004-02-29

2004-02-29

2003-07-28

14-2 Operator's ManualVITROS DT II System

Rev. 2004-03-30

Chemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products ALB DT Slides

AIRDTAlbumin

Intended UseFor in vitro diagnostic use only.VITROS ALB DT Slides quantitatively measure albumin (ALB) concentration in serum and plasma.

Summary and Explanation of the TestOf all serum proteins, albumin is present in the highest concentration. It maintains the plasma oncotic pressure and thetransport of many substances. Increased serum albumin may indicate dehydration or hyperinfusion with albumin; a decrease isfound in rapid hydration, overhydration, severe malnutrition and malabsorption, severe diffuse liver necrosis, chronic activehepatitis, and neoplasia. Albumin is commonly reduced in chronic alcoholism, pregnancy, renal protein loss, thyroiddysfunction, peptic ulcer disease, and chronic inflammatory diseases.1

Principles of the ProcedureThe VITROS ALB DT Slide method is performed using the VITROS ALB DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60 II Chemistry Systems.The VITROS ALB DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.When the fluid penetrates the reagent layer, the bromcresol green (BCG) dye diffuses to the spreading layer and binds toalbumin from the sample. This binding results in a shift in wavelength of the reflectance maximum of the free dye. The colorcomplex that forms is measured by reflectance spectrophotometry. The amount of albumin-bound dye is proportional to theconcentration of albumin in the sample.

Reaction Sequence

albumin + bromcresol green (BCG) BCG-albumin complex

Test Type and ConditionsTest Type and Conditions for ALB DT

Test TypeColorimetric

VITROS DT60 IIModuleDTSC II

ApproximateIncubation Time

3 minutesTemperature37°C (98.6°F)

Wavelength630 nm

Sample DropVolume

10 uL

Warnings and PrecautionsFor in vitro diagnostic use only.Take care when handling materials and samples of human origin. Since no test method can offer complete assurance thatinfectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens,solid and liquid waste, and test components in accordance with local regulations and NCCLS Guideline M292 or otherpublished biohazard safety guidelines.For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the instructionsfor use for the appropriate VITROS product, or to other manufacturer's product literature.

Version 1.0 Pub. No. C-355

AlBDTAlbumin

INSTRUCTIONS FOR USEReagents

Reagents

Slide Ingredients

Reactive ingredients per cm2

Bromcresol green dye 104 ng.

Other ingredientsPolymer beads, binders, buffer, and surfactants.

I

Slide Diagram

Slide Handling

Do not use slides with damaged or incompletely sealed packaging.

1. Upper slide mount2. Spreading layer

(beads)3. Reagent layer

• bromcresol green dye• buffer, pH 3.1

4. Support layer5. Lower slide mount

Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-28 °C (64 °-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18"-28 X:(64 °-82 °F) for >48 hours.

1. Remove the unopened slide from the box.2. \Narm the unopened slide for 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to

refrigerator or freezer storage.3. Remove the packaging and place the slide into the loading station within 15 minutes after opening.

Slide Storage and Stability

VITROS ALB DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for ALB DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Refrigerated 2°-8°C (36°-46°F)Frozen <-18°C (<0°F)Room temperature 18°-28°C (64°-82°F)

Stability<48 hoursUntil expiration dateUntil expiration date<15 minutes

Specimen RequirementsHandle specimens as biohazardous material.

Specimens Recommended• Serum• Plasma:3 Heparin

IMPORTANT: Certain collection devices have been reported to affect other analytes and tests.4

Confirm that your collection devices are compatible with this test.

Serum and Plasma

Specimen Collection and PreparationCollect specimens using standard laboratory procedures.56

Patient Preparation• No special patient preparation is necessary.

Special Precautions• For the effect of hemolysis on test results, refer to "Limitations of the Procedure."• Albumin concentrations vary with posture. Results from an upright posture may be approximately 0.3 g/dL (3 g/L) higher

than those from a recumbent posture.7

• Centrifuge specimens and remove the serum or plasma from the cellular material within 3 days of collection.8

Pub. No. C-355 Version 1.0

INSTRUCTIONS FOR USE AIR DTTesting Procedure Albumin

Specimen Handling and Storage• Handle and store specimens in stoppered containers to avoid contamination and evaporation.• Mix samples by gentle inversion and bring to room temperature, 18°-28°C (64°-82°F), prior to analysis.

Specimen Storage and Stability for ALB DT: Serum and Plasma8

StorageRoom temperatureRefrigeratedFrozen

Temperature18°-28°C(64°-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<7 days<1 monthIndefinite

Testing ProcedureMaterials Provided

• VITROS Chemistry Products ALB DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II

| • Isotonic saline or reagent-grade water• VITROS DT Pipette

Operating Instructions• Refer to the operator's manual for your VITROS DT60 II Chemistry System.

PANT; Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior toanalysis.

Sample DilutionIf albumin concentrations exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with one part isotonic saline or reagent-grade water to 10 parts sample.2. Reanalyze.3. Multiply the results by 1.1 to obtain an estimate of the original sample's albumin concentration.

Calibration

Required CalibratorsVITROS Chemistry Products DT Calibrator Kit, bottles 1, 2, and 4

Calibrator Preparation, Handling, and StorageRefer to the instructions for use for VITROS DT Calibrator Kit.

Calibration ProcedureRefer to the operator's manual for your VITROS DT60 II Chemistry System.

When to CalibrateCalibrate:• When the slide lot number changes.• When critical system parts are replaced due to service or maintenance.• When government regulations require.

- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.

The VITROS ALB DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 630 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, albumin concentration in unknown samples can be determined using the software-resident endpoint colorimetricmath model and the response obtained from each unknown test slide.

Version 1.0 Pub. No. C-355 3

ALBDT INSTRUCTIONS FOR USEAlbumin Quality Control

Validity of a CalibrationCalibration parameters are automatically assessed by the VITROS DT60 II Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.

Reportable (Dynamic) Range

Reportable (Dynamic) Range for ALB DTConventional (g/dL)

1.0-6.0SI Units (g/L)

10-60

For out-of-range samples, refer to "Sample Dilution."

Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for albumin are traceable to the Certified NIST (NationalInstitute of Standards and Technology) Total Protein Standard Reference Material, SRM* (Standard Reference Material) 927c.The Ortho-Clinical Diagnostics calibration laboratory uses SRM" 927c to assign values to a series of working human albuminstandards prepared from purified human albumin. The working standard series is used to calibrate a bromcresol green albuminmethod9 to support value assignment for the VITROS DT Calibrator Kit.

Quality Control

Procedure Recommendations

| WARNING: Handle quality control materials as biohazardous material.

• Choose control levels that check the clinically relevant range.• Analyze quality control materials in the same manner as patient samples, before or during patient sample processing.• To verify system performance, analyze control materials:

- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT60 II System.

• If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results.• For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principles

and Definitions; Approved Guideline-Second Edition10 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60II Chemistry System.

Quality Control Material Selection

IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60 II

Chemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other albumin methodsif they:- Depart from a true h uman matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

I • Controls low in carbon dioxide concentration may show a negative bias11 that can be avoided by reconstituting lyophilateswith a bicarbonate diluent instead of water.

I • Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and StorageRefer to the instructions for use for VITROS Chemistry Products DT Control I & II or to other manufacturer's product literature.


[3 VMTFJCpS

INSTRUCTIONS FOR USEExpected Values and Reporting Units

ALBDTAlbumin

Expected Values and Reporting UnitsReference Interval

Reference Interval for ALB DT12

Conventional Units (g/dL)3.5-5.0

SI Units (g/L)35-50

Each laboratory should confirm the validity of these intervals for the population it serves.

Reporting Units and Unit Conversion

The VITROS DT60 II Chemistry System may be programmed to report albumin results in conventional and SI units.

Reporting Units and Unit Conversion for ALB DTConventional Units

g/dLSI Units

g/L (g/dL x 10)

Limitations of the ProcedureKnown Interferences

The VITROS ALB DT Slide method was screened for interfering substances following NCCLS Protocol EP7.13 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for ALB DT

Interferent*

Hemoglobin

Interferent Concentration

Conv. (mg/dL]100

200400

Si (g/L)(1.0)(2.0)(4.0)

Albumin ConcentrationConv. (g/dL)

3.5

3.53.5

SI(g/L)35

3535

Bias

Conventional6%

13%26%

SI6%

13%26%

* It is possible that other interfering substances may be encountered. These results are representative; however, your results may differsomewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.

Other Limitations• Certain drugs and clinical conditions are known to alter albumin concentrations in vivo. For additional information, refer to

one of the published summaries.141S


AlBDTAlbumin

INSTRUCTIONS FOR USEPerformance Characteristics

Performance Characteristics

Method Comparison

I The plots and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzed

using the bromcresol green dye-binding comparative method.11

Method Comparison for ALB DT: Serum

Conventional Units

QWO

70-

60-

50-

40

30 •

20 >

10-

0

SI Units

y = x

Comparative Method: Bromcresol Green(9/dL)

0 10 20 30 40 50 60Comparative Method: Bromcresol Green

(gfl.)

70

Method Comparison

DT60 II System vs.comparative method

for ALB DT:

n Slope

79 0.98

Serum

CorrelationCoefficient

0.992

Conventional Units (g/dL)

Range ofSample Cone.

1.4-5.8

Intercept Sy.x

0.06 0.14

SI Units (g/L)


14-58

Intercept

0.59

Sy.x

1.44

PrecisionPrecision was evaluated with quality control materials on the VITROS DT60 II System following NCCLS Protocol EP5.16

The data presented are a representation of test performance and are provided as a guideline. Variables such as samplehandling and storage, reagent handling and storage, laboratory environment, and system maintenance can affectreproducibility of test results.

Precision for ALB DT: Serum

System

VITROS DT60 II

Conventional Units

MeanCone.

2.5

4.4

WithinDay SD*

0.02

0.04

<g>dL)Within

Lab SD**

0.06

0.10

MeanCone.

25

44

SI Units (g/L)

WithinDay SD*

0.2

0.4

WithinLab SD**

0.6

1.0

WithinLab

CV%**

2.6

2.3

No.Observ.

88

88

No.Days

22

22

Within Day precision was determined using two runs/day with two replications.Within Lab precision was determined using a single lot of slides and calibrating weekly.


INSTRUCTIONS FOR USEReferences

AlBDTAlbumin

References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 328-329; 1987.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, and

Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.

5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;1991.

6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS;1991.

7. Tietz NW. Textbook of Clinical Chemistry. Philadelphia: WB Saunders; 589; 1986.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.9. Doumas BT, Biggs HG. Determination of serum albumin. Standard Methods in Clinical Chemistry. 7:175-188; 1972.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. Corcoran RM, Durnan SM. Albumin Determination by a Modified Bromcresol Green Method. Clin. Chem. 23(4):765; 1977.12. Peters T. All about Albumin. San Diego: Academic Press; 256; 1996.13. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.14. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.15. Friedman RB. Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.16. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.

Glossary of SymbolsThe Glossary of Symbols table defines the symbols used on the VITROS Chemistry Products packaging and on the VITROSChemistry Products Assay Sheets.

Glossary of Symbols

Do Not Reuse

Use by or ExpirationDate (YYYY-MM-DD)

Lot Number

Manufacturer's SerialNumber

Catalog Number orProduct Code

Attention: SeeInstructions for Use. X

Manufacturer

Authorized Representative

Contains Sufficient for "n"Tests

For In Vitro Diagnostic Use

Store At or Below

Store At or Above

I

Store Between

Consult Instructions forUse

Fragile, Handle withCare.

Keep Dry

This end up


ALBDTAlbumin

VITR_[fi5 0

INSTRUCTIONS FOR USERevision History

Revision HistoryDate ofRevision2003-10-01

Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimen Storage and Stability - updated stability values• Materials Required But Not Provided and

Sample Dilution - added reagent-grade water• Quality Control Material Selection - added statements regarding controls low in

carbon dioxide concentration and ethylene glycol• Known Interferences - updated values• Method Comparison - updated all data and the plot• Precision - updated all data• References - added all except 7

The change bars indicate the position of a technical amendment to the text with respect to the previous version of the document.

When this Instructions For Use is replaced, sign and date below and retain as specified by local regulations or laboratorypolicies, as appropriate.

Signature Obsolete Date

C€Ortho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland

Ortho-Clinical Diagnostics, Inc.100 Indigo Creek DriveRochester, NY 14626-5101

' Ortho-Clinical Diagnosticsa ^e/hmtm^fotmmn company

VITROS is a trademark of Ortho-Clinical Diagnostics, Inc.© Ortho-Clinical Diagnostics, Inc., 2003.All rights reserved. Printed in USA.


VITRChemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products ALKP DT Slides

ALKP OTAlkaline Phosphatase

Intended UseFor in vitro diagnostic use only.VITROS ALKP DT Slides quantitatively measure alkaline phosphatase (ALKP) activity in serum and plasma.

Summary and Explanation of the TestAlkaline phosphatase is present mainly in bone, liver, kidney, intestine, placenta, and lung. Serum alkaline phosphatase maybe elevated in increased bone metabolism, for example, in adolescents and during the healing of a fracture; primary andsecondary hyperparathyroidism; Paget's disease of bone; carcinoma metastatic to bone; osteogenic sarcoma; and Hodgkin'sdisease if bones are invaded. Hepatobiliary diseases involving cholestasis, inflammation, or cirrhosis increase alkalinephosphatase activity; alkaline phosphatase activity may be increased in renal infarction and failure and in the complications ofpregnancy. Low alkaline phosphatase activity may occasionally be seen in hypothyroidism.1

Principles of the ProcedureThe VITROS ALKP DT Slide method is performed using the VITROS ALKP DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS ALKP DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thespreading layer contains the p-nitrophenyl phosphate substrate and other components needed for the reaction. The ALKP inthe sample catalyzes the hydrolysis of the p-nitrophenyl phosphate to p-nitrophenol at alkaline pH. The p-nitrophenol diffusesinto the underlying layer, and it is monitored by reflectance spectrophotometry. The rate of change in reflection density isconverted to enzyme activity.

Reaction Sequence

p-nitrophenyl phosphateALKP

Mg ,AMPp-nitrophenol + H3PO4

Test Type and ConditionsTest Type and Conditions for ALKP DT

Test TypeRate

VITROS DT60/DT60 IIModule

DTSC/DTSC II



Wavelength400 nm

Sample DropVolume

10 |JL



A1KPDTAlkaline Phosphatase

VITRI


Reagents

Slide IngredientsReactive ingredients per cm2

p-nitrophenyl phosphate 55 ug; 2-amino-2-methyl-1-propanol (AMP) 0.1 mg; andmagnesium sulfate 1.6 ug.

Other ingredientsPigment, binders, buffers, surfactants, cross-linking agent and stabilizer.

Slide Diagram

Slide Handling

i

- 2

, - ' , 3

" ~ - -. 4

5

1. Upper slide mount2. Spreading layer (BaSO4)

• magnesium sulfate• AMP• p-nitrophenyl phosphate

3. Reagent layer• buffer, pH 10.5



Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-28°C (64°-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18°-28°C(64°-82°F) for >48 hours.

1. Remove the individual slides from the box.2. Warm the unopened slide for at least 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to


Slide Storage and StabilityVITROS ALKP DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for ALKP DTSlides

Unopened

Opened



Specimen Requirements

Handle specimens as biohazardous material.


I IMPORTANT; Certain collection devices have been reported to affect other analytes and tests4


Specimens Not Recommended• Plasma:5 EDTA

CitrateFluoride oxalate

• Do not use hemolyzed specimens.


|S] VITRJIS

INSTRUCTIONS FOR USE ALKPDTTesting Procedure Alkaline Phosphatase

Serum and Plasma

Specimen Collection and PreparationCollect specimens using standard laboratory procedures.6 7


Special Precautions• For the affect of high concentration of bilirubin on test results, refer to "Limitations of the Procedure."

• Centrifuge specimens and remove the serum from the cellular material within 4 hours of collection.5

Specimen Handling and Storage


• Handle and store specimens in stoppered containers to avoid contamination and evaporation.• Mix samples by gentle inversion and bring to room temperature, 18°-28°C (64°-82°F), prior to analysis.

Specimen Storage and Stability for ALKP DT: Serum and Plasma5


Temperature18°-28OC(64°-82OF)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<4 days<4 days<4 days

Testing Procedure

Materials Provided• VITROS Chemistry Products ALKP DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA

| « VITROS DT Pipette• Isotonic saline

Operating Instructions• Refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

iMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior toanalysis.

Sample DilutionIf alkaline phosphatase activities exceed the system's reportable (dynamic) range:

| 1. Dilute with isotonic saline or VITROS 7% BSA.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's alkaline phosphatase activity.

Calibration



Calibration ProcedureRefer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


VI"TFj[C|3"S 0

AIKPDT INSTRUCTIONS FOR USEAlkaline Phosphatase Quality Control



The VITROS ALKP DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 400 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, alkaline phosphatase activity in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide.

Validity of a CalibrationCalibration parameters are automatically assessed by the VITROS DT60/DT60 II Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.


Reportable (Dynamic) Range for ALKP DTConventional and SI Units (U/L)

15-1500For out-of-range samples, refer to "Sample Dilution."

Traceability of the CalibrationI Values assigned to the VITROS Chemistry Products DT Calibrator Kit for alkaline phosphatase are traceable to the alkaline

phosphatase method recommended by the International Federation of Clinical Chemistry (IFCC),8'9 adapted to a centrifugalI analyzer at 37°C.

Quality Control


| Handle quality control materials as biohazardous material.


- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT60/DT60II

System.


and Definitions; Approved Guideline-Second Edition10 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


INSTRUCTIONS FOB USEExpected Values and Reporting Units

ALKPDTAlkaline Phosphatase

Quality Control Material SelectionVITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other alkalinephosphatase methods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.• Do not use control materials stabilized with ethylene glycol.



This reference interval is the central 95% of results from an internal study of 273 apparently healthy adults from a workingpopulation (154 females and 119 males).

Reference Interval for ALKP DTConventional and SI Units (U/L)

38-126


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report ALKP DT results in conventional and SI units.

Reporting Units for ALKP DTConventional and SI Units

U/L


The VITROS ALKP DT Slide method was screened for interfering substances following NCCLS Protocol EP7." Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for ALKP DT

Interferent*

BilirubinMethotrexateNitrofurantoin

InterferentConcentration

20 mg/dL (342 umol/L)200 ug/mL (440 umol/L)40ug/mL (168 umol/L)

Alkaline PhosphataseActivity

Conv./SI Units (U/L)120130120

Average Bias

Conv./SI Units (U/L)18.024.029.0

* It is possible that other interfering substances may be encountered. These results are representative;however, your results may differ somewhat due to test-to-test variation. The degree of interference atconcentrations other than those listed might not be predictable.

Other Limitations• Some drugs that have significant light absorbance in the region of 400 nm can cause a spectral interference.• Certain drugs and clinical conditions are known to alter alkaline phosphatase activity in vivo. For additional information,

refer to one of the published summaries.12 13


ALKPDTAlkaline Phosphatase



Method ComparisonThe plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II Chemistry System with thoseanalyzed using the Modified IFCC comparative method8 9 adapted to a centrifugal analyzer at 37°C. Testing followed NCCLSProtocol EP9.r"

Method Comparison for ALKP DT: Serum

Conventional and SI Units .

1600'

1200

800

oa: 400

400 800 1200 1600

Comparative Method: Modified IFCC(U/L)

Method Comparison for ALKP DT: Serum


n

94

Slope

0.99

Correlation Coefficient

0.994

Conventional and SI

Range of Sample Activity

36-1348

Units (U/L)

Intercept

5.78

Sy.x

39.10



Precision for

System

VITROS DT60

ALKP DT: Serum

II

Conventional and SI Units (U/L)

Mean Activity Within Day SD* Within Lab SD**

113

446

1.9 3.9

6.4 12.7

Within Lab CV%**

3.5

2.9

No. Observ.

88

88

No. Days

22

22Within Day precision was determined using two runs/day with two replications.Within Lab precision was determined using a single lot of slides and calibrating weekly.


|3 VITROS


ALKP DTAlkaline Phosphatase



Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.

5. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,IL: College of American Pathologists; 1992.



8. Bretaudiere JP, Vassault A, et al. Criteria for establishing a standardized method for determining alkaline phosphatase activity inhuman serum. Clin. Chem. 23:2263-2274; 1977.

9. Tietz NW, Rinker AD, Shaw L M. IFCC Methods for the Measurement of Catalytic Concentration of Enzymes, Part 5. IFCC Method forAlkaline Phosphatase.. J Clin. Chem., Clin. Biochem. 21:731-748; 1983.

10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.NCCLS Document C24. Wayne, PA: NCCLS; 1999.

11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, RA:

NCCLS; 1995.15. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


Glossary of Symbols

Do Not Reuse


Lot Number



Attention: SeeInstructions for Use.

XX

Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


A1KPDTAlkaline Phosphatase

VITRI



Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimen Storage and Stability - updated all stability values• Sample Dilution - added 7% BSA as a diluent• Materials Required But Not Provided - added VITROS DT Pipette• Quality Control Material Selection - added the statement regarding ethylene

glycol• Limitations of the Procedure - removed theophylline, added bilirubin,

methotrexate, and nitrofurantoin• Method Comparison - updated comparison values and plot• Precision - updated all values• References - added all

* The change bars indicate the position of a technical amendment to the text with respect to the previous version of the document.



C€

REPOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


Ortho-Clinical Diagnosticscompany



I Products-

VITRCD5Chemistry I

INSTRUCTIONS FOR USEVITROS Chemistry Products ALT DT Slides

AITDTAlanine Aminotransferase

Intended UseFor in vitro diagnostic use only.VITROS ALT DT Slides quantitatively measure alanine aminotransferase (ALT) activity in serum and plasma.

Summary and Explanation of the TestAlanine aminotransferase is present in high activity in liver, skeletal muscle, heart, and kidney. Serum ALT increases rapidly inliver cell necrosis, hepatitis, hepatic cirrhosis, liver tumors, obstructive jaundice, Reye's syndrome, extensive trauma to skeletalmuscle, myositis, myocarditis, and myocardial infarction.1

Principles of the ProcedureThe VITROS ALT DT Slide method is performed using the VITROS ALT DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS ALT DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thespreading layer contains the ALT substrates L-alanine and sodium a-ketoglutarate. Alanine aminotransferase catalyzes thetransfer of the amino group of L-alanine to a-ketoglutarate to produce pyruvate and glutamate. Lactate dehydrogenase (LDH)then catalyzes the conversion of pyruvate and NADH to lactate and NAD+.The rate of oxidation of NADH is monitored by reflectance spectrophotometry. The rate of change in reflection density isproportional to enzyme activity.

Reaction Sequence

alanine + a-ketoglutarate

pyruvate + NADH + H+ —

ALT

pyridoxal-5-phosphate

LDH

pyruvate + glutamate

- > • lactate + NAD*

Test Type and ConditionsTest Type and Conditions for ALT DT

Test TypeRate


DTSC/DTSC II


5 minutesTemperature

37°C (98.6°F)Wavelength

340 nm

Sample DropVolume

10 ML



AITDTAlanine Aminotransferase


Reagents


Lactate dehydrogenase (porcine muscle, E.C.1.1.1.27) 0.12 U;L-alanine 0.86 mg; sodium a-ketoglutarate 54 ng; nicotinamide adeninedinucleotide, reduced 35 ng; and sodium pyridoxal-5-phosphate 11 g.

Other ingredientsPigment, binders, buffer, surfactants, cross-linking agent and stabilizer.

Slide Diagram

Slide Handling

CAUTION:

1

. 2

- 5

1.2.

3.

4.6.

Jpper slide mountSpreading layer (BaSO4)• sodium a-ketoglutarate• L-alanineleagent layer

buffer, pH 8.0> lactate dehydrogenase> NADH

pyridoxal-5-phosphateSupport layer.ower slide mount


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18 °-28 °C (64 °~82 °F), before the wrapper isopened.Do not use unopened slides that have been at room temperature, 18°-28QC(64 °-82 °F) for >48 hours.

1. Remove the unopened slide from the box.2. Warm the unopened slide for 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to



VITROS ALT DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for ALT DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Refrigerated 2°-8°C (36°-46°F)Frozen <-18°C (<0°F)Room temperature 18°-28°C (64°-82° F)


Specimen RequirementsWARNING: Handle specimens as biohazardous material.

Specimens Recommended• Serum• Plasma: EDTA

Heparin

IMPORTANT: Certain collection devices have been reported to affect other analytes and tests3


Specimens Not Recommended• Do not use hemolyzed specimens.4

Serum and PlasmaSpecimen Collection and PreparationCollect specimens using standard laboratory procedures.56



INSTRUCTIONS FOR USE ALTDTTesting Procedure Alanine Aminotransferase

Special Precautions• Centrifuge specimens and remove the serum or plasma from the cellular material within 3 days of collection.7


V Handle specimens as biohazardous material.


IMPORTANT: Do not freeze the specimen.

Specimen Storage and Stability for ALT DT: Serum and Plasma7


Temperature18°-28°C (64O-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<3 days<1 weekNot recommended

Testing Procedure

Materials Provided• VITROS Chemistry Products ALT DT Slides


| • VITROS Chemistry Products 7% BSA or isotonic saline. VITROS DT Pipette


IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior toanalysis.

Sample DilutionIf alanine aminotransferase activities exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA or isotonic saline.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's alanine aminotransferase activity.

Calibration







ALTDT INSTRUCTIONS FOR USEAlanine Aminotransferase Quality Control

The VITROS ALT DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 340 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, alanine aminotransferase activity in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide.



Reportable (Dynamic) Range for ALT DTConventional and SI Units (U/L)

3-950


Traceability of the Calibration

I Values assigned to the VITROS Chemistry Products DT Calibrator Kit for alanine aminotransferase are traceable to the alanine

aminotransferase method recommended by the International Federation of Clinical Chemistry (IFCC),8 adapted to a centrifugalanalyzer at 37°C.

Quality Control


| WARMING: Handle quality control materials as biohazardous material.


- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT60/DT60 II

System.




I IMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60IIChemistry System. Evaluate the performance of other commercial control fluids for

| compatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other alanineaminotransferase methods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

I * Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.• Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and Storage

Refer to the instructions for use for VITROS Chemistry Products DT Control I & II or to other manufacturer's product literature.

4 Pub. No. C-336 Version 1.0


ALTDTAlanine Aminotransferase


These reference intervals are the central 95% of results from an internal study of 2444 apparently healthy adults (547 femalesand 1897 males).

Reference Interval for ALT DT

Adult

Females

Males

Conventional and SI Units (U/L) .

13-69 .

9-52

21-72


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report alanine aminotransferase results in units.

Reporting Units for ALT DTConventional and

U/LSI Units


None identified.

Other LimitationsCertain drugs and clinical conditions are known to alter alanine aminotransferase activity in vivo. For additional information,refer to one of the published summaries.1011

Performance CharacteristicsMethod Comparison

IThe plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzed

using the VITROS 950 System. Testing followed NCCLS Protocol EP9.'2

Method Comparison for ALT DT: Serum

Conventional and SI Units10110

3 800 •

600

401) •

o200

y = x

0 200 400 600 800 1000

Comparative Method: VITROS 950 System(U/L)


A1TDT INSTRUCTIONS FOR USEAlanine Aminotransferase References

Method Comparison for ALT DT: Serum


Correlationn Slope Coefficient

59 1.03 0.999


Range ofSample Activity Intercept Sy.x

6-863 -3.92 11.22

PrecisionPrecision was evaluated with quality control materials on the VITROS DT60II System following NCCLS Protocol EP5.13


Precision for ALT DT: Serum

System

VITROS DT60 II


Mean Activity

35

190

Within Day SD* Within Lab SD**

1.6 2.0

1.7 3.4

Within Lab CV%**

5.7

1.8

No. Observ.

84

84

No. Days

21

21



Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.

4. Young DS. Effects of Preanalytical Variables on Clinical Laboratory Tests. Washington D.C.: AACC Press; 3-7; 1993.5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;

1991.



8. Bergmeyer HU, Horder M, Rej R. Approved Recommendation (1985) on IFCC Methods for the Measurement of Catalytic Concentrationof Enzymes. Part 3. IFCC Method for Alanine Aminotransferase. J. Clin. Chem. Clin. Biochem. 24:481; 1986.


10. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.11. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.12. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


INSTRUCTIONS FOR USEGlossary of Symbols



Glossary of Symbols

SNREF|

Do Not Reuse


Lot Number




^ J Manufacturer

| ec | HEP | Authorized Representative



Store At or Below

Store At or Above1

I

If

Store Between



Keep Dry

This end up



VITRCpB



Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Materials Required But Not Provided and

Sample Dilution - added VITROS 7% BSA• Quality Control Material Selection - added statements regarding enzyme activity

and ethyline glycol• Reference Interval - updated all data• Known Interferences - removed statement regarding high total protein• Method Comparison - updated the comparison and plot• Precision - updated all values• References - added all except 8






Ortho-Clinical DiagnosticsefcMtsH company

VITROS is a trademark of Ortho-Clinical Diagnostics, Inc.©Ortho-Clinical Diagnostics, Inc., 2003.All rights reserved. Printed in USA.


(Products

VITRCD5Chemistry I

INSTRUCTIONS FOR USEVITROS Chemistry Products AMYL DT Slides

AMY1 DTAmylase

Intended UseFor in vitro diagnostic use only.VITROS AMYL DT Slides quantitatively measure amylase (AMYL) activity in serum and plasma.

Summary and Explanation of the TestAmylase is an amylolytic digestive enzyme produced by the exocrine pancreas and salivary glands. Amylase is increased inacute pancreatitis, pancreatic abscess or pseudocyst, pancreatic trauma, amyloidosis, pancreatic neoplasm, common-bile-ductobstruction, and after thoracic surgery. Increased amylase activity may be found in mumps parotitis and renal insufficiency.1

Principles of the ProcedureThe VITROS AMYL DT Slide method is performed using the VITROS AMYL DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS AMYL DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thespreading layer contains the dyed starch substrate (dye covalently linked to amylopectin) for the reaction. The amylase in thesample catalyzes the hydrolysis of this dyed starch into smaller dyed saccharides. These dyed saccharides diffuse into theunderlying reagent layer. The reflection density is proportional to the activity of amylase present in the sample.

Reaction Sequence

dyed amylopectinamylase

->• dyed saccharides

Test Type and ConditionsTest Type and Conditions for AMYL DT

Test TypeEndpoint


DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL



AMYLDTAmylase


Reagents

Slide .Ingredients

IReactive ingredients per cm2

Dyed amylopectin 320 ug.Other ingredientsPigment, binders, buffers, mordant, surfactants and stabilizer.

Slide Diagram

Slide Handling


1. Upper slide mount2. Spreading layer (BaSO,>)

• dyed amylopectin• buffer, pH 7.2



Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-28 °C (64 "-82 °F), before the wrapper isopened.




Slide Storage and StabilityVITROS AMYL DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for AMYL DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Refrigerated 2°-8°C (36°-46°F)Frozen <-18°C(<0°F)Room temperature 18°-28°C (64°-82°F)



Specimens Recommended• Serum• Plasma: Heparin3

iTOTE; Plasma activities are approximately 20 U/L higher than serum activities.3

Certain collection devices have been reported to affect other analytes and tests.4

Confirm that your collection devices are compatible with this test

Specimens Not Recommended• Plasma:5 Citrate

EDTAFluoride oxalate


INSTRUCTIONS FOR USE AMY1DTTesting Procedure Amylase

Serum and Plasma



Special Precautions





IMPORTANT; Do not freeze the specimen.

Specimen Storage and Stability for AMYL DT: Serum and Plasma8


Temperature18O-28°C(64O-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<7 days<1 monthNot recommended


• VITROS Chemistry Products AMYL DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• Isotonic saline• VITROS DT Pipette



Sample DilutionIf amylase activities exceed the system's reportable (dynamic) range:

I 1. Dilute the sample with a patient sample with low amylase activity or with isotonic saline.2. Reanalyze.3. If necessary, correct for amylase activity in the diluent.4. Multiply the results by the dilution factor to obtain an estimate of the original sample's amylase activity.

Calibration




AMVLDT INSTRUCTIONS FOR USEAmylase Quality Control




The VITROS AMYL DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 555 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, amylase activity in unknown samples can be determined using the software-resident endpoint colorimetric mathmodel and the response obtained from each unknown test slide.


Re portable (Dynamic) Range

Reportable (Dynamic) Range for AMYL DTConventional and SI Units (U/L)

5-900


Traceability of the CalibrationI Values assigned to the VITROS Chemistry Products DT Calibrator Kit for amylase are traceable to the paranitrophenol| maltopentaoside method9 at 37°C.

Quality Control


| WARN i NO; Handle quality control materials as biohazardous material.



System.




[3 VITROS

INSTRUCTIONS FOR USE AMYLDTExpected Values and Reporting Units Amylase


I IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids for

I compatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other Amylasemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Serum controls with porcine or bovine amylase may give lower values that may vary from method to method.11

• Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.I • Do not use control materials stabilized with ethylene glycol.


Expected Values and Reporting Units

Reference IntervalThe serum reference interval is the central 95% of results from an internal study of 98 apparently healthy individuals from aworking population (55 females and 43 males).No significant differences between results from the male and female populations were observed.

Reference Interval for AWIYL DTConventional and SI Units (U/L)

30-110* Plasma concentrations are approximately

20 U/L higher than serum concentrations.3

** Adults; normal intervals for children <1year old are lower. '2


Reporting Units

The VITROS DT60/DT60 II Chemistry System may be programmed to report Amylase results in conventional and SI units.

Reporting Units for AMYL DTConventional and SI Units

U/L


None identified.

Other LimitationsCertain drugs and clinical conditions are known to alter amylase activity in vivo. For additional information, refer to one of thepublished summaries.13'u


AMY1DTAmylase



Method Comparison

IThe plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzed

using the Paranitrophenol Maltopentaoside comparative method.9

Method Comparison for AMYL DT: Serum

Conventional and SI Units1000 •

900 '

800"

700

600 "

500 •

400 '

300

200 •

100 •

0

5

I

0 200 400 600 800 1000Comparative Method: Paranitrophenol Maltopentaoside

(U/L)

Method Comparison for AMYL DT: Serum



69 0.98 0.990



42-888 3.89 35.99



Precision for AMYL DT: Serum

System

VITROS DT60 II

Conventional and

Mean Activity

100

422

Within Day

4.5

13.3

SI Units (U/L)

SD* Within Lab SD**

5.2

16.1

Within Lab CV%**

5.2

3.8

No. Observ.

88

88

No. Days

22




AMYLDTAmylase



Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 5. Philadelphia: WB Saunders; 376; 2001.6. NCCLS. Procedures for the. Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;

1991.7. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS;

1991.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.9. Mauck LA. A Kinetic Colorimetric Method for the Determination of Total Amylase Activity in Serum. Clin. Chem. 31:1007; 1985.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. Lee VW, Willis C. Activity of Human and Nonhuman Amylases on Different Substrates Used in Enzymatic Kinetic Assay Methods—a

Pitfall in Interlaboratory Quality Control. Am. J. Clin. Path. 77:290-296; 1982.12. Gillard BK, Simbala JA, Goodnick L. Reference Intervals for Amylase Isoenzymes in Serum and Plasma of Infants and Children. Clin.

Chem. 29:1119; 1983.13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.15. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


Glossary of Symbols

Do Not Reuse


Lot Number

C M Manufacturer's SerialOlM Number

_ — — Catalog Number orK t i " Product Code


^m Manufacturer

EC I REP I Authorized Representative



Store At or Below

Store At or AboveI

Store Between


Fragile; Handle withCare.

Keep Dry

This end up


AMYLDTAmylase

VITRI



Version1.0

Description of Technical Changes"

• New format> New organization and sections consistent with IVD Directive> Specimen Storage and Stability - updated stability> Sample Dilution - added isotonic saline as a diluent; removed 2% bovine serum

albumin in saline, pH 7.4• Method Comparison - updated the data and plot• Precision - updated all data> References - added all but 3




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Ortho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


' Ortho-Clinical Diagnostics^ofaMOH company



[Products-

ViTRmSChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products AST DT Slides

ASTDTAspartate Aminotransferase

Intended UseFor in vitro diagnostic use only.VITROS AST DT Slides quantitatively measure aspartate aminotransferase (AST) activity in serum and plasma.

Summary and Explanation of the TestAspartate aminotransferase is present in high activity in heart, skeletal muscle, and liver. Increased serum AST activitycommonly follows myocardial infarction, pulmonary emboli, skeletal muscle trauma, alcoholic cirrhosis, viral hepatitis, and drug-induced hepatitis.1

Principles of the ProcedureThe VITROS AST DT Slide method is performed using the VITROS AST DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS AST DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thespreading layer contains the AST substrates aspartate and a-ketoglutarate. In the assay for aspartate aminotransferase, theamino group of L-aspartate is transferred to a-ketoglutarate in the presence of pyridoxal-5-phosphate (P-5-P) to produceglutamate and oxaloacetate. Malate dehydrogenase (MDH) then catalyzes the conversion of oxaloacetate and NADH to malateand NAD*.The rate of oxidation of NADH is monitored by reflectance spectrophotometry. The rate of change in reflection density isproportional to enzyme activity in the sample.

Reaction Sequence

aspartate + a-ketoglutarate

oxaloacetate + NADH + H* -

AST

pyridoxal-5-phosphate

MDH

->• oxaloacetate + glutamate

- > malate + NAD+

Test Type and ConditionsTest Type and Conditions for AST DT

Test TypeRate


DTSC/DTSC II



Wavelength340 nm

Sample DropVolume

10 ML





Reagents


Lactate dehydrogenase (porcine muscle, E.C.1.1.1.27) 0.12 U; malatedehydrogenase (porcine heart, E.C. 1.1.1.3) 0.11 U; sodium aspartate 0.5 mg;sodium a-ketoglutarate 32 ug; nicotinamide adenine dinucleotide, reduced36 ug; and sodium pyridoxal-5-phosphate 16 ug.

Other ingredientsPigment, binders, buffer, surfactants, cross-linking agent and stabilizer.

Slide Diagram

- • 1 •

*

. - i — -

- s

1. Upper slide mount2. Spreading layer (BaSOJ

3. 1

sodium u-ketoglutarateL-aspartate

Reagent layerbuffer, pH 8.0lactate dehydrogenasemalate dehydrogenaseNADHpyridoxal-5-phosphate


Slide Handling


Slide Preparation

The slide must reach room temperature, 18 °-28 °C (64 "-82 f), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 °-28 °C(64°-82°F) for >48 hours.



Slide Storage and StabilityVlTROS AST DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for AST DTSlidesUnopened

Opened



Specimen RequirementsWARMS: Handle specimens as biohazardous material.

Specimens Recommended• Serum• Plasma: Heparin

I MPORTANT: Certain collection devices have been reported to affect other analytes and tests.:


Specimens Not Recommended• Plasma: EDTA

• Citrate' Fluoride oxalate

• Do not use hemolyzed specimens because of high levels of AST activity in erythrocytes.4


INSTRUCTIONS FOR USE AST OTTesting Procedure Aspartate Aminotransferase

Serum and Plasma

Specimen Collection and Preparation• Collect specimens using standard laboratory procedures.5 6

• Due to the very low density of platelets, it is important to centrifuge plasma specimens at a minimum of 1000 X g for aminimum of ten minutes in order to avoid contamination of plasma with AST derived from platelets.


Special Precautions• Plasma, specimens must be collected in tubes that are at least half full. Smaller volumes may give falsely high AST

results.7

• Avoid agitation or mixing of plasma samples after centrifugation. Re-suspension of platelets into previously centrifugedplasma may lead to artificially elevated AST results because of high AST activity in platelets.4

• Centrifuge specimens and remove the serum or plasma from the cellular material within 3 days of collection.8




Do not freeze the specimen.

Specimen Storage and Stability for AST DT: Serum and Plasma8



<-18°C(<0°F)

Stability<3 days<7 days<3 months


• VITROS Chemistry Products AST DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA or isotonic saline. VITROS DT Pipette


I IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior to

analysis.

Sample DilutionIf aspartate aminotransferase activities exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA or isotonic saline.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's aspartate aminotransferase activity.

Calibration




AST DT INSTRUCTIONS FOR USEAspartate Aminotransferase Quality Control

Calibration ProcedureRefer to the operator's manual for your VlTROS DT60/DT60 II Chemistry System.



The VlTROS AST DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VlTROS DT60/DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 340 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, aspartate aminotransferase activity in unknown samples canbe determined from the rate of change in reflectance measured for each unknown test slide.

Validity of a CalibrationCalibration parameters are automatically assessed by the VlTROS DT60/DT60 II Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.


Reportable (Dynamic) Range for AST DTConventional and SI Units (U/L)

4-950


Traceability of the CalibrationI Values assigned to the VlTROS Chemistry Products DT Calibrator Kit for aspartate aminotransferase are traceable to the

aspartate aminotransferase method recommended by the International Federation of Clinical Chemistry (IFCC),9 adapted to aI centrifugal analyzer at 37°C.

Quality Control




- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VlTROS DT60/DT60II

System.


and Definitions; Approved Guideline-Second Edition™ or other published guidelines.• For additional information, refer to the operator's manual for your VlTROS DT60/DT60 II Chemistry System.





IIMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other aspartateaminotransferase methods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

I » Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.• Do not use control materials stabilized with ethylene glycol.



Reference IntervalThese reference intervals are the central 95% of results from an internal study of 189 apparently healthy adults from a workingpopulation (90 females and 99 males).

Reference Interval for AST DT

Adult

Females

Males


15-46

14-36

17-59


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report aspartate aminotransferase results inconventional and SI units.

Reporting Units for AST DTConventional and

U/LSI Units


I Heparin at activities greater than 50 U/mL cause AST results to be falsely high.7 Refer to "Specimen Collection andPreparation."

Other LimitationsCertain drugs and clinical conditions are known to alter aspartate aminotransferase activity in vivo. For additional information,refer to one of the published summaries.1112



VITRCpSgJ



Method Comparison

I The plot and table show the results of a comparison of samples analyzed on the VlTROS DT60 II System with those analyzed

using the VlTROS 950 System. Testing followed NCCLS Protocol EP9.13

Method Comparison for AST DT: Serum

Conventional and SI Units

1000 '

<=!

I

oa.>

800

600

400 •

200

200 400 600 800 1000

Comparative Method: VlTROS 950 System(U/L)

Method Comparison for AST DT: Serum

DT60 II System vs.950 System

n

73

Slope

1.01


0.997

Conventional and


15-848

SI Units (U/L)

Intercept

-8.46

Sy.x

21.68

PrecisionPrecision was evaluated with quality control materials on the VlTROS DT60 II System following NCCLS Protocol EP5.14


Precision for AST DT: Serum

System

VlTROS DT60 II

Conventional and SI

Mean Activity

40

193

Within Day SD

1.7

3.2

Units (U/L)

* Within Lab SD**

3.04.1

Within Lab CV%**

7.4

2.1

No. Observ.

84

84

No. Days

21

21



INSTRUCTIONS FOR USE ASTDTReferences Aspartate Aminotransferase

References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 369-371; 1987.

2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids andTissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.

3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.4. Young DS. Effects of Preanalytical Variables on Clinical Laboratory Tests, ed. 2. Washington D C : AACC Press; 3-69, 3-70; 1997.5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.7. Berg JD, Romano G, Bayley NF, Buckley BWI. Heparin Interferes with Aspartate Aminotransferase Activity Determined in the

Ektachem 700. Clin Chem. 34:174; 1988.


9. Bergmeyer H U, Horder M, Rej R. Approved Recommendation on IFCC Methods for the Measurement of Catalytic Concentration ofEnzymes. Part 2, IFCC Method for Aspartate Aminotransferase. J. Clin. Chem. Clin. Biochem. 24:497-510; 1986.


11. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.12. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D C : AACC Press; 1990.13. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

SN"RIFI

Do Not Reuse


Lot Number




Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up





Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimens Not Recommended - added citrate• Materials Required But Not Provided and


and ethylene glycol• Reference Interval - updated all data• Known Interferences - added statement regarding heparin; removed statement

regarding high total protein• Method Comparison - updated the comparison and plot• Precision - upated all values• References - added all




C€

ECOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


'Ortho-Clinical DiagnosticsM|jefcMtBn company



VITRCDSChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products BUN/UREA DT Slides

RUN/UREADT

Urea Nitrogen

Intended UseFor in vitro diagnostic use only.VITROS BUN/UREA DT Slides quantitatively measure urea concentration, reported either as urea nitrogen (BUN) or as urea(UREA), in serum and plasma.

Summary and Explanation of the TestThe major pathway of nitrogen excretion is in the form of urea that is synthesized in the liver, released into the blood, andcleared by the kidneys. A high serum urea nitrogen occurs in glomerulonephritis, shock, urinary tract obstruction,pyelonephritis, and other causes of acute and chronic renal failure. Severe congestive heart failure, hyperalimentation, diabeticketoacidosis, dehydration, and bleeding from the gastrointestinal tract elevate urea nitrogen. Low urea nitrogen often occurs innormal pregnancy, with decreased protein intake, in acute liver failure, and with intravenous fluid administration.1

Principles of the ProcedureThe VITROS BUN/UREA DT Slide method is performed using the VITROS BUN/UREA DT Slide and the VITROS ChemistryProducts DT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS BUN/UREA DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Water and nonproteinaceous components then travel to the underlying reagent layer, where the urease reaction generatesammonia. The semipermeable membrane allows only ammonia to pass through to the color-forming layer, where it reacts withthe indicator to form a dye.The reflection density of the dye is measured and is proportional to the concentration of urea in the sample.

Reaction Sequence

H2NCONH2 + H2O - > 2NH3 + CO2

NH3 + ammonia indicator -> dye

Test Type and ConditionsTest Type and Conditions for BUN/UREA DT



.DT60/DT60II



Wavelength660 nm

Sample DropVolume

10 ML

Warnings and PrecautionsFor in vitro diagnostic use only.Take care when handling materials and samples of human origin. Since no test method can offer complete assurance thatinfectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens,solid and liquid waste, and test components in accordance with local regulations and NCCLS Guideline M292 or otherpublished biohazard safety guidelines.

For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the instructionsfor use for the appropriate VITROS product, or to other manufacturer's product literature.


BUN/UREA DTUrea Nitrogen


Reagents

Slide IngredientsSlide Diagram

yA •

1. Upper slide mount; 2. Spreading layer (TIO2)

3. Reagent layer• urease• buffer.pH 7.8

4. Semipermeable membrane5. Indicator layer

s • ammonia indicator6. Support layer7. Lower slide mount

Reactive ingredients per cmUrease flack beans, E.C.3.5.1.5) 1.2 U and N-propyl-4-(2,6-dinitro-4-chlorobenzyl)-quinolonium ethane sulfonate (ammonia indicator) 0.26 mg.

Other ingredientsPigment, binders, buffer, surfactants, stabilizers, chelator and cross-linking agent

Slide Handling

CAUTION: Do not use slides with damaged or incompletely sealed packaging.

Slide Preparation

IMPORTANT: The slide must reach room temperature, 18 °-28 °C (64 °-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 "-28 °C(64 °-82 T) for >48 hours.



Slide Storage and StabilityVITROS BUN/UREA DT Slides are stable until the expiration date on the carton when they are stored and handled asspecified.

Slide Storage andSlidesUnopened

Opened

Stability for BUN/UREA DTStorage Condition

Room temperatureRefrigeratedFrozenRoom temperature

18°-282°-8°C<-18°C18°-28

'C (64°-82°(36°-46°F)(<0°F)'C (64°-82°

F)

F)


Specimen RequirementsWAR Mi HQ; ' Handle specimens as biohazardous material.

Specimens Recommended• Serum

• • Plasma:3 EDTA| Meparin

I IMPORTANT: Certain collection devices have been reported to affect other analytes and tests.4


Specimens Not Recommended• Plasma:3 Sodium fluoride (fluoride inhibits the enzyme urease)

Serum and PlasmaSpecimen Collection and Preparation• Collect specimens using standard laboratory procedures.5 6



INSTRUCTIONS FOR USE RUN/UREA OTTesting Procedure Urea Nitrogen

Special Precautions• For the effect of sample hemolysis on test results, refer to "Limitations of the Procedure."• Centrifuge serum and plasma specimens and remove the serum from the cellular material within 4 hours of collection.3




Specimen Storage and Stability for BUN/UREA DT: Serum and Plasma3


Temperature18°-28OC(64O-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<1 day<5 days<6 months


. VITROS Chemistry Products BUN/UREA DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• Isotonic saline or reagent-grade water• VITROS DT Pipette


I IMPORTANT; Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), priorto

analysis.

Sample DilutionIf urea nitrogen concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's urea nitrogen concentration.

Calibration







BUN/UREA DT INSTRUCTIONS FOR USEUrea Nitrogen Quality Control

The VITROS BUN/UREA DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 660 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, urea nitrogen concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for BUN/UREA DTConventional (mg/dL)

1-100SI Units (mmol/L)

0.4-35.7


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for BUN/UREA are traceable to the CertifiedNIST (National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 912a.The Ortho-Clinical Diagnostics calibration laboratory uses SRM* 912a to calibrate the CDC Urease/GLDH method7 to supportBUN/UREA value assignment for the VITROS DT Calibrator Kit.

Quality Control


| ' Handle quality control materials as biohazardous material.



System.




rftftiT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

Control materials other than VITROS DT Controls I & II may show a difference when compared with other urea nitrogenmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.Do not use control materials stabilized with ethylene glycol.Some controls that are low in carbon dioxide concentration may show a negative bias (>10% at CO2 <8 mmol/L) that maybe avoided by reconstituting lyophilates with a bicarbonate diluent instead of with water.Ammonium bicarbonate diluent should not be used as it will cause a positive bias in test results.


[S| VITR!


BUN/UREA OTUrea Nitrogen

• Proficiency survey samples may show a negative bias similar to controls low in CO2. Contact the testing agency forinstructions because reconstituting with special diluents may affect other analyte values (e.g., reconstituting with sodiumbicarbonate will affect sodium proficiency scores).



The serum reference interval is the central 95% of results from an internal study of 3160 apparently healthy adults from aworking population (612 females and 2548 males).

Reference Interval for BUN/UREA DT

MaleFemale

Conventional Units (mg/dL)9-207-17

SI Units (mmol/L)3.2-7.12.5-6.1


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report urea nitrogen results in conventional and SI units.

Reporting Units and Unit Conversion for BUN/UREA DTConventional Units

mg/dL urea NSI Units

mmol/L urea (mg/dL urea N x 0.3569)


• Ammonium ions may cause an increase in measured BUN/UREA value equivalent to the specimen's nitrogen content.9

The VITROS BUN/UREA DT Slide method was screened for interfering substances following NCCLS Protocol EP7.10 Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for BUN/UREA DT

Interferent*

Hemoglobin


50 mg/dL • (0.5 g/L)

Blood Urea NitrogenConcentration

Conv. (mg/dL) SI (mmol/L)28 10

BiasConv. (mg/dL) SI (mmol/L)

1.1 0.4


Other LimitationsCertain drugs and clinical conditions are known to alter blood urea nitrogen concentration in vivo. For additional information,refer to one of the published summaries.11 12





Method Comparison


using the VITROS 950 System. Testing followed NCCLS Protocol EP9.Method Comparison for BUN/UREA DT: Serum

Conventional Units

120

3 100

80

60

40

20

Ol

Q

20

oE

20 40 60 100 120

Comparative Method: VITROS 950 System(mg/dL)

40

3(1

20

10

SI Units

y = x

0 10 20 30 40Comparative Method. VITROS 950 System

(mmol/L)

Method Comparison for BUN/UREA DT: Serum



62 0.98 0.998

Conventional Units (mg/dL)

Range ofSample Cone. Intercept Sy.x

5-89 -0.10 1.61

SI Units (mmol/L)


1.8-31.7 -0.03 0.58



Precision for BUN/UREA

System

VITROS DT60 II

DT: SerumConventional Units (mg/dL)

MeanCone.

18

51

WithinDay SD*

0.5

1.4

WithinLab SD**

0.7

1.9

SI

MeanCone.

6.3

18.4

Units (mmol/L)

WithinDay SD*

0.18

0.49

WithinLab SD**

0.26

0.69

WithinLab

CV%**

4.1

3.7

No.Observ.

88

88

No.Days

22

22





References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 967; 1987.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.7. Sampson Rl, et al. A coupled-enzyme equilibrium method for measuring urea in serum: optimization and evaluation of the AACC study

group on urea candidate reference method. Clin. Chem. 26:816-26; 1980.8. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.9. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 676-679; 1987.10. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.11. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.12. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.13. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




X

Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


BUN/UREA DIUrea Nitrogen

VITFJCpS H



Version1.0

Description of Technical Changes*New format

> New organization and sections consistent with IVD DirectiveSpecimens Recommended - plasma: added EDTASpecimen Storage and Stability - updated stability values

> Quality Control Material Selection - added data> Method Comparison - updated all comparisons and the plot> Precision - updated all data

References - added all




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Chemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products Ca DT Slides

CaOTCalcium

Intended UseFor in vitro diagnostic use only.VITROS Ca DT Slides qualitatively measure calcium (Ca) concentration in serum and plasma.

Summary and Explanation of the TestCalcium is the major mineral component of bone; 99% of the body's calcium is in bone. Calcium ions play an important role inthe transmission of nerve impulses and in maintaining normal muscle contraction. Abnormal concentrations of serum calciummay indicate malfunction of the parathyroid glands, bone diseases, carcinoma, malnutrition and malabsorption syndrome,vitamin D deficiency, overdose with calcium-containing antacids, and renal diseases.1

Principles of the ProcedureThe VITROS Ca DT Slide method is performed using the VITROS Ca DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS Ca DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thebound calcium is dissociated from binding proteins, allowing the calcium to penetrate through the spreading layer into theunderlying reagent layer. There, the calcium forms a complex with Arsenazo III dye, causing a shift in the absorption maximum.After incubation, the reflection density of the colored complex is measured spectrophotometrically. The amount of coloredcomplex formed is proportional to the calcium concentration in the sample.

Reaction Sequence

Ca+2 + Arsenazo IpH5.6

colored complex

Test Type and ConditionsTest Type and Conditions for Ca DT



DTSC/DTSC II



Wavelength680 nm

Sample DropVolume

10 pL



CaDTCalcium

VITRJJD5 Q


ReagentsSlide Ingredients


| Arsenazo III dye 60 |xg.

Other ingredients| Pigment, binders, surfactants, buffer, cross-linking agent and mordant.

Slide Diagram

Slide Handling

CAUTION:

1

. 2

. 3

~~ " ~ 4

. . ' - • - '

1.2.3.

4.S.

Upper slide mountSpreading layer (TIO2)Reagent layer• Arsenazo III dye• buffer, pH 5.6Support layerLower slide mount


Slide Preparation

The slide must reach room temperature, 18°-28°C (64°-82°F), before the wrapper isopened.





VITROS Ca DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for Ca DTSlides

Unopened

Opened

StorageRoom temperatureRefrigeratedFrozenRoom temperature

Condition18°-28°C(64°-82°2°-8°C (36°-46°F)<-18°C (<0°F)18°-28°C(64°-82°

F)

F)



CAUTION:

NOTE:

Protective gloves manufactured with calcium carbonate powders may causeelevated test results because of the contamination of sample handling supplies(for example, pipette tips, transfer pipettes, sample cups and caps). Suppliesthat have come in contact with powdered gloves may subsequently contaminatethe test specimen during sample metering.

Gloves labeled as "powder-free" may contain some contaminating powder agents onthe inside of the glove.


INSTRUCTIONS FOR USE Ca DTTesting Procedure Calcium




Specimens Not Recommended• Plasma:5 EDTA*

Fluoride oxalate*Citrate*

"These substances chelate calcium, causing negative bias. 5

• Do not use blood from patients on EDTA therapy.



Special Precautions• Results from recumbent patients may be 3% lower.8

• Blood collected with stasis may have calcium concentrations 15% higher.8

• Centrifuge specimens and remove the serum and plasma from the cellular material within 2 days of collection.9


Specimen Storage and Stability for Ca DT: Serum and PlasmaStorageRoom temperatureRefrigerated9

Frozen9

Temperature18°-28OC(64O-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<4 hours<22 days<1 year


. • VITROS Chemistry Products Ca DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• Isotonic saline• Reagent-grade water. VITROS DT Pipette


Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior toanalysis.


VITFJCpIS 0

CaDT INSTRUCTIONS FOR USECalcium Calibration

Sample DilutionIf calcium concentrations exceed the system's reportable (dynamic) range:1. Dilute with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's calcium concentration.

Calibration



Special PrecautionsIf the laboratory's ambient temperature has changed ±5°F (±3°C), or more, from the temperature at the time that the calciumtest was calibrated, then the quality-control materials should be checked. If the quality-control materials are out of control,recalibrate the analyzer for calcium and record the temperature at the time of calibration for future reference.




The VITROS Ca DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Calculations

I Reflectance from the slide is measured at 680 nm after the fixed incubation time. Once a calibration has been performed for

each slide lot, calcium concentration in unknown samples can be determined using the software-resident endpoint colorimetricmath model and the response obtained from each unknown test slide.

Validity of a Calibration

I Calibration parameters are automatically assessed by the VITROS DT60/DT60 II Chemistry System against a set of quality

parameters resident within the analyzer software. The quality control results should be used to determine the validity ofa calibration.

Reportable (Dynamic) RangeReportable (Dynamic) Range for Ca DT

SerumConventional (mg/dL)

3.00-14.00SI Units (mmol/L)

0.75-3.49


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for calcium are traceable to the Certified NIST (NationalInstitute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 915a. The Ortho-ClinicalDiagnostics calibration laboratory uses SRM® 915a to calibrate the Flame Atomic Absorption Spectroscopy method10 to supportcalcium value assignment for the VITROS Chemistry Products DT Calibrator Kit.


INSTRUCTIONS FOR USE Ca DTQuality Control Calcium

Quality Control

Procedure RecommendationsI Handle quality control materials as biohazardous material.


- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT System.


and Definitions; Approved Guideline-Second Edition" or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


IIMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other calcium methodsif they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Do not use control materials stabilized with ethylene glycol.



Reference Interval

These reference intervals are based on an external study.12

Reference Interval for Ca DTConventional Units (mg/dL)


2.10-2.55



The VITROS DT60/DT60 II Chemistry System may be programmed to report calcium results in conventional and SI units.

Reporting Units and Unit Conversion for Ca DTConventional Units

mg/dLSI Units

mmol/L (mg/dL x 0.2495)


CaDTCalcium

INSTRUCTIONS FOR USELimitations of the Procedure

Limitations of the Procedure

Known Interferences• Blood from patients receiving Hypaque radiographic contrast agent cannot be used.

I * Suramin, an antiparasitic drug, has been reported to cause a bias of -10% in calcium results at a suramin concentration of300 ug/mL.13

Other Limitations• Keeping the sample in an open container at room temperature may increase the reported calcium concentration by up to

0.4 mg/dL (0.1 mmol/L). Changes are due to the loss of carbon dioxide, which results in an increase in pH of the specimen.The increase is minimized by anaerobic handling procedures and prompt analysis. Adherence to these procedures isespecially important for pediatric samples where the sample volume is small.

Certain drugs and clinical conditions are known to alter calcium concentration in vivo. For additional information, refer to one ofthe published summaries.1'1'15


Method ComparisonThe plots and tables show the results of a comparison of samples analyzed on the VITROS DT60 II System with thoseanalyzed using the Atomic Absorption comparative method.10 Testing followed NCCLS Protocol EP9.16

Method Comparison for Ca DT: Serum

Conventional Units

15

I

•8

12

9

6

3

0

y = x

15Comparative Method: Atomic Absorption

(mg/dL)

CO

ot

8 !

SI Units

y = x

Comparative Method: Atomic Absorption(mmol/L)

Method Comparison for Ca DT: Serum


n

77

Slope

0.98


0.997

Conventional


3.0-12.9

Units or (mg/dL)

Intercept Sy.x

0.21 0.20

SI Units


0.76-3.21

(mmol/L)

Intercept

0.05

Sy.x

0.05


{•I VITRJ


CaDTCalcium



Precision for Ca DT: Serum

System

DT60 II System


MeanCone.

9.1

11.4

WithinDay SD*

0.10

0.09

WithinLab SD**

0.18

0.21

SI

MeanCone.

2.26

2.85

Units (mmol/L)

WithinDay SD*

0.03

0.02

WithinLab SD**

0.04

0.05

WithinLab

CV%**

2.0

1.8

No.Observ.

88

87

No.Days

22

22


References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 705-713; 1987.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and


Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Tietz NW. Textbook of Clinical Chemistry, ed. 2. Philadelphia: WB Saunders; 66-67,1900; 1994.6. NCCLS. Procedures forthe Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;

1991.7. NCCLS. Procedures forthe Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS;

1991.

8. Tietz NW. Textbook of Clinical Chemistry, ed. 2. Philadelphia: WB Saunders; 60, 80; 1994.9. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.10. Cali JP, et al. Atomic Absorption. NBS Reference Method (modified). Clin. Chem. 19:1208; 1987.11. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.12. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 947; 1987.13. Gregory, et al. Suramin Interferes with Measurements of Total Calcium and Serum Amylase by the Kodak Ektachem 700 Analyzer and

May Inhibit Liver Enzyme Activity. Clin. Chem. 38:2552-2553; 1992.14. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.15. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.16. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


CaDTCalcium

VITRCpS 0



Glossary of Symbols

Q<J Do Not Reuse

2 Use by or Expiration

Date (YYYY-MM-DD)| LOT | Lot Number

Q K I Manufacturer's SerialO l N Number



REF

Manufacturer

EC I REP I Auth'orized Representative



Store At or Below

Store At or Above

Xm!Store Between



Keep Dry

This end up


Version1.0

Description of Technical Changes*• New organization and sections consistent with IVD Directive• Specimen Handling and Storage - updated stabilities; removed "Serum should

not be frozen."• Specimen Collection and Preparation - updated all statements under Special

Precautions• Limitations of the Procedure - added suramin• Method Comparison - updated comparison data and plots• Precision - updated all data• References - added 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 13, 16, 17






' Ortho-Clinical Diagnostics8H company



viTRrasChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products CHE DT Slides

CHEOTCholinesterase

Intended UseFor in vitro diagnostic use only.VITROS CHE DT Slides quantitatively measure cholinesterase (CHE) activity in serum and plasma.

Summary and Explanation of the TestThere are two types of cholinesterase:• Acetylcholinesterase (EC.3.1.1.7), which is found in red blood cells and nerve tissues.• Cholinesterase (E.C.3.1.1.8), which is found in plasma, liver, heart, and other tissues.These measurements are useful in the diagnosis of pesticide poisoning, liver diseases and sensitivity to succinylcholineadministration.12

• Pesticide poisoning. Organophosphate and carbamate pesticides are inhibitors of both cholinesterase andacetylcholinesterase. Although the toxic effect is caused by inhibition of acetylcholinesterase in nerve endings,cholinesterase is often used clinically because it is present in serum in high activities and is easy to measure.

• Liver diseases. Cirrhosis, hepatitis, and carcinoma with metastasis to the liver are known to lower cholinesterase activity.A decrease in CHE activity is considered a sensitive measure of a drop in liver synthetic capacity, because high activities ofcholinesterase are normally present in serum.

• Sensitivity to succinylcholine administration. Succinylcholine is a short-acting muscle relaxant administered duringsurgery. It is a reversible inhibitor of acetylcholinesterase and is hydrolyzed by serum cholinesterase. Individuals withoutsufficient serum cholinesterase activity or with certain genetic variants may be unable to metabolize the drug quickly,resulting in prolonged apnea. Low CHE activities may be chronic for the individual or transient due to pesticide exposure,liver disorder, pregnancy, or the use of oral contraceptives.

Principles of the ProcedureThe VITROS CHE DT Slide method is performed using the VITROS CHE DT Slide and the VITROS Chemistry ProductsDT Specialty Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS CHE DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Cholinesterase hydrolyzes butyrylthiocholine to thiocholine. The liberated thiocholine reduces potassium hexacyanoferrate III(potassium ferricyanide) to potassium hexacyanoferrate II (potassium ferrocyanide). The rate of color loss is monitored byreflectance spectrophotometry. The rate of change in reflection density is proportional to the cholinesterase activity in thesample.

Reaction Sequence

butyrylthiocholine + H2OCHE

2 thiocholine + 2 potassium ferricyanide

thiocholine + butyrate

dithiobis(choline) + 2 potassium ferrocyanide

Test Type and ConditionsTest Type and Conditions for CHE DT

Test TypeRate


DTSC/DTSC II



Wavelength400 nm

Sample DropVolume

10 ML


CHEDTCholinesterase

INSTRUCTIONS FOR USEWarnings and Precautions


Reagents

Slide Ingredients


I Potassium ferricyanide 180 ug and butyrylthiocholine iodide 290 ug.

Other ingredientsPigment, binders, buffer, surfactants and cross-linking agent.

Slide Diagram

Slide Handling

CAUTSQN:

— 1

2

y' ..-3

1.2.

3.

4.5.

Upper slide mountSpreading layer (TIO2)• butyrylthiocholine iodideReagent layer« potassium ferricyanide• buffer, pH 7.6Support layerLower slide mount


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18"-28 °C (64 °-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 °-28 °C(64 °-82 °F) for >48 hours.




VITROS CHE DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for CHE DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Frozen <-18°C(<0°F)Room temperature 18°-28°C (64°-82°F)

Stability<48 hoursUntil expiration date<15 minutes

Specimen RequirementsWA R H! N S: Handle specimens as biohazardous material.


I IMPORTANT: Certain collection devices have been reported to affect other anaiytes and tests.4

I Confirm that your collection devices are compatible with this test.

Specimens Not Recommended• Do not use visibly hemolyzed specimens.5


[¥J VITRI

INSTRUCTIONS FOR USE CHEDTTesting Procedure Cholinesterase

Serum and Plasma

Specimen Collection and PreparationCollect specimens using standard laboratory procedures.6'


Special Precautions



41N6: Handle specimens as biohazardous material.


Specimen Storage and Stability for CHE DT: Serum and Plasma8


Temperature18°-28°C (64°-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<6 hours<7 daysNot recommended


• VITROS Chemistry Products CHE DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Specialty Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II

I • VITROS Chemistry Products 7% BSA or isotonic saline• VITROS DT Pipette


IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), priortoanalysis.

Sample DilutionIf cholinesterase activities exceed the system's reportable (dynamic) range:

I 1. Dilute the sample with VITROS 7% BSA or isotonic saline.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's cholinesterase activity.

Calibration

Required CalibratorsVITROS Chemistry Products DT Specialty Calibrator Kit, bottles 1, 2, and 4

Calibrator Preparation, Handling, and StorageRefer to the instructions for use for VITROS DT Specialty Calibrator Kit.



GHEDT INSTRUCTIONS FOR USECholinesterase Quality Control


- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.The VITROS CHE DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 400 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, cholinesterase activity in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide.



Reportable (Dynamic) Range for CHE DTConventional (U/mL)

0.20-12.50SI Units (U/L)

200-12500



I Values assigned to the VITROS Chemistry Products DT Specialty Calibrator Kit for cholinesterase are traceable to the

butyrylthiocholine-based ferricyanide cholinesterase method recommended by the German Society for Clinical Chemistry,9

measured on a centrifugal analyzer at 37°C.

Quality ControlProcedure Recommendations

| WARMING: Handle quality control materials as biohazardous material.



System.





CHEDTCholinesterase


IMP VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other cholinesterasemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




These reference intervals are the central 95% of results from an internal study of 240 apparently healthy adults from a workingpopulation (101 females and 139 males).

Reference Interval for CHE DT

MaleFemale

Conventional Units(U/mL)

5.90-12.224.65-10.44

SI Units(U/L)

5900-122204650-10440


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report cholinesterase results in conventional andSI units.

Reporting Units and Unit Conversion for CHE DTConventional Units

U/mLSI Units

U/L (U/mL x 1000)


The VITROS CHE DT Slide method was screened for interfering substances following NCCLS Protocol EP7.11 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for CHE DT

Interferent*

Procainamide

Phenazopyridine

L-dopa


4 mg/mL

10 mg/mL

80 ug/dL

80 ng/dL

300 (.ig/mL

17 mmol/L

42 mmol/L

3.2 (.imol/L

3.2 |.imol/L

1.5 mmol/L

Cholinesterase Activity

Conv. (U/mL)

6.5

6.5

4.5

6.5

6.0

SI (U/L)

6500

65004500

6500

6000

Bias

Conv. (U/mL)

-0.48

-1.05

-0.74

-0.73

-1.11

SI (U/L)

-477

-1050

-740

-730

-1114* It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ

somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.

Other Limitations• Low pH (6.8) causes a 15% negative bias.• Certain drugs and clinical conditions are known to alter cholinesterase activity in vivo. For additional information, refer to

one of the published summaries.12 13


GHEDICholinesterase



Method Comparison


using the VITROS 950 System. Testing followed NCCLS Protocol EP9.14

Method Comparison for CHE DT: Serum

Conventional Units

15 V =

I l2

CO

&to

3 6 9 12Comparative Method: VITROS 950 System

(U/mL)

] 5000

3 12000 -

9000

6000

t 3000>

SI Units

0 3000 6000 9000 12000 15000Comparative Method: VITROS 950 System

(U/L)

Method Comparison for CHE DT: Serum


n

73

Slope

1.03


0.998

Conventional

Range ofSample Activity

1.44-12.13

Units (U/mL)

Intercept Sy.x

0.13 0.17

SI Units (U/L)

Range ofSample Activity Intercept

1436-12130 131.01

Sy.x

172.77



Precision for CHE DT: Serum

System

VITROS DT60 II

Conventional Units (U/mL)

MeanActivity

3.76

7.39

WithinDay SD*

0.02

0.04

WithinLab SD"

0.05

0.11

MeanActivity

3760

7391

SI Units (U/L)

WithinDay SD*

23.2

38.8

WithinLab SD**

52.8

105.8

WithinLab

CV%**

1.4

1.4

No.Observ.

88

88

No.Days

22

22




CHEDTCholinesterase

References1. MossDW, Henderson AR, Kachman JF. Enzymes. In Textbook of Clinical Chemistry, NWTietz, ed., Philadelphia, PA: WB Saunders;

746-751, 1986.2. Trundle D, and Marcial G. Detection of Cholinesterase Inhibition. Annals of Clinical and Laboratory Science. 5:345-352, 1988.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBIM 1-56238). NCCLS, Wayne, PA 19087; 1997.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 5. Philadelphia: WB Saunders; 387; 2001.6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfieid,

IL: College of American Pathologists; 1992.9. Method recommended by the "Working Group on Enzymes of the German Society for Clinical Chemistry", European Journal of Clinical

Chemistry, Clinical Biochemistry. 30:163-170; 1992.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


CHEDTCholinesterase



Version1.0

•

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Materials Required But Not Provided

Sample Dilution - added VITROS 7% BSA; removed reagent-grade water> Known Interfering Substances table - removed ibuprofen; updated values• Method Comparison - updated all comparisons and the plot> Precision -updated data> References - added all except 13




C€

REP



'Ortho-Clinical Diagnostics



Chemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products CHOL DT Slides

CHOIDTCholesterol

Intended UseFor in vitro diagnostic use only.VITROS CHOL DT Slides quantitatively measure cholesterol (CHOL) concentration in serum and plasma.

Summary and Explanation of the TestCholesterol is present in tissues and in serum and plasma either as cholesterol or as cholesterol esters bound to proteins.Cholesterol is an essential structural component of cell membranes and the outer layer of plasma lipoproteins and is theprecursor of all steroid hormones, including sex and adrenal hormones, bile acids, and vitamin D.Cholesterol measurements are used to evaluate the risk of developing coronary artery occlusion, atherosclerosis, myocardialinfarction, and cerebrovascular disease. Coronary atherosclerosis correlates with a high cholesterol level. Cholesterolconcentrations are increased in primary hypercholesterolemia; secondary hyperlipoproteinemia, including nephrotic syndrome;primary biliary cirrhosis; hypothyroidism; and in some cases diabetes mellitus. Low cholesterol concentrations may be found inmalnutrition, malabsorption, advanced malignancy, and hyperthyroidism. Serum cholesterol concentration depends on manyfactors, including age and gender.1

Principles of the ProcedureThe VITROS CHOL DT Slide method is performed using the VITROS CHOL DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS CHOL DT Slide is a multilayered, analytical element coated on a polyester support. The method is based on anenzymatic method similar to that proposed by Allain et al.2

A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. TheTriton X-100 (TX100) surfactant in the spreading layer aids in dissociating the cholesterol and cholesterol esters fromlipoprotein complexes present in the sample. Hydrolysis of the cholesterol esters to cholesterol is catalyzed by cholesterol esterhydrolase. Free cholesterol is then oxidized in the presence of cholesterol oxidase to form cholestenone and hydrogenperoxide. Finally, hydrogen peroxide oxidizes a leuco dye in the presence of peroxidase to generate a colored dye.The density of dye formed is proportional to the cholesterol concentration present in the sample and is measured by reflectancespectrophotometry.

Reaction Sequence

lipoprotein cholesterol + cholesterol esters + proteins

cholesterol esters + H2Ocholesterol ester hydrolase

cholesterol + fatty acids

cholesterol + O2

H2O2 + leuco dye

cholesterol oxidasecholest-4-en-3-one + H2O2

peroxidase - > dye + 2H2O

Test Type and ConditionsTest Type and Conditions for CHOL DT



DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL


CHOL DTCholesterol



Slide DiagramReagents

Slide Ingredients


I Triton X-100 0.8 mg; cholesterol oxidase (Nocardia E.C.1.1.3.6) 0.2 U;

cholesterol ester hydrolase (Candida rugosa, E.C.3.1.1.13) 0.7 U;peroxidase (horseradish root, E.C. 1.11.1.7) 5.3 U; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl) imidazole (leuco dye) 0.2 mg.Other ingredientsPigment, binder, buffer, surfactants, stabilizers and cross-linking agent.

Slide Handling

2

, - * • " • " " " "

- . • — ,

. . — • ' ' - - • — •

1.2.

3.

4.6.

Jpper slide mountSpreading layer (BaSO2)> Triton X-100» cholesterol ester

hydrolase> cholesterol oxidase• peroxidase> leuco dye

leagent layer• buffer, pH 6.25Support layerLower slide mount


Slide Preparation


Do not use unopened slides that have been at room temperature, 18°-28°C(64 °-82 °F) for >48 hours.

1. Remove the unopened slide from the box.2. Warm the unopened slide for at least 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to


Slide Storage and StabilityVITROS CHOL DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for CHOL DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Refrigerated 2°-8°C (36°-46°F)Frozen <-18°C(<0°FlRoom temperature 18°-28°C (64°-82°F)


Specimen RequirementsG: Handle specimens as biohazardous material.





INSTRUCTIONS FOR USE CHO1DTTesting Procedure Cholesterol

Specimens Not Recommended• Plasma:5 Fluoride oxalate

EDTASodium citrate

Serum and PlasmaSpecimen Collection and PreparationCollect specimens using standard laboratory procedures.6 7


Special Precautions





Specimen Storage and Stability for CHOL DT: Serum and Plasma8


Temperature18O-28OC(64°-82°F)2°-8°C (36°-46°F)

<-18°C (<0°F)

StabilityNot recommended<3 days<3 weeks


. VITROS Chemistry Products CHOL DT Slides




Sample DilutionIf cholesterol concentrations exceed the system's reportable (dynamic) range:1. Dilute with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's cholesterol concentration.

Calibration





CHOLDT INSTRUCTIONS FOR USECholesterol Quality Control

When to CalibrateCalibrate:• When the slide lot number changes.• ' When critical system parts are replaced due to service or maintenance.• When government regulations require.


The VITROS CHOL DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 555 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, cholesterol concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for CHOL DTConventional (mg/dL)


1.3-8.4


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for cholesterol are traceable to the Certified NIST(National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 911b. TheOrtho-Clinical Diagnostics calibration laboratory uses SRM19 911b to calibrate the Centers for Disease Control (CDC) ModifiedAbell-Kendall method9 to support cholesterol value assignment for the VITROS DT Calibrator Kit.

Quality Control



• Choose control levels that check the clinically relevant range.• Analyze quality control materials in the same manner as patient samples, before or during patient sample processing. .• To verify system performance, analyze control materials:


t If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results.• For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principles

and Definitions; Approved Guideline-Second Edition™ or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.



CHOIDTCholesterol

Quality Control Material SelectionIMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other Cholesterolmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




This reference interval is recommended by NCEP.1

Reference Interval for CHOL DT

DesirableBorderline HighHigh

Conventional Units (mg/dL)<200

200-239>240

SI Units (mmol/L)<5.2

5.2-6.2>6.2


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report CHOL DT results in conventional and SI units.

Reporting Units and Unit Conversion for CHOL DTConventional Units

mg/dL

SI Unitsmmol/L (mg/dL x 0.02586)


Known Interferences• Total protein, 9 g/dL (90 g/L), may elevate results by 4.9%.The VITROS CHOL DT Slide method was screened for interfering substances following NCCLS Protocol EP7." Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for CHOL DT

Interferent*

Gentisic acidN-acetylcysteineEthamsylateL-Dopa


5 mg/dL (0.32 mmol/L)10 mg/dL (0.61 mmol/L)3 mg/dL (0.114 mmol/L)

0.6 mg/dL (0.030 mmol/L)

CholesterolConv.

(mg/dL)210210210210

ConcentrationSI

(mmol/L)5.4

5.45.4

5.4

Conv.(mg/dL)

-29

-27-11-11

BiasSI

(mmol/L)-0.8-0.7-0.3-0.3

* It is possible that other interfering substances may be encountered. These results are representative; however, your results maydiffer somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not bepredictable.

Other LimitationsCertain drugs and clinical conditions are known to alter cholesterol concentration in vivo. For additional information, refer to oneof the published summaries.13 u


GHOLDTCholesterol



Method Comparison

I The plots and table show the results of a comparison of samples analyzed on the VITROS DT60 II Chemistry System with

those analyzed using the Modified Abell-Kendall comparative method.9 Testing followed NCCLS Protocol EP9.Method Comparison for CHOL DT: Serum

Conventional Units

350 i

g- 300

1 250 H

I 200w

i i5°° 100

I »0

0 50 100 150 200 250 300Comparative Method: Modified Abell-Kendall

(mg/d/L)

350

a.>

10

SI Units

y = x

2 4 6 S 10Comparative Method: Modified Abell-Kendall

Method Comparison for CHOL DT: Serum


n

56

Slope

1.00


0.997

Conventional


56-313

Units (mg/dL)

Intercept Sy.x

0.75 6.11

SI Units (mmol/L)

Range ofSample Cone. Intercept

1.4-8.1 0.02

Sy.x

0.16

PrecisionPrecision was evaluated with quality control materials on VITROS the DT60 II System following NCCLS Protocol EP5.16


Precision for CHOL DT:

System

VITROS DT60 II

SerumConventional Units (mg/dL)

MeanCone.

149

235

WithinDay SD*

3.2

3.8

WithinLab SD"

3.5

5.0

SI

MeanCone.

3.8

6.1

Units (mmol/L)

WithinDay SD*

0.08

0.10

WithinLab SD**

0.09

0.13

WithinLab

CV%**

2.3

2.1

No.Observ.

88

88

No.Days

22




CHOLDTCholesterol

References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 448-468; 1987.

2. Allain CC, et al. Enzymatic Determination of Total Cholesterol in Serum. Clin. Chem. 20:470; 1974.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. NCEP. Recommendations for improving cholesterol measurement. A report from the Laboratory Standardization Panel of the National

Cholesterol Education Program. NIH Publication No. 90-2964; 1990.6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.8. Burtis CA, Ashwood ER. eds. Textbook of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 849; 1999.9. Duncan IW, Mather A, Cooper GR. The procedure for the proposed cholesterol reference method. Atlanta, GA: Centers for Disease

Control; 1982.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. NCEP. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of

High Blood Cholesterol in Adults (Adult Treatment Panei III); Executive Summary. NIH Publication No. 01-3670. NationalInstitutes of Health. Bethesda. Maryland: May, 2001.

12. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.15. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer

j 6c | REP j Authorized Representative



¥ Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


CHOIDTCholesterol



Version1.0

Description of Technical Changes*

• New format> New organization and sections consistent with IVD Directive• Specimens Not Recommended - added the section» Serum and Plasma: Special Precautions - "added within 3 hours of collection"> Specimen Handling and Storage - updated all stabilities> Quality Control Material Selection - added statement regarding ethylene glycol• Method Comparison - updated comparison values and plots• Precision - updated all values> References - added all new references




C€

I EC REPj

ml



' Ortho-Clinical DiagnosticsaAtMSH company



[Product*

VITRCD5Chemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products CK DT Slides

CKDTCreatine Kinase

Intended UseFor in vitro diagnostic use only.VITROS CK DT Slides quantitatively measure creatine kinase (CK) activity in serum and plasma.

Summary and Explanation of the TestCreatine kinase, also referred to as creatine phosphokinase, is a cellular enzyme with a wide tissue distribution. CK is foundmainly in skeletal and cardiac muscle. CK's physiological role is associated with ATP generation for contractile or transportsystems. Serum CK is almost always increased following acute myocardial infarction or skeletal muscle damage. The enzymeis commonly elevated in myocarditis of any cause, cerebrovascular accidents, rhabdomyolysis, polymyositis, and acutephysical exertion. CK is also increased in the muscular dystrophies; in Duchenne's muscular dystrophy, CK elevations of20-200 times normal are common. Low CK may reflect decreased muscle mass or muscle wasting. Reference values for CKmust consider the age, gender, and physical activity of the person. Low serum CK activities are common in the elderly, in thebedridden, and in patients with advanced malignancy.1

Principles of the ProcedureThe VITROS CK DT Slide method is performed using the VITROS CK DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS CK DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thislayer also contains W-acetylcysteine (NAC) to activate CK without pretreating the sample.When the sarnple is deposited on the slide, creatine kinase catalyzes the conversion of creatine phosphate and ADP tocreatine and ATP. In the presence of glycerol kinase (GK), glycerol is phosphorylated to L-a-glycerophosphate by ATP.Oxidation of L-a-glycerophosphate to dihydroxyacetone phosphate and hydrogen peroxide occurs in the presence ofL-a-glycerophosphate oxidase (a-GPO). Finally, leuco dye is oxidized by hydrogen peroxide in the presence of peroxidase toform a dye.Reflection densities are monitored during incubation. The rate of change in reflection density is proportional to enzyme activity.

Reaction Sequence

creatine phosphate + ADP

glycerol + ATP

CK

NAC, Mg->• creatine + ATP

GK

L-a-glycerophosphate + O2

H2O2 + leuco dye

a-GPO

L-a-glycerophosphate + ADP

>• dihydroxyacetone phosphate + H2O2

peroxidasedye + 2H2O

Test Type and ConditionsTest Type and Conditions for CK DT

Test TypeRate


DTSC/DTSC II



Wavelength680 nm

Sample DropVolume

10 uL


GKDTCreatine Kinase



Reagents


L-alpha-glycerophosphate oxidase (Aerococcus viridans, E.C. 1.1.3.21) 0.4 U;peroxidase (horseradish root, E.C.1.11.1.7) 1.4 U; glycerol kinase (E.coli,E.C.2.7.1.30) 0.5 U; creatine phosphate 170 ug; N-acetylcysteine 54 ug;magnesium acetate 20 ug; glycerol 20 ug; 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl) imidazole (leuco dye) 20 ug; and adenosinediphosphate 20 ug.

Other ingredientsPigment, binder, buffers, surfactants, inhibitors, stabilizers, cross-linking agent,dye solubilizer, scavenger and chelator.

Slide Diagram

- 1 1-- — • " • ' 2

s 23.

-••" ' ... 3

* — - f

— - - ~ S 4.6.

Jpper slide mount

Spreading layer (TiO2)• W-acetylcysteine

Reagent layer» buffer, pH ?.O> adenosine diphosphate> glycerol, magnesium

acetate> glycerol kinase, leuco dye» peroxidase• glycerophosphate oxidase» creatine phosphate

Support layer

-ower slide mouont

Slide Handling


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-2B°C (64°-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 "-28 °C(64 °-82 °F) for >48 hours.




VITROS CK DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for CK DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Frozen <-18°C(<0°F)Room temperature 18°-28°C (64°-82°F)


Specimen Requirementsv * ::•! • Handle specimens as biohazardous material.


IMPORTANT: Certain collection devices have been reported to affect other analytes and tests."Confirm that your collection devices are compatible with this test.


INSTRUCTIONS FOR USE CKDTTesting Procedure Creatine Kinase

Specimens Not Recommended• Do not use grossly hemolyzed specimens.5

Serum and PlasmaSpecimen Collection and PreparationCollect specimens using standard laboratory procedures.6 '


Special Precautions• CK is unstable in serum. Centrifuge specimens and remove the serum from the cellular material within 4 hours of

collection.8


Specimen Storage and Stability for CK DT: Serum and Plasma8



<-18°C(<0°F)

Stability<4 hours<5 days<1 month


. VITROS Chemistry Products CK DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I or VITROS Chemistry Products DT Isoenzyme

Control I and VITROS Chemistry Products DT Control II• VITROS Chemistry Products 7% BSA. VITROS DT Pipette



analysis.

Sample DilutionIf creatine kinase activities exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's creatine kinase activity.

| Sample dilution results in higher creatine kinase activities than expected.9

CalibrationRequired Calibrators

VITROS Chemistry Products DT Calibrator Kit, bottles 1,2, and 4




CKDT INSTRUCTIONS FOR USECreatine Kinase Quality Control



The VITROS CK DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 680 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, creatine kinase activity in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide



Reportable (Dynamic) Range for CK DTConventional and SI Units (U/L)

20-1600



I Values assigned to the VITROS Chemistry Products DT Calibrator Kit for creatine kinase (CK) are traceable to a modification

of the Scandinavian Committee on Enzymes, recommended method1011 for the determination of creatine kinase at 37°C.

Quality Control





System.


and Definitions; Approved Guideline-Second Edition''2 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


INSTRUCTIONS FOR USE GKDTExpected Values and Reporting Units Creatine Kinase


IMPORTANT: VITROS DT Controls are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls may show a difference when compared with other creatine kinasemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

| • Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and StorageRefer to the instructions for use for VITROS Chemistry Products DT Control I & II and VITROS Chemistry ProductsDT Isoenzyme Control I or to other manufacturer's product literature.


Reference Interval

Reference Interval for CK DT13

Females

Males


30-135

55-170

The upper limit of the reference interval is reported to be affected by population characteristics such as the degree of physicalactivity" and race.15 Distributions of CK values from normal, healthy subjects often demonstrate a positive skew,16 leading tovariable upper reference limit estimates.Each laboratory should confirm the validity of these intervals for the population it serves.

Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report creatine kinase results in conventional andSI units.

Reporting Units for CK DTConventional and

U/LSI Units


Known InterferencesI • Carbon dioxide at a level of 40 mmol/L may cause up to a 30% negative bias in creatine kinase.

Other LimitationsCertain drugs and clinical conditions are known to alter creatine kinase activity in vivo. For additional information, refer to oneof the published summaries 17,18


CKDTCreatine Kinase



Methpd Comparison

I The plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzed


Method Comparison for CK DT: Serum


IXOO i

e

t

atoo

1500 -

1200 •

900

600 •

:K)0 •

0

y = x

0 300 600 900 1200 1500 1800Comparative Method: VITROS 950 System

(U/L)

Method Comparison for CK DT: Serum


n

53

Slope

1.01


0.999

Conventional and


34-1379

SI Units (U/L)

Intercept

11.10

Sy.x

17.24



Precision for

System

VITROS DT60

CKDT:

II

SerumConventional and SI Units (U/L)

Mean Activity

129

813


4.0 7.9

13.6 24.7

Within Lab CV%**

6.1

3.0

No Observ.

88

88

No. Days

22




CKDTCreatine Kinase

References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 373-377; 1987.


3. Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, andEvaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:1:151-153; 1989.

4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 376-377; 1987.6. NCCLS. Procedures forthe Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.9. Tietz NW(ed). Textbook of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 662; 1999.10. Scandinavian Committee on Enzymes: Recommended Method for the Determination of Creatine Kinase in Blood. Scand. J. Clin. Lab.

Invest. 39:1-5; 1979.

11. Scandinavian Committee on Enzymes: Recommended Method for the Determination of Creatine Kinase in Blood. Scand. J. Clin. Lab.Invest. 36:711-23; 1976.


13. Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Philadelphia: WB Saunders; 2088; 1979.14. Krahn J. Upper Reference Limit for Creatine Kinase. Clin. Chem. 31(1):158; 1985.15. Black HR. Quallich H-D, and Garlect CB. Racial Difference in Serum Creatine Kinase Levels. Amer. J. Med. 81:479-487; 1986.16. Miller WG. Chinchilli HD, Nance WD. Sampling from a Skewed Population Distribution as Exemplified by Estimation of the Creatine

Kinase Upper Reference Limit. Clin. Chem. 30(1): 18-23; 1984.17. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.18. Friedman RB. Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.19. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


CKDTCreatine Kinase



Version1.0


• New format• New organization and sections consistent with IVD Directive• Specimens Recommended, Special Precautions - removed the statement

regarding EDTA and fluoride oxilate• Materials Required But Not Provided and

Sample Dilution - added VITROS 7% BSA; removed isotonic saline• Sample Dilution - added that dilution may result in higher CK activities than

expected• Reference Interval - updated the statement regarding the determination of a more

specific reference range• Known Interferences - added values• Method comparison - updated all data and the plot• Precision - updated all values• References - added all except 1, 9,10,14,15,16,13






' Ortho-Clinical Diagnostics« m company



VITRCD5Chemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products CKMB DT Slides

CKMB DTCreatine Kinase MB

Intended UseFor in vitro diagnostic use only.VITROS CKMB DT Slides quantitatively measure creatine kinase MB (CK-MB) activity in serum.

Summary and Explanation of the TestThe MB isoenzyme of creatine kinase is found primarily in cardiac muscle; however, trace amounts are present in skeletalmuscle. CK-MB is elevated in acute myocardial infarction, where the test has its greatest use.CK-MB usually peaks between 12 and 24 hours after myocardial infarction and returns to normal in 48 to 72 hours in anuncomplicated case. CK-MB is also increased in myocarditis, Duchenne's muscular dystrophy, polymyositis, rhabdomyolysis,and other myocardial or myopathic disorders.1

Principles of the ProcedureThe VITROS CKMB DT Slide method is performed using the VITROS CKMB DT Slide and the VITROS Chemistry ProductsDT Isoenzyme Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS CKMB DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thislayer contains surfactants; N-acetylcysteine (NAC), which activates CK without pretreatment of the sample; and goatantihuman CK-M antibodies, which inhibit CK-MM (muscle) activity and ~50% of the CK-MB (heart) activity. The remainingCK activity represents 50% of the total CK-MB isoenzyme concentration plus any-CK-BB (relatively rare).In the reagent layer, creatine kinase in the sample catalyzes the conversion of creatine phosphate and adenosinediphosphate (ADP) to creatine and adenosine triphosphate (ATP). In the presence of glycerol kinase, glycerol isphosphorylated to L-a-glycerophosphate which is then oxidized to dihydroxyacetone phosphate and H2O2 in the reactioncatalyzed by L-a-glycerophosphate oxidase. Finally, leuco dye is oxidized by hydrogen peroxide in the presence of peroxidaseto form a dye.The low wavelength light cutoff filter on the slide support minimizes the blank rate effects of incident light during dyedevelopment.The rate of change in reflection density is converted to enzyme activity.

Reaction Sequence

CK-MM + CK-MBanti CK-M antibody

-> • CK-M inhibition

creatine phosphate + ADPcreatine kinase-B

NAC, Mg->• creatine + ATP

glycerol + ATPglycerol kinase

-> • L-a-glycerophosphate + ADP


H2O2 + leuco dye

L-a-glycerophosphate oxidase dihydroxyacetone phosphate + H2O2


Test Type and ConditionsTest Type and Conditions for CKMB DT

Test TypeRate


DTSC/DTSC II



Wavelength680 nm

Sample DropVolume

10 uL


CKMBDTCreatine Kinase MB



Reagents

Slide Ingredients


L-a-glycerophosphate oxidase (Aerococcus viridans, E.C.1.1.3.21) 0.39 U;peroxidase (horseradish root, E.C.1.11.1,7) 1.4 U; glycerol kinase (£. coli orCellulomonas sp, E.C.2.7.1.30) 0.45 U; creatine phosphate 0.17 mg;N-acetylcysteine 43 ug; goat anti-human CK-M antibody 0.25 mg; magnesiumacetate 68 ug; glycerol 23 ug; 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl) imidazole (leuco dye) 20 ug; and adenosinediphosphate 8.4 ug.

Other ingredientsPigment, binder, buffers, surfactants, inhibitors, stabilizers, cross-linkingagent, dye solubilizer, filter dyes, scavenger and chelator.

Slide Diagram

Slide Handling

t 1 . Upper sl ide mount" 2 . Spreading layer (TIO2)

/ %

7^7-— - 4

~"^~--^ 5 *

- " •

• N-acetylcysteine• goat antihuman CK-M

antibodyReagent layer• adenosine diphosphate• Mg acetate

leuco dyeglycerol kinaseperoxidaseL-a-glycerophosphateoxidasecreatine phosphateglycerolbuffer, pH 7.0

4. Support layer6. Filter

• low wavelength light cutofffilter

6. Lower slide mount


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18 -28 °C (64 °-82 °F), before the wrapper isopened.





VITROS CKMB DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for CKMB DTSlides

Unopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Frozen <-18QC (<0°F)Room temperature 18°-28°C (64°-82°F)



Q VITRtpS

INSTRUCTIONS FOR USE CKMBDTSpecimen Requirements Creatine Kinase MB



Specimens Recommended• SerumIMPORTANT; Certain collection devices have been reported to affect other analytes and tests.3


Specimens Not Recommended• Plasma: EDTA

Heparin

SerumSpecimen Collection and PreparationCollect specimens using standard laboratory procedures.4 5


Special Precautions• Centrifuge specimens and remove the serum from the cellular material within 4 hours of collection.6


WARNING: Handle specimens as biohazardous material.


Specimen Storage and Stability for CKMB DT: Serum6



<-18°C(<0°F)



• VITROS Chemistry Products CKMB DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Isoenzyme Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Isoenzyme Control I• VITROS Chemistry Products 7% BSA• Reagent-grade water• VITROS DT Pipette



Sample DilutionIf Creatine Kinase MB concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with VITROS 7% BSA or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's creatine kinase MB activity.


GKMBDT INSTRUCTIONS FOR USECreatine Kinase MB Calibration

Calibration

Required CalibratorsVITROS Chemistry Products DT Isoenzyme Calibrator Kit

Calibrator Preparation, Handling, and StorageRefer to the instructions for use for VITROS DT Isoenzyme Calibrator Kit.




The VITROS CKMB DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Calculations

I Based on sequential readings of the slide's reflectance at 680 nm over the defined incubation period, a rate of change in

reflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, creatine kinase activity in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide.


Reportable (Dynamic) RangeReportable (Dynamic) Range for CKMB DT

Conventional and SI Units (U/L)1.0-300.0



I Values assigned to the VITROS Chemistry Products DT Isoenzyme Calibrator Kit for creatine kinase MB isoenzyme (CK-MB)

are traceable to a CK-M immunoinhibition method with quantitation of the remaining CK-B subunit activity by a modification ofthe Scandinavian Committee on Enzymes78 recommended method for the determination of creatine kinase activity at 37°C.

Quality Control


| WARNING: Handle quality control materials as blohazardous material.



System.

• If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results.


INSTRUCTIONS FOR USE CKMRDTInterpretation of Results and Expected Results Creatine Kinase MB

• For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principlesand Definitions; Approved Guideline-Second Edition9 or other published guidelines.

• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Quality Control Material SelectionIIPORWT: VITROS DT Isoenzyme Control I is recommended for use with the VITROS

DT60/DT60 II Chemistry System. Evaluate the performance of other commercialcontrol fluids for compatibility with this test before using for quality control.

• Control materials other than VITROS DT Isoenzyme Control I may show a difference when compared with other creatinekinase MB methods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.I • Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and StorageRefer to the instructions for use for VITROS Chemistry Products DT Isoenzyme Control I or to other manufacturer's productliterature.

Interpretation of Results and Expected Results

Interpretation of ResultsElevated CK-MB activities are a sensitive and specific indicator of myocardial infarction (Ml). The diagnosis of myocardialinfarction should not be based solely on CK-MB results but should be supported by other clinical and laboratoryparameters. Clinical judgment is required to interpret CK-MB results.Judgments based on single determinations are of limited value because the CK-MB peak is of short duration. As with anyCK-MB method, if the sample is obtained significantly before or after the peak, the result may be negative. Most clinical studieshave recommended that samples be taken every 8 to 12 hours.CK-MB results are usually considered positive when three criteria are met:1. A significant level of CK-MB activity must be present. A decision value of 16 U/L is recommended.10 Values of less than

16 U/L should be reported as negative for CK-MB and % CK-MB should not be calculated.2. The CK-MB results should fall between 4% and 25% of the total CK value. If % CK-MB is outside this range, the elevation

may have arisen from factors other than myocardial infarction.

% CK-MB = CK-MB x 100CK

For example:. CK-MB < 4%.

Skeletal muscle contains some CK-MB and significant skeletal muscle damage can result in elevated CK-MB activity. Thepercentage of CK-MB in muscle is low, however, and CK-MB as a percentage of total CK may remain normal (<4%).

• CK-MB > 25%.The slide results are actually a measure of the B subunit of CK-MB; therefore, the presence of CK-BB or macro CK type Ior type II can cause up to twice the measured CK-MB result that would be expected based on total CK activity. Resultsgreater than 25% may indicate presence of CK-BB or macro CK type I or type II. These results should be confirmed by analternate method.

3. The rise in CK-MB activity to a peak approximately 18 hours after the infarction and the subsequent fall in activity ischaracteristic of myocardial infarction. CK variants are relatively stable in circulation and do not show the rise-and-fallpattern.

The suggested decision criteria for diagnosis of myocardial infarction have been provided by Dr. T. C. Kwong.10 These criteriaare based on a study of 134 patients consecutively admitted to the coronary care unit of the University of Rochester MedicalCenter in Rochester, New York. Each laboratory should confirm the validity of this protocol for the population it serves.Criteria were chosen to maximize the diagnostic efficiency of the test where:

Diagnostic Efficiency (%) = True Positives + True Negatives x 100Total Patients

Decision criteria may vary from laboratory to laboratory depending on age, sex, diet, and racial composition of the population,as well as the prevalence of myocardial infarction. Decision criteria may be adjusted to favor either a positive predictive valueor a negative predictive value, depending on the intended use of the assay. The table below shows how different cutoff valuesfor peak CK-MB affects the sensitivity and specificity of the test, compared with an electrophoretic procedure. Use the flowchartin figure 1 as a quick reference guide.



VITRCpB El

INSTRUCTIONS FOR USEInterpretation of Results and Expected Results

An alternative use of the test is to screen samples from patients with possible myocardial infarction and to confirm positiveresults by an alternative method. A total CK value within the normal range is not a reliable index to exclude analysis ofCK-MB.11

Effects on Sensitivity and Specificity of Various Cutoff Values for Peak CK-MB

CK-MB Cutoff (U/L)1012141618202224

Sensitivity (%)9696939185827878

Specificity (%)7989939495969698

Efficiency (%)8692939391908990

Reporting Units and Unit ConversionThe VITROS Chemistry System may be programmed to report CK-MB results in conventional, SI, and alternate units.

Reporting Units and Unit Conversion for CKMB DT

Conventional and SI UnitsU/L

Figure 1. Interpretation of Results: Quick Reference Guide

r alternative diagnoses

Yes

Perform serial CK-MB assays

Proper mserpretatjtm af CK-MB results reqyeresserial determinations in all circumstances

"Normal" Total CK is not 8 reliable index toexclude CK-MB determ

<-- , , % MB at ieasf 4%? . ^ • >

< T %MBI6SS«KHS2S%? J ^ "

Yes * •

< C Rise-and-fall pattern? ~^>-

-5 ! •

So ^

' Negative tor CK-MB " " \

IHtjh U/L M8 liul low ~o MBsyo^ftsts skoictiil muscle damage) l

{ Ntgativft foi CK-Mfl "~"\

{%, MB greater than 25%suggests macro CK ar CK-BBI

Resiilts siintiki 1H> confimuHt by analter native method arid «v3luat*)d tJ$i!i(j

t other cSinicfil and laisorator^'parameters ,

f Negative tor CK-MB " \

(Consistent but elevated CK-MB^ may be atypical macro or BB1 /




Limitations of the ProcedureKnow.n Interferences

• CK-BB (present in neonates,12 brain ischemia, cerebellar hematoma, shock,13 and carcinomas14) and macro CK type I andtype II falsely elevate CK-MB results. These can be differentiated from true CK-MB by the lack of the characteristic CK-MBtime pattern. Refer to "Interpretation of Results."

• Total CK activity greater than 1000 U/L may result in falsely elevated CK-MB results. Samples with TCK >1000 U/L shouldbe diluted prior to analysis.

The VITROS CKMB DT Slide method was screened for interfering substances following NCCLS Protocol EP7.16 Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for CKMB DT

Interferent*

Ascorbic acid

Diatrizoate sodium(Hypaque)Dipyrone


3mg/dL (170 umol/L)

835mg/dL (13.1 mmol/L)

6mg/dL (180 Mmol/L)

Creatine KinaseActivity

Conv./SI Units (U/L)

40

40

48

Average BiasConv./SI Units (U/L)

-6

-12

-4.3

It is possible that other interfering substances may be encountered. These results are representative; however, yourresults may differ somewhat due to test-to-test variation. The degree of interference at concentrations other thanthose listed might not be predictable.

Other LimitationsCertain drugs and clinical conditions are known to alter creatine kinase MB activity in vivo. For additional information, refer toone of the published summaries.16 17 18


Method ComparisonThe plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzedusing the Immunoinhibition comparative method with quantitation of the remaining CK-B subunit activity by a modification of theScandinavian Committee on Enzymes.7 8 Testing followed NCCLS Protocol EP9.19

Method Comparison for CKMB DT: Serum


."mi

25ii

200

ISO

too

50

0

y = x

10 100 150 300 250 300 350Comparative Method: Immunoinhibition

(U/L)




Method Comparison for CKMB DT: Serum



77 1.00 0.999



2-292 0.41 4.32



Precision for CKMB DT:

System

VITROS DT60 II

SerumConventional and SI Units (U/L)

Mean Activity Within Day SD*

11

29

0.3

0.6

Within Lab SD**

0.6

1.0

Within Lab CV%**

5.5

3.5

No. Observ.

88

88

No. Days

22

22

Within Day precision was determined using two runs/day with two replications.

Within Lab precision was determined using a single lot of slides and calibrating weekly.


Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.4. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.7. Scandinavian Committee on Enzymes: Recommended Method for the Determination of Creatine Kinase in Blood. Scand. J. Clin. Lab.

Invest. 36:711-723; 1976.

8. Scandinavian Committee on Enzymes: Recommended Method for the Determination of Creatine Kinase in Blood. Scand. J. Clin. Lab.Invest. 39:1-5; 1979.


10. Kwong TC. Studies conducted at the University of Rochester Medical Center, Rochester, New York; 1986.11. Yusuf S, et al. Significance of Elevated MB Isoenzyme with Normal Creatine Kinase in Acute Myocardial Infarction. Am. J. Cardiol.

59:245; 1989.12. Jedukin R, et al. Creatine Kinase Isoenzymes in Serum from Cord Blood and the Blood of Healthy Full-Term Infants during the First

Three Postnatal Days. Clin. Chem. 28:2; 1982.13. Gerhardt W, et al. Creatine Kinase and Creatine Kinase B-Subunit Activity in Serum Cases of Suspected Myocardial Infarction. Clin.

Chem. 28:2; 1982.14. Stein W, et al. Macro Creatine Kinase Type 2: Results of a Prospective Study in Hospitalized Patients. Clin. Chem. 31:12; 1985.15. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.16. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.17. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.18. Tryding N, Tufvesson C, Sonntag O (eds). Drug Effects in Clinical Chemistry, ed. 7. Stockholm: The National Corporation of Swedish

Pharmacies, Pharmasoft AB, Swedish Society for Clinical Chemistry; 1996.19. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.





Glossary of Symbols

Do Not Reuse


Lot Number

A M Manufacturer's SerialOlN Number



XX

Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


Version. 10

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimens Not Recommended - removed fluoride oxalate• Specimen Storage and Stability - updated stability values• Materials Required But Not Provided and

Sample Dilution - added VITROS 7% BSA; deleted isotonic saline• Limitations of the Procedure - updated values for Dipyrone in the Known

Interfering Substances table• Method Comparison - updated all data and the plot• Precision - updated all data• References - added 1,2,3,4,5,6,9, 15,18, 19,20







C€



'Ortho-Clinical Diagnostics8 ^otuwoH^efwHum company



(Products;

VITRIIISChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products CI" DT Slides

Cl DTChloride

Intended UseFor in vitro diagnostic use only.VITROS Cl" DT Slides quantitatively measure chloride (Cl) concentration in serum and plasma.

Summary and Explanation of the TestChloride is the major anion in the extracellular water space; its physiological significance is in maintaining proper body waterdistribution, osmotic pressure, and normal anion-cation balance in the extracellular fluid compartment. Chloride is increased indehydration, in renal tubular acidosis (hyperchloremia metabolic acidosis), and in excessive infusion of isotonic saline. Chlorideis decreased in overhydration, chronic respiratory acidosis, salt-losing nephritis, metabolic alkalosis, and congestive heartfailure.1

Principles of the ProcedureThe VITROS Cl" DT Slide method is performed using the VITROS Cl" DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS Cl" DT Slide is a multilayered, analytical element coated on a polyester support that uses direct potentiometry2 formeasurement of chloride ions. The slide consists of two ion-selective electrodes, each containing a protective layer, a silverlayer and a silver chloride layer coated on a polyester support. The protective layer inhibits interference from normal levels ofbromide and uric acid.A drop of patient sample and a drop of VITROS DT Reference Fluid on separate halves of the slide results in migration of bothfluids toward the center of the paper bridge. A stable liquid junction is formed connecting the reference electrode to the sampleindicator electrode.Each electrode produces an electrical potential in response to the activity of chloride ions applied to it. The potential differencepoised between the two electrodes is proportional to the chloride concentration in the sample.

Test Type and ConditionsTest Type and Conditions for Cl DT

Test Type

Potentiometric


DTE/DTE II

Approximate Incubation Time

180 seconds

Temperature

25°C (77°F)

Drop VolumeSample:

10 ML

ReferenceFluid: 10 uL



Cl DTChloride


Reagents

Slide Ingredients


Silver 0.4 mg; and silver chloride 0.2 mg.

Other ingredientsPolymer, plasticizer, surfactant and nickel.

Slide Diagram

Slide Handling

CAUTION:

1. Upper frame2. Paper bridge3. Protective layer4. Sliver, silver chloride

layer6. Support layer6. Lower frame


Slide Preparation





Slide Storage and StabilityVITROS CT DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for Cl DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Refrigerated 2°-8°C (36°-46°F)Frozen <-18°C (<0°F)Room temperature 18O-28°C (64°-82°F)





Confirm that your collection devices are compatible with this test.Specimen Collection and PreparationCollect specimens using standard laboratory procedures.5 6


Special Precautions• Do not draw specimen from an arm receiving an intravenous transfusion.• Fibrin clots may cause incomplete sampling of the specimen.7

- Allow specimens to clot completely in order to prevent fibrin clots.- Inspect plasma specimens for the presence of fibrin clots.

e Centrifuge specimens and remove the serum from the cellular material within 4 hours of collection.'


INSTRUCTIONS FOR USE Cl DTTesting Procedure Chloride




Specimen Storage and Stability for Cl DT; Serum and Plasma8



<-18°C (<0°F)

Stability<7 days<4 weeksIndefinite


• VITROS Chemistry Products Cl" DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products DT Reference Fluid• VITROS DTE Dual Sample Cups• VITROS DTE Pipette


I MPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior to

analysis.

Sample DilutionChloride concentrations outside the reportable (dynamic) range are not expected. Diluted samples should not be analyzed withVITROS Cl" DT Slides because dilution changes both the concentration of solids in plasma water and the ionic strength of thesample.

Calibration

Required CalibratorsVITROS Chemistry Products DT Calibrator Kit, bottles 1 and 2



NOTE: Calibrate choloride in duplicate by running each bottle twice.


- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.• When the VITROS DT Reference Fluid lot number changes.The VITROS Cl" DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


Cl DT INSTRUCTIONS FOR USEChloride Quality Control

CalculationsThe VITROS DT60/DT60 II Chemistry System measures the potential difference in millivolts between the two electrodes of apotentiometric slide—one in contact with the sample to be analyzed and the other in contact with the electrolyte reference fluid.A linear relationship exists between the measured potential difference observed on the slide and the logarithm of chlorideconcentration, i.e. the Nernst equation for ion-selective electrodes. Once the calibration has been established for each slide lot,unknown chloride concentrations for a given sample can be determined using the software-resident math model and themeasured potential difference.

Validity of a CalibrationCalibration parameters are automatically assessed by the VITROS DT60/DT60II Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.


Reportable (Dynamic) Range for CI" DTConventional and SI Units (mmol/L)

65-140


Traceability of the CalibrationI Values assigned to the VITROS Chemistry Products DT Calibrator Kit for chloride are traceable to the Certified NIST (National

Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 919a. The Ortho-ClinicalDiagnostics calibration laboratory uses SRM® 919a to calibrate the coulometric-amperometric titration method9'10 to support

I chloride value assignment for the VITROS DT Calibrator Kit.

Quality Control


| . " " > , . Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition'1'1 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


I IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other chloride methodsif they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.





CIDTChloride


Reference IntervalThis reference interval is the central 95% of results from an internal study of 60 apparently healthy individuals from a workingpopulation.No significant differences between results from the male and female populations were observed.

Reference Interval for CI" DT

Adult

Conventional and SI Units (mmol/L)

98-107



The VITROS DT60/DT60 II Chemistry System may be programmed to report chloride results in conventional and SI units.

Reporting Units for CI" DTConventional and SI Units

mmol/L


Known InterferencesBromide and iodide from therapeutic drugs and ointments may cause a bias of approximately 3 mmol/L and 4 mmol/L,respectively, for each mmol of halide. Normal physiological levels of bromide and iodide do not interfere.

Other LimitationsCertain drugs and clinical conditions are known to alter chloride concentration in vivo. For additional information, refer to one ofthe published summaries.1213




Method Comparison for CI DT: Serum


175

1 50 •

125

100

75 •

y = x

SO 75 100 125 150 175Comparative Method: VITROS 950

(mmol/L)


Cl DTChloride


Method Comparison for Cl' DT: Serum


n

51

Slope

0.96


0.995

Conventional and SI


75-132

Units (mmol/L)

Intercept

5.67

Sy.x

1.24



Precision for

System

VITROS DT60

Cl

II

DT: SerumConventional and SI Units (mmol/L)

Mean Cone.

78

100

Within Day SD*

0.2

0.4

Within Lab SD**

0.8

1.2

Within Lab CV%**

1.1

1.2

No. Observ.

88

88

No. Days

22

22


References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 620-621; 1987.2. Siggard-Anderson O. Electrochemistry, in Tietz NW (ed). Textbook of Clinical Chemistry. Philadelphia: WB Saunders; 110-125; 1986.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and



1991.7. Slockbower JM, Blumenfeld TA (ed.). Collection and Handling of Laboratory Specimens. Philadelphia: Lippincott Co; 201; 1983.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.9. Dietz AA, Bond EE, Chloride, Coulomeric-amperometric Methods, in: Faulkner WR, Meites S, eds. Selected Methods of Clinical

Chemistry, Washington: American Association for Clinical Chemistry. 9:149-152.; 1982.10. Velapoldi RA, Paule RC, Schaffer R, Mandel TJ, Gramlich JW. Standard reference materials: A reference method for the determination

of chloride in serum. National Institute of Standards and Technology Special Publication 260-67. Washington, D.C.; 1979.11. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.



CIDTChloride


Glossary of Symbols

2

SN"RIFI

A

Do Not Reuse


Lot Number



Attention: SeeInstructions for Use. i

Manufacturer




Store At or Below

Store At or Above

X

It

Store Between



Keep Dry

This end up


Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimens Recommended - updated wording• Specimen Storage and Stability - updated stability values• Quality Control Material Selection - added the statement regarding ethylene

glycol• Method Comparison - updated all data and the plot• Precision - updated all data• References - added all





CIDTChloride

VITRIJ35 0


C€

EC I REPOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


'Ortho-Clinical Diagnostics^e&tMroH company



VITRCD5Chemistry!

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products CO2 DT Slides

CO2DTCarbon Dioxide

Intended UseFor in vitro diagnostic use only.VITROS CO2 DT Slides quantitatively measure carbon dioxide (CO2) concentration in serum and plasma.

Summary and Explanation of the TestTotal carbon dioxide measurements are used together with other clinical and laboratory information (pH, pCO2) for theevaluation of acid-base status.

Principles of the ProcedureThe VITROS CO2 DT Slide method is performed using the VITROS CO2 DT Slides and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS CO2 DT Slide is a multilayered, analytical element coated on a polyester support that uses direct potentiometryfor measurement of ionic carbon dioxide.The slide consists of two ion-selective electrodes, each containing a buffer layer, an ion selective membrane layer, a referencelayer, and a silver and a silver chloride layer coated on a polyester support.The buffer layer adjusts the sample pH to 8.4 and maintains CO2, HCO3", and CO3"

2 in proper equilibrium. The ion-selectivemembrane layer contains an ion exchanger trioctylpropylammonium chloride (TOPA Cl) and a CO3'2 ionophoredecyltrifluoroacetophenone(DTFA).A drop of patient sample and a drop of VITROS DT Reference Fluid on separate halves of the slide results in migration of bothfluids toward the center of the paper bridge. A stable liquid junction is formed connecting the reference electrode to the sampleindicator electrode.Each electrode produces an electrical potential in response to the concentration of carbon dioxide applied to it. The potentialdifference poised between the two electrodes is proportional to the carbon dioxide concentration in the sample.

Test Type and ConditionsTest Type and Conditions for CO2 DT

Test Type

Potentiometric


DTE/DTE II


3 minutes

Temperature

25°C (77°F)

Drop VolumeSample:

10 ML

ReferenceFluid: 10 |JL



CO2DTCarbon Dioxide


Reagents

Slide Ingredients


Silver 0.4 mg; silver chloride 0.2 mg; sodium chloride 0.2 mg; potassiumchloride 63 ng; trioctylpropylammonium chloride 0.3 mg; anddecyltrifluoroacetophenone 0.8 mg.

Other ingredientsBinders, plasticizers, surfactants, stabilizer, buffers and nickel.

Slide Diagram

- 9

* • - .

b

GT

1.2.3.

4.

6.

6.7.

Upper framePaper BridgeIon-selectivemembrane• TOPA Cl• DTFAReference layer• KCI• NaCISilver, sliver chloridelayerSupport layerLower frame

Slide Handling

Slide Preparation


The slide must reach room temperature, 18°-28°C (64°-82f), before the wrapper isopened.




Slide Storage and StabilityVITROS CO2 DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide StorageSlidesUnopened

Opened

and Stability for CO2 DTStorage Condition


18°-28°C (64°-82°F)2°-8cC (36°-46°F)<-18°C (<0°F)18O-28°C(64°-82°F)







NOTE: For details on minimum fill volume requirements, refer to the operator's manual foryour VITROS Chemistry System.



Q VITR^S

INSTRUCTIONS FOR USETesting Procedure

CO2DTCarbon Dioxide

Special Precautions• Do not draw specimen from an arm receiving an intravenous transfusion.• Do not use specimens from patients receiving radiographic contrast agents containing diatriazoate sodium. Refer to

"Limitations of the Procedure."• Every effort should be made to fill vacuum tubes completely when collecting blood because a decrease of up to 3 mmol/L

can be observed with partially filled tubes.6

• Fibrin clots may cause incomplete sampling of the specimen.7

- Allow specimens to clot completely in order to prevent fibrin clots.- Inspect plasma specimens for fibrin clots.





Specimen Storage and Stability for CO2 DT: Serum and Plasma8

StorageRoom temperature, tightly cappedRefrigeratedFrozen

Temperature180-280C(640-820F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<24 hours<3 days<1 month


• VITROS Chemistry Products CO2 DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products DT Reference Fluid• VITROS DTE Dual Sample Cups• VITROS DTE Pipette



Sample DilutionCarbon dioxide concentrations outside the reportable (dynamic) range are not expected. Diluted samples should not beanalyzed with VITROS CO2 DT Slides.

Calibration




Special PrecautionsCalibrate CO2 in duplicate by running each calibrator bottle twice.


VITQI

C02 DT INSTRUCTIONS FOR USECarbon Dioxide Quality Control


- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.• When the VITROS DT Reference Fluid lot number changes.The VITROS CO2 DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60II Chemistry System.

CalculationsThe VITROS DT60/DT60 II Chemistry System measures the potential difference in millivolts between the two electrodes of apotentiometric slide—one in contact with the sample to be analyzed and the other in contact with the electrolyte reference fluid.A linear relationship exists between the measured potential difference observed on the slide and the logarithm of carbondioxide concentration, i.e. the Nernst equation for ion-selective electrodes. Once the calibration has been established for eachslide lot, unknown carbon dioxide concentrations for a given sample can be determined using the software-resident math modeland the measured potential difference.



Reportable (Dynamic) Range for CO; DTConventional and SI Units (mmol/L)

5-50

Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for carbon dioxide are traceable to the CertifiedNIST (National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 192b. TheOrtho-Clinical Diagnostics calibration laboratory uses SRM®192b to calibrate the Corning Model 965 analyzer,9 lc utilizingthermal conductivity detection, to measure total carbon dioxide in support of carbon dioxide value assignment for theVITROS Chemistry Products DT Calibrator Kit.

Quality Control


I WARNING; Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition^ or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


|*J VITRI


COzDTCarbon Dioxide

Quality Control Material SelectionIMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other Carbon Dioxidemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




This reference interval is the central 95% of results from a study of 60 apparently healthy adults from a working population(34 females and 26 males).

Reference Interval for CO? DT

Conventional and SI Units (mmol/L)22-30


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report carbon dioxide results in conventional and SIunits.

Reporting Units for CO, DTConventional and SI Units

mmol/L


• Lactate, hippurate, and other organic acids at significantly elevated concentrations have been reported to increase CO2

results.12

• Diatrizoate sodium may increase CO2 results. Do not use specimens from patients receiving radiographic contrast agentscontaining this substance.

The VITROS CO2 Slide method was screened for interfering substances following NCCLS Protocol EP7.13 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for CO2 DT

Interferent*

BromideIodideNitrate

Interferent ConcentrationConv./SI Units (mmol/L)

2

13

Carbon Dioxide Cone.

Conv./SI Units (mmol/L)252525

Average BiasConv./SI Units (mmol/L)

2411

It is possible that other interfering substances may be encountered. These results are representative; however, yourresults may differ somewhat due to test-to-test variation. The degree of interference at concentrations other than thoselisted might not be predictable.


COzDTCarbon Dioxide


Other LimitationsCertain drugs and clinical conditions are known to alter total carbon dioxide concentration in vivo. For additional information,refer to one of the published summaries.1415


Method Comparison



Method Comparison for CO2 DT: Serum


40 1

I 30 1

20

y = x


(mmol/L)

Method Comparison for CO2 DT: Serum



82 0.92 0.990

Conventional and SI Units(mmol/L)


13-38 2.13 0.82



Precision for CO2 DT: Serum

System

VITROS DT60 II


Mean Cone

24

18

. Within Day SD*

0.6

0.5

(mmol/L)

Within Lab SD**

0.7

0.6

Within Lab CV%**

3.1

3.2

No. Observ.

88

88

No. Days

22

22

* Within Day precision was determined using two runs/day with two replications.** Within Lab precision was determined using a single lot of slides and calibrating weekly.



CO2DTCarbon Dioxide

References1. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, and

Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA:. NCCLS;

1991.NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS;

1991.HerrRD, Swanson T. Serum Bicarbonate Declines With Sample Size In Vacutainer Tubes. AJCP. 97:213-216; 1992.Slockbower JM, Blumenfeld TA (ed.). Collection and Handling of Laboratory Specimens. Philadelphia: Lippincott Co; 201; 1983.Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.Van Slyke D C , Neil! J.M. J. Biol. Chem., 1924; 61: 523-526.

Corning 965 Carbon Dioxide Analyzer Instruction Manual, Corning Medical, Medfield, MA., 1977.NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.12. Young DS. Effects of Preanalytical Variables on Clinical Laboratory Tests. Washington D.C.: AACC Press; 3-80; 1993.13. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.14. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.15. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.

16. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:NCCLS; 1995.

17. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;1992.

2.

9.10,11.


Glossary of Symbols

SNREF

Do Not Reuse


Lot Number




Manufacturer

EC REP I Authorized Representative

V Contains Sufficient for "n"Tests


Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


C02DTCarbon Dioxide



Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive> Specimen Storage and Stability - updated stability> Reference Interval - updated data» Limitations of the Procedure - added carbon dioxide concentration and bias for

known interfering substances; removed the note• Method Comparison - updated the data and plot> Precision - updated all data« References - added all









VITRCDSChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products CREA DT Slides

CREAOTCreatinine

Intended UseFor in vitro diagnostic use only.VITROS CREA DT Slides quantitatively measure creatinine (CREA) concentration in serum and plasma.

Summary and Explanation of the TestSerum creatinine excretion is a function of lean body mass in normal persons and shows little or no response to dietarychanges. The serum creatinine concentration is higher in men than in women.Serum creatinine is increased in acute or chronic renal failure, urinary tract obstruction, reduced renal blood flow, shock,dehydration, and rhabdomyolysis. Causes of low serum creatinine concentration include debilitation and decreased musclemass. Exercise may cause an increased creatinine clearance.

Principles of the ProcedureThe VITROS CREA DT Slide method is performed using the VITROS CREA DT Slide, the VITROS NH3 DT Slide, and theVITROS Chemistry Products DT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.Refer to the VITROS NH3 DT Instructions for Use for an explanation of the principles of the procedure.The VITROS CREA DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the VITROS CREA DT Slide. The specimen is evenly distributed by the spreadinglayer to the underlying layers. Water and nonproteinaceous components travel to the underlying buffered reagent layer.Creatinine iminohydrolase catalyzes the hydrolysis of creatinine to produce ammonia. Both the ammonia produced in theprevious reaction and endogenous ammonia from the sample diffuse through the semipermeable membrane to react with anammonia indicator to produce a blue dye.After a fixed incubation time, the reflection density is proportional to the concentration of creatinine and endogenous ammoniain the sample. The software resident in the VITROS DT60/DT60 II System calculates a final creatinine concentration bysubtracting the endogenous ammonia concentration measured by the VITROS NH3 DT Slide from the creatinine andendogenous ammonia concentration measured by the VITROS CREA DT Slide.

Reaction Sequence

creatinine + H2Ocreatinine iminohydrolase

N-methylhydantoin + NH3

NH3 + bromphenol blue (ammonia indicator) blue dye

Test Type and ConditionsTest Type and Conditions for CREA DT



DT60/DT60 II


5 minutesTemperature37°C (98.6°F).

Wavelength605 nm

Sample DropVolume

10 ML


CREADTCreatinine


Warnings and PrecautionsFor in vitro diagnostic use only.Take care when handling materials and samples of human origin. Since no test method can offer complete assurance thatinfectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens,solid and liquid waste, and test components in accordance with local regulations and NCCLS Guideline M29' or otherpublished biohazard safety guidelines.For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the instructionsfor use for the appropriate VITROS product, or to other manufacturer's product literature.

Reagents


Creatinine iminohydrolas'e (Bacillus species, EC.3.5.4.21) 0.5 U andbromphenol blue 27 ng.

Other ingredientsPigment, binders, surfactants, buffer and stabilizer.

Slide Diagram

Slide Handling

CAUTION:

y/ , ' ' *

'*° ' ^'

• 4

; "w~" — £

,—- -— '"" r

1. Upper slide mount2. Spreading layer (T1O2)3. Reagent layer

• creatinine iminohydrojase• buffer. pH 9.3

4. Semtpermeablemembrane

6. indicator layer• bromphenol blue



Slide Preparation

IMPORTANT; The slide must reach room temperature, 18 "-28 °C (64 °~82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18-28 "C(64 "-82 °F) for >48 hours.



Slide Storage and StabilityVITROS CREA DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.


Opened

and Stability for CREA DTStorage Condition


18°-282°-8°C<-18°C18°-28

C (64°-82°(36°-46°F)(<0°F)'C (64°-82°

F)

F)

Stability<48 hours<4 weeksUntil expiration date<15 minutes

Specimen RequirementsWARMING: Handle specimens as biohazardous material.

Specimens Recommended• Serum• Plasma:2

IMPORTANT:

EDTAHeparin (except ammonium heparin)

Certain collection devices have been reported to affect other analytes and tests3



INSTRUCTIONS FOR USITesting Procedure

CREADTCreatinine


Patient Preparation

• No special patient preparation is necessary.

Special Precautions

NOTE: Avoid using ammonia-containing cleaning solutions or hand creams in the areaaround the analyzer.

• Centrifuge specimens and remove the serum from the cellular material within 15 minutes of collection.2



• Handle and store specimens in stoppered containers to avoid contamination and evaporation.• Mix samples by gentle inversion and bring to room temperature, 18°-28°C (64°-82°F), prior to analysis.• Two slides are used in the analysis of creatinine (the VITROS CREA DT Slide and the VITROS NH3 DT Slide). The

VITROS NH3 DT Slide provides a blank correction value for normal concentrations of ammonia present in serum.Therefore, it is important to minimize the formation of ammonia during specimen storage.

Specimen Storage and Stability for CREA DT: Serum and Plasma2



<-18°C (<0°F)

Stabilitynot recommended<3 hours<24 hours


. VITROS Chemistry Products CREA DT Slides

Materials Required But Not Provided. VITROS Chemistry Products NH3 DT Slides. VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II. VITROS 7% BSA or reagent-grade water. VITROS DT Pipette


NOTE: The VITROS NH3 DT Slide provides a blank correction value for normalconcentrations of ammonia present in serum. The VITROS CREA DT Slide must berun first, followed by the VITROS NH3 DT Slide. The analyzer displays "INSERT NH3

SLIDE." When VITROS CREA DT or VITROS NH3 DT Slides are present in theincubator, the analyzer displays "ANALYZER READY-CREA/NH3 ONLY." No tests canbe run until the CREA/NH3 results are complete.

IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F); analyzeimmediately.

Sample DilutionIf creatinine concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with VITROS 7% BSA or reagent-grade water.2. Reanalyze.3. Multiply the result by the dilution factor to obtain an estimate of the original sample's creatinine concentration.


CREA DT INSTRUCTIONS FOR USECreatinine Calibration

Calibration

Required CalibratorsVITROS Chemistry Products DT Calibrator Kit, bottles 1, 2, 3, and 4

Calibrator Preparation, Handling, and Storage

NOTE: To avoid ammonia formation, calibrator fluids should be prepared only when ready tocalibrate and should be run within 1 hour after preparation.

NOTE: Because ammonia is produced in the VITROS BUN/UREA DT Slide reaction, theanalyzer will display a warning message "ANALYER READY—NO CREA/NH3" duringcalibration of VITROS BUN/UREA DT Slides. Therefore, it is recommended thatcreatinine and ammonia be the first tests calibrated after the preparation of calibratorfluids.

Refer to the instructions for use for VITROS DT Calibrator Kit.


When to Calibrate

NOTE: The VITROS CREA DT test is dependent on correct calibration of the VITROS NH3 DTSlides used as blanks. Therefore, the VITROS NH3 DT Slides must be calibratedwhenever VITROS CREA DT Slides are calibrated.

Calibrate:• When the slide lot number changes.• When critical system parts are replaced due to service or maintenance.• When government regulations require.


The VITROS CREA DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsBecause the VITROS CREA DT Slide measures both creatinine and endogenous ammonia, the VITROS CREA DT Slideresponse is proportional to the concentration of both substances in the sample. A second slide, reactive only to ammonia, issequentially measured for the blank correction of the VITROS CREA DT Slide response. Reflectance from both slides ismeasured at 605 nm after the fixed incubation time. Calibration using the blank-corrected calibration model consists of twoparts—calibration of the VITROS NH3 DT Slide (blank), followed by calibration of the VITROS CREA DT Slide. Once acalibration has been performed for each slide lot of VITROS NH3 DT Slides and VITROS CREA DT Slides, creatinineconcentration in unknown samples can be determined using the software-resident endpoint colorimetric, blank-corrected mathmodel and the responses obtained from both the VITROS CREA DT and VITROS NH3 DT Slides.



Reportable (Dynamic) Range for CREA DTConventional (mg/dL)

0.01-15.0SI Units <umol/L)

1-1326



INSTRUCTIONS FOR USE CREA DTQuality Control Creatinine

Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for creatinine are traceable to the Certified NIST(National Institute of Standards and Technology) Reference Material, SRM* (Standard Reference Material) 914a. TheOrtho-Clinical Diagnostics calibration laboratory, uses SRM® 914a to calibrate selected measurement procedures, including anHPLC (High Performance Liquid Chromatography)6 method and a rate Jaffe' method, to support creatinine value assignmentfor the VITROS DT Calibrator Kit.

Quality Control

Procedure Recommendations| : Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition* or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Quality Control Material SelectionMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other creatininemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Commercial control fluids that contain ammonia concentrations above the VITROS NH3 DT Slide reportable range(500 umol/L) will not allow a creatinine result to be calculated.




Reference IntervalThese reference intervals are the central 95% of results from an internal study of apparently healthy adults from a workingpopulation (90 females, 105 males).

Reference Interval for CREA DT

FemaleMale

Conventional Units(mg/dL)

0.7-1.2 mg/dL0.8-1.5 mg/dL

SI Units(umol/L)

62-106 umol/L71-133 umol/L



CREADTCreatinine


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report creatinine results in conventional and SI units.

Reporting Units and Unit Conversion for CREA DTConventional Units

mg/dLSl Units

Mmol/L (mg/dL x 88.4)


Known Interferences• Falsely elevated creatinine results have been reported for patients who have been given 5-fluorocytosine (flucytosine).9 An

alternate method should be used to determine serum creatinine from these patients.| • Glucose at 600 mg/dL (33.3 mmol/L) may cause a decrease of 0.15 mg/dL (13.3 umol/L) in the creatinine result.

IMPORTANT: VITROS CREA DT testing should not be done when any VITROS BUN/UREA DTSlides are in the incubator.

| • If a VITROS CREA DT Slide follows a VITROS BUN/UREA DT Slide immediately, high BUN values may increasecreatinine values. A BUN value up to 40 mg/dL (14.3 mmol/L) may increase creatinine value by 0.3 mg/dL (26.6 umol/L)and an R18 code will be printed next to the creatinine result. Discard the result and repeat the sample without the VITROSBUN/UREA DT Slide in the incubator.

Other LimitationsCertain drugs and clinical conditions are known to alter creatinine concentration in vivo. For additional information, refer to oneof the published summaries.10 "


Method Comparison


using the HPLC comparative method.6

Method Comparison for CREA DT: Serum

Conventional Units

IS

2 p

12 15

1400

1200

1000

800

600

400

200

0

SI Units

y = x

Comparative Method: HPLC(mg/dL)

0 200 400 600 800 1000 1200 1400Comparative Method: HPLC

(Mmol/L)

Method Comparison for CREA DT: Serum


n

39

Slope

1.03


0.992

Conventional


0.7-11.5

Units (mg/dL)

Intercept Sy.x

0.04 0.44

SI Units (|jmol/L)


58-1017 3.61

Sy.x

39.23



CREADTCreatinine



Precision for CREA DT:

System

VITROS DT60 II

SerumConventional Units

MeanCone.

1.0

5.1

WithinDay SD*

0.05

0.15

(mg/dL)

WithinLab SD"

0.06

0.20

SI

MeanCone.

93

455

Units (umol/L)

WithinDay SD*

4.1

13.5

WithinLab SD"

5.6

17.5

WithinLab

CV%**

6.1

3.8

No.Observ.

83

84

No.Days

21

21




IL: College of American Pathologists; 1992.3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.4. NCCLS. Procedures forthe Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;

1991.


6. Ambrose RT, Ketchum DF, Smith JW. Creatinine Determined by "High Performance" Liquid Chromatography. Clin. Chem. 29: 256-259;1983.

7. Jaffe M. Uber den Niederschlag welchen Pikrinsaure in normalen Harn erzeugt und uber eine neue Reaktion des Kreatinins. Z PhysiolChem. 10: 391-400; 1886.


9. Mitchell RT, Marshall LH, Lefkowitz LB, Stratton CW. Falsely Elevated Serum Creatinine Levels Secondary to the Presence of 5-Fluorocytosine. Am. J. Clin. Path. 84: 251-253; 1985.

10. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.11. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.12. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer

REJ> J Authorized Representative

"\ v / Contains Sufficient for "n"V Tests


Store At or Below

| Store At or Above

Store Between



Keep Dry

This end up


CREADTCreatinine



Version1.0

Description of Technical Changes*> New format

New organization and sections consistent with IVD Directive> Specimens Recommended - updated wording for heparin; added EDTA> Specimen Storage and Stability - updated stability values> Sample Dilution - added VITROS 7% BSA; removed isotonic saline> Reference Interval - updated data> Limitations of the Procedure - updated values> Method Comparison - updated all comparisons and the plots> Precision - updated all data> References - added all






' Ortho-Clinical Diagnostics^eUmon company



(Products

VITRfflSChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products CRSC DT Slides

CRSCDTCreatinine

Intended UseFor in vitro diagnostic use only.VITROS CRSC DT Slides quantitatively measure creatinine concentration in serum and plasma.

Summary and Explanation of the TestSerum creatinine excretion is a function of lean body mass in normal persons and shows little or no response to dietarychanges. The serum creatinine concentration is higher in men than in women.Serum creatinine is increased in acute or chronic renal failure, urinary tract obstruction, reduced renal blood flow, shock,dehydration, and rhabdomyolysis. Causes of low serum creatinine concentration include debilitation and decreased musclemass. Exercise may cause an increased creatinine clearance.

Principles of the ProcedureThe VITROS CRSC DT Slide method is performed using the VITROS CRSC DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS CRSC DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Creatinine diffuses to the reagent layer, where it is hydrolyzed to creatine in the rate-determining step. The creatine isconverted to sarcosine and urea by creatine amidinohydrolase. The sarcosine, in the presence of sarcosine oxidase, isoxidized to glycine, formaldehyde, and hydrogen peroxide. The final reaction involves the peroxidase-catalyzed oxidation of aleuco dye to produce a colored product.Following addition of the sample, the slide is incubated. During the initial reaction phase, endogenous creatine in the sample isoxidized. The rate of change in reflection density is proportional to the concentration of creatinine present in the sample.

Reaction Sequence

creatinine + H2O

creatine + H2O -

creatinine amidohydrolase

creatine amidinohydrolase

creatine

sarcosine + urea

sarcosine + O2 + H2O

H2O2 + leuco dye

sarcosine oxidase glycine + formaldehyde + H2O2


Test Type and ConditionsTest Type and Conditions for CRSC DT

Test TypeRate


DTSC/DTSC II



Wavelength680 nm

Sample DropVolume

10 ML


CRSC orCreatinine



Reagents

Slide Ingredients


Creatinine amidohydrolase (Flavobacterium sp., E.C.3.5.2.10) 0.20 U; creatineamidinohydrolase {Flavobacterium sp., E.C.3.5.3.3) 4.7 U; sarcosine oxidase(Bacillus sp., E.C.1.5.3.1) 0.55 U; peroxidase (horseradish root, E.C.1.11.1.7)1.6 U; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl)imidazole (leuco dye) 32 ng.

Other ingredientsPigment, binders, surfactants, stabilizer, scavenger, chelator, buffer, dyesolubilizer and cross-linking agent.

Slide Diagram

Slide Handling

1. Upper slide mount2. Spreading layer (TIO2)3. Reagent layer

• creatinine amidohydrolase• creatine amidinohydrolase• sarcosine oxidase• peroxidase• leuco dye• buffer, pH 7.0



Slide Preparation

IMPORTANT; The slide must reach room temperature, 18°-28°C (64°-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 "-28 °C(64°-82°F) for >48 hours.



Slide Storage and StabilityVITROS CRSC DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for CRSC DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Frozen <-18°C (<0°F)Room temperature 18°-28°C (64°-82°F)



INSTRUCTIONS FOR USE CRSGDTSpecimen Requirements Creatinine




I MPORTANT: Certain collection devices have been reported to affect other analytes and tests3


Specimens Not Recommended• Do not use specimens obtained through catheters used to infuse hyperalimentation fluid. Refer to "Limitations of the

Procedure."

Serum and Plasma



Special Precautions• Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection.6


Specimen Storage and Stability for CRSC DT: Serum and Plasma6


Temperature18°-28OC(64°-82OF)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<5 days<30 days<lndefinite

Testing Procedure

Materials Provided• VITROS Chemistry Products CRSC DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II. VITROS Chemistry Products 7% BSA• Isotonic saline. VITROS DT Pipette



Sample DilutionIf creatinine concentrations exceed the system's reportable (dynamic) range or if the analyzer displays an L-11 or L-13 errorcode (indicating high background density, usually due to an elevated creatine concentration):1. Dilute the sample with 7% BSA or isotonic saline.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's creatinine concentration.


CRSCDT INSTRUCTIONS FOR USECreatinine Calibration

Calibration






The VITROS CRSC DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 680 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, creatinine concentration in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide.



Reportable (Dynamic) Range for CRSC DTConventional (mg/dL)

0.1-16.5SI Units (umol/L)

4-1459


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for creatinine are traceable to the Certified NIST(National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 914a. TheOrtho-Clinical Diagnostics calibration laboratory, uses SRM® 914a to calibrate selected measurement procedures, including anHPLC (High Performance Liquid Chromatography)7 method and a rate Jaffe8 method, to support creatinine value assignmentfor the VITROS DT Calibrator Kit.

Quality Control


| • " Handle quality control materials as biohazardous material.



System.



CRSC DTCreatinine





• Control materials other than VITROS DT Controls I & II may show a difference when compared with other creatininemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Liquid serum often contain high creatine levels and may give L-11 or L-13 error codes.• Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and StorageRefer to the instructions for use for VITROS Chemistry Products DT Control I & I or to other manufacturer's product literature.


These reference intervals are the central 95% of results from an internal study of apparently healthy adults from a workingpopulation (105 males, 90 females).

Reference Interval for CRSC DT

MaleFemale

Conventional Units(mg/dL)0.8-1.50.7-1.2

SI Units(umol/L)

71-13362-106



The VITROS DT60/DT60 II Chemistry System may be programmed to report creatinine results in conventional and SI units.

Reporting Units and Unit Conversion for CRSC DTConventional Units

mg/dLSI Units

umol/L (mg/dL x 88.4)


Creatine: At a creatinine concentration of 1.5 mg/dL (133 umol/L), creatine greater than 8 mg/dL (707 umol/L) will beflagged with an L-11 error code (because highly elevated creatine concentrations may cause excessive backgrounddensity). For unflagged samples, residual bias because of creatine will be less than 0.15 mg/dL (13 umol/L) at lowcreatinine concentrations. Residual bias for unflagged samples will be less than 4% at high creatinine concentrations. Referto "Sample Dilution" for dilution instructions.Proline: Patients receiving hyperalimentation fluids containing proline may show an increase of 0.2 mg/dL (18 umol/L). Donot collect specimens from intravenous fluid lines contaminated with hyperalimentation fluid.Dobutamine: Specimens contaminated with dobutamine from intravenous fluid have been reported to show a significantnegative bias. A dobutamine concentration of 83 ug/mL caused a decrease of 2.7 mg/dL (239 umol/L) from an initialcreatinine concentration of 4.8 mg/dL (424 umol/L).10

Lidocaine: Patients on long-term lidocaine therapy may show an increase of up to 1.0 mg/dL (88 umol/L) due to ametabolite of lidocaine, N-ethyl glycine (NEG).11


CRSC DTCreatinine


The VITROS CRSC DT Slide method was screened for interfering substances. The substances listed in the table, when testedat the concentrations indicated, caused the bias shown.

Known Interfering Substances for CRSC DT

Interferent*

Dipyrone (Metamizol)

/V-acetylcysteine


40mg/dL (1138 Mmol/L)

90 mg/dL (5.50 mmol/L)

Creatinine ConcentrationConv. (mg/dL)

1.0

1.3 mg/dL

SI (umol/L)

(88)

(115 pmol/L)

Average

Conv. (mg/dL)-0.6

-0.4 mg/dL

BiasSI (|jmol/L)

(-53)

(-35 umol/L)


Other LimitationsCertain drugs and clinical conditions are known to alter creatinine concentration in vivo. For additional information, refer to oneof the published summaries.12 "


Method Comparison

I The plots and table show the results of a comparison of the VITROS DT60 II Chemistry System with the VITROS 950

Chemistry System.Method Comparison for CRSC DT: Serum

Conventional Units

DwO

IX

15 -

12

9

6

y = x

12 15 ISComparative Method: VITROS 950 System

(mg/dL)

1O

1500

1200

900

600

300

0

SI Units

y = x

300 600 900 1200 1500Comparative Method: VITROS 950 System

(Mmol/L)

Method Comparison for CRSC DT: Serum


n

70

Slope

0.97


0.999

Conventional


0.7-12.2

Units (mg/dL)

Intercept Sy.x

0.1 0.19

SI Units (Mmol/L)


58-1077 8.86

Sy.x

16.72



CRSCDTCreatinine

PrecisionPrecision was evaluated with quality control materials on VITROS the DTSC II System following NCCLS Protocol EP5.'4


Precision for CRSC DT:

System

VITROS DT60 II

SerumConventional Units (mg/dL)

MeanCone.

1.2

5.9

WithinDay SD*

0.01

0.06

WithinLab SD**

0.02

0.10

SI

MeanCone.

110

521

Units (umol/L)

WithinDay SD*

1.1

5.1

WithinLab SD**

1.5

8.8

WithinLab

CV%**

1.3

1.7

No.Observ.

88

88

No.Days

22

22




Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.4. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.7. Ambrose RT, Ketchum DF, Smith JW. Creatinine Determined by "High Performance" Liquid Chromatography. Clin. Chem. 29: 256-259;

1983.8. Jaffe M. Uber den Niederschlag welchen Pikrinsaure in normalen Harn erzeugt und uber eine neue Reaktion des Kreatinins. Z Physiol

Chem. 10:391-400; 1886.9. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.10. DalyT, Kempe K, Scott M. "Bouncing" Creatinine Levels. NEJM. 334(26): 1749; 1996.11. Sena SF, Syed D, Romeo R, Krzymowski GA, McComb RB. Lidocaine Metabolite and Creatinine Measurements in the Ektachem 700:

Steps to Minimize its Impact on Patient Care. Clin. Chem. 34:10; 1988.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer

[ EC [ BEP | Authorized Representative

\ £ / Contains Sufficient for "n"\ / Tests


Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


CRSC DTCreatinine

VITR^IS 0



Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimen Storage and Stability - updated values for room temperature and

refrigerated• Materials Required But Not Provided - added VITROS 7% BSA; deleted isotonic

saline• Reportable (Dynamic) Range - corrected SI units• Quality Control Material Selection - removed the statement regarding Tris buffer• Limitations of the Procedure - updated information and corrected creatinine

concentration in SI units• Method Comparison - updated all data and plots• Precision - updated all data• References - added all


When this Instructions For Use is replaced, sign and date beiowand retain as specified by local regulations or laboratorypolicies, as appropriate.




' Ortho-Clinical DiagnosticsweH company



Chemistry

Prodwcts

INSTRUCTIONS FOR OSEVITROS Chemistry Products Fe DT Slides

FeDTIron

Intended UseFor in vitro diagnostic use only.VITROS Fe DT Slides quantitatively measure iron (Fe) concentration in serum and plasma.

Summary and Explanation of the TestMost body iron is found in hemoglobin. The serum measurement of iron is useful in the differential diagnosis of anemia, irondeficiency anemia, thalassemia, possible sideroblastic anemia, and iron poisoning.Serum iron is increased in hemosiderosis, hemolytic anemias, thalassemia, sideroblastic anemias, hepatitis, acute hepaticnecrosis, hemochromatosis, inappropriate iron therapy, and iron poisoning. Serum iron is decreased in cases of insufficientdietary iron, chronic blood loss, inadequate absorption of iron, impaired release of iron stores (commonly observed ininflammation), infection, and chronic diseases.1

Principles of the ProcedureThe VITROS Fe DT Slide method is performed using the VITROS Fe DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60 II Chemistry Systems.The VITROS Fe DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Iron(as ferric ion) is removed from transferrin at acidic pH and migrates to the reducing layer, where ascorbic acid reduces iron tothe ferrous form.The ferrous ion then is bound to the dye and forms a colored complex in the reagent layer. The rate of change in reflectiondensity is proportional to the iron concentration in the sample.

Reaction Sequence

transferrin - Fe*pH4.0

-> • transferrin + Fe+:

Fe + ascorbic acid - > F e +

Fe+2 + dye ->• Fe+2 - dye (colored complex)

Test Type and ConditionsTest Type and Conditions for Fe DT

Test TypeRate




Wavelength630 nm

Sample DropVolume

10 uL



FeDTIron


Reagents


Ascorbic acid 160 ug; and N-(4-(2,4-bis(1,1-dimethylpropyl) phenoxy)butyl)-5-methoxy-6((2,3,6,7-tetrahydro-8-1H,5H-benzo-(ij)-quinolizin-9-yl)azo)-3-pyridine sulfonamide (dye) 5 ug.

Other ingredientsBinders, buffer, pigment, surfactants, stabilizer, chelator, dye solubilizer andcross-linking agent.

Slide Diagram

Slide Handling

--y'

/' ' 3

- s

• $

1.2.3.

4.

6.6.

Upper slide mountSpreading layer (BaSOit)Reducing layer• ascorbic acidReagent layer• buffer, pH 4.0• dyeSupport layerLower slide mount


Slide Preparation

IMPORTANT: The slide must reach mom temperature, 18°-28°C (64°-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18°-28°C(64 °-82 °F) for >48 hours.



Slide Storage and StabilityVITROS Fe DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for Fe DTSlidesUnopened

Opened





IMPORTANT; Certain collection devices have been reported to affect other analytes and tests.3


Specimens Not Recommended• Do not use hemolyzed specimens because of the high concentration of iron in hemoglobin.1


[•] VITRI

INSTRUCTIONS FOR USE FeDTTesting Procedure Iron



Special Precautions• Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection.6




Specimen Storage and Stability for Fe DT: Serum and Plasma6



<-18°C(<0°F)



• VITROS Chemistry Products Fe DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• Iron-free reagent-grade water• VITROS DT Pipette


I Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior to

analysis.

Sample DilutionIf iron concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with iron-free reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's Iron concentration.

Calibration





FeDT INSTRUCTIONS FOR USEIron Quality Control



The VITROS Fe DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.

CalculationsReflectance from the slide is read at 630 nm during the incubation period, and the rate of change in reflectance is calculated.Once a calibration has been performed for each slide lot, iron concentration in unknown samples can be determined using thesoftware-resident two-point rate math model and the change in reflectance calculated for each unknown test slide.



Reportable (Dynamic) Range for Fe DTConventional (ug/dL)

10-500SI Units ((jmol/L)

1.8-89.6


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for iron are traceable to the Certified NIST (NationalInstitute of Standards and Technology) Reference Material, SRM" (Standard Reference Material) 937. The Ortho-ClinicalDiagnostics (OCD) calibration laboratory uses SRM" 937 to calibrate the proposed NCCLS standard iron method,7 modifiedaccording to the International Committee for Standardization in Hematology (ICSH) recommendation to use ferene dye,8 tosupport iron value assignment for the VITROS DT Calibrator Kit.

Quality Control




- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT60 II System.

• If control results fall outside your acceptable range, investigate the cause before deciding whether to report patient results.• For general quality control recommendations, refer fo Statistical Quality Control for Quantitative Measurements: Principles

and Definitions; Approved Guideline-Second Edition9 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.



FeDTIron

Quality Control Material SelectionIMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other Iron methods ifthey:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilisers, or other nonphysiological additives.



Reference IntervalThese reference intervals are the central 95% of results from an internal study of 529 apparently healthy adults from a workingpopulation (382 females and 147 males).

Reference Interval for Fe DT

FemalesMales

Conventional Units(Mg/dL)37-17049-181

SI Units(umol/L)6.6-30.48.8-32.4


Reporting Units [and Unit Conversion]The VITROS DT60 II Chemistry System may be programmed to report Fe results in conventional and SI units.

Reporting Units and Unit Conversion for Fe DTConventional Units

Mg/dL

SI UnitsMmol/L (ug/dL x 0.1791)


The VITROS Fe DT Slide method was screened for interfering substances following NCCLS Protocol EP7.10 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.• Desferol (Deferoxamine Mesylate) at a concentration of 250 mg/dL and higher results in iron concentrations below the

system range.| • Imferon produces a positive iron bias of 5 ,ug/dL for each 100 i-ig/dL of imferon.

Other LimitationsCertain drugs and clinical conditions are known to alter Iron concentration in vivo. For additional information, refer to one of thepublished summaries.11'12


FeDTIron



Method Comparison



Method Comparison for Fe DT: Serum

Conventional Units

8

600 •

500 "

400

300 '

2O0 •

100 "

0

y=x

100 200 300 400 500 600

Comparative Method: VITROS 950(Mg/dL)

E

O

100

80

60

20

SI Units

20 40 60 80Comparative Method: VITROS 950

(Mmol/L)

too

Method Comparison for Fe DT: Serum



53 1.03 0.999

Conventional Units (pg/dL)


19-448 -1.47 4.71

SI Units (umol/L)


3.5-80.2 -0.26 0.84



Precision for Fe

System

VITROS DT60 II

DT: SerumConventional Units

MeanCone.

72

240

WithinDay SD*

1.6

4.6

(Mg/dL)

WithinLab SD**

2.2

6.7

SI

MeanCone.

12.8

43.0

Units (Mmol/L)

WithinDay SD*

0.28

0.83

WithinLab SD**

0.39

1.20

WithinLab

CV%**

3.0

2.8

No.Observ.

88

88

No.Days

22



INSTRUCTIONS FOR USE FeDTReferences Iron

References1.

.2.Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 819-821; 1987.NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and



1991.


7. NCCLS. The Determination of Serum Iron and Total iron binding-capacity; Proposed Standard. NCCLS Document H17-P. Wayne, PA:NCCLS; 1990.

8. Iron Panel of the International Committee for Standardization in Haematology. Revised Recommendations for the Measurements ofSerum Iron In Human Blood. Br J Haematology. 75:615-616; 1990.


10. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.11. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.12. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.13. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




^1 Manufacturer

| EC [ HEP j Authorized Representative

S, v'7 Contains Sufficient for "n"V Tests


JT Store At or Below

Jf Store At or Above

Store Between



Keep Dry

This end up


FeDTIron

VI"TFJCp*S 0



Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive> Quality Control Material Selection - added statement regarding ethylene glycol> Known Interferences - removed statement regarding cupramine; updated bias

value for imferon> Method Comparison - updated all comparisons and plots

Precision - updated all data> References - added all except 4,11,12




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VITRChemistry

Produ cts

INSTRUCTIONS FOR USEVITROS Chemistry Products GGT DT Slides

GGTDTGamma Glutamyltransferase

Intended UseFor in vitro diagnostic use only.VITROS GGT DT Slides quantitatively measure gamma glutamyltransferase (GGT) activity in serum and plasma.

Summary and Explanation of the Testy-Glutamyltransferase plays a major role in glutathione metabolism and in resorption of amino acids from the glomerular filtrate.It is also important in the absorption of amino acids from the intestinal lumen. GGT is found mainly in the liver, pancreas, andkidney, although lower activities can be demonstrated in most other organs.Serum GGT is a sensitive indicator of hepatobiliary disease and is useful in the diagnosis of obstructive jaundice and chronicalcoholic liver disease, in the follow-up of chronic alcoholics undergoing treatment, and in the detection of hepatotoxicity. GGTis more responsive to biliary obstruction than AST, ALT, or ALKP. GGT is also increased in hepatoma, carcinoma of thepancreas, and carcinoma metastatic to the liver.1

Principles of the ProcedureThe VITROS GGT DT Slide method is performed using the VITROS GGT DT Slide.and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS GGT DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. GGTcatalyzes the transfer of the y-glutamyl portion of L-y-glutamyl-p-nitroanilide to glycylglycine, simultaneously producingp-nitroaniline. The rate of change in reflection density is measured and is used to calculate the enzyme activity of GGT.

Reaction Sequence

L-y-glutamyl-p-nitroanilide + glycylglycine p-nitroaniline + y-glutamyl glycylglycine

Test Type and ConditionsTest Type and Conditions for GGT DT

Test TypeRate


DTSC/DTSC II



Wavelength400 nm

Sample DropVolume

10 uL





Reagents


Glycylglycine 0.2 mg; and L-y-glutamyl-p-nitroanilide 16 ug.

Other ingredientsPolymer beads, binders and surfactants.

Slide Diagram

Slide Handling

. t 1.2.

. * 3.

3\r -"" '_,

4.

^ - 8

Upper slide mountSpreading layer (beads)Reagent layer• buffer, pH 8.0• glycylglycine• L-7-glytamyl-p-nitroanilide

Support layerLower slide mount


Slide Preparation

IMPORTANT: Theslide must reach room temperature, 18°-28°C (64°-82°F), before the wrapperisopened.

Do not use unopened slides that have been at room temperature, 18°-28°C(64 "-82 °F) for >48 hours.



Slide Storage and StabilityVITROS GGT DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for GGT DT

SlidesUnopened

Opened





Heparin





Special Precautions• For the affect of high concentration of bilirubin on test results, refer to "Limitations of the Procedure."• Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection.6



| i | V1TRI

INSTRUCTIONS FOR USE GGT DTTesting Procedure Gamma Glutamyltransferase



Specimen Storage and Stability for GGT DT: Serum and Plasma6



<-18°C(<0°F)



• VITROS Chemistry Products GGT DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA• Isotonic saline. VITROS DT Pipette


IMPORTANT; Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior toanalysis.

Sample DilutionIf gamma glutamyltransferase concentrations exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA or isotonic saline.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's gamma glutamyltransferase activity.

Calibration






The VITROS GGT DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


GGTDT INSTRUCTIONS FOR USEGamma Glutamyltransferase Quality Control

CalculationsBased on sequential readings of the slide's reflectance at 400 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, gamma-glutamyltransferase activity in unknown samples canbe determined from the rate of change in reflectance measured for each unknown test slide.



Reportable (Dynamic) Range for GGT DTConventional and SI Units (U/L)

5-1400


Traceability of the CalibrationI Values assigned to the VITROSChemistry Products DT Calibrator Kit for gamma-glutamyltransferase are traceable to the

gamma-glutamyltransferase method recommended by the International Federation of Clinical Chemistry (IFCC),7 adapted to aI centrifugal analyzer at 37°C.

Quality Control


| WA R N l N G: Handle quality control materials as biohazardous material.



System.




I IMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other gammaglutamyltransferase methods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.• Do not use control materials stabilized with ethylene glycol.






Reference IntervalThese reference intervals are the central 95% of results from an external study of 493 apparently healthy adult volunteers(277 females and 216 males).9 The study was conducted following NCCLS Protocol C28.10

Reference Interval for GGT DT

Adult

Females

Males

Conventional and SI Units(U/L)

12-58

12-43

15-73


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report gamma glutamyltransferase results inconventional and SI units.

Reporting Units for GGT DT

Conventional and SI UnitsU/L


The VITROS GGT DT Slide method was screened for interfering substances following NCCLS Protocol EP7.11 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for GGT DT

Interferent*

Bilirubin**


40 mg/dL (684 umol/L)40 mg/dL (684 umol/L)

GammaGlutamyltransferase

ActivityConv./SI Units (U/L)

1901100

Average BiasConv./SI Units (U/L)

+6-460


** Grossly elevated concentrations

Other LimitationsCertain drugs and clinical conditions are known to alter gamma glutamyltransferase activity in vivo. For additional information,refer to one of the published summaries.12 13





Method Comparison



Method Comparison for GGT DT: Serum


1500 1 y = x

1200 "

900 "

600 •

300 "o

0300 600 900 1200 1500

Comparative Method: VITROS 950 Systam(U/L)

Method Comparison for GGT DT: Serum


n

60

Slope

1.00


0.999


Range ofSample Activity

18-1296

Intercept

4.63

(U/L)

Sy.x

20.83



Precision for GGT DT: Serum

System

VITROS DT60 II

Conventional and

Mean Activity

77

417

Within Day

0.5

3.4

SI Units (U/L)

SD* Within Lab SD**

1.0

4.7

Within Lab

1.3

1.1

CV%** No Observ.

88

87

No. Days

22

22Within Day precision was determined using two runs/day with two replications.

Within Lab precision was determined using a single lot of slides and calibrating weekly.



GCTDTGamma Glutamyltransferase


Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Calam RR. Specimen Processing Separator Gels: An Update. J. Clin. Immunoassay. 11:86-90; 1988.4. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.7. Shaw L M, Stromme J H, London JL, Theodorsen L. IFCC methods for the measurement of catalytic concentration of enzymes. Part

4. IFCC method forgamma-glutamyltransferase. J, Clin. Chem. Clin. Biochem. 21: 633-646; 1983.8. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.9. Neels H, Van Boeckel E, Wauters A. Algemeen Ziekenhuis Middelheim, 1998. Data on file.10. NCCLS. How to Define and Determine Reference Intervals in the Clinical Laboratory; Approved Guideline. NCCLS document

C28-A (ISBN 1-56238-269-1). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087, 1995.11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

SNREF

A

Do Not Reuse


Lot Number




Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up





Version1.0


4

1

> New format• New organization and sections consistent with IVD Directive« Specimen Collection and Preparation - removed statement regarding hemolyzed

specimens.> Materials Required But Not Provided - added VITROS 7% BSA• Reference Interval - updated all data> Limitations of the Procedure - added the Known Interfering Substances table• Method Comparison - updated comparisons and the plot> Precision - updated all values> References - added all except 9, 10






'Ortho-Clinical Diagnostics<4^ofMMeH company



I P roducts

VITRmBChemistry!

INSTRUCTIONS f OR USEVITROS Chemistry Products GLU DT Slides

GLUDTGlucose

Intended UseFor in vitro diagnostic use only.VITROS GLU DT Slides quantitatively measure glucose (GLU) concentration in serum and plasma.

Summary and Explanation of the TestGlucose is a primary cellular energy source. Fasting plasma glucose concentrations and tolerance to a dose of glucose areused to establish the diagnosis of diabetes mellitus and disorders of carbohydrate metabolism. Glucose measurements areused to monitor therapy in diabetics and in patients with dehydration, coma, hypoglycemia, insulinoma, acidosis, andketoacidosis.1

Principles of the ProcedureThe VITROS GLU DT Slide method is performed using the VITROS GLU DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS GLU DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Theoxidation of sample glucose is catalyzed by glucose oxidase to form hydrogen peroxide and gluconate. This reaction isfollowed by an oxidative coupling catalyzed by peroxidase in the presence of dye precursors to produce a dye. The intensity ofthe dye is measured by reflected light.The dye system used is closely related to that first reported by Trinder.2The chemistry of the glucose slides has been describedby Curme, et al.3

Reaction Sequence

p-D-glucose + O2 + H2Oglucose oxidase

2H2O2 + 4-aminoantipyrine + 1,7-dihydroxynaphthalene

D-gluconic acid + H2O2

peroxidase ->• red dye

Test Type and ConditionsTest Type and Conditions for GLU DT



DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 |jL



GLUDTGlucose

VITR




Glucose oxidase (Aspergillus Niger, E.C.1.1.3.4) 0.77 U; peroxidase (horseradishroot, E.C.1.11.1.7) 3.6 U; 1,7-dihydroxynaphthalene (dye precursor) 67 \ig and4-aminoantipyrine hydrochloride (dye precursor) 0.11 mg.

Other ingredientsPigment, binders, buffer, surfactants, stabilizers and cross-linking agent.

Slide Diagram

Slide Handling

CAUTION:

__ - - ' 1.

t 2-

*~ - - 4 4.S.

Upper slide mountSpreading layer (TIO2)Reagent layer• glucose oxidase• peroxidase• dye precursors• buffer, pH 5.0Support layerLower slide mount


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18 "-2B <C (64 "-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18°-28X!(64 "-82 °F) for >48 hours.



Slide Storage and StabilityVITROS GLU DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for GLU DTSlides

Unopened*

Opened

Specimen Type Used

All recommended specimens

Plasma (Sodium fluoride/potassium oxalate)Serum, Plasma (EDTA, Heparin)

All recommended specimens

Storage Condition

Frozen

Refrigerated

RefrigeratedRoomtemperature

<-18°C (<0°F)

2°-8°C (36°-46°F)

2°-8°C (36°-46°F)

18°-28°C(64°-82°F)

Stability

Until expiration date

<4 months

Until expiration date

<15 minutes

Do not store with or near hydrogen peroxide.

Specimen RequirementsW&RN1NG: Handle specimens as biohazardous material.

Specimens Recommended• Serum. Plasma: EDTA

HeparinI Sodium fluoride/potassium oxalate (see the Slide Storage and Stability table for slide storage when usingI this specimen type)

I IMPORTANT: Certain collection devices have been reported to affect other analytes and tests5


Serum and Plasma



0 VITF-jjnpS

INSTRUCTIONS FOR USE GLURTTesting Procedure Glucose


Special Precautions• For the effect of sample hemolysis on test results, refer to "Limitations of the Procedure."• Grossly lipemic samples must be diluted prior to analysis. Refer to "Sample Dilution "for dilution instructions.• For the effect of elevated lipids on test results, refer to "Limitations of the Procedure."• Particulate matter (for example, fibrin) in sufficient quantity may coat the spreading layer and limit diffusion of oxygen,

causing a negative interference. To minimize particulate matter, do not centrifuge specimens until clotting is complete.• Serum:

- Centrifuge specimen at 1000X g for 10 minutes and remove serum from the clot within 30 minutes after collecting thespecimen to avoid metabolism of glucose by the cells (approximately 7% per hour at room temperature).6

• Heparin or EDTA plasma:- Follow manufacturer's recommendations for mixing anticoagulant with specimens.- Centrifuge specimen at 1000X g for 10 minutes and remove plasma from the cells within 30 minutes after collecting the

specimen to avoid metabolism of glucose by the cells (approximately 7% per hour at room temperature).6

• Sodium fluoride/potassium oxalate plasma:- Follow manufacturer's recommendations for mixing anticoagulant with specimens.- Centrifuge specimens and remove the plasma from the cells within 24 hours of collection.8

IMPORTANT: See the Slide Storage and Stability table for slide storage when using sodiumfluoride/potassium oxalate plasma.


" *j Handle specimens as biohazardous material.


Specimen Storage and Stability for GLU DT: Serum and Plasma8


Temperature18°-28OC(64°-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)


Testing Procedure

Materials Provided• VITROS Chemistry Products GLU DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• Isotonic saline• Reagent-grade water• VITROS DT Pipette



Sample DilutionIf glucose concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's glucose concentration.


GLUDT INSTRUCTIONS FOR USEGlucose Calibration

Calibration






The VITROS GLU DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Calculations


each slide lot, glucose concentration in unknown samples can be determined using the software-resident endpoint colorimetricmath model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for GLU DTConventional (mg/dL)


1.1-25.0


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for glucose are traceable to the Certified NIST (NationalInstitute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 917b. The Ortho-ClinicalDiagnostics calibration laboratory uses SRM® 917b to calibrate the CDC Hexokinase method9 to support glucose valueassignment for the VITROS DT Calibrator Kit.

Quality Control


| > ' ' - Handle quality control materials as biohazardous material.



System.




GLUDTGlucose

• For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principlesand Definitions; Approved Guideline-Second Bditionm or other published guidelines.




• Control materials other than VITROS DT Controls I & II may show a difference when compared with other glucose methodsif they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




These reference intervals are based on external studies for serum.1

Reference Interval for GLU DT

Fasting adultsConventional Units (mg/dL)


4.1-5.9



The VITROS DT60/DT60 II Chemistry System may be programmed to report glucose results in conventional and SI units.

Reporting Units and Unit Conversion for GLU DTConventional Units

mg/dLSI Units



• In fresh specimens, catalase released from the lysis of red blood cells causes a negative bias in glucose results. Thedegree of bias is proportional to the degree of hemolysis. In fresh samples, a negative bias of up to 10% may be observedwith a level of hemolysis associated with a hemoglobin concentration of 250 mg/dL (2.5 g/L).

NOTE: Catalase activity decreases with sample storage. Aged samples that are hemolyzedmay exhibit a positive bias of up to 10% due to the spectral interference ofhemoglobin. Therefore, the magnitude and direction of bias observed with hemolyzedspecimens will vary due to the level of catalase activity and concentration ofhemoglobin present in the sample.

• Elevated lipids may limit diffusion of oxygen to the reactants. Dilute grossly lipemic samples before analysis.The VITROS GLU DT Slide method was screened for interfering substances following NCCLS Protocol EP7.12 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interfered*

Substances for GLU DTInterferent

Concentration

5 g/dL (50 g/L)10g/dL (100 g/L)

Glucose ConcentrationConv. (mg/dL)

100100

SI (mmol/L)5.555.55

AverageConv. (mg/dL)

-5+6

Bias

SI (mmol/L)-0.28+0.33

It is possible that other interfering substances may be encountered. These results are representative; however, your results may differsomewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.

Version 1.0 Pub. No, C-300

GIUDTGlucose


Other LimitationsCertain drugs and clinical conditions are known to alter glucose concentrations in vivo. For additional information, refer to oneof the published summaries.13'u


Method Comparison



Method Comparison for GLU DT: Serum

Conventional Units

500 •

450 *

g- 400 •I 350 "I 300 "aft 250 '

I 2()<> "o 150 "

| 100 •

5 50 •0

30

£ 20a>

» 15

Q

100 200 300 400 500


10

5

0

SI Units

y = x


(mmol/L)

Method Comparison for GLU DT: Serum


n

55

Slope

1.02


1.000

Conventional


25-445

Units (mg/dL)

Intercept Sy.x

0.67 3.78

SI Units


1.4-24.7

(mmol/L)

Intercept

0.04

Sy.x

0.21

PrecisionPrecision was evaluated with quality control materials on the VITROS DT60 II System following NCCLS Protocol EP5.'6


Precision for GLU DT: Serum

System

VITROS DT60 II


MeanCone.

91

309

WithinDay SD*

1.0

3.8

WithinLab SD**

1.7

4.4

SI

MeanCone.

5.0

17.2

Units (mmol/L)

WithinDay SD*

0.05

0.21

WithinLab SD**

0.09

0.25

WithinLab

CV%**

1.8

1.4

No.Observ.

88

88

No.Days

22

22




GLUDTGlucose

References1. Tietz NW(ed). Textbook of Clinical Chemistry, ed. 2. Philadelphia: WB Saunders; 928-960; 1994.2. Trinder P. Determination of Glucose in Blood Using Glucose Oxidase with an Alternative Oxygen Receptor. Ann. Clin. Biochem. 6:24;

1969.3. Curme HG, et al. Multilayer Film Elements for Clinical Analysis. Clin. Chem. 24:1335-1342; 1978.4. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and




IL: College of American Pathologists; 1992.9. Neese JW, Duncan P, Bayse DD, et al. Development and Evaluation of a Hexokinase/Glucose-6-phosphate Dehydrogenase

Procedure for Use as a National Glucose Reference Method. HEW Publication No. (CDC) 77-8330. HEW. USPHS, Centers forDisease Control; 1976.


11. Tietz NW (ed). Textbook of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 1815; 1999.12. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.15. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer

EC | REP I Authorized Representative

\ y / Contains Sufficient for "n"\ / Tests


Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


GLUDTGlucose



Version1.0


• New format• New organization and sections consistent with IVD Directive• Slide Storage and Stability - added the Specimen Type Used column; updated

storage values for opened cartridges• Specimens Recommended - added sodium fluoride/potassium oxalate• Reference Interval - updated data• Limitations of the Procedure - deleted statement regarding ascorbic acid;

updated data for hemolysis• Method Comparison - updated all comparisons and plots• Precision - updated values• References - added all




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IProducts

VITRQ35Chemistry!

INSTRUCTIONS FOR USEVITROS Chemistry ProductsDT Micro HDL Cholesterol Kit

HDLC DTMicro HDL Cholesterol

Intended UseFor in vitro diagnostic use only.For use in the quantitative measurement of HDL cholesterol (HDLC) concentration in serum and plasma.

Summary and Explanation of the TestHDL cholesterol is used to evaluate the risk of developing coronary heart disease (CHD). The risk of CHD increases withlower HDL cholesterol concentrations.

Principles of the ProcedureVITROS DT Micro HDL Cholesterol Kit is used to prepare and test samples for high density lipoprotein (HDL) cholesterol onVITROS DT60/DT60 II Chemistry Systems. The specimens must initially be treated with a reagent to remove other lipoproteinswhich also contain cholesterol, including the very low density (VLDL) and low-density (LDL) classes. The amount of HDLcholesterol can then be determined using VITROS Chemistry Products HDLC DT Slides.HDL is separated by the precipitation of LDL and VLDL using dextran sulfate (MW 50,000) and magnesium chloride1 that isprovided in the VITROS Chemistry Products DT Micro HDL Tube. The HDL lipoproteins remain in the liquid portion of the tubeafter centrifugation. This liquid portion is called the supernate and is the portion analyzed. The non-HDL fractions form a pelleton the bottom of the tube and are discarded.A drop of pretreated patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlyinglayers. The Triton X-100 (TX100) surfactant in the spreading layer aids in dissociating the cholesterol and cholesterol estersfrom lipoprotein complexes present in the sample. Hydrolysis of the cholesterol esters to cholesterol is catalyzed by cholesterolester hydrolase. Free cholesterol is then oxidized in the presence of cholesterol oxidase to form cholestenone and hydrogenperoxide. Finally, hydrogen peroxide oxidizes a leuco dye in the presence of peroxidase to generate a colored dye.The density of dye formed is proportional to the HDL cholesterol concentration present in the pretreated sample and ismeasured by reflectance spectrophotometry.

Reaction Sequence

high density lipoproteins

cholesterol esters + H2O

cholesterol + O2

H2O2 + leuco dye

->• cholesterol + cholesterol esters + proteins

cholesterol ester hydrolase

cholesterol oxidase

- > cholesterol + fatty acids

- — > • cholest-4-en-3-one + H2O2

peroxidase->• dye + 2H2O

Test Type and ConditionsTest Type and Conditions for HDLC DT


VITROS DT60/DT60 11Module

DT60/DT60 II



Wavelength660 nm

Sample DropVolume

10 uL

Version 2.0 Pub. No. C-354 EN


VITRCp5 0


Warnings and PrecautionsFor in vitro diagnostic use only.Take care when handling materials and samples of human origin. Since no test method can offer complete assurance thatinfectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens,solid and liquid waste, and test components in accordance with local regulations and NCCLS Guideline M292 or otherpublished biohazard safety guidelines.While VITROS HDLC Sample Diluent product is bovine in origin, it should be handled using the same precautions as with anyother blood or blood-derived product.For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the Instructionsfor Use for the appropriate VITROS product, or to other manufacturer's product literature.

Personal Protection and VentilationWear impervious gloves and proper protective clothing. Safety glasses are recommended. Good general ventilation in the workarea is recommended. Minimize the potential for production of aerosols.

Accidental Spillage and Disposal

WAP VITROS DT Micro HDL Tubes contain sodium azide. Disposal of reagent intosinks with copper or lead plumbing should be followed with plenty of water toprevent formation of potentially explosive metallic azides.

Absorb spilled material in vermiculite or other suitable absorbents; sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.VITROS HDL Cholesterol Reagent contains sodium azide (0.01%; 0.01 g/dL). Disposal of reagent into sinks with copper orlead plumbing should be followed with copious volumes of water to prevent formation of potentially explosive metallic azides.

First Aid

WARNSNC VITROS DT Micro HDL Tubes contain gentamicin sulfate and sodium azide.R22 - Harmful if swallowed.

• Inhalation - Remove to fresh air. Seek medical advice.• Skin - Wash skin after each contact with soap and plenty of water for at least 15 minutes. Seek medical attention if skin is

cut or punctured.• Eye - Immediately flush eyes, including under the eyelids, with plenty of water for at least 15 minutes and get medical

attention.• Ingestion - Drink 1 -2 glasses of water. Seek medical advice.

TransportationThis product is not classified as a dangerous substance for transportation purposes. However, package with adequateprotection to prevent breakage and ship under refrigerated conditions.

Reagents

HDLC DT Slide Ingredients


Triton X-100 0.8 mg; cholesterol oxidase (Nocardia, E.C.1.1.3.6) 0.2 U;cholesterol ester hydrolase (Candida rugosa, E.C.3.1.1.13) 0.7 U; peroxidase(horseradish root, E.C.1.11.1.7) 5.3 U; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl) imidazole (leucodye) 0.2 mg.

Other ingredientsPigment, binder, buffer, surfactants, stabilizers and cross-linking agent.

DT Micro HDL Tubes

Reactive IngredientsDextran sulfate (MW50,000) 0.08 mg, magnesium chloride hexahydrate 0.7 mg

Other ingredientssodium azide 0.22%, gentamicin sulfate <0.01%, dye and preservatives

Slide Diagram

1 1. Upper slide mount2. Spreading layer (BaSCUl

2 • Triton X-100cholesterol esterhydrolasecholesterol oxidaseperoxidaseleuco dye

3. Sublayer• buffer, pH 6.25


Pub. No. C-354 EN Version 2.0

INSTRUCTIONS FOR USESpecimen Requirements


HDLC Sample DiluentReactive IngredientsBovine serum albumin 7%

Other ingredientsSodium azide 0.05%, inorganic salts and preservatives

Slide Handling

Slide Preparation



Do not use unopened slides that have been at room temperature, 18 °-28 °C(64 °-82°F) for >48 hours.



Kit Storage and StabilityVITROS DT Micro HDL Cholesterol Kit components are stable until the expiration date on the carton when they are stored andhandled as specified.

Kit Storage andKit Component

Slide

Unopened

OpenedTubes

Sample Diluent*

Stability for HDLC DTStorage Condition

RefrigeratedFrozenRoom temperatureRoom temperature

RefrigeratedFrozen

RefrigeratedFrozen

2°-8°C (36°-46°F)<-18°C(<0°F)

18°-28OC(64°-82°F)18O-28°C(64O-82°F)

2°-8°C (36°-46°F)<-18°C(<0°F)

2°-8°C (36°-46°F)<-18°C(<0°F)

Stability

Until expiration dateUntil expiration date<48 hours<15 minutes

Until expiration dateUntil expiration date


* Discard if the solution becomes cloudy or turbid.

Verify performance with quality control materials:- If the system is turned off for more than 2 hours.



Certain collection devices have been reported to affect other analytes and tests."Confirm that your collection devices are compatible with this test.

Specimens Not Recommended. Plasma:5 EDTA


HDIC DTMicro HDL Cholesterol

VITH[fiS@

INSTRUCTIONS FOR USESpecimen Pretreatment and Testing Procedure

Serum and Plasma


Patient Preparation• No special patient preparation is necessary unless the HDL cholesterol test is part of a complete lipid profile. Then,

a 12- to 14-hour fast is necessary.1

Special Precautions• Centrifuge specimens and remove the serum from the cellular material within 3 hours of collection.8 If further processing is

delayed, store in the refrigerator at 2°-8°C (36°-46°F).


•' ' Handle specimens as biohazardous material.


Specimen Storage and Stability for HDLC DT: Serum and Plasma8

Storage Temperature | Stability

Original SpecimenRefrigeratedFrozen

2°-8°C (36°-46°F)<-18°C (SO°F)

<3 days<4 weeks*

Pretreated Specimen (Supemate)

Freezer<-20°C (<-4°F)<-70°C (<-94°F)

<3 months<2 years

* For longer storage, separate HDL fractions and freeze the supernate.

IMPORTANT: Avoid repeated freeze-thaw cycles.

Specimen Pretreatment and Testing ProcedureMaterials Provided

• 25 VITROS Chemistry Products HDLC DT Slides• 27 VITROS Chemistry Products DT Micro HDL Tubes• VITROS Chemistry Products HDLC Sample Diluent

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• VITROS Chemistry Products DT Controls I and II. VITROS DT Pipette• Pipette capable of accurately delivering 50 uL of serum or plasma to a VITROS DT Micro HDL Tube.• Centrifuge capable of generating forces of 1500 x g, or a microcentrifuge capable of generating forces of 12,600 x g.• Micro capillary collection device large enough to obtain at least 50 uL of serum or plasma.• A vortex mixer is recommended

Special Precautions• Use a vortex speed that will not cause the mixture to spill out of the sample tube.

Procedure

IMPORTANT;

IMPORTANT:

Do not pretreat calibrators.

Be sure to use components from the same kit lot number.

1. Allow at least 10 minutes for refrigerated VITROS DT Micro HDL Tubes and VITROS HDLC Sample Diluent to reach roomtemperature. If these materials are stored at -18°C (0°F), they will require a longer warm-up period (at least 30 minutes).Once opened, the VITROS Micro HDLC Sample Diluent should be stored tightly capped in the refrigerator between uses.

2. Pipette 50 uL of serum or heparin plasma into the VITROS DT Micro HDL Tube.


INSTRUCTIONS FOR USE HDLCDTCalibration Micro HDL Cholesterol

3. Cap and mix thoroughly for 30 seconds - a vortex mixer is recommended.

NOTE: The sample will become cloudy during mixing.

4. Let stand for a minimum of 5 minutes.5. Centrifuge the VITROS DT Micro HDL Tube for 10 minutes at 1,500 x g. Alternatively, you may centrifuge the tube for a

shorter duration using a microcentrifuge for 95 seconds at 12,600 x g.6. Visually check supernates for clarity. The non-HDL fractions form a pellet on the bottom of the tube. Do not disturb the

pellet. If the supernate is clear, transfer cleared supernate directly from the VITROS DT Micro HDL Tube to a sample cupfor analysis on the DT analyzer.

IMPORT ANT: Supernates should be removed from the pelleted precipitate as soon as possiblefollowing centrifugation. The supernates should be used within 15 minutes. If analysison the VITROS DT60/DT60 II Chemistry System is to be delayed more than one hour,the supernate should be refrigerated. If analysis is delayed longer than 8 hours, referto the "Specimen Handling and Storage" section.

7. Analyze treated sample as instructed in the operator's manual for your VITROS DT60/DT60 II Chemistry System.



Sample DilutionIf HDL concentrations exceed the system's reportable (dynamic) range or if the supernatant is cloudy or has floating particlesafter pretreatment:1. Dilute the untreated sample with an equal volume of VITROS HDLC Sample Diluent.2. Mix gently by inverting several times.3. Pipette 50 uL of the diluted specimen into a second VITROS DT Micro HDL Tube.4. Repeat steps 1 through 6 of the procedure above. Remember to multiply the result by the dilution factor of 2.0.5. Reanalyze.6. Multiply the results by 2 to obtain an estimate of the original sample's HDL concentration.

NOTE: Additional dilutions are not recommended.

Calibration


Calibrator Preparation, Handling, and StorageIMPORTANT: Do not pretreat calibrators.





The VITROS HDLC DT slides may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


HDICDT INSTRUCTIONS FOR USEMicro HDL Cholesterol Quality Control

CalculationsReflectance from the slide is measured at 660 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, high-density lipoprotein cholesterol concentration in unknown samples can be determined using the software-resident endpoint colorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for HDLC DTConventional (mg/dL)


0.03-2.84


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for High Density Lipoprotein-Cholesterol (HDLC)Reagent with VITROS HDLC DT slides are traceable to the Certified NIST (National Institute of Standards and Technology)Reference Material, SRM* (Standard Reference Material) 911b. The Ortho-Clinical Diagnostics Calibration Laboratory usesSRM® 911b to assign values to secondary standards for calibration of an HDLC Selected Method. The Selected Methodsupports VITROS HDL Cholesterol reagent value assignment for the VITROS DT Calibrator Kit. The HDLC Selected Methodincludes (MW 50,000) Dextran Sulfate precipitation of non-HDL lipoproteins according to the recommendations of the Centersfor Disease Control (CDC),10 followed by automated enzymatic determination of supernate (HDL fraction) cholesterolconcentration.

Quality Control

IMPORTANT: Controls must be pretreated.

Procedure Recommendations| .. Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition'1'' or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


IMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other HDL cholesterolmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.





HDIC DTMicro HDL Cholesterol


Interpretation of ResultsLDL cholesterol and VLDL cholesterol can be calculated from the results of the VITROS CHOL DT Slide, VITROS TRIG DTSlide, and the results for HDL cholesterol to provide complete lipoprotein profiles.

LDL = CHOL-HDLC-VLDLVLDL = TRIG/5 for conventional units (mg/dL)VLDL = TRIG/2.2 for SI units (mmol/L)

Calculation of LDL is not appropriate for samples with triglyceride concentrations greater than 400 mg/dL (4.57 mmol/L) or withsamples from patients who have type III hyperlipoproteinemia (electrophoresis "broad beta" lipoprotein) present.12

Expected ResultsThese guidelines have been recommended by the National Institutes of Health.'3

Reference Interval for HDLC DT

LowHigh

Conv. Units(mg/dL)

<40>60

SI Units(mmol/L)

<1.0>1.6


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report HDL cholesterol results in conventional andSI units.

Reporting Units and Unit Conversion for HDLC DTConventional Units

mg/dLSI Units



The VITROS DT Micro HDL Cholesterol Kit method was screened for interfering substances following NCCLS Protocol EP7."The substances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Ascorbic acidDipyroneDopamineN-acetylcysteine

Substances for HDLC DT

Interferent

Concentration3 mg/dL12 mg/dL4 mg/dL10 mg/dL

170umol/L3.6 mmol/L200 umol/L0.61 mmol/L

CommentsHigh Therapeutic

High IV Drip__ High IV Drip

Oral Therapeutic

HDL CholesterolConcentration

Conv. SI(mg/dL) (mmol/L)

40.9 1.0640.5 1.0544.6 1.1540.2 1.04

Bias**


-7 -0.18-7 -0.18-9 -0.22-6 -0.14


** The bias is an estimate of the maximum difference observed.

Other LimitationsCertain drugs and clinical conditions are known to alter HDL cholesterol concentration in vivo. For additional information, referto one of the published summaries.'516 "


HD1CDTMicro HDL Cholesterol



Method ComparisonThe plots and table show the results of a comparison of the VITROS HDL Cholesterol Method analyzed on the VITROS DT60 IIChemistry System using the Dextran Sulfate/Enzymatic10 comparative method using pretreated serum specimens.

Method Comparison for HDLC DT: Serum

Conventional Units

100

80

40

20

y = x

0 20 40 60 80 100

Comparative Method: Dextran Sulfate/Enzymatic (mg/dL)

3.0

2.5

2.0

1.5

1.0

0.5

0.0

SI Units

y = x

0.0 0.5 1.0 1.5 2.0 2.5 3.0

Comparative Method: DextranSulfate/Enzymatic (mmol/L)



n

43

Slope

1.00


0.998

Conventional


12-101

Units (mg/dL)

Intercept Sy.x

0.02 1.23

SI Units (mmol/L)


0.3-2.6 0.00

Sy.x

0.03



Precision for

System

VITROS DT60

HDLC DT: Serum

II


MeanCone.

30.8

52.1

WithinDay SD*

0.98

0.99

WithinLab SD"

1.12

2.14

SI

MeanCone.

0.80

1.35

Units (mmol/L)

WithinDay SD*

0.03

0.03

WithinLab SD"

0.03

0.06

WithinLab

CV%**

3.7

4.1

No.Observ.

92

91

No.Days

23

23





References1. Warnick GR, Benderson J, Albers JJ. Dextran Sulfate-Mg+2 Precipitation Procedure for Quantitation of High-Density Lipoprotein Cholesterol. In

Cooper GR (ed). Selected Methods of Clinical Chemistry. Washington, D.C.: American Association for Clinical Chemistry; 10:91-99; 1983.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue;

Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, and Evaluation of

"Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Recommendations for Improving Cholesterol Measurement: A Report from the Laboratory Standardization Panel of the National Education

Program. US Department of Health and Human Services Public Health Service, National Institutes of Health. NIH Publication No. 90-2964.February 1990.

6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS; 1991.7. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS; 1991.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield, IL: College

of American Pathologists; 1992.9. Warnick GR, Wood PD. National Cholesterol Education Program Recommendations for Measurements of High-Density Lipoprotein Cholesterol:

Executive Summary. Clin. Chem. (41)10:1427-1433; 1995.10. Kimberley MM, Leary ET, Cole TG, Waymack PP. Selection, Validation, Standardization and Performance of a Designated Comparison Method

for HDL-Cholesterol for Use in the Cholesterol Reference Laboratory Network. Clin. Chem. (45) 10:1803-1812; 1999.11. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition. NCCLS

Document C24. Wayne, PA: NCCLS; 1999.12. Friedewald WT, Levy Rl, Fredrickson DS. Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma without Use of the

Preparative Ultracentrifuge. Clin. Chem. 18:499; 1972.13. NCEP. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood

Cholesterol in Adults (Adult Treatment Panel III); Executive Summary. NIH Publication No. 01-3670. National Institutes of Health. Bethesda.Maryland: May, 2001.

14. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.15. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.16. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.17. Tryding N, Tufvesson C, Sonntag O (eds). Drug Effects in Clinical Chemistry, ed. 7. Stockholm: The National Corporation of Swedish

Pharmacies, Pharmasoft AB, Swedish Society for Clinical Chemistry; 1996.18. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS; 1992.


Glossary of Symbols

2

SNREF

Aml

Do Not Reuse

Use by or ExpirationDate(Year-Month-Day)

Lot Number

Serial Number



Manufacturer

Authorized Representative inthe European Community


In vitro Diagnostic MedicalDevice

Store At or Below

Store At or Above

Store Between

Consult Instructions for Use

M

Fragile, Handle with Care.

Keep Dry

This end up

Irritant

Manufacturer followspackaging managementprocedures


HDLCDTMicro HDL Cholesterol

VITRCpS 0



2003-08-11

Version2.0

1.0

Description of Technical Changes*4

<

i

> Slide Diagram - changed BaSO2 to BaSO4

> Method Comparison - replaced plots to show all available data> Updated Glossary of Symbols table> New format> New organization and sections consistent with IVD Directive> Limitations of the Procedure - updated values for HDL cholesterol concentration

and bias in the Known Interferences table> Method Comparison - updated comparison values and plots> Precision - updated all values> References - added all except 1, 8


\AAien this Instructions For Use is replaced, sign and date below and retain as specified by local regulations or laboratorypolicies, as appropriate.


C€Ortho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom



VITROS is a trademark of Ortho-Clinical Diagnostics, Inc.© Ortho-Clinical Diagnostics, Inc., 2004.All rights reserved.

10 Pub. No. C-354 EN Version 2.0

VITRCpSChemistry I

INSTRUCTIONS FOR USEVITROS Chemistry Products DT HDL Cholesterol Kit

HDLC DTHDL Cholesterol

Intended UseFor in vitro diagnostic use only.For use in the quantitative measurement of HDL cholesterol (HDLC) concentration in serum and plasma.

Summary and Explanation of the TestHDL cholesterol is used to evaluate the risk of developing coronary heart disease (CHD). The risk of CHD increases withlower HDL cholesterol concentrations.

Principles of the ProcedureVITROS DT HDL Cholesterol Kit is used to prepare and test samples for high density lipoprotein (HDL) cholesterol on VITROSDT60/DT60 II Chemistry Systems. The specimens must initially be treated with a reagent to remove other lipoproteins whichalso contain cholesterol, including the very low density (VLDL) and low-density (LDL) classes. The amount of HDL cholesterolcan then be determined using VITROS Chemistry Products HDLC DT Slides.HDL is separated by the precipitation of LDL and VLDL using dextran sulfate (MW 50,000) and magnesium chloride 1 that isprovided in the VITROS Chemistry Products HDL Tube. The HDL lipoproteins remain in the liquid portion of the tube aftercentrifugation. This liquid portion is called the supernate and is the portion analyzed. The non-HDL fractions form a pellet onthe bottom of the tube and are discarded.A drop of pretreated patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlyinglayers. The Triton X-100 (TX100) surfactant in the spreading layer aids in dissociating the cholesterol and cholesterol estersfrom lipoprotein complexes present in the sample. Hydrolysis of the cholesterol esters to cholesterol is catalyzed by cholesterolester hydrolase. Free cholesterol is then oxidized in the presence of cholesterol oxidase to form cholestenone and hydrogenperoxide. Finally, hydrogen peroxide oxidizes a leuco dye in the presence of peroxidase to generate a colored dye.The density of dye formed is proportional to the HDL cholesterol concentration present in the pretreated sample and ismeasured by reflectance spectrophotometry.

Reaction Sequence

high density lipoproteins

cholesterol esters + H2O

cholesterol + O2

H2O2 + leuco dye

Txioo

cholesterol ester hydrolase

cholesterol oxidase

cholesterol + cholesterol esters + proteins

>• cholesterol + fatty acids

— ^ cholest-4-en-3-one + H2O2


Test Type and ConditionsTest Type and Conditions for HDLC DT

Test TypeColori metric


DT60/DT60 II



Wavelength660 nm

Sample DropVolume

10 uL


HDLC DT INSTRUCTIONS FOR USEHDL Cholesterol Warnings and Precautions

Warnings and PrecautionsFor in vitro diagnostic use only.Take care when handling materials and samples of human origin. Since no test method can offer complete assurance thatinfectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens,solid and liquid waste, and test components in accordance with local regulations and NCCLS Guideline M292 or otherpublished biohazard safety guidelines.While VITROS HDLC Sample Diluent product is bovine in origin, it should be handled using the same precautions as with anyother blood or blood-derived product.For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the Instructionsfor Use for the appropriate VITROS product, or to other manufacturer's product literature.


Accidental Spillage and Disposal

WARNING: VITROS HDL Tubes contain sodium azide. Disposal of reagent into sinks withcopper or lead plumbing should be followed with plenty of water to preventformation of potentially explosive metallic azides.

Absorb spilled material in vermiculite or other suitable absorbents; sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.VITROS HDL Cholesterol Reagent contains sodium azide (0.01%; 0.01 g/dL). Disposal of reagent into sinks with copper orlead plumbing should be followed with copious volumes of water to prevent formation of potentially explosive metallic azides.

First Aid

VITROS HDL Tubes contain gentamicin sulfate and sodium azide.R22 - Harmful if swallowed.

• Inhalation - Remove to fresh air. Seek medical advice.• Skin-Wash skin after each contact with soap and plenty of water for at least 15 minutes. Seek medical attention if skin is

cut or punctured.• Eye - Immediately flush eyes, including under the eyelids, with plenty of water for at least 15 minutes and get medical

attention.• Ingestion - Drink 1 -2 glasses of water. Seek medical advice.


Reagents

HDLC DT Slide IngredientsReactive ingredients per cm2

Triton X-100 0.8 mg; cholesterol oxidase {Nocardia, E.C.1.1.3.6) 0.2 U;cholesterol ester hydrolase (Candida rugosa, E.C.3.1.1.13) 0.7 U; peroxidase(horseradish root, E.C.1.11.1.7) 5.3 U; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl) imidazole (leucodye) 0.2 mg.

Other ingredientsPigment, binder, buffer, surfactants, stabilizers and cross-linking agent.

HDL Tubes

Reactive IngredientsDextran sulfate (MW50,000) 0.8 mg, magnesium chloride hexahydrate 6.7 mg

Other ingredientsSodium azide 0.22%, gentamicin sulfate <0.01%, dye and preservatives


Slide Diagram

— . . - • • - " * *

z

1.2.

3.

4.6.

Jpper slide mountSpreading layer (BaSO4)> Triton X-100» cholesterol ester

hydrolase» cholesterol oxidase• peroxidase» leuco dyeSublayer> buffer, pH 6.25Support layerLower slide mount

INSTRUCTIONS FOR USESpecimen Requirements


HDLC Sample Diluent

Reactive IngredientsBovine serum albumin 7%

Other ingredientsSodium azide 0.05%, inorganic salts and preservatives

Slide Handling

Slide Preparation



Do not use unopened slides that have been at room temperature, 18°-28°C(64 "-82 °F) for >48 hours.



Kit Storage and StabilityVITROS DT HDL Cholesterol Kit components are stable until the expiration date on the carton when they are stored andhandled as specified.

Kit Storage andKit Component

Slide

OpenedTubes

Sample Diluent*

Stability for HDLC DTStorage Condition

RefrigeratedFrozenRoom temperatureRoom temperature

RefrigeratedFrozen

RefrigeratedFrozen

2°-8°C (36°-46°F)<-18°C(<0°F)

18°-28°C(64°-82°F)18O-28°C(64°-82°F)

2°-8°C (36°-46°F)<-18°C(<0°F)

2°-8°C (36°-46°F)<-18°C (<0°F)

Stability

Until expiration dateUntil expiration date<48 hours<15 minutes



* Discard if the solution becomes cloudy or turbid.• Verify performance with quality control materials:

- If the system is turned off for more than 2 hours.



IMPORTANT: Certain collection devices have been reported to affect other analytes and tests."Confirm that your collection devices are compatible with this test.



HDLCDTHDL Cholesterol

INSTRUCTIONS FOR USESpecimen Pretreatment and Testing Procedure

Serum and Plasma


Patient Preparation• No special patient preparation is necessary unless the HDL cholesterol test is part of a complete lipid profile. Then,

a 12- to 14-hour fast is necessary.1

Special Precautions• Centrifuge specimens and remove the serum or plasma from the cellular material within 3 hours of collection. ° If further

processing is delayed, store in the refrigerator at 2°-8°C (36°-46°F).


- , • ' • ' ) (••• Handle specimens as biohazardous material,


Specimen Storage and Stability for HDLC DT: Serum andStorage Temperature

Plasma '•*Stability

Original SpecimenRefrigeratedFrozen

2°-8°C (36°-46°F)<-18°C(<0°F)

<3 days<4 weeks*

Pretreated Specimen (Supernate)

Freezer <-20°C (<-4°F)<-70°C (<-94°F)

<3 months<2 years

For longer storage, separate HDL fractions and freeze the supernate.

IMPORTANT: Avoid repeated freeze-thaw cycles.

Specimen Pretreatment and Testing Procedure

Materials Provided• 25 VITROS Chemistry Products HDLC DT Slides• 27 VITROS Chemistry Products HDL Tubes• VITROS Chemistry Products HDLC Sample Diluent

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• VITROS Chemistry Products DT Controls I & II. VITROS DT Pipette• Centrifuge capable of generating forces of 1500 x g, or a microcentrifuge capable of generating forces of 12,600 x g• A vortex mixer is recommended

Special Precautions• Use a vortex speed that will not cause the mixture to spill out of the sample tube.

Procedure

IMPORTANT;

IMPORTANT;

Do riot pretreat calibrators.

Be sure to use components from the same kit lot number.

1. Allow at least 10 minutes for refrigerated VITROS HDL Tubes and VITROS HDLC Sample Diluent to reach roomtemperature. If these materials are stored at -18°C (0°F), they will require a longer warm-up period (at least 30 minutes).Once opened, the VITROS HDLC Sample Diluent should be stored tightly capped in the refrigerator between uses.

2. Pipette serum or heparin plasma to the 0.5 mL mark on the VITROS HDL Tube.

3. Cap and mix thoroughly for 30 seconds - a vortex mixer is recommended.

NOTE: The sample will become cloudy during mixing.

4. Let stand for a minimum of 5 minutes.


INSTRUCTIONS FOR USE HDLC DTCalibration HDL Cholesterol

5. Centrifuge the VITROS HDL Tube for 10 minutes at 1,500 x g. Alternatively, you may centrifuge the tube for a shorterduration using a microcentrifuge for 95 seconds at 12,600 x g.

6. Visually check supemates for clarity. The non-HDL fractions form a pellet on the bottom of the tube. Do not disturb thepellet. If the supernate is clear, transfer cleared supernate directly from the VITROS HDL Tube to a sample cup for analysison the DT analyzer.

IMPORTANT: Supernates should be removed from the pelleted precipitate as soon as possiblefollowing centrifugation. The supernates should be used within 15 minutes. If analysison the VITROS DT60/DT60 II Chemistry System is to be delayed more than one hour,the supernate should be refrigerated. If analysis is delayed longer than 8 hours, referto the "Specimen Handling and Storage" section.

7. Analyze treated sample as instructed in the operator's manual for your VITROS DT60/DT60 II Chemistry System.



Sample DilutionIf HDL concentrations exceed the system's reportable (dynamic) range or if the supernatant is cloudy or has floating particlesafter pretreatment:1. Dilute the untreated sample with an equal volume of VITROS HDLC Sample Diluent.2. Mix gently by inverting several times.3. Pipette 0.5 mL of the diluted specimen into a second VITROS HDL Tube.4. Repeat steps 1 through 6 of the procedure above. Remember to multiply the result by the dilution factor of 2.0.5. Reanalyze.6. Multiply the results by 2 to obtain an estimate of the original sample's HDL concentration.

MOTE; Additional dilutions are not recommended.

Calibration

Required CalibratorsVITROS Chemistry Products DT Calibrator Kit, bottles 1,2, and 4

Calibrator Preparation, Handling, and StorageIMPORTANT: Do not pretreat calibrators.




- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.The VITROS HDLC DT slides may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Version 2.0 Pub. No. C-341_EN

HDLCDT INSTRUCTIONS FOR USEHDL Cholesterol Quality Control

CalculationsReflectance from the slide is measured at 660 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, high-density lipoprotein cholesterol concentration in unknown samples can be determined using the software-resident endpoint colorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for HDLC DTConventional (mg/dL)


0.03-2.84


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for High Density Lipoprotein-Cholesterol (HDLC)Reagent with VITROS HDLC DT Slides are traceable to the Certified NIST (National Institute of Standards and Technology)Reference Material, SRM® (Standard Reference Material) 911b. The Ortho-Clinical Diagnostics Calibration Laboratory usesSRM® 911b to assign values to secondary standards for calibration of an HDLC Selected Method. The Selected Methodsupports VITROS HDL Cholesterol reagent value assignment for the VITROS DT Calibrator Kit. The HDLC Selected Methodincludes (MW 50,000) Dextran Sulfate precipitation of non-HDL lipoproteins according to the recommendations of the Centersfor Disease Control (CDC),10 followed by automated enzymatic determination of supernate (HDL fraction) cholesterolconcentration.

Quality ControlIMPORTANT: Controls must be pretreated.


Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition " or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other HDL cholesterolmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.







Interpretation of ResultsLDL cholesterol and VLDL cholesterol can be calculated from the results of the VITROS CHOL DT Slide, VITROS TRIG DTSlide, and the results for HDL cholesterol to provide complete lipoprotein profiles.

LDL = CHOL-HDLC-VLDLVLDL = TRIG/5 for conventional units (mg/dL)VLDL = TRIG/2.2 for SI units (mmol/L)

Calculation of LDL is not appropriate for samples with triglyceride concentrations greater than 400 mg/dL (4.57 mmol/L) or withsamples from patients who have type III hyperlipoproteinemia (electrophoresis "broad beta" lipoprotein) present. 12

Expected ResultsThese guidelines have been recommended by the National Institutes of Health. 13

Reference Interval for HDLC DT

LowHigh

Conv. Units(mg/dL)

<40

>60

SI Units(mmol/L)

<1.0

>1.6


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report HDL cholesterol results in conventional and SIunits.

Reporting Units and Unit Conversion for HDLC DTConventional Units

mg/dLSI Units



The VITROS DT HDL Cholesterol Kit method was screened for interfering substances following NCCLS Protocol EP7. " Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Ascorbic acidDipyroneDopamineN-acetylcysteine

Substances for HDLC DT

Interferent

Concentration3 mg/dL12 mg/dL4 mg/dL10 mg/dL

170umol/L3.6 mmol/L200 umol/L0.61 mmol/L

CommentsHigh Therapeutic

High IV DripHigh IV Drip

Oral Therapeutic

HDL CholesterolConcentration


40.9 1.0640.5 1.0544.6 1.1540.2 1.04

Bias**


-7 -0.18-7 -0.18-9 -0.22-6 -0.14


** The bias is an estimate of the maximum difference observed.

Other LimitationsCertain drugs and clinical conditions are known to alter HDL cholesterol concentration in vivo. For additional information, referto one of the published summaries.1516'17


HDLCDTHDL Cholesterol



Method ComparisonThe plots and table show the results of a comparison of the VITROS HDL Cholesterol Method analyzed on the VITROS DT60 IIChemistry System using the Dextran Sulfate/Enzymatic 10 comparative method using pretreated serum specimens. TheVITROS DT HDL Cholesterol method has met the requirements of the CDC/NCEP Lipid Standardization Program formanufacturers.


Conventional Units

- 100

1 80

I 60

g 40

os

20

0

y = x

0 20 40 60 80 100Comparative Method: Dextran Sulfate/Enzymatic (mg/dL)

3.0

I 2.5E

I 2.0

» 1.5

I 0.55

0.0

SI Units

y = x

0.0 0.5 1.0 1.5 2.0 2.5 3.0

Comparative Method: DextranSulfate/Enzymatic (mmol/L)



n

43

Slope

1.00


0.998

Conventional


12-101

Units (mg/dL)

Intercept Sy.x

0.02 1.23

SI Units (mmol/L)


0.3-2.6 0.00

Sy.x

0.03

PrecisionPrecision was evaluated with quality control materials on VITROS the DT60 II System following NCCLS Protocol EP5. 1S


Precision for HDLC DT: Serum

System

VITROS DT60 II

Conventional Units (mg/dL)MeanCone.

31.5

53.8

WithinDay SD*

0.56

0.90

WithinLab SD**

1.01

2.14

SI

MeanCone.

0.82

1.39

Units (mmol/L)

WithinDay SD*

0.01

0.02

WithinLab SD**

0.03

0.06

WithinLab

CV%**

3.2

4.0

No.Observ.

99

100

No.Days

25

25


Pub. No. C-341_EN Version 2.0


HDL6 DTHDL Cholesterol

References1. Warnick GR, Benderson J, Albers JJ. Dextran Sulfate-Mg+2 Precipitation Procedure for Quantitation of High-Density Lipoprotein Cholesterol. In

Cooper GR (ed). Selected Methods of Clinical Chemistry. Washington, D.C.: American Association for Clinical Chemistry, 10:91-99; 1983.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue;

Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, and Evaluation of

"Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Recommendations for Improving Cholesterol Measurement A Report from the Laboratory Standardization Panel of the National Education

Program. US Department of Health and Human Services Public Health Service, National Institutes of Health. NIH Publication No. 90-2964.February 1990.

6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS; 1991.7. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS; 1991.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield, IL: College

of American Pathologists; 1992.

9. Warnick GR, Wood PD. National Cholesterol Education Program Recommendations for Measurements of High-Density Lipoprotein Cholesterol:Executive Summary. Clin. Chem. (41)10:1427-1433; 1995.

10. Kimberley MM, Leary ET, Cole TG, Waymack PP. Selection, Validation, Standardization and Performance of a Designated Comparison Methodfor HDL-Cholesterol for Use in the Cholesterol Reference Laboratory Network. Clin. Chem. (45) 10:1803-1812; 1999.

11. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition. NCCLSDocument C24. Wayne, PA: NCCLS; 1999.

12. Friedewald WT, Levy Rl, Fredrickson DS. Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma without Use of thePreparative Ultracentrifuge. Clin. Chem. 18:499; 1972.

13. NCEP. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High BloodCholesterol in Adults (Adult Treatment Panel III); Executive Summary. NIH Publication No. 01-3670. National Institutes of Health. Bethesda.Maryland: May, 2001.

14. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.15. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.16. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.17. Tryding N, Tufvesson C, Sonntag O (eds). Drug Effects in Clinical Chemistry, ed. 7. Stockholm: The National Corporation of Swedish

Pharmacies, Pharmasoft AB, Swedish Society for Clinical Chemistry; 1996.

18. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS; 1992.


Glossary of Symbols

SNREF

Do Not Reuse


Lot Number

Serial Number



Manufacturer




Store At or Below

Store At or Above

Store Between


It


Keep Dry

This end up

Irritant



HDICDTHDL Cholesterol

VITRCflS 0



2003-08-11

Version2.0

1.0

Description of Technical Changes*> Slide Diagram - changed BaSO2 to BaSO,• Method Comparison - added that method meets requirements of CDC/NCEP

Lipid Standardization Program for manufacturers, replaced plots to show allavailable data

> Updated Glossary of Symbols table• New format> New organization and sections consistent with IVD Directive> Limitations of the Procedure - updated values for HDL cholesterol concentration

and bias in the Known Interferences table• Method Comparison - updated comparison values and plots• Precision - updated all values> References - added all except 1, 8




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ECOrtho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom





I Product*

VITRII3SChemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products K+ DT Slides

K DTPotassium

Intended UseFor in vitro diagnostic use only.VITROS K* DT Slides quantitatively measure potassium (K+) concentration in serum and plasma.

Summary and Explanation of the TestPotassium is the major cation of the intracellular fluid. Measurement of serum potassium is used for evaluation of electrolyteimbalance, cardiac arrhythmias, muscular weakness, hepatic encephalopathy, and renal failure and for the monitoring ofketoacidosis in diabetes mellitus and intravenous fluid replacement therapy.More than 90% of hypertensive patients with aldosteronism have a low K+; a low K* is also common in vomiting, diarrhea,alcoholism, and folic acid deficiency. High K* values occur in rapid K+ infusion, end stage renal failure, hemolysis, trauma,Addison's disease, metabolic acidosis, acute starvation, dehydration, and acute medical emergency.

Principles of the ProcedureThe VITROS IC DT Slide method is performed using the VITROS K+ DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS K+ DT Slide is a multilayered, analytical element coated on a polyester support that uses direct potentiometry formeasurement of ionic potassium. The slide consists of two ion-selective electrodes, each containing valinomycin (an ionophorefor potassium), a reference layer, and a silver and a silver chloride layer coated on a polyester support.A drop of patient sample and a drop of VITROS DT Reference Fluid on separate halves of the slide results in migration of bothfluids toward the center of the paper bridge. A stable liquid junction is formed connecting the reference electrode to the sampleindicator electrode.Each electrode produces an electrical potential in response to the activity of potassium applied to it. The potential differencepoised between the two electrodes is proportional to the potassium concentration in the sample.

Test Type and ConditionsTest Type and Conditions for K*

Test Type

Potentiometric


DTE/DTE II


90 or 180 seconds*

Temperature

25°C (77°F)

Drop VolumeSample:

10 MLReference

Fluid: 10 uLAssay time is determined by the Calibration Data Module (CDM).



K DTPotassium


Reagents

Slide Ingredients


Silver 0.4 mg; silver chloride 0.2 mg; potassium chloride 63 (.ig; andvalinomycin 55 \xg.

Other ingredientsBinders, plasticizers, stabilizer, surfactants and nickel.

Slide Diagram

Slide Handling

*. 3

. . - - "" *

7

1. Upper frame2. Paper Bridge3. Ion-selective

membrane• valinomycin

4. Reference layer• KCI

6. Silver, silver chloridelayer

6. Support layer7. Lower frame


Slide Preparation

fMPQRTANT: The slide must reach room temperature, 18o-28aC(64o-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 °-28 °C(64 °-82°F) for >48 hours.



Slide Storage and StabilityVITROS K* DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.


Opened

S t a b i l i t y f o r K D TStorage Condition


18°-282°-8°C<-18°C18°-28

3C (64°-82°(36°-46°F)(<0°F)'C (64°-82°

F)

F)






Specimens Not Recommended• Plasma:5 EDTA

CitrateFluoride oxalate

• Do not use hemolyzed specimens. Lysis of only 0.5% of the erythrocytes can increase potassium levels by 0.5 mmol/L.4


INSTRUCTIONS FOR USE K DTTesting Procedure Potassium

Serum and Plasma


Patient PreparationThe patient should avoid any exercise of the arm or hand before or during collection because opening and closing the fistincreases potassium concentration by 10% to 20%.4



• Do not refrigerate the specimen prior to centrifugation because potassium will leak from the red blood cells.6

• Centrifuge specimens and remove the serum or plasma from the cellular material within 2 hours of collection.5


" <: Handle specimens as biohazardous material.


Specimen Storage and Stability for K* DT: Serum and Plasma5



<-18°C (<0°F)

Stability<6 weeks<6 weeks<1 year

Testing Procedure

Materials Provided• VITROS Chemistry Products K* DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products DT Reference Fluid• VITROS DTE Dual Sample Cups. VITROS DTE Pipette


I IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82"F), prior toI analysis.

Sample DilutionPotassium concentrations outside the reportable (dynamic) range are not expected. Diluted samples should not be analyzedwith VITROS K* Slides because dilution changes the concentration of solids in plasma water and the ionic strength of thesample.


K D T INSTRUCTIONS FOR USEPotassium Calibration

Calibration



Calibration Procedure

Refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

NOTE: Calibrate potassium in duplicate by running each bottle twice.


- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.• When the VITROS DT Reference Fluid lot number changes.The VITROS K' DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsThe analyzer measures the potential difference in millivolts between the two electrodes of a potentiometric slide—one incontact with the sample to be analyzed and the other in contact with the electrolyte reference fluid. A linear relationship existsbetween the measured potential difference observed on the slide and the logarithm of potassium concentration, i.e. the Nernstequation for ion-selective electrodes. Once the calibration has been established for each slide lot, unknown potassiumconcentration for a given sample can be determined using the software-resident math model and the measured potentialdifference.



Reportable (Dynamic) Range for K* DTConventional and SI Units (mmol/L)

1.0-11.0

Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for potassium are traceable to the Certified NIST(National Institute of Standards and Technology) Reference Material, SRM" (Standard Reference Material) 918a. The Ortho-Clinical Diagnostics calibration laboratory uses SRM 918a to calibrate the flame atomic emission spectroscopy method9 tosupport potassium value assignment for the VITROS DT Calibrator Kit.


INSTRUCTIONS FOR USE K DTQuality Control Potassium

Quality Control

Procedure Recommendations| Handle quality control materials as biohazardous material.



System.



Quality Control Material SelectionI IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other potassiummethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.



Expected Values and Reporting UnitsThe serum reference interval is based on an external study.11

The plasma reference interval is based on an external study.4

Reference Interval for K+

Serum

Plasma


3.5-5.1 mmol/L

0.1-0.7 mmol/L lower than serum range


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report potassium results in conventional units.

Reporting Units for K+ DTConventional and

mmol/LSI Units


None have been identified.

Other LimitationsCertain drugs and clinical conditions are known to alter potassium concentration in vivo. For additional information, refer to oneof the published summaries.12 13


K DTPotassium



Method Comparison

IThe plot and table show the results of a comparison of the VITROS DT60 II Chemistry System with the VITROS 950 Chemistry

System. Testing followed NCCLS Protocol EP9.14

The table also shows the results of comparisons of the VITROS K* DT slide at an assay time of approximately 90 seconds withthe VITROS K* DT slide at an assay time of approximately 180 seconds.Method Comparison for K+ DT: Serum


12

5 IO •

- 8 "

I , .to ft

2 4 6 8 10

Comparative Method: VITROS 950 System(mmol/L)

12

Method Comparison for K* DT: Serum

DT60/DT60 II System vs.950 System

90 seconds vs.180 seconds


35 1.02 0.999

35 1.02 1.000



1.8-7.5 -0.20 0.06

1.6-7.3 -0.04 0.04



Precision for

System

VITROS DT60

K+

II


Mean Cone.

2.4

5.3

Within Day SD*

0.02

0.07

Within Lab

0.04

0.09

SD** Within Lab CV%**

1.5

1.7

No. Observ.

88

88

No. Days

22




KOTPotassium


Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, and

Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 617; 1987.Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;

1991.NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS;

1991.Slockbower JM, Blumenfeld TA (ed.). Collection and Handling of Laboratory Specimens. Philadelphia: Lippincott Co; 201; 1983.Velapoldi R.A., et al. A reference method for the determination of potassium in serum. National Institute of Standards and Technology

Special Publication 260-63. Gaithersburg, MD, 1978.NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 4. Philadelphia: WB Saunders; 809; 1996.

Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.

9.

10.

12.13.14.


Glossary of Symbols

_

Do Not Reuse


Lot Number




Manufacturer

s-e I ma* Authorized Representative



Store At or Below

Store At or Above

X1

Store Between



Keep Dry

This end up


KDTPotassium


Revision HistoryDate of'Revision2003-03-28

Version1.0


« New format• New organization and sections consistent with IVD Directive> Specimens Not Recommended - added citrate and fluoride oxalate> Patient Preparation - updated> Special Precautions - updated• Specimen Storage and Stability - updated stability values• Quality Control Material Selection - added the statement regarding ethylene

glycol« Expected Values and Reporting Units - updated values• Reference Interval - updated values• Method Comparison - updated all data and the plot• Precision - updated all data> References - added all




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Chcmbtry

INSTRUCTIONS FOR USEVITROS Chemistry Products LAC DT Slides

1ACDTLactate

Intended UseFor in vitro diagnostic use only.VITROS LAC DT Slides quantitatively measure lactate (LAC) concentration in plasma.

Summary and Explanation of the TestLactate is the end product of the anaerobic metabolism of glucose. The concentration of lactate in the blood is dependent onthe rate of production in muscle cells and erythrocytes and the rate of metabolism in the liver. Lactic acidosis usually resultsfrom overproduction or underutilization of lactate. Elevated lactate levels can occur as a result of tissue hypoxia; diabetesmellitus; phenformin therapy; malignancies; glycogen storage disease; ethanol, methanol, or salicylate ingestion; and metabolicacidosis.1

Principles of the ProcedureThe VITROS LAC DT Slide method is performed using the VITROS LAC DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS LAC DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Lactate in the sample is oxidized by lactate oxidase to pyruvate and hydrogen peroxide. The hydrogen peroxide generatedoxidizes the 4-aminoantipyrine, 1,7-dihydroxynaphthalene dye system in a horseradish-peroxidase-catalyzed reaction andresults in a dye complex. The slide is incubated and the intensity of the dye complex is measured spectrophotometrically.

Reaction Sequence

L-(+)-lactic acid + O2 •lactate oxidase

-> • pyruvate + H2O2

2H2O2 + 4-aminoantipyrine + 1,7-dihydroxynaphthaleneperoxidase

red dye

Test Type and ConditionsTest Type and Conditions for LAC DT

ITest TypeColorimetric


DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL



LACDTLactate


Reagents


I Lactate oxidase (Pediococcus sp., E.C.1.1.3.2) 0.3 U; peroxidase (horseradish

root, E.C.1.11.1.7) 1.5 U; 1,7-dihydroxynapthalene (dye precursor) 43 ug; and4-aminoantipyrine hydrochloride (dye precursor) 65 ug.Other ingredientsPigment, binders, buffer, stabilizers, cross-linking agent, surfactants andenzyme cofactor.

Slide Diagram

Slide Handling

, 2

" ' ' ' - - *

~*~~ 4

. - S

1.2.3.

4.6.

Upper slide mountSpreading layer (TIO2)Reagent layer• lactate oxidase• peroxidase• dye precursors• buffer, pH 6.25Support layerLower slide mount


Slide Preparation

The slide must reach room temperature, 18°-28°C (64 °-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 78°-28<C(64 °-82 °F) for >48 hours.



Slide Storage and StabilityVITROS LAC DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for LAC DTSlidesUnopened

Opened



Specimen RequirementsWARN I M(k Handle specimens as biohazardous material.

Specimens Recommended• Plasma:3 Fluoride oxalate• Heparinized plasma is acceptable, but precautions must be taken to retard glycoiysis by keeping the whole blood on ice."



Plasma


Patient Preparation• Venous specimens should be obtained without the use of a tourniquet or immediately after the tourniquet is applied.

Alternatively, the tourniquet should be removed after the puncture has been performed, and the blood should be allowed tocirculate for several minutes before the sample is withdrawn.4

• The patient should avoid any exercise of the arm or hand before or during collection of the specimen.4


INSTRUCTIONS FOR USE LAC DTTesting Procedure Lactate

Special Precautions• For fluoride oxalate plasma, specimens must be collected in tubes that are at least half full. Smaller volume's can result in

negative biases.• Centrifuge specimens and remove the plasma from the cellular material within 15 minutes of collection.3




Specimen Storage and Stability for LAC DT: Plasma3



<-18°C(<0°F)

Stability<8 hours<14days<1 month


• VITROS Chemistry Products LAC DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• Isotonic saline or reagent-grade water. VITROS DT Pipette


IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82'F), prior toanalysis.

Sample DilutionIf lactate concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's lactate concentration.

Calibration







LACDT INSTRUCTIONS FOR USELactate Quality Control

The VITROS LAC DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 555 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, lactate concentration in unknown samples can be determined using the software-resident endpoint colorimetricmath model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for LAC DTConventional and SI Units (mmol/L)

0.5-12.0


Traceability of the CalibrationI Values assigned to the VITROS Chemistry Products DT Calibrator Kit for lactate are traceable to gravimetrically prepared

standards made from reagent grade lactic acid. The Ortho-Clinical Diagnostics calibration laboratory uses the gravimetrically| prepared standard to calibrate an HPLC method for lactate8 to support value assignment for the VITROS DT Calibrator Kit.


| V ' A R ui Nc : Handle quality control materials as biohazardous material.



System.




I IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other lactate methodsif they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.





UCDTLactate


Reference IntervalThis reference interval is the central 95% of results from a study of 168 apparently healthy adults from a working population.The values for heparinized plasma may be higher because lactate rapidly increases in blood as a result of glycolysis.10

Reference Interval for LAC DT

Conventional and SI Units (mmol/L)0.7-2.1


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report lactate results in conventional and SI units.

Reporting Units for LAC DT

Conventional and SI Unitsmmol/L


None identified.

Other LimitationsCertain drugs and clinical conditions are known to alter lactate concentration in vivo. For additional information, refer to one ofthe published summaries.1112


I The plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzedI using the VITROS 950 System.

Method Comparison for LAC DT: Plasma


12

I Hi-E

I 8-j

= 6

& , jo 4 -oa:


(mmol/L)

Method Comparison for LAC DT: Plasma


n

58

Slope

1.00


1.000

Conventional and SI


0.8-10.3

Units (mmol/L)

Intercept

0.01

Sy.x

0.08


1ACDTLactate




Precision for

System

VITROS DT60

LAC DT: Plasma

II


Mean Cone.

1.6

4.0

Within Day SD*

0.02

0.04

Within Lab SD**

0.03

0.06

Within Lab CV%**

1.6

1.6

No. Observ.

84

83

No. Days

21

21


References1. Oliva PB. Am. J. Med. 48:209-225; 1970.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and


IL: College of American Pathologists; 1992.4. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 5. Philadelphia: WB Saunders; 451; 2001.5. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.

8. Smith JW, Ambrose RT. Determination of Lactic Acid in Human Serum by Ion Exchange Chromatography. Internal Eastman KodakCompany Report. 1982.


10. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 2. Philadelphia: WB Saunders; 940; 1976.11. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.12. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D C : AACC Press; 1990.13. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


gj VITFIJ


IACDTLactate


Glossary of Symbols

SNREF|

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Lot Number




Manufacturer

ee I KEI> I Authorized Representative



Store At or Below

X Store At or Above

I

M

Store Between



Keep Dry

This end up


Version1.0

Description of Technical Changes*> New format• New organization and sections consistent with IVD Directive« Test Type and Conditions - updated the wavelength> Reference Interval - updated text> Method comparison - updated all data and the plot> Precision - updated all values> References - added all except 1,10





LACDTLactate


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INSTRUCTIONS FOR USEVITROS Chemistry Products LDH DT Slides

LDHDTLactate Dehydrogenase

Intended UseFor in vitro diagnostic use only.VITROS LDH DT Slides quantitatively measure lactate dehydrogenase (LDH) activity in serum and plasma.

Summary and Explanation of the TestLactate dehydrogenase is an enzyme present in the cytosol of all human cells; it catalyzes the reversible reduction of pyruvateto lactate using NADH. Causes of high LDH include neoplastic states, hypoxic cardiorespiratory diseases, myocardialinfarctions, hemolytic anemias, megaloblastic anemias, hepatic cirrhosis, renal infarction, trauma, muscle damage, musculardystrophy, shock, and hypotension. In myocardial infarction cases, LDH begins to rise within about 12 hours after infarction andusually returns to normal after two to five days.1

Principles of the ProcedureThe VITROS LDH DT Slide method is performed using the VITROS LDH DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS LDH DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Lactate dehydrogenase catalyzes the conversion of pyruvate and NADH to lactate and NAD+. The oxidation of NADH, which ismonitored by reflectance spectrophotometry, is used to measure lactate dehydrogenase activity.

Reaction Sequence

pyruvate + NADH + H+ LDH-> • lactate + NAD+

Test Type and ConditionsTest Type and Conditions for LDH DT

Test TypeRate


DTSC/DTSC II



Wavelength340 nm

Sample DropVolume

10 uL





Reagents

Slide Ingredients


Nicotinamide adenine dinucleotide, reduced 44 ug and sodium pyruvate 17 ug.

Other ingredientsPolymer beads, binders, buffer, surfactants, cross-linking agent and stabilizer.

Slide Diagram

Slide Handling


1. Upper slide mount2. Spreading layer (beads)

• sodium pyruvate3. Reagent layer

• buffer, pH 7.25• NADH


Slide Preparation

IMPORTANT: The slide must reach room temperature, 78-28£C (64°-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18°-28 °C(64°-82°F) for >48 hours.




VITROS LDH DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for LDH DTSlidesUnopened

Opened



Specimen RequirementsWARMS: Handle specimens as biohazardous material.


I • Plasma:3 Heparin

NOTE: Serum and heparin plasma specimens produce similar LDH results on VITROSSystems. Some other methods, however, have shown substantial differences betweenserum and plasma results due to contamination by platelets in plasma separated bylow-speed centrlfugation.'1 The VITROS LDH DT Slide is insensitive to LDH containedwithin intact platelets;5 therefore, LDH results in comparative methods may not agreewith the VITROS System results for heparin plasma specimens.





|Sj VITRj

INSTRUCTIONS FOR USE IDH DTTesting Procedure Lactate Dehydrogenase

Serum and Plasma

Specimen Collection and PreparationCollect specimens using standard laboratory procedures.8'9


Special Precautions• Centrifuge specimens and remove the serum from the cellular material within 1 hour of collection.10


G: Handle specimens as biohazardous material.

Handle and store specimens in stoppered containers to avoid contamination and evaporation.Mix samples by gentle inversion and bring to room temperature, 18°-28°C (64°-82°F), prior to analysis.

Specimen Storage and Stability for LDH DT: Serum and Plasma1


Temperature18O-28°C(64°-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<2 daysNot recommended*Not recommended*

* LD4 and LD5 isoenzymes are labile at refrigerator and freezer temperatures.


• VITROS Chemistry Products LDH DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA or isotonic saline. VITROS DT Pipette


I MPORTANT; Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior to

analysis.

Sample DilutionIf lactate dehydrogenase activities exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA or isotonic saline.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's lactate dehydrogenase activity.

Calibration





1DHDT INSTRUCTIONS FOR USELactate Dehydrogenase Quality Control



The VITROS LDH DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 340 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, lactate dehydrogenase activity in unknown samples can bedetermined from the rate of change in reflectance measured for each unknown test slide.



Reportable (Dynamic) Range for LDH DTConventional and SI Units (U/L)

100-1750



I Values assigned to the VITROS Chemistry Products DT Calibrator Kit for lactate dehydrogenase are traceable to the pyruvate-

to-lactate (P->L) (Buhl) total lactate dehydrogenase method,12 adapted to a centrifugal analyzer at 37°C.

Quality Control





System.




INSTRUCTIONS FOR USE LDH DTExpected Values and Reporting Units Lactate Dehydrogenase




• Control materials other than VITROS DT Controls I & II may show a difference when compared with other lactatedehydrogenase methods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

| • Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.I • Do not use control materials stabilized with ethylene glycol.



Reference IntervalThese reference intervals are the central 95% of results from an internal study of 557 apparently healthy individuals.No significant differences between results from the male and female populations were observed.

Reference Interval for LDH DTConventional and SI Units (U/L)

313-618


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report lactate dehydrogenase results in conventionaland SI units.

Reporting Units for LDH DTConventional and SI Units

U/L


None identified.

Other Limitations• Certain drugs and clinical conditions are known to alter lactate dehydrogenase activity in vivo. For additional information,

refer to one of the published summaries.1415





Method Comparison


using the VITROS 950 System.Method Comparison for LDH OT: Serum


2000 •

„ 1600

I 1200

800

400


(U/L)

Method Comparison for LDH DT: Serum

DT60 II System vs.9S0 System

n

61

Slope

1.03


0.999

Conventional and SI


122-1418

Units (U/L)

Intercept

-13.36

Sy.x

14.94



Precision for

System

VITROS DT60

LDH DT: Serum

II


Mean Activity

458

1369

Within Day SD* Within Lab SD"

6.2 7.5

20.9 23.8

Within Lab CV%**

1.6

1.7

No. Observ.

84

84

No. Days

21







Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.4. Peake MJ, et al. Mechanism of Platelet Interference with Measurement of Lactate Dehydrogenase Activity in Plasma. Clin. .Chem.

30:518-520; 1984.5. Greenberg N, Byrne D. Plasma Lactate Dehydrogenase Activity Assayed with the Kodak Ektachem 700 Analyzer Is Unaffected by

Platelet Contamination. Clin. Chem. 31:1022; 1985.6. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.7. Young DS. Effects of Preanalytical Variables on Clinical Laboratory Tests. Ed. 2. Washington D C : AACC Press; 3-335, 1997.8. NCCLS. Procedures forthe Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.11. Tietz NW. Tietz Textbook of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 671; 1999.12. Buhl SN, Jackson KY, Graffunder B. Optimal Reaction Conditions for Assaying Human Lactate Dehydrogenase Pyruvate-to-Lactate

at 20, 30, and 37°C. Clin. Chem. 24:261-266; 1978.



1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer

<sc wa» I Authorized Representative



Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


1DHDTLactate Dehydrogenase



Version1.0


• New format• New organization and sections consistent with IVD Directive• Materials Required But Not Provided and


and ethylene glycol• Limitations of the Procedure - removed the statement regarding elevated total

protein levels• Method Comparison - updated all data and the plot• Precision - updated all values• References - added all except 1






' Ortho-Clinical DiagnosticsoH company



Chemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products Li DT Slides

UDTLithium

Intended UseFor in vitro diagnostic use only.VITROS Li DT Slides quantitatively measure lithium (Li) concentration in serum and plasma.

Summary and Explanation of the TestLithium is used in the treatment of bipolar (manic-depressive) illness. Lithium measurements are used to monitor patientcompliance and therapy and to diagnose potential overdose. Symptoms of lithium intoxication include sluggishness,drowsiness, muscle weakness, and ataxia.' 2

Principles of the ProcedureThe VITROS Li DT Slide method is performed using the VITROS Li DT Slide and the VITROS Chemistry ProductsDT Specialty Calibrator Kit on VITROS DT60 II Chemistry Systems.The VITROS Li DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlyinglayers. The lithium in the sample is specifically bound by the crown-ether azo dye (6-dodecyl-6-(2'-hydroxy-5'-(2"-4"-dinitrophenylazo)benzyl)-13, 13-dimethyl-1,4, 8,11-tetraoxacyclotetradecane). As the lithium ion binds to the crown-ether, a shift in the peak absorbance of the dye occurs. The increase in absorbance is proportional to the concentration oflithium in the sample. The intensity of the dye is measured by reflectance spectrophotometry at the end of incubation.

Reaction Sequence

lithium + crown-ether dye dye complex

Test Type and ConditionsTest Type and Conditions for Li DT





Wavelength630 nm

Sample DropVolume

10 uL



UDTLithium


Reagents


Reactive ingredients per cm(6-dodecyl-6-(2'-hydroxy-5'-(2"-4"-dinitrophenylazo)benzyl)-13,13-dimethyl-1,4,8,11-tetraoxacyclotetradecane) (crown-ether azo dye) 40 pg.

Other ingredientsPigment, binders, buffer, surfactants, dye solubilizer and cross-linking agent.

Slide Handling

CAUTION;

— -- ~~

_- - - — *

1.2.

3.

4.

S.6.

Upper slide mountSpreading layer (BaSC>4)• buffer, pH 11.0Buffer layer• buffer, pH 11.0Reagent layer• crowvether azo dyeSupport layerLower slide mount


Slide Preparation





Slide Storage and StabilityVITROS Li DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for Li DTSlidesUnopened

Opened

StorageRoom temperatureRefrigeratedFrozenRoom temperature

Condition18°-28°C(64°-82°2°-8°C (36°-46°F)<-18°C (<0°F)18°-28°C(64°-82O

F)

F)


Specimen RequirementsWA Handle specimens as biohazardous material.


Heparin

MPORTANT: Certain collection devices have been reported to affect other analytes and tests."Confirm that your collection devices are compatible with this test.

Specimens Not Recommended• Plasma: Fluoride oxalate

Lithium heparin



[3 N/ITFJCp'S

INSTRUCTIONS FOR USE Li DTTesting Procedure Lithium


Special Precautions• Samples are commonly drawn approximately 12 hours after the last dose of lithium has been taken.7



WARNING; Handle specimens as biohazardous material.


Specimen Storage and Stability for Li DT: Serum and PlasmaStorageRoom temperatureRefrigeratedFrozen


<-18°C(<0°F)

Stability<8 hours<24 hours<6 months


• VITROS Chemistry Products Li DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Specialty Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA• Reagent-grade water. VITROS DT Pipette


I IMPORTANT: Bring all fluids and samples to room temperature, 18°-28"C (64°-82°F), prior toI analysis.

Sample DilutionIf lithium concentrations exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's lithium concentration.

Calibration







LiDT INSTRUCTIONS FOR USELithium Quality Control

The VITROS Li DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 630 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, lithium concentration in unknown samples can be determined using the software-resident endpoint colorimetricmath model and the response obtained from each unknown test slide.

Validity of a CalibrationCalibration parameters are automatically assessed by the VITROS DT60II Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.


Reportable (Dynamic) Range for Li DTConventional and SI Units (mmol/L)

0.2-4.0


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Specialty Calibrator Kit for lithium are traceable to the CertifiedNIST (National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 924a. TheOrtho-Clinical Diagnostics calibration laboratory uses SRM® 924a to calibrate the flame atomic absorption spectroscopymethod9 to support lithium value assignment for the VITROS DT Specialty Calibrator Kit.

Quality Control


j WARNING; Handle quality control materials as biohazardous material.


- After calibration.- According to local regulations or at least once each day that the test is being performed.- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT60II System.


and Definitions; Approved Guideline-Second Edition™ or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.


I IMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60 IIChemistry System. Evaluate the performance of other commercial control fluids for

I compatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other lithium methods ifthey:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




[3 VITQCpS


UDTLithium


Reference IntervalThese serum lithium concentrations are based on the 12-hour standardized concentration, measured on a serum sampleobtained 12 hours after the last dose.11 12

Reference Interval for Li DT

Therapeutic13

Conventional and SI Units (mmol/L)0.6-1.2

Toxic14

PotentiallySeverely

>1.5>2.5



The VITROS DT60 II Chemistry System may be programmed to report lithium results in conventional and SI units.

Reporting Units for Li DTConventional and SI Units

mmol/L


The VITROS Li DT Slide method was screened for interfering substances following NCCLS Protocol EP7.15 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Methyl para ben**A/-AcetylcysteineHemoglobin

Substances for Li DT


150mg/dL (10 mmol/L)180mg/dL (11.0 mmol/L)100mg/dL (15.5 umol/L)250 mg/dL (38.8 umol/L)500 mg/dL (77.5 umol/L)

Lithium ConcentrationConv./SI Units

(mmol/L)1.01.01.21.21.2

Average BiasConv./SI Units

(mmol/L)-0.17-0.15+0.04+0.12+0.17


** A preservative found in some controls, proficiency fluids, and sterile saline flushes

Other LimitationsCertain drugs and clinical conditions are known to alter lithium concentration in vivo. For additional information, refer to one ofthe published summaries.16'17


UDTLithium



Method Comparison



Method Comparison for Li DT: Serum


y = x


Method Comparison for Li DT: Serum


n

62

Slope

1.01


0.998



0.2-3.9 -0.06

Sy.x

0.05



Precision for

System

VITROS DT60

Li

II


Mean Cone.

1.2

2.4

Within Day SD*

0.02

0.04

Within Lab SD**

0.04

0.05

Within Lab CV%**

3.2

2.1

No. Observ.

84

83

No. Days

21



g] VITRI


LiDTLithium

References1. Cade JFJ. Lithium Salts in the Treatment of Psychotic Excitement. Med. J. Aust. 2:349; 1949.2. Baastrup PC, Schou M. Lithium as a Prophylactic Agent: Its Effect against Recurrent Depressions and Manic-Depressive Psychosis.

Arch. Gen. Psychiat. 16:162; 1967.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and


1991.


7. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 5. Philadelphia: WB Saunders; 632; 2001.8. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle IV: Therapeutic Drug Monitoring/Toxicology.

Skokie, IL: College of American Pathologists; 1985.9. Levy AL, Katz EM. A Comparison of Serum Lithium Determinations Using Flame Photometry and Atomic Absorption

Spectrophotometry. Clin. Chem. 15:787; 1969.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. Gilman AG et al. Goodman and Gilman's The Pharmacological Basis of Therapeutics, ed. 8. 418-422; 1990.12. Ellenhorn MJ, Barceloux DG. Medical Toxicology: Diagnosis and Treatment of Human Poisoning. New York: Elsevier; 1042-1045;

1988.13. Burtis CA, Ashwood ER, (eds) Fundamentals of Clinical Chemistry, ed. 5. Philadelphia: WB Saunders; 1023; 2001.14. Burtis CA, Ashwood ER, (eds) Fundamentals of Clinical Chemistry, ed. 5. Philadelphia: WB Saunders; 632; 2001.15. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.16. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.17. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.18. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

REF

Do Not Reuse


Lot Number




| EC | REP j

\2)/V

Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


LiDTLithium



Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Specimens Not Recommended - added section• Specimen Storage and Stability - updated stability values• Materials Required But Not Provided and

Sample Dilution - replaced isotonic saline and distilled water withVITROS 7% BSA and reagent-grade water

• Known Interferences - updated values for hemoglobin• Method Comparison - updated all data and the plot• Precision - updated all values• References - added all except 1, 2,11,12,16,17,18




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I EC REP IOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


'Ortho-Clinical Diagnostics»ftwm company



Chemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products LIPA DT Slides

LIPA DTLipase

Intended UseFor in vitro diagnostic use only.VITROS LIPA DT Slides quantitatively measure lipase (LIPA) activity in serum and plasma.

Summary and Explanation of the TestLipase is a digestive enzyme that is mainly produced by the acinar cells of the exocrine pancreas. Its physiological role is tohydrolyze the long-chain triglycerides in the small intestine. Serum lipase increases rapidly in patients with acute and recurrentpancreatitis, pancreatic abscess or pseudocyst, pancreatic trauma, pancreatic cancer, common-bile-duct obstruction, andingestion of drugs that are toxic to the pancreas. It is also increased by most inflammatory conditions in the abdominal cavity,biliary tract disease, abdominal abscesses, and renal failure. Lipase is more specific than total amylase in the diagnosis ofacute pancreatitis.1

Principles of the ProcedureThe VITROS LIPA DT Slide method is performed using the VITROS LIPA DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60 II Chemistry Systems.The VITROS LIPA DT Slide is a multilayered, analytical element coated on a polyester support. The analysis is based on anenzymatic method described by Mauck.2

A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Themethod incorporates colipase which facilitates the adsorption of lipase to the substrate micelles in the presence of bile salts.Lipase then catalyzes the hydrolysis of water-insoluble triacylglycerol esters. The method uses the enzyme diacetinase toconvert the substrate 2,3-diacetylglycerol to glycerol. Glycerol kinase converts the glycerol to L-a-glycerophosphate.L-a-glycerophosphate oxidase catalyzes the oxidation of L-a-glycerophosphate to generate hydrogen peroxide. Peroxidaseoxidizes a leuco dye to produce a colored dye. The rate of change in reflection density is proportional to the activity of lipasepresent in the sample.

Reaction Sequence

1 -oleoyl-2,3-diacetylglycerol

2,3-diacetylglycerol

glycerol + ATP

lipase, colipasepH8.5

diacetinase

2,3-diacetylglycerol + oleic acid

glycerol + acetic acid

glycerol kinase


H2O2 + leuco dye

MgCI2

L- a -glycerophosphate oxidase


• dihydroxyacetone phosphate + H2O2


Test Type and ConditionsTest Type and Conditions for LIPA DT

Test TypeRate




Wavelength540 nm

Sample DropVolume

10 uL


LIPADTLipase



Reagents


Diacetinase (Bacillus subtilis, E.C.3.1.1-) 0.54 U; glycerol kinase (£. coli orCellulomonas sp, E.C.2.7.1.30) 0.32 U; L-a-glycerophosphate oxidase{Aerococcus viridans, E.C.1.1.3.21) 0.39 U; peroxidase (horseradish root,E.C.1.11.1.7) 0.62 U; colipase (porcine pancreas) 5.9 U; adenosine triphosphate0.16 mg; 1-oleoyl-2,3-diacetylglycerol 0.80 mg; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl)imidazo!e (leuco dye) 33 ng.

Other ingredientsPigment, binders, surfactants, enzyme cofactors, stabilizers, buffer, dyesolubilizer, scavenger and cross-linking agent.

Slide Diagram

^"T • '

~~*~~> "~ "

, 1. Upper slide mount2. Spreading layer {TIO2)

2 • colipase• 1-oleoyl-2,3-diace1ylglycerol

3. Reagent layer3 •buffer, pH 8.5

• diacetinase• glycerol kinase• ATP

4 • L-a-glycerophosphateoxidase

• peroxidase• leuco dye


Slide Handling


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-28X: (64°-82°F), before the wrapper isopened.


1. Remove the unopened slide from the box.2. Warm the unopened slide for at least 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to



VITROS LIPA DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for LIPA DTSlidesUnopened

Opened




Q VITRCpS

INSTRUCTIONS FOR USE UPADTSpecimen Requirements Lipase

Specimen RequirementsI VM Handle specimens as biohazardous material.




Specimens Not Recommended• Do not use grossly lipemic specimens. Refer to "Limitations of the Procedure."

Serum and Plasma .



Special Precautions• Ensure equipment is free from soap or giyceroi contamination. Collection tubes with glycerol-lubricated stoppers should not

be used.• Centrifuge specimens and remove the serum or plasma from the cellular material within 4 hours of collection.7


Specimen Storage and Stability for LIPA DT: Serum and Plasma7


Temperature18°-28°C(64O-82OF)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<7 days<3 weeks<5 months


• VITROS Chemistry Products LIPA DT Slides




Sample DilutionIf lipase activities exceed the system's reportable (dynamic) range or if samples are flagged with an L-11 or L-13 error code:1. Dilute with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's lipase activity.


1IPADI INSTRUCTIONS FOR USELipase Calibration

Calibration






The VITROS LIPA DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.

CalculationsBased on sequential readings of the slide's reflectance at 540 nm over the defined incubation period, a rate of change inreflectance is determined. This rate is used in the software-resident multi-point rate calibration model to compute enzymeactivity. Once a calibration has been performed for each slide lot, lipase activity in unknown samples can be determined fromthe rate of change in reflectance measured for each unknown test slide.



Reportable (Dynamic) Range for LIPA DTConventional and SI Units (U/L)

10-2000For out-of-range samples, refer to "Sample Dilution."


I Values assigned to the VITROS Chemistry Products DT Calibrator Kit for lipase are traceable to the measurement of lipase

activity in a standard triolein emulsion with a pH-Stat analyzer.8

Quality Control


| ' ' Handle quality control materials as biohazardous material.




and Definitions; Approved Guideline-Second Edition9 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60 II Chemistry System.


El VITRcffS


LIPADTLipase

Quality Control Material SelectionIMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 II


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other lipase methods ifthey:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

• Liquid controls are not recommended because they often contain high concentrations of glycerol, which result in L-11 orL-13 codes. Refer to "Limitations of the Procedure."

• Enzyme activity might also vary with enzyme source, diluent temperature, and activation time during reconstitution.• Do not use control materials stabilized with ethylene giycol.

• Quality Control Material Preparation and StorageRefer to the instructions for use for VITROS Chemistry Products DT Control I & II or to other manufacturer's product literature.


Reference IntervalThis reference interval is based on results from an internal study of 496 apparently healthy individuals, ages 10-90. Nosignificant differences in results between male and female populations were observed. Lipase activities tend to increasewith age.10

Reference Interval for LIPA DTConventional and SI Units (UL)

23-300



The VITROS DT60 II Chemistry System may be programmed to report LIPA DT results in conventional and SI units.

Reporting Units for LIPA PTConventional and SI Units

U/L


• Carboxylesterases generally do not interfere with lipase results. Extremely high activity of carboxylesterase(e.g., 51000 U/L) will show a bias of +240 U/L at a lipase activity of 35 U/L.

• Grossly lipemic samples may show a large negative bias.The VITROS LIPA Slide method was screened for interfering substances following NCCLS Protocol EP7.11 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for LIPA DT

Interferent*

5-Aminosalicylate


23mg/dL (1.5mmol/L)

Lipase ActivityConv./SI Units (U/L)

200

Average Bias

Conv./SI Units (U/L)-28

It is possible that other interfering substances may be encountered. These results are representative;however, your results may differ somewhat due to test-to-test variation. The degree of interference atconcentrations other than those listed might not be predictable.

Other Limitations• Normal endogenous concentrations of glycerol do not interfere with this method; however, samples containing high

concentrations of glycerol will be flagged with the L-11 or L-13 error code. Samples flagged with a L-11 or L-13 error codeshould be diluted and reanalyzed. Refer to "Sample Dilution." Highly elevated glycerol concentrations are usually caused bycontamination from rubber stoppers, latex gloves or hyperalimentation fluids. If the L-11 or L-13 error code was caused byglycerol contamination, the final lipase result may be normal.

• Certain drugs and clinical conditions are known to alter lipase activity in vivo. For additional information, refer to one of thepublished summaries.1213


LIPADTLipase



Methpd Comparison

I The plot and table show the results of a comparison of the VITROS DT60 II Chemistry System with the VITROS 700 Chemistry

System. Testing followed NCCLS Protocol EP9.14

Method Comparison for LIPA DT: SerumConventional and SI Units

y = x2000

1500

5 1000

DtoO

500 •


(U/L)

Method Comparison for LIPA DT: Serum


n

49

Slope

1.00


0.999

Conventional and SI


36-1800

Units (U/L)

Intercept

0.38

Sy.x

18.62

PrecisionPrecision was evaluated with quality control materials on VITROS DT60 II System following NCCLS Protocol EP5.16


Precision for

System

VITROS DT60

LIPA DT: Serum

II


Mean Activity

182

674


1.9 2.7

5.4 8.2

Within Lab CV%**

1.5

1.2

No. Observ.

88

88

No. Days

22 '

22* Within Day precision was determined using two runs/day with two replications.** Within Lab precision was determined using a single lot of slides and calibrating weekly.


I*J VITRI


LIPADTLipase

References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 399-400; 1987.2. Mauck JC, Weaver MS, Stanton C. Development of a Kodak Ektachem Clinical Chemistry Slide for Lipase (Abstract). Clin. Chem.

30:1058-1059; 1984.


4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.

8. Tietz, NW, Repique, EV. Proposed Standard Method for Measuring Lipase Activity in Serum by a Continuous Sampling Technique.Clin. Chem. 19:1268-1275; 1973.

9. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition..NCCLS Document C24. Wayne, PA: NCCLS; 1999.

10. Vankampen L, DiPaola J, Gambino R. Lipase Normals - Some Data. Lab Report 12 (November); 1990.11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

REF

Do Not Reuse


Lot Number




XI

Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


LIPflDTLipase



Version1.0

Description of Technical Changes*• New organization and sections consistent with IVD Directive• Specimens Not Recommended - plasma: removed oxalate/fluoride, citrate, and

EDTA• Specimen Storage and Stability - updated all stabilities• Quality Control Material Selection - added statements regarding liquid controls,

enzyme activity, and ethylene glycol• Limitations of the Procedure - removed sodium deoxycholate; updated bias due

to carboxylesterase; added L-13 error code and removed >AR• Method Comparison - corrected the slope value• Precision - updated all values• References - added all but 10






'Ortho-Clinical Diagnostics^c&mcH company



Chemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products Mg DT Slides

MgDTMagnesium

Intended UseFor in vitro diagnostic use only.VITROS Mg DT Slides quantitatively measure magnesium (Mg) concentration in serum and plasma.

Summary and Explanation of the TestMagnesium is predominantly an intracellular cation and is essential in enzyme reactions. Magnesium deficiency may causeweakness, tremors, tetany, and convulsions. Hypomagnesemia is associated with hypocalcemia, alcoholism, some types ofmalnutrition, malabsorption, chronic hemodialysis, and pregnancy. Increased serum magnesium concentrations occur inpatients with renal failure, dehydration, and Addison's disease.1

Principles of the ProcedureThe VITROS Mg DT Slide method is performed using the VITROS Mg DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS Mg DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Magnesium (both free and protein-bound) from the sample then reacts with the formazan dye derivative in the reagent layer;the high magnesium affinity of the dye dissociates magnesium from binding proteins. The resulting magnesium-dye complexcauses a shift in the dye absorption maximum. The amount of dye complex formed is proportional to the magnesiumconcentration present in the sample and is measured by reflection density.

Reaction Sequence

Mg2 + Ca+2 Mg*2 + Ca*2-chelator complex

Mg+2 + formazan dye derivative pH 9.75 Mg -dye complex

Test Type and ConditionsTest Type and Conditions for Mg DT



DT60/DT60 II



Wavelength660 nm

Sample DropVolume

10 uL

Warnings and PrecautionsFor in vitro diagnostic use only.Take care when handling materials and samples of human origin. Since no test method can offer complete assurance thatinfectious agents are absent, consider all clinical specimens, controls, and calibrators potentially infectious. Handle specimens,solid and liquid waste, and test components in accordance with local regulations and NCCLS Guideline M29Z or otherpublished biohazard safety guidelines.For specific warnings and precautions for calibrators, quality control materials, and other components, refer to the instructionsfor use for the appropriate VITROS product, or to other manufacturer's product literature.


NlgDTMagnesium

VITFJCpS gj


Reagents


Reactive ingredients per cm1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (calcium chelator) 242 (and 1,5-bis(2-hydroxy-3,5-dichlorophenyl)-3-cyanoformazan (dye) 38 \xg.

Other ingredientsPigment, binders, buffer, dye solubilizer, surfactants, cross-linking agent andstabilizer.

Slide Handling

1

~ 4

5

1.2.3.

4.5.

Upper slide mountSpreading layer (TiO2)Reagent layer• calcium chelator• buffer, pH 9.75• formazan dyeSupport layerLower slide mount


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-28X: (64°-82°F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 -28 °C(64 °-82 °F) for >48 hours.




VITROS Mg OT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for Mg DTSlidesUnopened

Opened




CAUTION: Protective gloves manufactured with magnesium stearate (talc) powders maycause elevated test results because of the contamination of sample handlingsupplies (for example, pipette tips, transfer pipettes, sample cups and caps).Supplies that have come in contact with powdered gloves may subsequentlycontaminate the test specimen during sample metering.

NOTE: Gloves labeled as "powder-free" may contain some contaminating powder agents onthe inside of the glove.





INSTRUCTIONS FOR USE Mg OTTesting Procedure Magnesium


Fluoride oxalateCitrate



Special Precautions• Hemolyzed specimens can cause falsely elevated results due to intracellular magnesium levels.8

• Centrifuge specimens and remove the serum or plasma from the cellular material as soon as possible after collection.1




Specimen Storage and Stability for Mg DT: Serum and Plasma5


Temperature18°-28°C(64°-82''F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<1 week<1 week<1 month


• VITROS Chemistry Products Mg DT Slides




Sample DilutionIf magnesium concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's magnesium concentration.


MgDT INSTRUCTIONS FOR USEMagnesium Calibration

Calibration






The VITROS Mg DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Calculations


each slide lot, magnesium concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.

Validity of a CalibrationCalibration parameters are automatically assessed by the VITROS DT60/DT60 ll.Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.


Reportable (Dynamic) Range for Mg DTConventional (mgfdL)


0.1-2.9



I Values assigned to the VITROS Chemistry Products DT Calibrator Kit for magnesium are traceable to the Certified

NIST (National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 929. TheOrtho-Clinical Diagnostics calibration laboratory uses SRM" 929 to calibrate the flame atomic absorption spectroscopy method9

to support magnesium value assignment for the VITROS DT Calibrator Kit.


| •••':•'••• Handle quality control materials as biohazardous material.

• Choose control levels that check the clinically relevant range.

• Analyze quality control materials in the same manner as patient samples, before or during patient sample processing.

• To verify system performance, analyze control materials:- After calibration.

- According to local regulations or at least once each day that the test is being performed.

- After specified service procedures are performed. Refer to the operator's manual for your VITROS DT60/DT60IISystem.




NlgDTMagnesium

• For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principlesand Definitions; Approved Guideline-Second Edition™ or other published guidelines.




• Control materials other than VITROS DT Controls I & II may show a difference when compared with other magnesiummethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




This reference interval is the central 95% of results from an internal study of 288 apparently healthy individuals from a workingpopulation (58 females and 230 males).

Reference Interval for Mg DTConventional Units (mg/dL)


0.7-1.0


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report magnesium results in conventional and SI units.

Reporting Units and Unit Conversion for Mg DTConventional Units

mg/dLSI Units



The VITROS Mg DT Slide method was screened for interfering substances following NCCLS Protocol EP7." The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Calcium

Substances for Mg DTInterferent

Concentration


Magnesium Concentration

Conv. (mg/dL)2.3

SI (mmol/L)0.9

AverageConv. (mg/dL)

+0.3

Bias

SI (mmol/L)+0.12

Other LimitationsCertain drugs and clinical conditions are known to alter magnesium concentrations in vivo. For additional information, refer toone of the published summaries.1213


NlgDTMagnesium

VITFJLpS Q



Method Comparison



Method Comparison for Mg DT: Serum

Conventional Units

I10ot


wO

SI Units

y - x


Method Comparison for Mg DT: Serum

DT60 II Sys.tem vs.950 System

n

63

Slope

0.98


0.998

Conventional


0.3-6.9

Units (mg/dL)

Intercept Sy.x

0.11 0.14

SI Units (mmol/L)


0.14-2.85 0.05

Sy.x

0.06



Precision for Mg DT: Serum

System

VITROS DT60 II


MeanCone.

2.3

5.0

WithinDay SD*

0.05

0.08

WithinLab SD**

0.06

0.12

SI

MeanCone.

1.0

2.0

Units (mmol/L)

WithinDay SD*

0.02

0.03

WithinLab SD**

0.02

0.05

WithinLab

CV%**

2.5

2.4

No.Observ.

88

88

No.Days

22

22




MgDTMagnesium



Evaluation of "Plasma Separator Tubes (PST)" Clin. Chem. 35:151-153; 1989.4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.8. Young DS. Effects of Preanalytical Variables on Clinical Laboratory Tests. Washington D.C.: AACC Press; 4-120; 1993.9. Kaplan L, Pesce A. Clinical Chemistry: Theory, Analysis, and Correlation. CV Mosby; 1069; 1984.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB. Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D C : AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


NlgDTMagnesium



Version1.0


> New format> New organization and sections consistent with IVD Directive> Specimens Recommended - plasma: updated to heparin> Limitations of the Procedure-removed inorganic phosphorous> Method Comparison -updated all comparisons and plots

Precision: updated valuesReferences - added all except 6, 8






' Ortho-Clinical DiagnosticsH company



Chemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products Na+ DT Slides

Na DTSodium

Intended UseFor in vitro diagnostic use only.VITROS Na+ DT Slides quantitatively measure sodium (Na+) concentration in serum and plasma.

Summary and Explanation of the TestSodium is the major cation of extracellular fluids. The kidneys regulate sodium content of the body. Low sodium levels may becaused by excessive urine loss, diarrhea, Addison's disease, and renal tubular disease. High sodium levels may occur insevere dehydration, some types of brain injury, diabetic coma, and excessive intake of sodium salts.1

Principles of the ProcedureThe VITROS Na+ DT Slide method is performed using the VITROS Na+ DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS Na* DT Slide is a multilayered, analytical element coated on a polyester support that uses direct potentiometry2

for measurement of sodium ions. The slide consists of two ion-selective electrodes, each containing methyl monensin (anionophore for sodium), a reference layer, and a silver layer and a silver chloride layer coated on a polyester support.A drop of patient sample and a drop of VITROS DT Reference Fluid on separate halves of the slide results in migration of bothfluids toward the center of the paper bridge. A stable liquid junction is formed that connects the reference electrode to thesample electrode.Each electrode produces an electrochemical potential in response to the activity of sodium. The potential difference betweenthe two electrodes is proportional to the sodium concentration in the sample.

Test Type and ConditionsTest Type and Conditions for Na* DT

Test Type

Potentiometric


DTE/DTE II


90 or 180 seconds*

Temperature

25°C (77°F)

Drop VolumeSample:

10 uLReference

Fluid: 10 uLAssay time is determined by the Calibration Data Module (CDM).



NaDTSodium




Silver 0.4 mg; silver chloride 0.2 mg; sodium chloride 0.3 mg andmethyl monensin 50 ng.

Other ingredientsBinders, buffer, plasticizers, stabilizer, surfactants and nickel.

Slide Diagram

Slide Handling

CAUTION:

___ 1

*_- 3

_ -— *

"'Y ~.7

1. Upper slide mount2. Paper Bridge3. Ion-selective

membrane• Methyl monensin

4. Reference layer• NaCI• Buffer, at pM 5.6

5. Silver, silver chloridelayer



Slide Preparation

IMPORTANT: The slide must reach room temperature, 18°-28 °C (64 °-82 f), before the wrapper isopened.





VITROS Na* DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for Na* DTSlidesUnopened

Opened




Specimens Recommended• Serum• Plasma:4 Heparin (Sodium heparin will increase the measured sodium value by approximately 0.5 mmol/L.)



Serum and Plasma

Specimen Collection and PreparationCollect specimens using standard laboratory procedures.6'7



INSTRUCTIONS FOR USE NaDTTesting Procedure Sodium



• Centrifuge specimens and remove the serum from the cellular material within 2 days of collection.9


Specimen Storage and Stability for Na* DT: Serum and Plasma9



<-18°C(<0°F)

Stability<4 days<1 week<6 months

Testing Procedure

Materials Provided• VITROS Chemistry Products Na* DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products DT Reference Fluid• VITROS DTE Dual Sample Cups. VITROS DTE Pipette



Sample DilutionSodium concentrations outside the reportable (dynamic) range are not expected. Diluted samples should not be analyzed withVITROS Na* DT Slides because dilution changes both the concentration of solids in plasma water and the ionic strength of thesample.

Calibration




MOTE: Calibrate sodium in duplicate by running each bottle twice.

When to CalibrateCalibrate:• When the slide lot number changes.• When the VITROS DT Reference Fluid lot number changes.• When critical system parts are replaced due to service or maintenance.• When government regulations require.



Na DT INSTRUCTIONS FOR USESodium Quality Control

The VITROS Na* DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsThe VITROS DT60/DT60 II Chemistry System measures the potential difference in millivolts between the two electrodes of apotentiometric slide—one in contact with the sample to be analyzed and the other in contact with the electrolyte reference fluid.A linear relationship exists between the measured potential difference observed on the slide and the logarithm of sodiumconcentration, i.e. the Nernst equation for ion-selective electrodes. Once the calibration has been established for each slide lot,unknown sodium concentrations for a given sample can be determined using the software-resident math model and themeasured potential difference.



Reportable (Dynamic) Range for Na* PTConventional and SI Units (mmol/L)

95-215


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for sodium are traceable to the Certified NIST (NationalInstitute of Standards and Technology) Reference Material, SRM" (Standard Reference Material) 919a. The Ortho-ClinicalDiagnostics calibration laboratory uses SRM" 919a to calibrate the flame atomic emission spectroscopy method10 to supportsodium value assignment for the VITROS DT Calibrator Kit.

Quality Control





System.


and Definitions; Approved Guideline-Second Edition'1'' or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.



• Control materials other than VITROS DT Controls I & II may show a difference when compared with other sodium methodsif they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.



INSTRUCTIONS FOR USE NaDTExpected Values and Reporting Units Sodium



Reference Interval• The serum reference interval is the central 95% of results from an internal study of 60 apparently healthy adults from a workingI population. No significant differences between results from the male and female populations were observed.

Reference Interval for Na+ DTConventional and SI Units (mmol/L)

137-145


Reporting UnitsThe VITROS DT60/DT60 II Chemistry System may be programmed to report sodium results in conventional and SI units.

Reporting Units for Na* DTConventional and SI Units

mmol/L


Specimens contaminated with cationic surfactants show a positive interference (e.g., benzalkonium chloride at 10 mg/L causeda 50 mmol/L apparent increase in sodium).

NOTE: Heparinized catheters may contain benzalkonium chloride. Specimens drawn throughthese catheters should not be used.

Other LimitationsCertain drugs and clinical conditions are known to alter sodium concentration in vivo. For additional information, refer to one ofthe published summaries.12'13


NaDTSodium



Method ComparisonThe plots and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzedusing the Flame Photometry comparative method.10 Testing followed NCCLS Protocol EP9."The table also shows the results of a comparison of the VITROS Na* DT Slide at an assay time of approximately 90 secondswith the VITROS Na+ DT Slide at an assay time of approximately 180 seconds.

Method Comparison for Na* DT: Serum


250 •

200

150

100

50

50 100 150 200 250Comparative Method: Flame Photometry

(mmol/L)

Method Comparison for Na

DT60II System vs.comparative method

90 seconds vs.180 seconds

n

58

59

*DT:

Slope

0.99

0.98

Serum


0.960

0.999

Conventional and SI

Range of Sample Cone.

117-166

101-185

Units (mmol/L)

Intercept

-1.43

+2.38

Sy.x

2.97

0.85

PrecisionPrecision was evaluated with quality control materials on the VITROS DT60 II System following NCCLS Protocol EP5.'6


Precision for Na* DT: Serum

System

VITROS DT60 II


Mean Cone

115

133

. Within Day SD* Within Lab SD**

0.7 1.3

0.8 1.4

Within Lab CV%**

1.2

1.0

No. Observ.

87

88

No. Days

22




Na DTSodium

References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 614-616; 1987.2. Siggard-Anderson O. Electrochemistry, in Tietz NW (ed). Textbook of Clinical Chemistry. Philadelphia: WB Saunders; 110-125; 1986.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and




1991.8. Slockbower JM, BlumenfeldTA (ed.). Collection and Handling of Laboratory Specimens. Philadelphia: Lippincott Co; 201; 1983.9. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.10. Velapoldi R.A., et al. A reference method for the determination of sodium in serum. National Institute of Standards and Technology

Special Publication 260-60, Gaithersburg. MD, 1978.


12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

REJF

Do Not Reuse


Lot Number




Manufacturer

BEP | Authorized Representative

Contains Sufficient for "n"\ / Tests


Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


Ha DTSodium



Version1.0

Description of Technical Changes*> New format> New organization and sections consistent with IVD Directive• Reference Interval - corrected the sample size> Limitations of the Procedure - removed the statement regarding ethanol> Method Comparison - updated all data and the plot> Precision - updated all values> References - added all






' Ortho-Clinical DiagnosticsjjjotmHm company



VITRChemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products NBIL DT Slides

NBIL DTNeonatal Bilirubin

Intended UseFor in vitro diagnostic use only.VITROS NBIL DT Slides quantitatively measure total bilirubin concentration in serum and plasma in neonates during the firstweeks of life.

Summary and Explanation of the TestNeonatal bilirubin (NBIL) is increased in erythroblastosis fetalis (hemolytic disease of the newborn), which causes jaundice inthe first two days of life. Other causes of neonatal jaundice include physiologic jaundice, hematoma/hemorrhage,hypothyroidism, and obstructive jaundice.

Principles of the ProcedureThe VITROS NBIL DT Slide method is performed using the VITROS NBIL DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS NBIL DT Slide is a multilayered, analytical element coated on a polyester support. The analysis is based on amodification of the classic diazo reaction.1

A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thislayer provides a reflective background for measuring the diazo products of bilirubin and contains all reagents necessary todetermine total bilirubin in neonates.The method uses dyphylline to dissociate unconjugated bilirubin from albumin. Unconjugated bilirubin and conjugated bilirubinsubsequently react with the diazonium salt 4-(A/-carboxymethylsulfonyl) benzenediazonium hexafluorophosphate to produceazobilirubin chromophores that have similar molar absorptivities.The change in reflection density is proportional to the bilirubin concentration in the sample.

Reaction Sequence

neonatal bilirubindyphylline

[4-(N-carboxymethylsulfonyl)-benzenediazonium hexafluorophosphate]azobilirubin chromophores

Test Type and ConditionsTest Type and Conditions for NBIL DT



DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL



NBILDTNeonatal Bilirubin


Reagents


Dyphylline 0.5 mg and 4-(N-carboxymethylaminosulfonyl) benzene diazoniumhexafluorophosphate 57 (.ig.

Other ingredientsPigment, binders, buffer, mordant, surfactants and stabilizer.

Slide Diagram

Slide Handling

CMJTiGM:

2

_ 3

~~~~ ~ 4

_ _ _ _ _ _ S

1.2.

3.

4.5.

Upper slide mountSpreading layer (BaSCXtl• dyphylline• diazonium saltReagent layer• buffer, pH 3.0Support layer *Lower slide mount


Slide Preparation


Do not use unopened slides that have been at room temperature, 18 "-28 °C(64°-82°F) for >48 hours.




VITROS NBIL DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for NBIL DTSlidesUnopened

Opened



Specimen RequirementsWARNiNG: Handle specimens as biohazardous material.


I • Plasma:3 Heparin



Specimens Not Recommended• Samples from patients other than neonates (newborns) are not recommended. These samples should be analyzed on the

VITROS TBIL DT Slide.

Serum and Plasma

Specimen Collection and PreparationCollect specimens using standard laboratory procedures.66



INSTRUCTIONS FOR USE NRIL DTTesting Procedure Neonatal Bilirubin

Special Precautions• For the effect of sample hemolysis on test results, refer to "Limitations of the Procedure."• Protect specimens from light.• Direct exposure to sunlight is reported to cause as much as a 50% loss of serum bilirubin in one hour, especially when the

specimen is kept in capillary tubes.1

• Exposure to normal laboratory light can result in a significant loss of serum bilirubin after two to three hours.





Specimen Storage and Stability for NBIL DT: Serum7


Temperature18°-28°C(64O-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stability<4 hours<7 days<6 months


• VITROS Chemistry Products NBIL DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA• VITROS DT Pipette



Sample DilutionIf bilirubin concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with VITROS 7% BSA.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's bilirubin concentration.

Calibration







VI"TFj[Cp"S | * |

NBILDT INSTRUCTIONS FOR USENeonatal Bilirubin Quality Control

The VITROS NBIL DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 555 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, neonatal bilirubin concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for NBIL DTConventional (mg/dL)


2-342


Traceability of the CalibrationI Values assigned to the VITROS Chemistry Products DT Calibrator Kit for neonatal bilirubin are traceable to internal Master

Lots of VITROS Chemistry Products BuBc Slides and VITROS Calibrator Kit 4. Performance of the Master Lot of VITROSi BuBc slides was initially established by comparison to the High Performance Liquid Chromatography (HPLC) method described

by Lauff et al.8 The Ortho-Clinical Diagnostics (OCD) calibration laboratory uses the Master Lot of VITROS BuBc Slides andMaster Lot of VITROS Calibrator Kit 4 for neonatal bilirubin value assignment for new lots of the VITROS DT Calibrator Kit.


| ' Handle quality control materials as biohazardous material.



System.




| IMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids for


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other neonatal bilirubinmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




NBIIDTNeonatal Bilirubin



Reference IntervalThis reference interval is the central 95% of results from a study of 40 apparently healthy neonates (average age 1.2 days) withnormal liver enzymes.

Reference Interval for NBIL DT

Neonates



17-180


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report neonatal bilirubin results in conventional andSI units.

Reporting Units and Unit Conversion for NBIL DTConventional Units

mg/dLSI Units



The VITROS NBIL Slide method was screened for interfering substances following NCCLS Protocol EP7.10 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Levodopa

4-Aminosalicylic acid

Phenazopyridine

Biliverdin

Hemoglobin

Substances for NBIL DTInterferent

Concentration

300 ug/mL**300 |.ig/mL**

8 mg/dL8 mg/dL8 mg/dL8 mg/dL4 mg/dL4 mg/dL

100 mg/dL200 mg/dL400 mg/dL100 mg/dL200 mg/dL400 mg/dL100 mg/dL200 mg/dL400 mg/dL

(1.52mmol/L)**(1.52 mmol/L)**(0.52 mmol/L)(0.52 mmol/L)(0.3 mmol/L)(0.3 mmol/L)

(69 umol/L)(69 umol/L)

d g/L)(2 g/L)(4 g/L)(1 g/L)(2 g/L)(4 g/L)(1 g/L)(2 g/L)(4 g/L)

Bilirubin

Conv. (mg/dL)0.417.80.417.60.4

17.40.316.40.50.5

0.5

10.510.510.515.015.015.0

Cone.SI (Mmol/L)

7304

7301

7298

5280999

180180180257257257

Bias

Conv. (mg/dL)+1.4-9.4+0.4+2.5+3.8+3.5

+0.5+0.7+0.1+0.4+ 1.3-1.0-1.2-1.0-1.2-1.7-1.9

SI (Mmol/L)+24-161+7

+43+65+60+9+12+2+7

+22

-17-21-17-21-29-32

It is possible that other interfering substances may be encountered. These results are representative; however, your results may differsomewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.This concentration may be present in the treatment of Parkinson's disease.


NBIL DTNeonatal Bilirubin


Other Limitations• It is important to maintain consistency in bilirubin methodology. If VITROS NBIL DT Slides are initially used to monitor a

patient, continue to monitor that patient with VITROS NBIL DT Slides. Do not switch to VITROS TBIL DT Slides regardlessof the patient's age.

• Results from the VITROS NBIL DT Slide may not be accurate at elevation greater than 6000 feet (approx. 1800 meters)above sea level.

• Cefotiam (Pansporin) has been reported to show very large positive biases on VITROS NBIL DT Slide results.11 This drugis normally cleared through the kidney. Biases will be largest in specimens from patients with renal insufficiency and maybe as large as 5 mg/dL (86 |.imol/L).

• Drugs and other compounds that are diazo-reactive or that absorb light in the vicinity of 555 nm may interfere.• Certain drugs and clinical conditions are known to alter total bilirubin concentration in vivo. For additional information, refer

to one of the published summaries.1213


Method ComparisonI The plot and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzedI using the VITROS 950 System and VITROS BuBc Slides to calculate NBIL. Testing followed NCCLS Protocol EP9.14

Method Comparison for NBIL DT: Serum

Conventional Units

25

t 20Er ! *>

f£ 10QWQ

SI Units

Oa:

>

400

300

200

100

10 15 20Comparative Method: VITROS 950 System

(mg/dL)


(Mmol/L)

Method Comparison for NBIL DT: Serum


n

104

Slope

0.99


0.998

Conventional


0.1-18.2

Units (mg/dL)

Intercept Sy.x

0.10 0.32

SI Units


2-312

(umol/L)

Intercept

1.63

Sy.x

5.48



Precision for NBIL DT: Serum

System

VITROS DT60 II


MeanCone.

1.3

14.5

WithinDay SD*

0.10

0.22

WithinLab SD**

0.10

0.29

SI

MeanCone.

23

248

Units (Mmol/L)

WithinDay SD*

1.6

3.8

WithinLab SD**

1.8

5.0

WithinLab

CV%**

7.8

2.0

No.Observ.

84

84

No.Days

21





References1. Routh Jl: Liver Function. In Tietz NW(ed). Fundamentals of Clinical Chemistry, ed 2. Philadelphia; WB Saunders; 1037; 1976.

2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids andTissue: Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.

3. Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, andEvaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.

4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.8. Lauff JJ, Kasper ME, Wu T.W, Ambrose RT. Isolation and preliminary characterization of a fraction of bilirubin in serum that is firmly

bound to protein. Clin. Chem. 28:629-637, 1982.

9. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions: Approved Guideline-Second Edition.NCCLS Document C24. Wayne, PA: NCCLS; 1999.

10. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.11. Pickert A, Riedlinger I, Stumvill M. Interference of Cefotiam with Total Bilirubin Measured with the Ektachem Analyzer. Clin. Chem.

38:599-600; 1992.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples: Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number

Q | L | Manufacturer's SerialO n ! Number

"^rzi Catalog Number orMfcX [ Product Code


Manufacturer

BC mf I Authorized Representative

\ y / Contains Sufficient for "n"V Tests

XFor In Vitro Diagnostic Use

Store At or Below

Store At or Above

Store Between



Keep Dry

This end up





Version1.0

Description of Technical Changes*> New format> New organization and sections consistent with IVD Directive> Known Interfering Substances - updated values; added phenazopyridine and

hemoglobin; changed 5-aminosalicylic acid to 4-aminosalicylic acid> Method Comparison - updated all comparisons and the plots> Precision - updated all values> References - added all except 6, 12,13




C€

I EC j REP IOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland





VITRChemhtry

INSTRUCTIONS FOR USEVITROS Chemistry Products NH3 DT Slides

NHsDTAmmonia

Intended UseFor in vitro diagnostic use only.VITROS NH3 DT Slides quantitatively measure ammonia (NH3) concentration in plasma.

Summary and Explanation of the TestAmmonia is a waste product of protein catabolism; it is potentially toxic to the central nervous system. Increased plasmaammonia may be indicative of hepatic encephalopathy, hepatic coma in terminal stages of liver cirrhosis, hepatic failure, acuteand subacute liver necrosis, and Reye's syndrome. Hyperammonemia may also be found with increasing dietary proteinintake.1

In addition to its use for endogenous ammonia determination, the VITROS NH3 DT Slides are also used in conjunction withVITROS CREA DT Slides for creatinine as described in the VITROS Chemistry Products CREA DT Instructions for Use (blank-corrected method).

Principles of the ProcedureThe VITROS NH3 DT Slide method is performed using the VITROS NH3 DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS NH3 DT Slide is a multilayered, analytical element coated on a polyester support.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.Water and nonproteinaceous components travel to the underlying buffered reagent layer, and the ammonium ions areconverted to gaseous ammonia. The semipermeable membrane allows only ammonia to pass through and prevents buffer orhydroxyl ions from reaching the indicator layer. After a fixed incubation period, the reflection density of the dye is measuredusing the white background of the spreading layer as a diffuse reflector.

Reaction Sequence

NH3 + bromphenol blue(ammonia indicator)

blue dye

Test Type and ConditionsTest Type and Conditions for NH3 DT



DT60/DT60 II



Wavelength605 nm

Sample DropVolume

10 uL



NHaDTAmmonia


Reagents

Slide Ingredients


Bromphenol blue 27 pg.

Other ingredientsPigment, binders, surfactants, buffer and stabilizer.

Slide Diagram

Slide Handling

N:

- 4

"- 5


1. Upper slide mount2. Spreading layer (TIO2)3. Reagent layer

• buffer, pH 9.34. Semlpermeable

membrane5. Indicator layer

• bromphenol blue6. Support layer7. Lower slide mount

Slide Preparation

The slide must reach room temperature, 18°-28 °C (64 °-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 -28 °C(64 °-82 °F) for >48 hours.



Slide Storage and StabilityVITROS NH? DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for NH3 DTSlidesUnopened

Opened




Specimens Recommended for Measurement of AmmoniaI • Plasma:3 EDTAI Meparin (except ammonia heparin)

NOTE: Serum should not be used for ammonia measurements because ammonia isproduced during the clotting process.3

I IMPORTANT: Certain collection devices have been reported to affect other analytes and tests."I Confirm that your collection devices are compatible with this test.

Specimens Recommended for Measurement of Creatinine Where Ammonia Serves as BlankI • Plasma:3 EDTA| Heparin (except ammonia heparin)

• Serum

I IMPORTANT: Certain collection devices have been reported to affect other analytes and tests4



INSTRUCTIONS FOR USE NHsDTTesting Procedure Ammonia


Plasma or Serum

Specimen Collection and Preparation

Piasma• Collect specimens using standard laboratory procedures.5 6

• Keep on ice until analysis.5 6

Serum• Collect specimens using standard laboratory procedures.5 6

• Do not put specimens on ice.

Patient Preparation

• No special patient preparation is necessary.

Special Precautions

NOTE: Avoid using ammonia-containing cleaning solutions or hand creams in the area

around the analyzer.

• Centrifuge specimens and remove the plasma from the cellular material within 15 minutes of collection.3

Specimen Handling and Storage\fi Handle specimens as biohazardous material.

• Handle and store specimens in stoppered containers to avoid contamination and evaporation.• Mix samples by gentle inversion and bring to room temperature, 18°-28°C (64°-82°F); analyze immediately.

Specimen Storage and Stability for NH3 DT: Plasma3


Temperature18°-28°C(64O-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)

Stabilitynot recommended<3 hours<24 hours


. VITROS Chemistry Products NH3 DT Slides




Sample DilutionIf ammonia concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's ammonia concentration.


NH.DT INSTRUCTIONS FOR USEAmmonia Calibration

Calibration

Required CalibratorsVITROS Chemistry Products DT Calibrator Kit, bottles 1, 2, 3, and 4

Calibrator Preparation, Handling, and Storage

NOTE: To avoid ammonia formation, calibrator fluids should be prepared only when ready tocalibrate and should be run within 1 hour after preparation.

NOTE; Because ammonia is produced in the VITROS BUN/UREA DT Slide reaction, theanalyzer will display a warning message "ANALYER READY—NO CREA/NH3" duringcalibration of VITROS BUN/UREA DT Slides. Therefore, it is recommended thatcreatinine and ammonia be the first tests calibrated after the preparation of calibratorfluids.



When to Calibrate

NOTE: The VITROS CREA DT test is dependent on correct calibration of the VITROS NH3 DTSlides used as blanks. Therefore, the NH3 DT Slides must be calibrated wheneverCREA DT Slides are calibrated.

Calibrate:• When the slide lot number changes.• When critical system parts are replaced due to service or maintenance.• When government regulations require.


The VITROS NH3 DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Calculations


each slide lot, ammonia concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.

Validity of a Calibration

I Calibration parameters are automatically assessed by the VITROS DT60/DT60 II Chemistry System against a set of quality

parameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.

Reportable (Dynamic) RangeReportable (Dynamic) Range for NH3 DTConventional and SI Units (umol/L)

1-500


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for ammonia are traceable to gravimetrically preparedstandards made from reagent grade ammonium sulfate. The Ortho-Clinical Diagnostics calibration laboratory uses thegravimetrically prepared standard to calibrate an enzymatic procedure using glutamate dehydrogenase to measure ammonia7

to support value assignment for the VITROS DT Calibrator Kit.


INSTRUCTIONS FOR USE NHsDTQuality Control Ammonia


| : llfJG Handle quality control materials as biohazardous material.



System.






• Control materials other than VITROS DT Controls I & II may show a difference when compared with other ammoniamethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




Reference IntervalThis reference interval is the central 95% of results from an internal study of 60 apparently healthy adults from a workingpopulation (34 females and 26 males). No significant differences between results from the male and female populations wereobserved.

Reference Interval for NH3 OTConventional and SI Units (umol/L)

9-30



The VITROS DT60/DT60 II Chemistry System may be programmed to report ammonia results in conventional and SI units.

Reporting Units for NH3 DTConventional and SI Units

umol/L


NHaDTAmmonia



Known Interferences• Glucose at 600 mg/dL (33.3 mmol/L) may cause a decrease of 40 umol/L j n ammonia concentration.• If an NH3 slide follows a BUN/UREA DT Slide immediately, high BUN values may increase ammonia values.

I - A BUN value up to 40 mg/dL (14.3 mmol/L) may increase ammonia values by 34 umol/L.- BUN values over 40 mg/dL (14.3 mmol/L) will cause the analyzer to print an R18 code next to the ammonia result.

Discard the result and repeat the sample without the BUN/UREA DT Slide in the incubator.

IMPORTANT: NH3 DT testing should not be done when any BUN/UREA DT Slides are in theincubator.

Other LimitationsCertain drugs and clinical conditions are known to alter ammonia concentration in vivo. For additional information, refer to oneof the published summaries.9'1C


Method Comparison



Method Comparison for NH3 DT


500

400

300

200

£

ooc I 00 •

100 200 300 4li(i

Comparative Method: VITROS 950 System(Mmol/L)

500

Method Comparison for NH3 DT


n

59

Slope

1.02


0.997

Conventional and SI

Range of Sample Cone.

5-460

Units (Mmol/L)

Intercept

3.71

Sy.x

10.73


gj VITRCpS


NHaDTAmmonia



Precision for

System

VITROS DT60

NH3DT

II

Conventional and SI Units (pmol/L)

Mean Cone.

69

235


6.3 6.8

14.6 16.2

Within Lab CV%**

10.0

6.9

No. Observ.

88

88

No. Days

22

22


References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 748; 1987.



4. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.

5 NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;1991.


7. Bruce WA, Leiendecker, CM, Freier EF. Two-Point Determination of Plasma Ammonia with the Centrifugal Analyzer.Clin. Chem. 24:782; 1978.


9. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.10. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.11. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer

[ EC [ na> [ Authorized Representative

\ v / Contains Sufficient for "n"V Tests


Store At or Below

Store At or Above

I

It

Store Between



Keep Dry

This end up


NHsDTAmmonia



Version1.0

Description of Technical Changes*> New format> New organization and sections consistent with IVD Directive> Specimens Recommended - updated wording for heparin; added EDTA• Specimen Storage and Stability - updated stability values> Reference Interval - updated upper limit> Limitations of the Procedure - updated interferent statements> Method Comparison - updated all comparisons and the plot> Precision - updated all data> References - added all




C€

EC i REP iOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


' Ortho-Clinical Diagnosticsa £ofMttm«^o&Mfm company



VITRChemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products PHOS DT Slides

PHOS DTPhosphorus

Intended UseFor in vitro diagnostic use only.VITROS PHOS DT Slides quantitatively measure phosphorus (PHOS) concentration in serum and plasma.

Summary and Explanation of the TestPhosphorus, as phosphate, is distributed throughout the body. Causes of high serum phosphorus include dehydration,hypoparathyroidism, hypervitaminosis D, metastases to bone, sarcoidosis, pulmonary embolism, renal failure, and diabetesmellitus with ketosis. Low serum phosphorus is found in primary hyperparathyroidism and other causes of serum calciumelevation, sepsis, vitamin D deficiency, renal tubular disorders, chronic hemodialysis, vomiting, and occasionally withdecreased dietary phosphate intake.1

Principles of the ProcedureThe VITROS PHOS DT Slide method is performed using the VITROS PHOS DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS PHOS DT Slide is a muitiiayered, analytical element coated on a polyester support. The analysis is based on thereaction of inorganic phosphate with ammonium molybdate to form an ammonium phosphomolybdate complex at acidic pH, asdescribed by Fiske and Subbarow.2 p-Methylaminophenol sulfate, an organic reductant reported by Gomori,3 reduces thecomplex to form a stable heteropoiymolybdenum blue chromophore.A drop of patient sample is deposited on the slide and is evenly distributed by the. spreading layer to the underlying layers.Phosphorus in the specimen forms a complex with ammonium moiybdate. This complex is reduced by p-methylaminophenolsulfate to give a blue complex.The concentration of phosphorus in the sample is determined by measuring the heteropoiymolybdenum blue complex byreflectance spectrophotometry.

Reaction Sequence

inorganic phosphate + ammonium molybdate

ammonium phosphomolybdate complex

pH4.2 —>• ammonium phosphomolybdate complex

p-methylaminophenol sulfate->• heteropolymolybdate blue

Test Type and ConditionsTest Type and Conditions for PHOS DT



DT60/DT60 II



Wavelength660 nm

Sample DropVolume

10 ML



PHOS DTPhosphorus


Reagents

Slide Ingredients

I

Slide Diagram

Reactive ingredients per cmp-methylaminophenol sulfate 350 ug; and ammonium molybdate 340 ug.

Other ingredientsPigment, binders, surfactants, buffer and stabilizers.

Slide Handling

CAUTiOH:

I

2

- —-__ ^__

.. - - - s

1.2.3.

4.6.

Upper slide mountSpreading layer (BaSO4)Reagent layer• p-methylaminophenol

sulfale• ammonium molybdate• buffer, pH 4.2Support layerLower slide mount


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18 °-28 °C (64 "-82 °F), before the wrapper isopened.

Do not use unopened slides that have been at room temperature, 18 °-28 "C(64°-82°F) for >48 hours.



Slide Storage and StabilityVITROS PHOS DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.


Opened

Stability for PHOS DTStorage Condition


18°-28°C(64°-82°2°-8°C (36°-46°F)<-18°C(<0°F)18°-28°C(64°-82°

F)

F)




IMPORTANT: Certain collection devices have been reported to affect other analytes and tests.e



Fluoride oxalateCitrate

• Do not use hemolyzed specimens. Hemolysis produces elevated phosphorus values due to the inorganic phosphates andphosphatases present in red blood cells.7


gl VITRI

INSTRUCTIONS FOR USE PHOS DTTesting Procedure Phosphorus

Serum and Plasma



Special Precautions• Centrifuge specimens and remove the serum from the cellular material within 4 hours of collection.10




Specimen Storage and Stability for PHOS PT: Serum and Plasma10


Temperature18°-28oC(64°-820F)2°-8°C (36°-46°F)

<-18°C (<0°F)



• VITROS Chemistry Products PHOS DT Slides




Sample DilutionIf phosphorus concentrations exceed the system's reportable (dynamic) range:1. Dilute with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's phosphorus concentration.

Calibration

Required Calibrators .VITROS Chemistry Products DT Calibrator Kit, bottles 1, 2, and 4




PHOSDT INSTRUCTIONS FOR USEPhosphorus Quality Control



The VITROS PHOS DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 660 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, phophorous concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for PHOS DTConventional (mg/dL)


0.16-4.20For out-of-range samples, refer to "Sample Dilution."

Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for phosphorus are traceable to the CertifiedNIST (National Institute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 200. TheOrtho-Clinical Diagnostics (OCD) calibration laboratory uses SRM®200 to calibrate the phosphomolybdate/phenylenediaminemethod11 to support value assignment for the VITROS DT Calibrator Kit.

Quality Control


| •" Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition12 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60II Chemistry System.


INSTRUCTIONS FOR USE PHOS DTExpected Values and Reporting Units Phosphorus



• Control materials other than VITROS DT Controls I & II may show a difference when compared with other phosphorusmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilfzers, or other nonphysiological additives.




Reference IntervalThe reference interval is the central 95% of results from an internal study of 297 apparently healthy adults from a workingpopulation.

Reference Interval for PHOS DTConventional Units (mg/dL)


0.81-1.45



The VITROS DT60/DT60 II Chemistry System may be programmed to report phosphorus results in conventional and SI units.

Reporting Units and Unit Conversion for PHOS DTConventional Unitsmg/dL

SI Unitsmmol/L (mg/dL x 0.3229)


Mannitol may increase phosphorus results. At 5 mg/dL (1.6 mmol/L) phosphorus, 640 mg/dL (35 mmol/L) D-mannitol caused a10% increase.

Other LimitationsCertain drugs and clinical conditions are known to alter phosphorus concentration in vivo. For additional information, refer toone of the published summaries.13 u


PHOSDTPhosphorus



Method ComparisonI The plots and table show the results of a comparison of samples analyzed on the VITROS DT60 II System with those analyzed

using the Fiske and Subbarow comparative method2, modified by Dryer, Tamnes, and Routh.11 Testing followed NCCLSProtocol EP9.15

Method Comparison for PHOS DT: Serum

Conventional Units

14-

la-

ic -

s '

6 -

4 •

2 .

0

|

D

2

0 10 12 14Comparative Method: Modified Fiske and Subbarow

(mg/dL)

QCOO

SI Units

Comparative Method: Modified Fiske and Subbarow(mmol/L)

Method Comparison for PHOS DT: Serum


n

69

Slope

0.96


0.982

Conventional


1.3-12.6

Units (mg/dL)

Intercept Sy.x

0.22 0.63

SI Units


0.43-4.08

(mmol/L)

Intercept

0.07

Sy.x

0.20

PrecisionPrecision was evaluated with quality control materials on VITROS the DT60/DT60 II System following NCCLS Protocol EP5.16


Precision for PHOS DT: Serum

System

VITROS DT60 II

Conventional Units

MeanCone.

3.2

7.0

WithinDay SD*

0.04

0.07

(mg/dL)

WithinLab SD**

0.08

0.14

SI

MeanCone.

1.03

2.27

Units (mmol/L)

Within WithinDay SD* Lab SD**

0.01

0.02

0.03

0.05

WithinLab

CV%**

2.6

2.0

No.Observ.

84

84

No.Days

21

21




PHOSDTPhosphorus

References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 706-716; 1987.2. Fiske CH, Subbarow Y. The Colorimetric Determination of Phosphorus. J. Biol. Chem. 66:375; 1925.3. Gomori G. A Modification of the Colorimetric Phosphorus Determination for Use with a Photoelectric Colorimeter. J. Lab. Clin. Med.

27:955; 1942.4. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and


Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.6. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.7. Tietz NW (ed). Textbook of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 1407; 1999.8. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.11. Dryer RL, Tamnes AR, Routh JL. The Determination of Phophorous and Phosphatase with N-Phenyl-p-phenylenediamine. J. Biol.

Chem. 222:177; 1957. AACC Proposed Selected Method.12. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D C : AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D C : AACC Press; 1990.15. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

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Lot Number




Manufacturer




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PHOSDTPhosphorus


Revision HistoryDate of•Revision2003-04-30

Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive» Specimens Not Recommended - added "Do not use hemolyzed specimens."• Specimen Storage and Stability - updated data» Materials Required But Not Provided - updated materials> Quality Control Material Selection - added statement regarding ethylene glycol> Method Comparison - updated data and plots> Precision - updated data> References - added all except 2, 3, 8




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VITRCD5C hem istr y I

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products TBIL DT Slides

TBIL DTTotal Biiirubin

Intended UseFor in vitro diagnostic use only.VITROS TBIL DT Slides quantitatively measure total biiirubin (TBIL) concentration in serum and plasma.

Summary and Explanation of the TestTotal biiirubin in serum and plasma is the sum of unconjugated biiirubin (Bu), mono- and di-glucuronide conjugated biiirubin(Be), and delta biiirubin (DELB), a biiirubin fraction covalently bound to albumin.With the exception of anicteric jaundice, total serum biiirubin is invariably increased in jaundice. Causes of jaundice areprehepatic, resulting from various hemolytic diseases; hepatic, resulting from hepatocellular injury or obstruction; andposthepatic, resulting from obstruction of the hepatic or common bile ducts.'

Principles of the ProcedureThe VITROS TBIL DT Slide method is performed using the VITROS TBIL DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS TBIL DT Slide is a multilayered, analytical element coated on a polyester support. The analysis is based on amodification of the classic diazo reaction.2

A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Thislayer provides a reflective background for measuring the diazo products of biiirubin and contains all reagents necessary todetermine total biiirubin.The method uses dyphylline to dissociate unconjugated biiirubin from albumin. Unconjugated biiirubin, conjugated biiirubin, andalbumin-linked biiirubin (delta) subsequently react with the diazonium salt 4-(A/-carboxymethylsulfonyl) benzenediazoniumhexafluorophosphate to produce azobilirubin chromophores that have similar molar absorptivities.The change in reflection density is proportional to the total biiirubin concentration present in the sample.

Reaction Sequence

total biiirubin(Bu, Be, and DELB)

dyphylline

[4-(A/-carboxymethylsulfonyl)-benzenediazonium hexafluorophosphate]azobilirubin chromophores

Test Type and ConditionsTest Type and Conditions for TBIL DT



DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL



TBILDTTotal Bilirubin


Reagents

Slide Ingredients


Dyphylline 0.5 mg and 4-(N-carboxymethylaminosulfonyl) benzene diazoniumhexafluorophosphate 57 ^g.

Other ingredientsPigment, binders, buffer, mordant, surfactants and stabilizer.

Slide Diagram

~ • 4

. 5

1. Upper slide mount2. Spreading layer (BaSO4)

• dyphylline• diazonium salt



Slide Handling


Slide Preparation

IMPORTANT: The slide must reach room temperature, 18 "-2B °C (64 °-82 °F), before the wrapper isopened.




Slide Storage and StabilityVITROS TBIL DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.


Opened

and Stability for TBIL DTStorage

Room temperatureFrozenRoom temperature

Condition18°-28°C(64<-18°C (<0°F18°-28°C(64

°-82°

°-82°

F)

F)




NOTE: Do not use this slide for specimens from neonatal patients less than 14 days old.Refer to "Limitations of the Procedure."

IMPORTANT: Certain collection devices have been reported to affect other analytes and tests.s


Serum and Plasma




INSTRUCTIONS FOR USE TBIL DTTesting Procedure Total Bilirubin

Special Precautions• For the effect of sample hemolysis on test results, refer to "Limitations of the Procedure."• Protect specimens from light.• Direct exposure to sunlight is reported to cause as much as a 50% loss of serum bilirubin in one hour, especially when the

specimen is kept in capillary tubes.2

• Exposure to normal laboratory light can result in a significant loss of serum bilirubin after two to three hours.• Centrifuge specimens and remove the serum from the cellular material within 4 hours of collection.8


WfiMUM(> Handle specimens as biohazardous material.


Specimen Storage and Stability for TBIL DT: Serum8



<-18°C(<0°F)



• VITROS Chemistry Products TBIL DT Slides


| • VITROS Chemistry Products 7% BSA or reagent-grade water• VITROS DT Pipette



Sample DilutionIf total bilirubin concentrations exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with VITROS 7% BSA or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's total bilirubin concentration.

Calibration







TBILDT INSTRUCTIONS FOR USETotal Bilirubin Quality Control

The VITROS TBIL DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is measured at 555 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, total bilirubin concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for TBIL DTConventional (mg/dL)


2-342



I Values assigned to the VITROS Chemistry Products DT Calibrator Kit for total bilirubin are traceable to the Certified NIST

(National Institute of Standards and Technology) Reference Material, SRM" (Standard Reference Material) 916a. TheOrtho-Clinical Diagnostics (OCD) calibration laboratory uses SRM 916a to calibrate the NCCLS credentialed Jendrassik-Grofmethod9 to support total bilirubin value assignment for the VITROS DT Calibrator Kit.

Quality Control





System.


and Definitions; Approved Guideline-Second Edition'10 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


I IMPORTANT; VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids for


• Control materials other than VITROS DT Controls I & II may show a difference when compared with other total bilirubinmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.



la V |T.S)INSTRUCTIONS FOR USEExpected Values and Reporting Units




This reference interval is the central 95% of results from a study of 110 apparently healthy adults with normal liver enzymesfrom a working population (85 females and 25 males).

Reference Interval for TBIL DTConventional Units (mg/dL)


3-22


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report total bilirubin results in conventional and SI units.

Reporting Units and Unit Conversion for TBIL DTConventional Units

mg/dLSI Units



The VITROS TBIL DT Slide method was screened for interfering substances following NCCLS Protocol EP7.11 The followingsubstances, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Levodopa

4-Aminosalicylic acid

Phenazopyridine

Biliverdin

Hemoglobin

Substances for TBIL DTInterferent

Concentration

300 ng/mL**300 ug/mL**

8 mg/dL8 mg/dL8 mg/dL8 mg/dL4 mg/dL4 mg/dL

100 mg/dL200 mg/dL400 mg/dL100 mg/dL200 mg/dL400 mg/dL100 mg/dL200 mg/dL

. 400 mg/dL

(1.52mmol/L)**(1.52mmol/L)**(0.52 mmol/L)(0.52 mmol/L)(0.3 mmol/L)(0.3 mmol/L)

(69 umol/L)(69 umol/L)

(1 g/L)(2 g/L)(4 g/L)(1 g/L)(2 g/L)(4 g/L)(1 g/L)(2 g/L)(4 g/L)

Bilirubin Cone.Conv. (mg/dL) SI (Mmol/L)

0.417.80.417.60.417.40.316.40.50.50.510.510.510.515.015.015.0

73047

3017

2985

280999

180180180257257257

BiasConv. (mg/dL)

+1.4-9.4+0.4+2.5+3.8+3.5+0.5+0.7+0.1+0.4+1.3-1.0-1.2-1.0-1.2-1.7-1.9

SI (Mmol/L)+24-161+7+43+65+60+9+12+2+7+22-17-21-17-21-29-32


** This concentration may be present in the treatment of Parkinson's disease.

Other Limitations• Accuracy of VITROS TBIL DT Slides results on specimens from neonates less than 14 days old has not been

demonstrated. Therefore, these specimens should be analyzed using VITROS NBIL DT Slides.• It is important to maintain consistency in bilirubin methodology. If VITROS NBIL DT Slides are initially used to monitor a

patient, continue to monitor that patient with VITROS NBIL DT Slides. Do not switch to VITROS TBIL DT Slides regardlessof the patient's age.

• Results from the VITROS TBIL DT Slide may not be accurate at elevation greater than 6000 feet (approx. 1800 meters)above sea level.


TBIIDTTotal Bilirubin

VITROS 0


Cefotiam (Pansporin) has been reported to show very large positive biases on VITROS TBIL DT Slide results.12 This drugis normally cleared through the kidney. Biases will be largest in specimens from patients with renal insufficiency and maybe as large as 5 mg/dL (86 (.imol/L).Drugs and other compounds that are diazo-reactive or that absorb light in the vicinity of 555 nm may interfere.Certain drugs and clinical conditions are known to alter total bilirubin concentration in vivo. For additional information, referto one of the published summaries.1314


Method Comparison


using the Jendrassik-Grof comparative method, Doumas modification.9

Method Comparison for TBIL DT: Serum

Conventional Units

y = x

10 15 20Comparative Method: Jendrassik-Grof Doumas Modification

(mg/dL)

400

200 300 400Comparative Method: Jendrassik-Grof Doumas Modification

(Mmol/L)

Method Comparison for TBIL DT: Serum


n

67

Slope

0.99


0.998

Conventional


0.1-17.8

Units (mg/dL)

Intercept Sy.x

0.02 0.31

SI Units (Mmol/L)


2-304 0.38

Sy.x

5.30


El VtTRtCpS





Precision for TBIL DT: Serum

System

VITROS DT60 II


MeanCone.

1.3

13.3

WithinDay SD*

0.06

0.18

WithinLab SD**

0.07

0.23

SI

MeanCone.

23

227

Units (umol/L)

WithinDay SD*

1.0

3.1

WithinLab SD**

1.2

3.9

WithinLab

CV%**

5.1

1.7

No.Observ.

88

88

No.Days

22

22


References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 730-736; 1987.2. Routh Jl: Liver Function. In Tietz NW(ed). Fundamentals of Clinical Chemistry, ed 2. Philadelphia; WB Saunders; 1037; 1976.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and


Evaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.5. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.6. NCCLS. Procedures forthe Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;



IL: College of American Pathologists; 1992.9. Doumas B.T., Bayse D.D., et al. A candidate reference method for determination of bilirubin in serum. Test for transferability. Clin.

Chem. 29; 297-301; 1983.10. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Pickert A, Riedlinger I, Stumvill M. Interference of Cefotiam with Total Bilirubin Measured with the Ektachem Analyzer. Clin. Chem.

38:599-600; 1992.

13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D C : AACC Press; 1990.15. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


Glossary of Symbols

Do Not Reuse


Lot Number




X

Manufacturer




Store At or Below

Store At or Above

mitif

Store Between



Keep Dry

This end up





Version1.0

Description of Technical Changes*• New format• New organization and sections consistent with IVD Directive• Materials Required But Not Provided and

Sample Dilution - added VITROS 7% BSA• Reference Interval - updated all data• Known interfering Substances - updated values; added hemoglobin;

changed 5-aminosalicylic acid to 4-aminosalicylic acid• Method Comparison - updated all comparisons and the plots• Precision - updated all values• References - added all except 6,13,14




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QihoClinical Diagnosticscompany

VITROS is a trademark of Ortho-Clinical Diagnostics, Inc.© Ortho-Ciinical Diagnostics, Inc., 2003.All rights reserved. Printed in USA.


[ Prodwcts

VITRII15Chemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products THEO DT Slides

THEO OTTheophylline

Intended UseFor in vitro diagnostic use only.VITROS THEO DT Slides quantitatively measure theophylline (THEO) concentration in serum and plasma.

Summary and Explanation of the TestTheophylline is a drug used in the treatment of asthma. Theophylline is an effective bronchodilator. The therapeutic and toxiceffects of theophylline are related to the plasma concentrations of the drug. Theophylline measurements are used to monitorpatient compliance and therapy and to diagnose potential overdose. Toxic effects include nausea, vomiting, diarrhea,headache, tachycardia, arrhythmias, and convulsions.'

Principles of the ProcedureThe VITROS THEO DT Slide method is performed using the VITROS THEO DT Slide and the VITROS Chemistry ProductsDT Specialty Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS THEO DT Slide is a multilayered, analytical element coated on a polyester support. The assay is based on theinhibition of beef liver alkaline phosphatase (ALKP) activity by theophylline, which acts as a potent uncompetitive inhibitor ofthis isoenzyme.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.p-Nitrophenyl phosphate (PNPP) migrates from the spreading layer to the reagent layer. If no theophylline is present, thealkaline phosphatase reaction proceeds at its maximum rate. If theophylline is present, it uncompetitively inhibits the beef liverisoenzyme, and the reaction rate is reduced. The assay is performed at pH 8.5 so that samples containing endogenous alkalinephosphatase (maximum activity at pH 10.5) will not interfere. The product, p-nitrophenol, remains in the transparent reagentlayer.The rate of change in reflection density is proportional to the theophylline concentration in the sample.

Reaction Sequence

p-nitrophenyl phosphatebeef liver ALKP

MgCI2- > p-nitrophenol + H3PO4

Test Type and ConditionsTest Type and Conditions for THEO DT

Test TypeRate


DTSC/DTSC II



Wavelength400 nm

Sample DropVolume

10 ML



THEODTTheophylline


Slide DiagramReagents

Slide Ingredients


Alkaline phosphatase (beef liver, E.C.3.1.3.1) 0.02 U; magnesium chloride 3 ug;and p-nitrophenyl phosphate 0.3 mg.

Other ingredientsPigment, binders, surfactant, buffer, enzyme cofactor, protein, stabilizer andcross-linking agent.

Slide Handling

_ 1

, 2

. 3

- $

1.2.

3.

4.5.

Upper slide mountSpreading layer (BaSO4)• p-nitrophenyl phosphateReagent layer• ALKP• buffer, pM 8.5Support layerLower slide mount


Slide Preparation


Do not use unopened slides that have been at room temperature, 18 -28 'C(64 °-82 °F) for >48 hours.



Slide Storage and StabilityVITROS THEO DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for THEO DTSlidesUnopened

Opened







Specimens Not Recommended• Plasma4 Substances that chelate magnesium such as:

- EDTA- Citrate- Fluoride oxalate




INSTRUCTIONS FOR USE THEO DTTesting Procedure Theophylline

Special Precautions





Specimen Storage and Stability for THEO DT: Serum and Plasma7



<-18°C(<0°F)

Stability<7 days<7 days<60 days


• VITROS Chemistry Products THEO DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Specialty Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II

| • VITROS Chemistry Products 7% BSA or reagent-grade water• VITROS DT Pipette



Sample DilutionIf theophylline concentrations exceed the system's reportable (dynamic) range:

I 1. Dilute the sample with VITROS 7% BSA or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's theophylline concentration.

Calibration





THEODT INSTRUCTIONS FOR USETheophylline Quality Control

When to CalibrateCalibrate:• When the slide lot number changes.• ' When critical system parts are replaced due to service or maintenance.• When government regulations require.


The VITROS THEO DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60II Chemistry System.

CalculationsReflectance from the slide is read at 400 nm during the incubation period, and the rate of change in reflectance is calculated.Once a calibration has been performed for each slide lot, theophylline concentration in unknown samples can be determinedusing the software-resident rate math model and the change in reflectance calculated for each unknown test slide.


Re portable (Dynamic) Range

Reportable (Dynamic) Range for THEO DTConventional Units (ug/mL)


5.6-222.0


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Specialty Calibrator Kit for theophylline are traceable to gravimetricallyprepared standards made from reagent grade theophylline. The Ortho-Clinical Diagnostics calibration laboratory uses thegravimetrically prepared standard to calibrate an HPLC (High Performance Liquid Chromatography) method for theophylline8 tosupport value assignment for the VITROS DT Specialty Calibrator Kit.

Quality Control


| , • < . Handle quality control materials as biohazardous material.

• Choose control levels that check the clinically relevant range.• Analyze quality control materials in the same manner as patient samples, before or during patient sample processing. .• To verify system performance, analyze control materials:


System.





THEO DTTheophylline

Quality Control Material SelectionVITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

Control materials other than VITROS DT Controls I & II may show a difference when compared with other theophyllinemethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.

Quality-control and proficiency survey specimens that contain salicylate may show a positive bias compared with theirtarget theophylline concentrations. Refer to "Limitations of the Procedure."Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and StorageRefer to the instructions for use for VITROS Chemistry Products DT Control I & I or to other manufacturer's product literature.


This reference interval is based on an external study.10

Reference Interval for THEO DT

Therapeutic rangeConventional Units (ug/mL)


55.5-111.0

Each laboratory should confirm the validity of these intervals for the population it serves.In some cases the most effective therapeutic concentration may be outside this range. Monitor patients for efficacy of treatmentand for adverse symptoms.


The VITROS DT60/DT60 II Chemistry System may be programmed to report theophylline results in conventional and SI units.

Reporting Units and Unit Conversion for THEO DTConventional Units

ug/mLSI Units

umol/L (ug/mL x 5.55)


• Uremic specimens have shown positive biases of 3-5 ug/mL (17-28 umol/L) in the therapeutic range for theophylline.The VITROS THEO DT Slide method was screened for interfering substances following NCCLS Protocol EP7.1' Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering Substances for THEO DT

Interferent*

SalicylateAlkaline Phosphatase


30mg/dL (2.17 mmol/L)700 U/L

Theophylline Concentration

Conv. (ug/mL)2020

SI (umol/L)

111111

BiasConv. (ug/mL)

3.02.0

SI (pmol/L)16.711.1


Other LimitationsCertain drugs and clinical conditions are known to alter theophylline concentration in vivo. For additional information, refer toone of the published summaries.1213


THEO DTTheophylline



Method Comparison



Method Comparison for THEO DT: Serum

Conventional Units

.?u •

40 •

?0«

20 •

10-

0 •

JJ*

y = x

(0 20 30 40Comparative Method: VITROS 950 System

(Mg/mL)

50

Q

o

250

200

150

100

so

0

SI Units

y = X


((Jmol/L)

Method Comparison for THEO DT: Serum


n

60

Slope

0.97


0.991

Conventional


0.6-37.9

Units (ug'mL)

Intercept Sy.x

1.31 1.37

SI Units


3.5-210.5

(umol/L)

Intercept

7.27

Sy.x

7.62



Precision for THEO DT:

System

VITROS DT60 II

SerumConventional Units (ug/mL)

MeanCone.

12.9

21.7

WithinDay SD*

0.49

0.67

WithinLab SD**

0.65

0.93

SI

MeanCone.

71.3

120.2

Units (umol/L)

WithinDay SD*

2.74

3.73

WithinLab SD**

3.63

5.16

WithinLab

CV%**

5.1

4.3

No.Observ.

88

88

No.Days

22

22




THEO DTTheophylline

References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 859; 1987.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.3. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.4. Kaplan L, PesceA. Clinical Chemistry: Theory, Analysis, and Correlation, ed. 2. CVMosby; 900; 1989.5. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;

1991.6. NCCLS. Procedures for the. Collection of Diagnostic Blood Specimens by Skin Puncture. NCCLS Document H4. Wayne, PA: NCCLS;

1991.7. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle IV: Therapeutic Drug Monitoring/Toxicology.

Skokie, IL: College of American Pathologists; 1985.8. Lauff J. A Reference Procedure for the Determination of Theophylline and Related Xanthines in Serum by Dynamic Ion-Exchange HPLC.

J. Chrom. 417:99-109; 1987.


10. Hendele L, Weinberger MM. Theophylline Therapeutic Use and Serum Concentration Monitoring, in Taylor WJ and Finn AL (eds).Individualizing Drug Therapy—Practical Applications of Drug Monitoring. New York: Gross, Townsend, Frank; 1:31-65; 1981.

11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.13. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.14. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:

NCCLS; 1995.15. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS; 1992.


Glossary of Symbols

Do Not Reuse


Lot Number




ml Manufacturer

| t t [ m$t> I Authorized Representative

V r 7 Contains Sufficient for "n"V Tests


Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


THEODTTheophylline

VITFJCpS Q



Version1.0


» New format> New organization and sections consistent with IVD Directive> Materials Required But Not Provided and

Sample Dilution - added VITROS 7% BSA; removed isotonic saline> Limitations of the Procedure - updated values> Method Comparison - updated all data and plots• Precision - updated all values• References - added all




C€

FU5POrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


Qtho-Clinical Diagnosticscompany



INSTRUCTIONS FOR USEVITROS Chemistry Products TP DT Slides

TPDTTotal Protein

Intended UseFor in vitro diagnostic use only.VITROS TP DT Slides quantitatively measure total protein (TP) concentration in serum and plasma.

Summary and Explanation of the TestSerum proteins transport drugs and metabolites and maintain plasma osmotic pressure. Most serum proteins are synthesizedin the liver, with the exception of gamma globulins. One of the most important serum proteins produced in the liver is albumin.Total serum protein concentration can be used for evaluation of nutritional status.Causes of high total serum protein concentration include dehydration, Waldenstrom's macroglobulinemia, multiple myeloma,hyperglobulinemia, granulomatous diseases, and some tropical diseases. Total protein concentration is occasionally increasedin collagen diseases, lupus erythematosus, and other instances of chronic infection or inflammation. Causes of low total serumprotein concentration include pregnancy, excessive intravenous fluid administration, cirrhosis or other liver diseases, chronicalcoholism, heart failure, nephrotic syndrome, glomerulonephritis, neoplasia, protein-losing enteropathies, malabsorption, andsevere malnutrition.1

Principles of the ProcedureThe VITROS TP DT Slide method is performed using the VITROS TP DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS TP DT Slide is a muitilayered, analytical element coated on a polyester support. The method of analysis is basedon the biuret reaction,2 which produces a violet complex when protein reacts with cupric ion (Cu*2) in an alkaline medium.A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers.When the fluid penetrates the reagent layer, the reagent diffuses up to the spreading layer and reacts with protein. The reactionbetween protein and copper tartrate takes place largely in the spreading layer where the protein is confined because of its highmolecular weight.The amount of colored complex formed is proportional to the amount of total protein in the sample and is measured byreflectance spectrophotometry.

Reaction Sequence

protein + copper tartrate- -> • colored complex

Test Type and ConditionsTest Type and Conditions for TP DT



DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL



TPDTTotal Protein


Reagents

Slide Ingredients


Copper sulfate 0.9 mg; tartaric acid 1.2 mg; and lithium hydroxide 1.3 mg.

Other ingredientsPolymer beads, binders and surfactants.

Slide Diagram

Slide Handling

CAUTION:

1

2

. 3

4

5

1.2.3.

4.5.

Upper slide mountSpreading layer (beads)Reagent layer• copper sulfate• tartaric acid• lithium hydroxideSupport layerLower slide mount


Slide Preparation





Slide Storage and StabilityVITROS TP DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for TP DTSlidesUnopened

Opened



Specimen Requirements" ' Handle specimens as biohazardous material.




Specimens Not Recommended• Plasma:6 Fluoride oxalate


Patient Preparation• Patients should be recumbent; tourniquet application should be minimal.


INSTRUCTIONS FOR USE TPDTTesting Procedure Total Protein

Special Precautions





Specimen Storage and Stability for TP DT: Serum and Plasma6


Temperature18°-28OC(64°-82°F)2°-8°C (36°-46°F)

<-18°C(<0°F)



• VITROS Chemistry Products TP DT Slides




Sample DilutionIf total protein concentrations exceed the system's reportable (dynamic) range:1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's total protein concentration.

Calibration



Calibration ProcedureRefer to the operator's manual for your VITROS DT60/DT60 II Chemistry System. .


- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.The VITROS TP DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


TPDT INSTRUCTIONS FOR USETotal Protein Quality Control

CalculationsReflectance from the slide is measured at 555 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, total protein concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for TP DTConventional (g/dL)


20-110


Traceability of the CalibrationI Values assigned to the VITROS Chemistry Products DT Calibrator Kit for total protein are traceable to the Certified

NIST (National Institute of Standards and Technology) Reference Material, SRM' (Standard Reference Material) 927c.The Ortho-Clinical Diagnostics calibration laboratory uses SRM" 927c to calibrate the NCCLS credentialed Biuret method9 to

I support total protein value assignment for the VITROS DT Calibrator Kit.

Quality Control





System.


and Definitions; Approved Guideline-Second Edition™ or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.



• Control materials other than VITROS DT Controls I & II may show a difference when compared with other total proteinmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.





TPDTTotal Protein


Reference IntervalThis reference interval is the central 95% of results from an internal study of 125 apparently healthy adults from a workingpopulation (56 females and 69 males). No significant differences between results from the male and female populations wereobserved.

Reference Interval for TP DTConventional Units (g/dL)


63-82



The VITROS DT60/DT60 II Chemistry System may be programmed to report total protein results in conventional and SI units.

Reporting Units and Unit Conversion for TP DTConventional Unitsg/dL

SI Unitsg/L (g/dL x 10.0)


The VITROS TP DT Slide method was screened for interfering substances following NCCLS Protocol EP7.11 The substanceslisted in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Hemoglobin

Substances for TP DTInterferent

Concentration

200 mg/dL (2 g/L)400 mg/dL (4 g/L)

Total Protein

Conv. (g/dL)77

Concentration

SI (g/L)7070

BiasConventional

3%9%

SI3%9%


Other LimitationsResults from plasma samples may be up to 4% higher than those from serum.12

Certain drugs and clinical conditions are known to alter total protein concentration in vivo. For additional information, refer toone of the published summaries.1314


TPDTTotal Protein



Method Comparison


using the VITROS 950 System.Method Comparison for TP DT: Serum

Conventional Units

>

10 •

x •

6

4 "

2 •

0

0 2 4 6 8 10Comparative Method: VITROS 950 System

(9'dL)

12

QCO

s

150

100

50

SI Units

50 100 150Comparative Method: VITROS 950 System

(g'L)

Method Comparison for TP DT: Serum



49 0.97 0.995

Conventional Units (g'dL)


2.2-10.7 0.10 0.24

SI Units (g/L)


22-107 1.04 2.39

PrecisionPrecision was evaluated with quality control materials on the VITROS DT60 II System following NCCLS Protocol EP5.1S


Precision for TP DT: Serum

System

VITROS DT60 II

Conventional Units (g/dL)

MeanCone.

3.7

6.7

WithinDay SD*

0.09

0.16

WithinLab SD**

0.11

0.20

MeanCone.

37

67

SI Units (g/L)

WithinDay SD*

0.9

1.6

WithinLab SD**

1.1

2.0

WithinLab

CV%**

3.1

2.9

No.Observ.

88

88

No.Days

22

22



[•I vi~rFij


TPDTTotal Protein

References1. TietzNW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 314-324; 1987.

2. Kingsley GR. The Direct Biuret Method for Determination of Serum Proteins as Applied to Photoelectric and Visual Coiorimetry. J. Lab.Clin. Med. 27:840-845; 1942.


4. Doumas BT, et al. Differences Between Values for Plasma and Serum in Tests Performed in the Ektachem 700 XR Analyzer, andEvaluation of "Plasma Separator Tubes (PST)." Clin. Chem. 35:151-153; 1989.

5. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.




9. Doumas BT, et al. A Candidate Reference Method for Determination of Total Protein in Serum: 1. Development and Validation. Clin.Chem. 27:1642-1650; 1981.


11. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.12. Tietz NW. Textbook of Clinical Chemistry. Philadelphia: WB Saunders; 487; 1986.13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D C : AACC Press; 1990.15. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;

1992.


Glossary of Symbols

Do Not Reuse


Lot Number




^a Manufacturer

| EC I REP [ Authorized Representative



Store At or Below

Store At or AboveI

Store Between



Keep Dry

This end up


TPDTTotal Protein



Version1.0

Description of Technical Changes*> New format> New organization and sections consistent with IVD Directive> Specimens Not Recommended - added section• Specimen Storage and Stability - updated stability values> Known Interfering Substances table - removed dextran, updated hemoglobin> Method Comparison - updated data for all comparisons and plots> Precision - updated values

References - added all









Chemistry

P rodu cts

INSTRUCTIONS FOR USEVITROS Chemistry Products TRIG DT Slides

TRIG DTTriglycerides

Intended UseFor in vitro diagnostic use only.VITROS TRIG DT Slides quantitatively measure triglycerides (TRIG) concentration in serum and plasma.

Summary and Explanation of the TestTriglycerides, fatty acid esters of glycerol, represent the major form of fat found in the body; their primary function is to storeand provide cellular energy. The concentration of triglycerides in the plasma at any given time is a balance between the rates ofentry and removal. Triglyceride concentrations in the plasma vary with age and gender. Moderate increases occur duringgrowth and development. Triglycerides are used for the evaluation of hyperlipidemias; high concentrations may occur withhypothyroidism, nephrotic syndrome, glycogen storage diseases, and diabetes mellitus. Extremely high triglycerideconcentrations are common in acute pancreatitis.1

Principles of the ProcedureThe VITROS TRIG DT Slide method is performed using the VITROS TRIG DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS TRIG DT Slide is a multilayered, analytical element coated on a polyester support. The analysis is based on anenzymatic method as described by Spayd et al.2

A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. TheTriton X-100 surfactant in the spreading layer aids in dissociating the triglycerides from lipoprotein complexes present in thesample. The triglyceride molecules are then hydrolyzed by lipase to yield glycerol and fatty acids. Glycerol diffuses to thereagent layer, where it is phosphorylated by glycerol kinase in the presence of adenosine triphosphate (ATP). In the presenceof L-a-glycerol-phosphate oxidase, L-a-glycerophosphate is then oxidized to dihydroxyacetone phosphate and hydrogenperoxide. The final reaction involves the oxidation of a leuco dye by hydrogen peroxide, catalyzed by peroxidase, to producea dye.The density of the dye formed is proportional to the triglyceride concentration present in the sample and is measured byreflectance spectrophotometry.

Reaction Sequence

lipoproteins

triglycerides + H2O

glycerol + ATP

lipase

->• triglycerides + proteins

^- glycerol + fatty acids

glycerol kinase

MgCI2

L-a-glycerophOSphate + O2 L-a-glycerol-phosphate oxidase


^ dihydroxyacetone phosphate + H2O2

H2O2 + leuco dyeperoxidase

->• dye + 2H2O

Test Type and ConditionsTest Type and Conditions for TRIG DT



DT60/DT60 II



Wavelength555 nm

Sample DropVolume

10 uL





Reagents


Lipase (Candida rugosa, E.C.3.1.1.3) 0.15 U; peroxidase (horseradish root,E.C.1.11.1.7) 0.52 U; glycerol kinase (Cellulomonas sp., E.C.2.7.1.30) 0.35 U;L-a-glycerophosphate oxidase (Pediococcus sp., E.C.1.1.3.-) 0.19 U; Triton X-1000.62mg;2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl)imidazole (leuco dye) 0.04 mg; and adenosine triphosphate 0.14 mg.

Other ingredientsPigment, binders, buffer, surfactants, stabilizers, scavenger, enzyme cofactors, dyesolubilizer and cross-linking agent.

Slide Diagram

Slide Handling

1. Upper slide mount2. Spreading layer (TiO2)

Triton X-100lipase

3. Reagent layerbuffer, pH 8.0glycerol kinaseATPL-a-glycerophosphateoxidaseperoxidaseleuco dye



Slide Preparation

IMPORTANT; The slide must reach room temperature, 18 "-28 °C (64 °-82 °F), before the wrapper isopened.


1. Remove the individual slides from the box.2. Warm the unopened slide for 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to



VITROS TRIG DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for TRIG DTSlidesUnopened

Opened

Storage ConditionRoom temperature 18°-28°C (64°-82°F)Refrigerated 2°-8°C (36°~46°F)Frozen s-18°C(<0°F)Room temperature 18°-28°C (64°-82° F)




I * Serum is the specimen of choice because it is the basis for the US National Institutes of Health recommendations relatinglipid levels with cardiac risk. Heparin plasma results have been reported as being within 1% of serum results.4




INSTRUCTIONS FOR USE TRIGDTTesting Procedure Triglycerides

Specimens Not Recommended• Plasma: EDTA"

Serum and PlasmaSpecimen Collection and PreparationCollect specimens using standard laboratory procedures.6 '

Patient Preparation• Collect specimens from patients fasting for at least 12 Hours.8

Special Precautions• Equipment must be soap-free and glycerol-free.• Do not use collection tubes with glycerol-lubricated stoppers.• Centrifuge specimens and remove the serum and plasma from the cellular material within 4 hours of collection.9




Specimen Storage and Stability for TRIG DT: Serum and Plasma9



<-18°C(<0°F)


IMPORTANT; Avoid repeated freeze-thaw cycles.

Testing Procedure

Materials Provided• VITROS Chemistry Products TRIG DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials, such as VITROS Chemistry Products DT Control I & II• VITROS Chemistry Products 7% BSA• Isotonic saline

I • Reagent-grade water. VITROS DT Pipette


IMPORTANT: Bring all fluids and samples to room temperature, 18°-28°C (64°~82°F), prior toanalysis.

Sample DilutionIf triglycerides concentrations exceed the system's reportable (dynamic) range:1. Dilute with VITROS 7% BSA, isotonic saline, or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's triglycerides concentration.


TRIGDT INSTRUCTIONS FOR USETriglycerides Calibration

Calibration





- For example, in the USA, CLIA regulations require calibration or calibration verification at least once every six months.The VITROS TRIG DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

Calculations


each slide lot, triglyceride concentration in unknown samples can be determined using the software-resident endpointcolorimetric math model and the response obtained from each unknown test slide.

Validity of a CalibrationCalibration parameters are automatically assessed by the VITROS DT60/DT60 II Chemistry System against a set of qualityparameters resident within the analyzer software. Failure to meet any of the pre-defined quality parameters results in a failedcalibration. The calibration report should be used in conjunction with quality control results to determine the validity ofa calibration.'


Reportable (Dynamic) Range for TRIG DTConventional (mg/dL)


0.17-4.52


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for triglyceride are traceable to the CDC chromotropicacid reference procedure.10 The Ortho-Clinical Diagnostics (OCD) calibration laboratory uses value assigned human serumpools, from a CDC Reference network Certified Laboratory, to calibrate a glycerol phosphate oxidase triglyceridespectrophotometric method11 to support triglyceride value assignment for the VITROS DT Calibrator Kit.

Quality Control


| , Handle quality control materials as biohazardous material.



System.





• For general quality control recommendations, refer to Statistical Quality Control for Quantitative Measurements: Principlesand Definitions; Approved Guideline-Second Editionu or other published guidelines.



Chemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control,

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other triglyceridesmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives.




These reference intervals are recommended by NCEP.13

Reference Interval for TRIG DT

Normal

Borderline High

High

Very High


<150

150-199

200-499

>500

SI Units(mmol/L)

<1.69

1.69-2.25

2.26-5.64

>5.65



The VITROS DT60/DT60 II Chemistry System may be programmed to report triglycerides results in conventional and SI units.

Reporting Units and Unit Conversion for TRIG DTConventional Units

mg/dLSI Units

. mmol/L (mg/dL x 0.01129)


Known Interferences• Free glycerol14

Free (nonesterified) glycerol in serum is measured along with the glycerol from the hydrolysis of triglycerides anddiglycerides. Certain clinical conditions (e.g., diabetes mellitus and cardiac ischemia) show high endogenous free glycerollevels. Some drugs used in the treatment of lipemia also produce elevated glycerol levels. Triglyceride results fromsamples of such patients will not reflect actual serum triglyceride content.

Other LimitationsCertain drugs and clinical conditions are known to alter triglyceride concentration in vivo. For additional information, refer to oneof the published summaries.1516





Method Comparison


using the Enzymatic Total Glycerol comparative method."Method Comparison for TRIG DT: Serum

Conventional Units

DW

o

500

400

300

S 200

100

y = x

100 200 300 400 500Comparative Method: Enzymatic Total Glycerol

(mg/d/L)

IQ

1 1 -

SI Units

Comparative Method: Enzymatic Total Glycerol(mmol/L)

Method Comparison for TRIG DT: Serum


n

36

Slope

1.00


0.987

Conventional


40-394

Units (mg/dL)

Intercept Sy.x

1.84 15.92

SI Units (mmol/L)


0.45-4.45 0.02

Sy.x

0.18



Precision for TRIG DT: Serum

System

VITROS DT60 II

Conventional Units

MeanCone.

110

265

WithinDay SD*

2.0

3.4

(mg/dL)

WithinLab SD**

2.8

6.1

SI

MeanCone.

1.24

2.99

Units (mmol/L)

WithinDay SD*

0.02

0.04

WithinLab SD**

0.03

0.07

WithinLab

CV%**

2.6

2.3

No.Observ.

84

84

No.Days

21

21





References1. Tietz NW (ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 452-453; 1987.2. Spayd R, et al. Multilayer Film Elements for Clinical Analysis. Clin. Chem. 24:1348-1350; 1978.3. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and

Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.4. NCEP. Recommendations for improving cholesterol measurement. A report from the Laboratory Standardization Panel of the National

Cholesterol Education Program. NIH publication no. 90-2964:26-27; 1990.5. Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.6. NCCLS. Procedures for the Collection of Diagnostic Blood Specimens by Venipuncture. NCCLS Document H3. Wayne, PA: NCCLS;


1991.8. NCEP. Recommendations for improving cholesterol measurement. A report from the Laboratory Standardization Panel of the National

Cholesterol Education Program. NIH publication no. 90-2964:28-29; 1990.9. Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.10. ColeTG, Klotzach SG, McNamara JR. Measurement of Triglyceride Concentration, Rifai N, Warnick GR, DominiczakMK (eds).

Handbook of Lipoprotein Testing, ed. 2. Washington DC: AACC Press, 207-219; 2000.11. Fossati P, Prencipe L. Clin. Chem. 28:2077-2080; 1982.12. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.13. NCEP. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of

High Blood Cholesterol in Adults (Adult Treatment Panel III); Executive Summary. NIH Publication No. 01-3670. NationalInstitutes of Health. Bethesda. Maryland: May, 2001.

14. Stein EA, et al. National Cholesterol Education Program Recommendations for Triglyceride Measurement: Executive Summary. Clin.Chem. 41:1421-1426; 1995.


1992.


Glossary of Symbols

REF

Do Not Reuse


Lot Number




t

Manufacturer




Store At or Below

Store At or Above

Store Between



Keep Dry

This end up


TRIGDTTriglycerides


Revision HistoryDate of•Revision2003-04-30

Version1.0


> New format> New organization and sections consistent with IVD Directive> Specimen Collection and Preparation - removed statement regarding grossly

lipemic specimens> Reference Interval - updated all values> Method Comparison - updated all data and the plot> Precision - updated all data> References - added all but number 9




C€



'Ortho-Clinical Diagnosticsu^cfMww company



VIHTRBChemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products urCR DT Slides

urCR DTUrine Creatinine

Intended UseFor in vitro diagnostic use only.VITROS urCR DT Slides quantitatively measure creatinine concentration in urine.

Summary and Explanation of the TestUrinary creatinine excretion is a function of lean body mass in normal persons and shows little or no response to dietarychanges. Since urinary creatinine is excreted mainly by glomerular filtration, with only small amounts due to tubular secretion, a24-hour urine creatinine and a serum creatinine measurement can be used to calculate creatinine clearance, which is anestimate of the glomerular filtration rate.Exercise may cause an increased creatinine clearance. The creatinine clearance rate is unreliable if the urine flow is low.

Principles of the ProcedureThe VITROS urCR DT Slide method is performed using the VITROS urCR DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS urCR DT Slide is a multilayered, analytical element coated on a polyester support.A drop of diluted patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlyinglayers. Creatinine diffuses to the reagent layer, where it is hydrolyzed to creatine in the rate-determining step. The creatine isconverted to sarcosine and urea by creatine amidinohydrolase. The sarcosine, in the presence of sarcosine oxidase, isoxidized to glycine, formaldehyde, and hydrogen peroxide. The final reaction involves the peroxidase-catalyzed oxidation of aleuco dye to produce a colored product. The rate of change in reflection density is proportional to the concentration ofcreatinine in the sample.

Reaction Sequence

creatinine + H2O

creatine + H2O -

creatinine amidohydrolase

creatine amidinohydrolase

-> • creatine

-> • sarcosine + urea

sarcosine + O2 + H2O

H2O2 + leuco dye —

sarcosine oxidase glycine + formaldehyde + H2O2


Test Type and ConditionsTest Type and Conditions for urCR DT

Test TypeRate


DTSC/DTSC II



Wavelength680 nm

Sample DropVolume

10 uL




VITFj[Cp*S El


Reagents

Slide Ingredients

Reactive ingredients per cmCreatinine amidohydrolase (Flavobacterium sp., E.C.3.5.2.10) 0.20 U; creatineamidinohydrolase {Flavobacterium sp., E.C.3.5.3.3) 4.7 U; sarcosine oxidase(Bacillus sp., E.C.1.5.3.1) 0.55 U; peroxidase (horseradish root, E.C.1.11.1.7)1.6 U; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dirnethylaminophenyl)imidazole (leuco dye) 32 jig.

Other ingredientsPigment, binders, surfactants, stabilizer, scavenger, chelator, buffer, dyesolubilizer and cross-linking agent.

Slide Handling

CAUTION:

Slide Diagram

—— - - " '

~ • - 4

„- - '

1.2.3.

4.5.

Jpper slide mountSpreading layer (TiO2)Reagent layer

creatinine amidohydrolase• creatine amidinohydrolase» sarcosine oxidase

peroxidaseleuco dye

> buffer, pH 7.0Support layer-ower slide mount


Slide Preparation


Do not use unopened slides that have been at room temperature, 18 "-28 °C(64 "-82 °F) for >48 hours.




VITROS urCR DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for urCR DTSlidesUnopened

Opened




Specimens Recommended• Urine



UrineSpecimen Collection and Preparation• Collect specimens using standard laboratory procedures.3

• Keep refrigerated until analysis.


Special Precautions• Urine specimens must be pretreated prior to processing. Refer to "Specimen Pretreatment" for instructions.


INSTRUCTIONS FOR USE urCR DTSpecimen Pretreatment Urine Creatinine


Specimen Storage and Stability for urCR DT: Urine4


Temperature18°-28OC(64O-82°F)2°-8°C (36°-^6°F)

<-18°C (<0°F)

Stability<3 days<5 days<lndefinite

Specimen PretreatmentUrine

Predilution1. Mix 1 part sample with 20 parts of reagent-grade water.2. Analyze.3. Multiply the results by 21 to obtain the creatinine concentration in the original urine sample.

For example:1. Fill a 100 mL graduated cylinder with 60 mL reagent-grade water.2. Add a 3.0 mL aliquot of well mixed urine specimen to the graduated cylinder. The 3 mL pipette used to reconstitute

VITROS DT Calibrators can be used to measure the 3 mL.3. Cover the graduated cylinder and mix well.

Testing Procedure

Materials Provided• VITROS Chemistry Products urCR DT Slides

Materials Required But Not Provided• VITROS Chemistry Products DT Calibrator Kit• Quality control materials• Reagent-grade water• VITROS DT Pipette


sJNT: Bring all fluids and samples to room temperature, 18°-28°C (64°-82°F), prior toanalysis.

Sample DilutionIf urine creatinine concentrations exceed the system's reportable (dynamic) range or if the analyzer displays an L-11 errorcode:1. Mix 1 part prediluted sample with 1 part reagent-grade water.2. Reanalyze.3. Multiply the results by 42 to obtain an estimate of the creatinine concentration in the original sample.

Calibration





V/|T"Rj|CpfS ElnrCRDT INSTRUCTIONS FOR USEUrine Creatinine Quality Control



The VITROS urCR DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.

CalculationsReflectance from the slide is read at 680 nm during the incubation period, and the rate of change in reflectance is calculated.Once a calibration has been performed for each slide lot, urine creatinine concentration in unknown samples can bedetermined using the software-resident rate math model and the change in reflectance calculated for each unknown test slide.



Reportable (Dynamic) Range for urCR DTConventional Units (mg/dL)

1.05-346.5*SI Units (umol/L)

92.8-30630.6*'After multiplying by a dilution factor of 21.


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for creatinine are traceable to the Certified NIST(National Institute of Standards and Technology) Reference Material, SRM1*' (Standard Reference Material) 914a. TheOrtho-Clinical Diagnostics calibration laboratory, uses SRM 914a to calibrate selected measurement procedures, including anHPLC (High Performance Liquid Chromatography)5 method and a rate Jaffe6 method, to support creatinine value assignmentfor the VITROS DT Calibrator Kit.

Quality Control

Procedure Recommendations| WARMING: Handle quality control materials as biohazardous material.



System.


and Definitions; Approved Guideline-Second Edition7 or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60II Chemistry System.


El v/|"r.s^P"^INSTRUCTIONS FOR USE urCRDTExpected Values and Reporting Units Urine Creatinine

Quality Control Material Selection• Urine controls often contain high creatine levels and may give an L-11 error codes.• For urine specimens, use commercially available urine control materials.• Do not use control materials stabilized with ethylene glycol.

Quality Control Material Preparation and StorageRefer to the manufacturer's product literature.


These reference intervals are the central 95% of results from an internal study of apparently healthy adults from a workingpopulation (67 subjects).

Reference Interval for urCR DT

24-hourConventional Units800-2800 mg/day*

SI Units7000-25000 umol/day**

* Creatinine concentration (mg/dL) x 24-hour volume (dL) = mg/day.** Creatinine concentration (|jmol/L) x 24-hour volume (L) = |jmol/day.


Reporting Units and Unit ConversionThe VITROS DT60/DT60 II Chemistry System may be programmed to report urine creatinine results in conventional andSI units.

Reporting Units and Unit Conversion for urCR DTConventional Units

mg/dLSI Units



None identified.

Other LimitationsCertain drugs and clinical conditions are known to alter creatinine concentration in vivo. For additional information, refer to oneof the published summaries.8 9





Method Comparison


using the HPLC comparative method.5 Testing followed NCCLS Protocol EP9.10

Method Comparison for urCR DT: Urine

Conventional Units

400

I 300 •

= 200

100

100 200 .300 400

Comparative Method: HPLC(mg/dL)

40000

30000

20000

O 10000o:

SI Units

10000 20000 30000 40000

Comparative Method: HPLC(pmol/L)

Method Comparison for urCR DT: Urine



76 1.00 0.999



9.0-323.4 -0.05 4.06

SI Units ((jmol/L)


798-28589 -4.39 358.50

PrecisionPrecision was evaluated with quality control materials on the VITROS DT60 II System following NCCLS Protocol EP5.1' Thedata presented are a representation of test performance and are provided as a guideline. Variables such as sample handlingand storage, reagent handling and storage, laboratory environment, and system maintenance can affect reproducibility of testresults.

Precision for urCR DT: Urine

System

VITROS DT60 II

Conventional Units

MeanCone.

153.9

49.8

WithinDay SD*

3.19

1.36

(mg/dL)

WithinLab SD**

3.56

1.73

SI

MeanCone.

13606

4405

Units (umol/L)

WithinDay SD*

281.6

119.8

WithinLab SD**

314.6

152.5

WithinLab

cv%**2.3

3.5

No.Observ.

88

88

No.Days

22

22






Tissue; Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.Calam RR. Specimen Processing Separator Gels: An Update. J Clin Immunoassay. 11:86-90; 1988.NCCLS. Urinalysis and Collection, Transportation, and Preservation of Urine Specimens; Approved Guideline. NCCLS Document

GP16. Wayne, PA: NCCLS; 1995.Clinical Laboratory Handbook for Patient Preparation and Specimen Handling. Fascicle VI: Chemistry/Clinical Microscopy. Northfield,

IL: College of American Pathologists; 1992.Ambrose RT, Ketchum DF, Smith JW. Creatinine Determined by "High Performance" Liquid Chromatography. Clin. Chem. 29: 256-259;

1983.Jaffe M. Uber den Niederschlag welchen Pikrinsaure in normalen Ham erzeugt und uber eine neue Reaktion des Kreatinins. Z Physiol

Chem. 10: 391-400; 1886.NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition.

NCCLS Document C24. Wayne, PA: NCCLS; 1999.Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990

10. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:NCCLS; 1995.

11. NCCLS. User Evaluation of Precision Performance with Clinical Chemistry Devices. NCCLS Document EP5. Wayne, PA: NCCLS;1992.

4.

5.

6.

7.

9.


Glossary of Symbols

Do Not Reuse


Lot Number




Manufacturer




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Store At or Above

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WCR DTUrine Creatinine

VITRCpS 0



Version1.0


> New formatNew organization and sections consistent with IVD Directive

• Specimen Storage and Stability - updated stability values• Specimen Pretreatment - added section> Method Comparison - updated all data and plots• Precision - updated all data> References - added all except 8, 9,10,11




C€

TEC I REP IOrtho-Clinical DiagnosticsMandeville House62 The BroadwayAmershamBuckinghamshire HP7 OHJEngland


'Ortho-Clinical Diagnostics^otowon company



Chem i str y

P rodu cts

INSTRUCTIONS FOR USEVITROS Chemistry Products URIC DT Slides

URIC OTUric Acid

Intended UseFor in vitro diagnostic use only.VITROS URIC DT Slides quantitatively measure uric acid (URIC) concentration in serum and plasma.

Summary and Explanation of the TestUric acid is the end product of purine metabolism. Elevations of uric acid occur in renal failure, prerenal azotemia, gout, leadpoisoning, excessive cell destruction (e.g., following chemotherapy), hemolytic anemia, and congestive heart failure and aftermyocardial infarction. Uric acid is also increased in some endocrine disorders, acidosis, toxemia of pregnancy, hereditary gout,and glycogen storage disease type I. A low uric acid concentration may be found following treatment by some drugs (e.g., low-dose aspirin), with low dietary intake of purines, in the presence of renal tubular defects, and in xanthinuria.1

Principles of the ProcedureThe VITROS URIC DT Slide method is performed using the VITROS URIC DT Slide and the VITROS Chemistry ProductsDT Calibrator Kit on VITROS DT60/DT60 II Chemistry Systems.The VITROS URIC DT Slide is a multilayered, analytical element coated on a polyester support. The method is similar to thosedescribed by Kageyama2 and Trivedi et al.3

A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. Uricacid from the sample migrates to the reagent layer, where it is oxidized in the presence of uricase to form allantoin andhydrogen peroxide. Hydrogen peroxide oxidzes a leuco dye in the presence of peroxidase to generate a colored dye. Thereflection density of the dye is measured by reflectance spectrophotometry.

Reaction Sequence

2H2O + uric acid

H2O2 + leuco dyeperoxidase

->• allantoin + H2O2 + CO2

— > . dye + 2H2O

Test Type and ConditionsTest Type and Conditions for URIC DT



DT60/DT60 II



Wavelength660 nm

Sample DropVolume

10 ML



URIC DTUric Acid


Reagents

Slide Ingredients


Uricase {Candida utilis, E.C.1.7.3.3) 0.02 U; peroxidase (horseradish root, E.C.1.11.1.7)0.6 U; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis-(4-dimethylaminophenyl)imidazole (leucodye) 14 ug.

Other ingredientsStabilizers, pigment, binders, buffer, surfactants, dye solubilizer, scavenger and cross-linking agent.

Slide Diagram

Slide Handling


1. Upper slide mount2. Spreading layer

3. Reagent layer• uricase• peroxidase• leuco dye• buffer at pH 8.7


Slide Preparation

The slide must reach room temperature, 18 "-28 °C (64 °-82 °F), before the wrapper isopened.


1. Remove the unopened slide from the box.2. V\farm the unopened slide for 15 minutes. Unopened slides that remain in the sealed wrapper may be returned to


Slide Storage and StabilityVITROS URIC DT Slides are stable until the expiration date on the carton when they are stored and handled as specified.

Slide Storage and Stability for URIC DT

SlidesUnopened

Opened






| • Plasma:6 Heparin





Special Precautions• Centrifuge specimens and remove the serum and plasma from the cellular material within 4 hours of collection.5


INSTRUCTIONS FOR USE URIC DTTesting Procedure Uric Acid




Specimen Storage and Stability for URIC DT: Serum and Plasma9



<-18°C(<0°F)


Testing Procedure

Materials Provided• VITROS Chemistry Products URIC DT Slides




analysis.

Sample DilutionIf uric acid concentrations exceed the system's reportable (dynamic) range:

| 1. Dilute the sample with isotonic saline or reagent-grade water.2. Reanalyze.3. Multiply the results by the dilution factor to obtain an estimate of the original sample's uric acid concentration.

Calibration






The VITROS URIC DT test may also need to be calibrated:• If quality control results are consistently outside acceptable range.• After certain service procedures have been performed.For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


URIC DT INSTRUCTIONS FOR USEUric Acid Quality Control

CalculationsReflectance from the slide is measured at 660 nm after the fixed incubation time. Once a calibration has been performed foreach slide lot, uric acid concentration in unknown samples can be determined using the software-resident endpoint colorimetricmath model and the response obtained from each unknown test slide.



Reportable (Dynamic) Range for URIC DTConventional (mg/dL)

0.3-16SI Units (Mtnol/L)

18-952


Traceability of the CalibrationValues assigned to the VITROS Chemistry Products DT Calibrator Kit for uric acid are traceable to the Certified NIST (NationalInstitute of Standards and Technology) Reference Material, SRM® (Standard Reference Material) 913a.The Ortho-Clinical Diagnostics calibration laboratory uses SRM^giSa to calibrate the CDC Uricase method10 to supporturic acid value assignment for the VITROS DT Calibrator Kit.

Quality Control





System.


and Definitions; Approved Guideline-Second Edition" or other published guidelines.• For additional information, refer to the operator's manual for your VITROS DT60/DT60 II Chemistry System.


I IMPORTANT: VITROS DT Control I & II are recommended for use with the VITROS DT60/DT60 IIChemistry System. Evaluate the performance of other commercial control fluids forcompatibility with this test before using for quality control.

• Control materials other than VITROS DT Controls I & II may show a difference when compared with other uric acidmethods if they:- Depart from a true human matrix.- Contain high concentrations of preservatives, stabilizers, or other nonphysiological additives,

i • Do not use control materials stabilized with ethylene glycol.




URICDTUric Acid


Reference IntervalThe serum reference interval is the central 95% of results from a study of 3880 apparently healthy males and a study of272 apparently healthy females.

Reference Interval for URIC DT

MaleFemale


3.5-8.5 mg/dL2.5-6.2 mg/dL

SI Units((jmol/L)

208-506 umol/L149-369 umol/L



The VITROS DT60/DT60 II Chemistry System may be programmed to report uric acid results in conventional and SI units.

Reporting Units and Unit Conversion for URIC DTConventional Units

mg/dLSI Units



• Hydralazine is used as an antihypertensive agent. Interference tests show hydralazine causes approximately 16% negative| bias in serum per 1.0 mg/dL of hydralazine.

The VITROS URIC DT Slide method was screened for interfering substances following NCCLS Protocol EP7.12 Thesubstances listed in the table, when tested at the concentrations indicated, caused the bias shown.

Known Interfering

Interferent*

Gentisic acid

Substances for URIC DTInterferent

Concentration


Uric Acid ConcentrationConv. (mg/dL)

10

SI (umol/L)

59

Average Bias

Conventional and SI

-22%* It is possible that other interfering substances may be encountered. These results are representative; however, your results may differ

somewhat due to test-to-test variation. The degree of interference at concentrations other than those listed might not be predictable.

Other LimitationsCertain drugs and clinical conditions are known to alter uric acid concentration in vivo. For additional information, refer to one ofthe published summaries.13'u


URIC DTUric Acid

INSTRUCTIONS FOR OSEPerformance Characteristics


Method Comparison

I The plots and table show the results of a comparison of samples analyzed on the VlTROS DT60 II System with those analyzed

using the VlTROS 950 System. Testing followed NCCLS Protocol EP9.15

Method Comparison for URIC DT: Serum

Conventional Units

1 8 •

3 15"

| 12 "

I 9i

6 '

3 '

0

DW

s

0

SI Units

1000

800

600

400

200

0

y = x

12 15 18Comparative Method: VlTROS 950 System

(mg/dL)

200 400 600 800 1000Comparative Method: VlTROS 950 System

Method Comparison for URIC DT: Serum


n

58

Slope

1.03


0.999

Conventional


1.0-14.8

Units (mg/dL)

Intercept Sy.x

-0.08 0.16

SI Units (umol/L)


62-878 -4.69

Sy.x

9.75

PrecisionPrecision was evaluated with quality control materials on VlTROS the DT60 II System following NCCLS Protocol EP5.16


Precision for URIC DT: Serum

System

VlTROS DT60 II

Conventional Units

MeanCone.

4.3

11.9

WithinDay SD*

0.04

0.11

(mg/dL)

WithinLab SD"

0.08

0.23

SI

MeanCone.

257

707

Units ((jmol/L)

Within WithinDay SD* Lab SD**

2.5 4.76.3 13.4

WithinLab

CV%**

1.8

1.9

No.Observ.

88

88

No.Days

22

22



[•] VITROS


URIC DTUric Acid

References1. Tietz NW(ed). Fundamentals of Clinical Chemistry, ed. 3. Philadelphia: WB Saunders; 684-686; 1987.2. Kageyama N. A Direct Colorometric Determination of Uric Acid in Serum and Urine with Uricase-Catalysts System. Clin. Chem. Acta.

31:421; 1971.3. Trivedi RC, Rabar L, Berta EN, et al. New Enzymatic Method for Serum Uric Acid at 500 nm. Clin. Chem. 24:1908-191; 1978.4. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and





IL: College of American Pathologists; 1992.10. Schultz AL. Uric Acid. In: Pesce AJ, Kaplan LA, eds. Methods in Clinical Chemistry, St. Louis: The CV Mosby Company; 27-34; 1987.11. NCCLS. Statistical Quality Control for Quantitative Measurements: Principles and Definitions; Approved Guideline-Second Edition..

NCCLS Document C24. Wayne, PA: NCCLS; 1999.12. NCCLS. Interference Testing in Clinical Chemistry. NCCLS Document EP7. Wayne, PA: NCCLS; 1986.13. Young DS. Effects of Drugs on Clinical Laboratory Tests, ed. 4. Washington D.C.: AACC Press; 1995.14. Friedman RB, Young DS. Effects of Disease on Clinical Laboratory Tests. Washington, D.C.: AACC Press; 1990.15. NCCLS. Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline. NCCLS Document EP9. Wayne, PA:


1992.


Glossary of Symbols

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Lot Number


~l Catalog Number orJ Product Code


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r"'T!"1 Consult Instructions forLJ-iJ Use

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*t* Keep Dry

j t t 1 This end up


URICDTUric Acid

VITRCflS Q



Version1.0


» New format> New organization and sections consistent with IVD Directive> Pre-dilution Procedure - changed distilled water to reagent-grade water• Limitations of the Procedure - added hydralazine and gentisic acid> Method Comparisons - updated all comparisons and plots• Precision - updated all values» References - added all






'Ortho-Clinical Diagnostics^Je&Mtm company



I Products

VITRCD5Chemistry!

INSTRUCTIONS FOR USEVITROS Chemistry ProductsDT Calibrator Kit

DT Calibrator

Intended UseFor in vitro diagnostic use only.VITROS Chemistry Products DT Calibrator Kit is specially formulated for use as calibrators for ALB, ALKP, ALT, AMYL, AST,TBIL, NBIL, BUN/UREA, Ca, CHOL, CK, CI", CO2, CREA, CRSC, Fe, GGT, GLU, HDLC, K+, LAC, LDH, LIPA, Mg, Na+, NH3,PHOS, TP, TRIG, urCR, and URIC on VITROS DT Chemistry Systems.

ReagentsThe VITROS DT Calibrators are prepared from bovine serum albumin and processed bovine serum to which enzymes,electrolytes, stabilizers, preservatives and other organic analytes have been added. Enzymes added to the product and theirsources are shown below:

Enzymes Added to the Product and the Enzyme SourcesEnzymes Added to Bovine Serum Base PoolAlanine AminotransferaseAlkaline PhosphataseAmylaseAspartate AminotransferaseCreatine KinaseGamma GlutamyltransferaseLactate DehydrogenaseLipase

(ALT)(ALKP)(AMYL)(AST)(CK)(GGT)(LDH)(LIPA)

SourcePorcine HeartPorcine KidneyPorcine PancreasPorcine HeartPorcine HeartPorcine KidneyChicken HeartPorcine Pancreas

VITROS DT Calibrator Diluents are prepared from processed water to which inorganic salts have been added.

Nominal Values and TraceabilityNominal values are representative target concentrations used during the calibrator manufacturing process. The particularSupplementary Assigned Value (SAV) for an analyte in each vial is generation specific for VITROS Chemistry Products DTSlides, and is provided on the VITROS Chemistry Products Calibration Data Module (CDM) installed on the VITROS DTChemistry System. Refer to the analyte specific Instructions For Use for additional calibration information.

Nominal Values Used for the ManufactureAnalyteAlbuminAlkaline PhosphataseAlanine AminotransferaseAmmoniaAmylaseAspartate AminotransferaseTotal BilirubinBlood Urea NitrogenCalciumCarbonateChlorideCholesterolCreatine KinaseCreatinineGamma Glutamyl TransferaseGlucoseHDL CholesterolIronLactateLactate DehydrogenaseLipase

Calibrator 1*1.3(13.0)62200(0)20220.8(13.7)4(1.4)3.4 (0.85)8.07045(1.16)450.3 (27)1535(1.94)__10(1.79)0.227545

of VITROS Chemistry Products DT Calibrator KitCalibrator 2*3.5 (35.0)400270596 (350)15025711.0(188.1)27 (9.6)9.0 (2.25)36145145 (3.75)5257.0(619)235200(11.10)—170(30.45)3.0750275

Calibrator 3*———170(100)970—20.0 (342)92 (32.8)14.0 (3.49)——390(10.09)—4.2(371)—445 (24.70)——11.5——

Calibrator 4*6.0 (60.0)1500900128 (75)—850——————170013.2(1167)1400—15(0.38)490 (87.76)—17901900

Units (SI)g/dL (g/L)U/LU/Lug/dL (umol/L)U/LU/Lmg/dL (umol/L)mg/dL (mmol/L)mg/dL (mmol/L)mmol/Lmmol/Lmg/dL (mmol/L)U/Lmg/dL (Mmol/L)U/Lmg/dL (mmol/L)mg/dL (mmol/L)ug/dL (umol/L)mmol/LU/LU/L

Version 3.0 Pub. No. J23110 EN

DT Calibrator


MagnesiumPotassiumPhosphorusSodiumTotal ProteinTriglyceridesUric Acid

0.7 (0.29)1.81.0(0.32)1002.0 (20.0)30 (0.34)1.3(77.3)

2.6(1.08)10.05.0(1.61)2005.9 (59.0)135(1.52)7.5(446.1)

6.5 (2.69)———10.8(108.0)350 (3.95)15.0(892.2)

——12.5(4.04)————

mg/dL (mmol/L)mmol/Lmg/dL (mmol/L)mmol/Lq/dL(g/L)mg/dL (mmol/L)mg/dL (Mmol/L)

•Concentration is when calibrator is reconstituted with 3.0 mL of corresponding diluent.

MOTE: For those analytes that are not targeted in a calibrator bottle a dash is used.

Traceability of Values AssicAnalyteAlbuminAlkaline PhosphataseAlanine AminotransferaseAmmoniaAmylaseAspartate AminotransferaseTotal BilirubinBlood Urea NitrogenCalciumCO2

ChlorideCholesterolCreatine KinaseCreatinineGamma Glutamyl TransferaseGlucoseHDL CholeseterolIronLactateLactate DehydrogenaseLipaseMagnesiumPotassiumPhosphorusSodiumTotal ProteinTriglyceridesUric AcidNBILurCR

ned to the VITROS ChemistryReference MaterialNIST SRM 927cNot ApplicableNot ApplicableAmmonium Sulfate**Not ApplicableNot AvailableNIST SRM 916aNIST SRM 912aNIST SRM 915aNIST SRM 192bNIST SRM 919aNIST SRM 911bNot AvailableNIST SRM 914aNot AvailableNIST SRM 917bNIST SRM 911bNIST SRM 937Lactic Acid, L (+) **Not ApplicableNot AvailableNIST SRM 929NIST SRM 918aNIST SRM 200NIST SRM 919aNIST SRM 927cAssigned Human SerumNIST SRM 913aNIST SRM 916aNIST SRM 914a

Products DT Calibrator KitReference MethodBromcresol Green 1

IFCC/37C J

IFCC/NRSCL RS4-A/37C 3

Enzymatic/37CA

PG5/37C 5

IFCC/NRSCL RS2-A/37C 6

Jendrassik-Grof7 8

CDC (Urease/GLDH) 9

Atomic Absorption 10

Thermal ConductivityCoulometry 11

Abell-Kendall12

IFCC/NRSCL RS14-P/37C "HPLC "/Jaffe 15

IFCC/NRSCL RS17-P/37C 16

AACC/CDC (Hexokinase/G6PDH)17

Dextran Sulfate/Enzymatic 1S

NCCLS/Ferenedye1920

HPLC 21

NCCLS/P->L/37C22

pH Stat2i

Flame Atomic Absorption M

Flame PhotometerPhosphomolybdate/p-semidine HCI2S

Flame Photometer2'Biuret28

CDC chromotropic acid 29/unblankedUricase/UV30

HPLC 31

HPLC "/Jaffe 1S

** Reagent-grade commercial preparation

Warnings and PrecautionsFor in vitro diagnostic use only.While these products are bovine in origin, they should be handled using the same precautions as with any other blood or blood-derived product.

. . ' The packaging (vial stopper) of this product contains dry natural rubber, whichmay cause allergic reactions in some individuals.


Accidental Spillage and DisposalAbsorb spilled material in vermiculite or other suitable absorbents; sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.

Pub. No. J23110 EN Version 3.0

INSTRUCTIONS FOR USEReconstitution DT Calibrator

First AidInhalation - Remove to fresh air. Seek medical advice. Skin - Wash skin after each contact with plenty of soap and water. Getmedical attention if skin is cut or punctured. Eye - Immediately flush eyes with plenty of water for at least 15 minutes and getme.dical attention. Ingestion - Drink 1-2 glasses of water. Seek medical advice.


ReconstitutionNOTE: Each bottle of calibrator lyophilate has a corresponding diluent labeled by number.

Use the appropriate diluent in the reconstitution of the lyophilate.

1. Materials should be at room temperature before constitution. Vials should sit out at room temperature approximately 30minutes if stored in the refrigerator, or 60 minutes if stored in the freezer.

2. Slowly invert the diluent bottle several times to mix the contents thoroughly. DO NOT SHAKE.3. Gently tap the lyophilate vial on the counter several times to dislodge any material adhering to the stopper.4. Remove the seal and stopper from each bottle just prior to the addition of the diluent. Do not leave vials unstoppered.5. Add exactly 3.0 mL of the appropriate diluent to each lyophilate vial.

fiOTE; Do not interchange calibrators and diluents.

Use a clean, dry pipette for each vial. A Class A volumetric pipette, or an automated pipette of equivalent accuracy, isrecommended because of the importance of this reconstitution procedure to the accuracy of the results. Discard anyremaining diluent.

6. Replace the stopper and hold it firmly in place. Invert the vial gently. DO NOT SHAKE. Reconstitution time is typically 10minutes using a rotator or rocker. Manual reconstitution, with occasional inversion, may take up to 30 minutes.Visually verify that all freeze-dried material is dissolved prior to use.

7. Keep all fluids tightly stoppered when not in use. At the time of reconstitution, it is recommended the operator date andinitial the vial.

8. Reconstituted product should be used immediately or stored in the refrigerator between 2-8°C (36-46°F) to maximizestability.

StorageCalibration Kit Storage and Stability for DT Calibrator KitDT Calibrator KitUnopened

Reconstituted

Storage ConditionFrozen <-18°C (<0°F)Refrigerated 2°-8°C (36°-46°F)Refrigerated . 2°-8°C (36°-46°F)

StabilityUntil expiration date<100 days if tightly stoppered<24 hours if tightly stoppered

Refer to the analyte specific Instructions for Use for special calibration precautions.

Materials Provided• 3 vials each of lyophilized calibrator 1,2,3 and 4.• 3 vials each of calibrator diluent 1, 2, 3 and 4 containing 5 mL.

Materials Required, But Not ProvidedA Class A volumetric pipette or an automated pipette of equivalent accuracy for the addition of diluent to lyophilate.


VITR^DS [Sg

INSTRUCTIONS FOR USEDT Calibrator Test Procedure

Test ProcedureNOTE; For HDLC calibration, do not pretreat calibrators with VITROS Chemistry Products

HDL Reagent Tubes.

NOTE; Be sure to use components from the same kit lot number.

1. Remove reconstituted material stored in the refrigerator.

2. Mix vial thoroughly by gently inverting several times.

3. Place a portion of fluid in a cup and cap the cup.

4. Restopper the vial and immediately return it to the refrigerator.

5. Bring the cup to room temperature before analysis (approximately 15 minutes).

6. Analyze according to calibration instructions found in the Operator's Manual.

7. Discard any unused portion in the cup following testing.

8. Discard the calibrators after 24 hours.

Limitations of the ProcedureThe commutability of the VITROS Chemistry Products DT Calibrator Kit for the analytes listed above has been demonstratedamong the VITROS DT Chemistry Systems. Commutability of this calibrator has not been established with other methods.

References1. DoumasBT, Biggs HG. Determination of serum albumin. Standard methods of clinical chemistry\972; 7:175-188.

2. Bretaudiere JP, Vassault A, et al. Criteria for establishing a standardized method for determining alkaline phosphatase activity in human serum.Clin. Chem. 1977; 23:2263-74.

3. Bergmeyer HV, Horder M, Rej R. Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part3, IFCC method for alanine aminotransferase (EC 2.6.1.2). Clin. Chem. Clin. Biochem. 1986; 24:481-95.

4. Bruce WA, Leiendecker CM, Freier EF. Two-Point Determination of Plasma Ammonia with the Centrifugal Analyzer. Clin. Chem. 24:782; 1978.5. Mauck LA. A Kinetic colorimetric method for the determination of total amylase activity in serum. Clin. Chem. 31:1007; 1985.6. Bergmeyer HV, Horder M, Rej R. Approved recommendation on IFCC methods for the measurement of catalytic concentration of enzymes. Part

2, IFCC method for aspartate aminotransferase. J Clin. Chem. Clin. Biochem. 1986; 24:497-510.7. Jendrassik L, Grof P. Vereinfachte photometrische Methoden zur bestimmung des blutbilirubin. Biochem Z1938; 297: 81-89.8. Doumas BT, Perry BW, Sasse EA, et al. Standardization in Bilirubin Assays: Evaluation of Selected Methods and Stability of Bilirubin Solutions.

Clin. Chem. 19:984-993; 1973.9. Sampson EJ, et al. A coupled-enzyme equilibrium method for measuring urea in serum: optimization and evaluation of the AACC study group on

urea candidate reference method. Clin. Chem. 1980; 26:816-26.10. Cali JP, et al. Atomic Absorption. NBS Reference Method (modified). Clin. Chem. 19:1208; 1987.11. Velapoldi RA, Paule RC, Schaffer R, Mandel TJ, Gramlich JW. Standard reference materials: a reference method for the determination of chloride

in serum. National Institute of Standards and Technology Special Publication 260-67, Washington, DC, 1979.12. Abell L I , Levy BB, Brodie BB, Kendall RB. A Simplified Method for the Estimation of Total Cholesterol in Serum and Demonstration of its

Specificity. J S/o/. Chem., 1952; 195: 357-366.13. Scandinavian Committee on Enzymes. Recommended Method for the Determination of Creatine Kinase in Blood. Scand. J Clin. Lab. Invest.

36:711-23; 1976; ibid., 39:1-5: 1979.14. Ambrose RT, Ketchum DF, Smith JW. Creatinine Determined by "High Performance" Liquid Chromatography. Clin. Chem. 29:256-259; 1983.15. Jaffe M. Uber den Niederschlag welchen Pikrinsaure in normalen Harn erzeugt und uber eine neue Reaktion des Kreatinins. Z Physiol Chem

1886; 10:391-400.16. Evans DS, Kringle RO. G-Glutamyltransferase: Response surface co-optimization of reaction conditions with g-Glutamyl-3-carboxy-4-nitroanilide

as the substrate. Clin. Chem. 27:1036; 1981.17. Neese, J.W., Duncan, P., Bayse, D.D. etal, Development and evaluation of a hexokinase/glucose-6-phosphatedehydrogenase procedure for use

as a national glucose reference method. HEW Publication No. (CDC) 77-8330. HEW. USPHS, Centers for Disease Control, 1976.18. Kimberley MM, Leary ET, Cole TG, Waymack PP. Selection, Validation, Standardization and Performance of a Designated Comparison Method

for HDL-Cholesterol for Use in the Cholesterol Reference Laboratory Network. Clin. Chem. (45) 10:1803-1812; 1999.19. National Committee for Clinical Laboratory Standards. Determination of Serum Iron and Total Iron-Binding Capacity; Proposed Standard. NCCLS

Publication H17-P. Villanova, PA, NCCLS, 1990.20. ICSH. Revised Recommendations for the Measurements of the Serum Iron in Human Blood. British Journal of Hemotology. 75:616; 1990.21. Smith JW, Ambrose RT. Determination of Lactic Acid in Human Serum by Ion Exchange Chromatography. Internal Eastman Kodak Company

Report. 1982.22. Buhl SN, Jackson KY, Graffunder B. Optimal reaction condition for assaying human lactate dehydrogenase pyruvate-to-lactate at 25, 30 and

37°C. Clin. Chem. 1978; 24: 261-6.23. Tietz NW, Repique EV. Proposed Standard Method for Measuring Lipase Activity in Serum by a Continuous Sampling Technique. Clin. Chem.

19:1268-1275; 1973.

24. Kaplan L, Pesce A. Clinical Chemistry: Theory, Analysis, and Correlation. CV Mosby, 1069; 1984.

4 Pub. No. J23110 EN Version 3.0

INSTRUCTIONS FOR USEGlossary of Symbols DT Calibrator

25. Velapoldi RA, et al. A reference method for the determination of potassium in serum. NIST Special Publication 260-63, US Department ofCommerce, National Institute of Standards and Technology, Gaithersburg, MD, 1978.

26. Dryer RL, Tamnes AR, Routh JL The Determination of Phosphorus and Phosphatase with N-Phenyl-p-phenyienediamine. J. Biol. Chem.222:177; 1957. AACC Proposed Selected Method.

27. Velapoldi RA, et al. A reference method for the determination of sodium in serum. NIST Special Publication 260-60, US Department ofCommerce, National Institute of Standards and Technology, Gaithersburg, MD, 1978.

28. Doumas BT, Bayse DD, Carter RJ, et al. A candidate reference method for determination of total protein in serum. I. Development andvalidation. Clin Chem 1981; 27:1642-50.

29. Cole T.G., Klotzach S.G. and McNamara J.R. Measurement of Triglyceride Concentration. In: Handbook of Lipoprotein Testing, 2nd edition, RifaiN., Warnick G.R. and Dominiczak M.K., Eds. AACC Press, Washington, 2000, pp 207-219.

30. Duncan, P., Gochman, N., Cooper, G, et al, Development and Evaluation of a Candidate Reference Method for Uric Acid in Serum, 1979, CDC,US Dept. of HHS, Atlanta, GA.

31. Ferris R. Immunoaffinity pretreatment method for improved chromatographic determination of fractionated biiirubin (Abstract). Clin Chem 1987;33: 1012.

Glossary of SymbolsThe Glossary of Symbols table defines the symbols used on the VITROS Chemistry Products packaging and on theVITROS Chemistry Products Assay Sheets.

Glossary of Symbols

Do Not Reuse


Lot Number

Serial Number



Manufacturer

XXX




Store At or Below

Store At or Above

Store Between


ff§

Xi

X

Fragile, Handle with Care

Keep Dry

This end up

Irritant



DT Calibrator

VITR^S Q


Revision History

Date ofRevision2004-03-31

2004-02-29

2003-01-31

Version3.0

2.0 (905660h)

1.0

Description of Technical Changes*New format, technically equivalent to 905660h with the following minorchanges:• Updated Glossary of Symbols table

• Storage-Removed "IMPORTANT: For Creatine Kinase only: Oncereconstituted, calibrators should be used immediately. Calibrators can beused within 6 hours if stored between 2-8°C (36-46°F)."

• TEST PROCEDURE-Removed "For Creatine Kinase: Calibrators can beused within 6 hours if stored between 2-8°C (36-46°F)."

• Values assigned to calibrators-HDL Cholesterol

• Added names of calibrators used for calibrating individual tests• Added SI Units in the nominal values table• Added reference materials and methods table• Added Note under Reconstitute section• Reworded title to Test Procedure• Added information about Creatine Kinase storage• Added Limitations section• Added References section• Added Glossary of Symbols, Revision History, signature block, CE mark,

and authorized representative information




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ECOrtho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom


'Ortho-Clinical Diagnostics4efcHfeM company



j Products

VITRCD5Chemistry I

INSTRUCTIONS FOR USEVITROS Chemistry ProductsDT Isoenzyme Calibrator Kit

DT Isoenzyme Calibrator

Intended UseFor in vitro diagnostic use only.VITROS DT Isoenzyme Calibrator Kit is specially formulated for use as calibrators for CKMB on Vitros DT Chemistry Systems.

ReagentsVITROS DT Isoenzyme Calibrators are prepared from bovine serum albumin to which human heart tissue CKMB, inorganicsalts, stabilizers and preservatives have been added. VITROS DT Isoenzyme Calibrator Diluents are prepared from processedwater.

Nominal Values and TraceabilityNominal values are representative target concentrations used during the calibrator manufacturing process. The calibratorvalues used for calibrating CKMB are generation specific for VITROS Chemistry Products DT Slides and are provided on theVITROS Product Calibration Data Module (CDM) installed on the analyzer. Refer to the analyte specific Instructions for Use foradditional calibration information.

Nominal Values Used for the Manufacture of VITROS Chemistry Products DT Isoenzyme Calibrator KitAnalyteCKMB

Calibrator 1*5

Calibrator 2*50

Calibrator 4*275

UnitsU/L

"Concentration is when calibrator is reconstituted with 3.0 mL of corresponding diluent

Traceability of Values Assigned to the VITROS Chemistry Products DT Isoenzyme Calibrator KitThe values assigned to the VITROS Chemistry Products DT Isoenzyme Calibrator Kit are traceable to aCK-MB immuno-inhibition method, with residual CK-B activity quantified using the Scandinavian Committee on Enzymesrecommended method for total CK.1

Warnings and PrecautionsFor in vitro diagnostic use only.

HANDLE AS IF CAPABLE OF TRANSMITTING DISEASE. This product isprepared from bovine serum albumin to which human tissue extracts have beenadded. The tissue donors used in preparation of the product have been testedand found to be nonreactive for hepatitis B surface antigen (HBsAg), antibody toHCV, and antibody to HIV using FDA approved methods. However, since no testcan offer complete assurance that infectious agents are absent, this productshould be handled following the recommendations in NCCLS Guideline M29 2 orother published biohazard safety guidelines. This product should be handledusing the same precautions as with any other blood or blood-derived product.

WAF The packaging (vial stopper) of this product contains dry natural rubber, whichmay cause allergic reactions in some individuals.


Accidental Spillage and DisposalAbsorb spilled material in vermiculite or other suitable absorbents, sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.



INSTRUCTIONS FOR USEReconstitution

First AidInhalation - Remove to fresh air. Seek medical advice. Skin - Wash skin after each contact with soap and plenty of water. Getmedical attention if skin is cut or punctured. Eye - Immediately flush eyes with plenty of water for at least 15 minutes and getmedical attention. Ingestion -Drink 1-2 glasses of water. Seek medical advice.


ReconstitutionNOTE: Each bottle of calibrator lyophilate has a corresponding diluent labeled by number.


1. Materials should be at room temperature before reconstitution. Vials should sit out approximately 60 minutes at roomtemperature when taken from freezer storage.

2. Slowly invert the diluent bottle several times to mix the contents thoroughly. DO NOT SHAKE.3. Gently tap the lyophilate vial on the counter several times to dislodge any material adhering to the stopper.4. Remove the seal and stopper from each bottle just prior to the addition of the diluent. Do not leave vials unstoppered.5. Add exactly 3.0 ml_ of the appropriate diluent to each vial.

NOTE; Do not interchange calibrators and diluents.

Storage

Use a clean, dry pipette for each vial. A Class A volumetric pipette, or an automated pipette of equivalent accuracy isrecommended because of the importance of this reconstitution procedure to the accuracy of the results. Discard anyremaining diluent.

6. Replace stopper and hold it firmly in place. Invert the vial gently. DO NOT SHAKE. Reconstitution time is less than 10minutes using a rotator or rocker. Manual reconstitution, with occasional inversion, may take up to 30 minutes. Visuallyverify that all freeze-dried material is dissolved prior to use.

7. Keep all fluids tightly stoppered when not in use. At the time of reconstitution, it is recommended the operator date andinitial vial.


Calibration Kit Storage and Stability for DT Isoenzyme Calibrator KitCalibration KitUnopenedReconstituted

Storage ConditionFrozen <-18°C (S0°F)Refrigerated 2°-8°C (36°-46cF)

StabilityUntil expiration date<24 hours if tightly stoppered

Exposure to light must be minimized to preserve creatine kinase.Refer to the analyte specific Instructions for Use for special calibration precautions.

Materials Provided• 4 vials each of lyophilized calibrator 1, 2 and 4.• 4 vials each of calibrator diluent 1, 2 and 4 containing 5 mL.



INSTRUCTIONS FOR USETest Procedure DT Isoenzyme Calibrator

Test ProcedureBe sure to use components from the same kit lot number.

1. Remove reconstituted material stored in the refrigerator.2. Mix vial thoroughly by gentle inversion. DO NOT SHAKE.3. Place a portion of fluid in a cup and cap the cup.4. Restopper the vial and immediately return it to the refrigerator.5. Bring the cup to room temperature before analysis (approximately 15 minutes).6. Analyze according to instructions found in the Operator's Manual.7. Discard any unused portion in the cup following testing.8. Discard reconstituted material after 24 hours.

Limitations of the ProcedureThe commutability of the VITROS Chemistry Products DT Isoenzyme Calibrator Kit for CK-MB has been demonstrated only forVITROS DT Chemistry Systems. Commutability of this calibrator has not been established with other CK-MB methods.

References1. Scandinavian Committee on Enzymes. Recommended Method for the Determination of Creatine Kinase in Blood. Scand. J. Clin. Lab. Invest.

36:711; 1976.2. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue;

Approved Guideline. NCCLS Document M29 (OSBN 1-56238). NCCLS, Wayne, PA 19087; 1997.

Glossary of SymbolsThe Glossary of Symbols table defines the symbols used on the VITROS Chemistry Products packaging and on the VITROSChemistry Products Assay Sheets

Glossary of Symbols

SNREF

• Do Not Reuse


Lot Number

Serial Number



Manufacturer

V

Ix




Store At or Below

Store At or Above

Store Between


W Fragile, Handle with Care.

^ f * Keep Dry

I f f This end up

Irritant





Revision History


2003-01-31

Version2.0

1.0(905659g)

Description of Technical Changes*New format, technically equivalent to 905659g with the following minorchanges:• Updated Glossary of Symbols table

• Added SI Units to the Nominal Values table• Add information about traceability• Added reference to NCCLS• Reworded Precautions to match carton• Add note in Reconstitution section• Changed wording to Test Procedures• Further defined Materials Required but Not Provided• Added Limitations section• Added References section• Added Glossary of Symbols, Revision History, signature block, CE mark,

and authorized representative informationThe change bars indicate the position of a technical amendment to the text with respect to the previous version of the document.

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Ortho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom





I Products

viTRmsChemi stry E

INSTRUCTIONS FOR USEVITROS Chemistry ProductsDT Specialty Calibrator Kit

DT Specialty Calibrator

Intended UseFor in vitro diagnostic use only.VITROS DT Specialty Calibrator Kit is specially formulated for use as calibrators for CHE, Li and THEO on VITROS DTChemistry Systems.

ReagentsVITROS DT Specialty Calibrators are prepared from processed human serum to which cholinesterase from equine serum,lithium chloride, theophylline, electrolytes, organic analytes, stabilizers and preservatives have been added.VITROS DT Specialty Calibrator Diluents are prepared from processed water to which inorganic salts have been added.

Nominal Values and TraceabilityNominal values are representative target concentrations used during the calibrator manufacturing process. The calibratorvalues used for calibrating CHE, Li and THEO are generation specific for VITROS Chemistry Products DT Slides and areprovided on the VITROS Chemistry Products Calibration Data Module (CDM) installed on the VITROS DT Chemistry System.Refer to the analyte specific Instructions for Use for additional calibration information.

Nominal Values Used for the Manufacture of VITROS Chemistry Products DT Specialty Calibrator KitAnalyteCholinesterase (CHE)Lithium (Li)Theophylline (THEO)

Calibrator 1*0.00 (0)0.21.5(8.33)

Calibrator 2*5.00 (5000)1.510.0(55.50)

Calibrator 4*12.30(12300)4.035.0(194.25)

Conv. Units/(SI Units)U/mL (U/L)mmol/Lug/mL (umol/L)

"Concentration is when calibrator is reconstituted with 3.0 mL of corresponding diluent.

Traceability of Values AssicAnalyteCholinesterase (CHE)Lithium (Li)Theophylline (THEO)

ned to the VITROS ChemistryReference MaterialNot ApplicableSRM 924aTheophylline*

Products DT Specialty Calibrator KitReference MethodButyrylthiocholine/ferricyanide 'Atomic Absorption 2

HPLC•Reagent grade commercial preparation


Warning HANDLE AS IF CAPABLE OF TRANSMITTING DISEASE. This product isprepared from human serum and human enzymes. Each donor unit used inpreparation of the product was tested and found to be nonreactive for hepatitisB surface antigen (HBsAg), antibody to HCV, and antibody to HIV using FDAapproved methods. However, since no test can offer complete assurance thatinfectious agents are absent, this product should be handled following therecommendations in NCCLS Guideline M294 or other published biohazardsafety guidelines.

Warning: The packaging (vial stopper) of this product contains dry natural rubber, whichmay cause allergic reactions in some individuals.


Version 2,0 Pub. No. J23115 EN

\/ITF?Cp"S ElINSTRUCTIONS FOR USE

DT Specialty Calibrator Reconstitution

Accidental Spillage and DisposalAbsorb spilled material in vermiculite or other suitable absorbents, sweep up and dispose of with clinical waste! Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.

First AidInhalation - Remove to fresh air. Seek medical advice. Skin - Wash skin after each contact with plenty of soap and water. Getmedical attention if skin is cut or punctured. Eye - Immediately flush eyes with plenty of water for at least 15 minutes and getmedical attention. Ingestion - Drink 1-2 glasses of water. Seek medical advice.


ReconstitutionNote: Each bottle of calibrator lyophilate has a corresponding diluent labeled by number.


1. Materials should be at room temperature before reconstitution.Vials should sit out approximately 30 minutes if stored in the refrigerator, or 60 minutes if stored in the freezer.

2. Slowly invert the diluent vial several times to mix the contents thoroughly. DO NOT SHAKE.3. Gently tap the lyophilate on the counter several times to dislodge any material adhering to the stopper.4. Remove the seal and stopper from each bottle just prior to the addition of the diluent. Do not leave vials unstoppered.5. Add exactly 3.0 mL of the appropriate diluent to each vial.

Note: Do not interchange calibrators and diluents.

Storage

Use a clean, dry pipette for each vial. A Class A volumetric pipette, or an automated pipette of equivalent accuracy, isrecommended because of the importance of this reconstitution procedure to the accuracy of the results. Discard anyremaining diluent.

6. Replace stopper and hold it firmly in place. Invert the vial gently. DO NOT SHAKE. Reconstitution time is less than 10minutes using a rotator or rocker. Manual reconstitution, with occasional inversion, may take up to 30 minutes. Visuallyverify that all freeze-dried material is dissolved prior to use.

7. Keep all fluids tightly stoppered when not in use. At the time of reconstitution, it is recommended the operator date andinitial the vial.


Calibration Kit Storage and Stability for PT Specialty Calibrator KitDT SpecialtyCalibrator KitUnopened

Reconstituted

Storage ConditionRefrigerated 2°-8°C (36°-46°F)Frozen <-18°C(<0°F)Refrigerated 2°-8°C (36°-46°F)

StabilityUntil expiration dateUntil expiration date<24 hours if tightly stoppered

Refer to the analyte specific Instructions for Use for special calibration precautions..

Materials Provided• 4 vials each of lyophilized calibrator 1, 2 and 4.• 4 vials each of calibrator diluent 1,2 and 4 containing 5 mL.



INSTRUCTIONS FOR USETest Procedure DT Specialty Calibrator

Test ProcedureBe sure to use components from the same kit lot number.

1. Remove reconstituted material stored in the refrigerator.2. Mix vial thoroughly by gently inverting several times. DO NOT SHAKE.3. Place a portion of fluid in a cup and cap the cup.4. Restopper the vial and immediately return it to the refrigerator.5. Bring the cup to room temperature before analysis (approximately 15 minutes).6. Analyze according to calibration instructions found in the Operator's Manual.7. Discard any unused portion in the cup following testing.8. Discard reconstituted material after 24 hours.

Limitations of the ProcedureThe commutability of the VITROS Chemistry Products DT Specialty Calibrator Kit for the analytes listed above has beendemonstrated among the VITROS DT Chemistry Systems. Commutability of this calibrator has not been established with othercholinesterase, lithium or theophylline methods.

References1. Method recommended by the "Working Group on Enzymes of the German Society for Clinical Chemistry," European Journal of Clinical Chemistry,

Clinical Biochemistry. 30:163-170; 1992.2. A Reference Method of Determination of Lithium in Serum. U.S. Dept. of Comm., NBS Publication 260-69.3. Lauff J. A Reference Procedure for the Determination of Theophylline and Related Xanthines in Serum by Dynamic Ion-Exchange HPLC. J.

Chrom. 417:99-109; 1987.4. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue;



Glossary of Symbols

Do Not Reuse


Lot Number

n i l Manufacturer's SerialOlM Number



Manufacturer




Store At or Below

Store At or Above

Store Between

Consult Instructionsfor Use


Keep Dry

This end up


DT Specialty Calibrator


Revision History


2003-01-31

Version2.0

1.0(906294g)

Description of Technical Changes*New format, technically equivalent to 906294g with the following minorchanges:• Updated Glossary of Symbols table

• Added SI'Units in the nominal values table• • Added reference materials and methods table• Update Precautions to match package labels• Added reference to NCCLS• Added Note under Reconstitution section• Reworded title to Test Procedure• Added Limitations section• Added References section• Added Glossary of Symbols, Revision History, signature block, CE mark,



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Ortho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom


'Ortho-Clinical Diagnostics^efHWOM company



VITROD5Chemistry

Products

INSTRUCTIONS FOR USEVITROS Chemistry Products DT Controls DT Controls

Intended UseFor in vitro diagnostic use only.VITROS DT Control is designed for use in monitoring the performance of VITROS DT Chemistry Systems.

ReagentsVITROS DT Control is prepared from processed human serum to which enzymes, electrolytes, stabilizers, preservatives andother organic analytes have been added.

Enzymes Added to the Product and the Enzyme SourcesEnzymes Added to Human Serum Base PoolAlanine AminotransferaseAlkaline PhosphataseAmylaseAspartate AminotransferaseCholinesteraseCreatine KinaseGamma GlutamyltransferaseLactate DehydrogenaseLipase

SourcePorcine HeartPorcine KidneyPorcine PancreasPorcine HeartHuman SerumPorcine HeartBovine KidneyChicken HeartPorcine Pancreas

VITROS DT Control Diluent is manufactured from processed water to which inorganic salts have been added.


WARNING: HANDLE AS IF CAPABLE OF TRANSMITTING DISEASE.This product is prepared front human serum. Each donor unit used in thepreparation of the product has been tested and found to be nonreactive forhepatitis B surface antigen (HBsAg), antibody to HCV, and antibody to HIV usingFDA approved methods. However, since no test can offer complete assurancethat infectious agents are absent, this product should be handled following therecommendations made in NCCLS Guideline M29' or other published biohazardsafety guidelines. This product should be handled using the same precautionsas with any other blood or blood-derived product.

ING; The packaging (vial stopper) of this product contains dry natural rubber, whichmay cause allergic reactions in some individuals.


Accidental Spillage and DisposalAbsorb spilled material in vermiculite or other suitable absorbents, sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.

First AidInhalation - Remove to fresh air. Seek medical advice. Skin - Wash skin after each contact with plenty of soap and water. Getmedical attention if skin is cut or punctured. Eye-Immediately flush eyes with plenty of water for at least 15 minutes and getmedical attention. Ingestion - Drink 1-2 glasses of water. Seek medical advice.


VI~TF;IJ]S El

INSTRUCTIONS FOR USEDT Controls Reconstitution


ReconstitutionNOTE; Each bottle of control has a corresponding diluent labeled by number. Use the

appropriate diluent in the reconstitution of the lyophilate.

1. Materials should be at room temperature before reconstitution. Vials should sit out approximately 30 minutes if stored in therefrigerator, or 60 minutes if stored in the freezer.

2. Slowly invert the diluent bottle several times to mix the contents thoroughly. DO NOT SHAKE.3. Gently tap the lyophilate vial on the counter several times to dislodge any material adhering to the stopper.4. Remove the seal and stopper from each bottle just prior to the addition of the diluent. Do not leave vials unstoppered.5. Add exactly 3.0 ml_ of the appropriate diluent to each vial. Use a clean, dry pipette for each vial. A Class A volumetric

pipette, or an automated pipette of equivalent accuracy is recommended because of the importance of this reconstitutionprocedure to the accuracy of the results. Discard any remaining diluent.

6. Replace stopper and hold it firmly in place. Invert the vial gently. DO NOT SHAKE. Reconstitution time is typically 10minutes using a rotator or rocker. Manual reconstitution, with occasional inversion, may take up to 30 minutes.Visually verify that all freeze-dried material is dissolved prior to use.

7. Keep all control fluids tightly stoppered when not in use. At the time of reconstitution, it is recommended the operator dateand initial vial.


Storage

Storage andDT ControlUnopened

Reconstituted

Stability for VITROS DT ControlStorage Condition

FrozenRefrigeratedRefrigerated

<-18°C (<0°F)2°-8°C (36°-46°F)2°-8°C (36°-46°F)

StabilityUntil expiration date<6 monthsStore tightly stoppered*

'Refer to the Assay Sheet for analyte-specific stability information.

Exposure to light will affect bilirubin and creatine kinase results.Ammonia concentration increases with time.

Materials Provided• 12 vials of lyophilized control.• 12 vials of diluent containing 5 mL each.


ProcedureAfter reconstitution, the control serum should be assayed in the same manner as a patient sample. The reported values canthen be compared with those given on the assay sheet.

NOTE; Be sure to use components from the same kit lot number.

1. Remove reconstituted material stored in the refrigerator.2. Mix thoroughly by gently inverting several times. DO NOT SHAKE.3. Place a portion of fluid in a cup and cap the cup.4. Restopper the vial and immediately return it to the refrigerator.5. Bring the cup to room temperature before analysis (approximately 15 minutes).6. Analyze according to instructions found in the Operator's Manual.7. Discard any unused portion in the cup following testing.8. Discard reconstituted control after 7 days.


INSTRUCTIONS FOR USEAssay Values DT Controls

Assay Values• The assay values for VITROS DT Control can be found on the assay sheet specific for the lot number. Be sure that the lot

number on the control assay sheet is the same as the lot number printed on the label of the vial being used. The intervalsof acceptable values are intended for use only with the VITROS DT Chemistry Systems.

• If separate generation-specific ranges are listed, use the appropriate range given for the generation of slides being used.Generation-specific ranges are attributed to differences between freeze-dried materials and fresh specimens. They do notindicate a change in the accuracy of patient results.

• Each range has been determined on a number of VITROS DT Chemistry Systems in a single laboratory. If your results donot fall within the published range specified on the assay sheet, you should investigate reconstitution error (e.g., pipettingwrong volume of diluent, or loss of freeze-dried material during reconstitution).

• Additional performance information can be found on the appropriate Instructions for Use sheet.

References1. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue;



Glossary of Symbols

SNREF

ml

Do Not Reuse


Lot Number

Serial Number



Manufacturer




Store At or Below

Store At or Above

Store Between


a


Keep Dry

This end up

Irritant



DT Controls


Revision History


2003-05-30

Version2.0

1.0(905662h)

Description of Technical Changes*New format, technically equivalent to 905662h with the following minorchanges:• Updated Glossary of Symbols• Updated list of enzymes added to the human serum base pool and their

sources

• Clarified product use and assay acceptability• Added reference to NCCLS• Reworded Precautions to match the carton• Reworded title to Test Procedure• Added Note to Reconstitution and Test Procedure• Further defined Materials Required but Not Provided• Added Glossary of Symbols, Revision History, signature block, CE mark,





C€

EC I REPOrtho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom




Pub. No. J23111_EN Version 2.0

j P roducts

VITR[fl5Chemistry!

INSTRUCTIONS FOR USEVITROS Chemistry Products DT isoenzyme controlDT Isoenzyme Control

Intended UseFor in vitro diagnostic use only.VITROS DT Isoenzyme Control is designed for use in monitoring the performance of VITROS DT Chemistry Systems.

ReagentsVITROS DT Isoenzyme Control is prepared from bovine serum albumin to which human CKMM from skeletal muscle, humanCKMB from heart tissue, inorganic salts, stabilizers, and preservatives have been added. VITROS DT Isoenzyme ControlDiluent is prepared from processed water. This product is specially formulated for use on VITROS DT Chemistry Systems.


HANDLE AS IF CAPABLE OF TRANSMITTING DISEASE. This product isprepared from bovine serum albumin to which human tissue extracts have beenadded. The tissue donors used in preparation of the product have been testedand found to be nonreactive for hepatitis B surface antigen (HBsAg), antibody toHCV, and antibody to HIV using FDA approved methods. However, since no testcan offer complete assurance that infectious agents are absent, this productshould be handled following the recommendations in NCCLS Guideline NI29V orother published biohazard safety guidelines. This product should be handledusing the same precautions as with any other blood or blood-derived product.

The packaging (vial stopper) of this product contains dry natural rubber, whichmay cause allergic reactions in some individuals.

Personal Protection and VentilationWear impervious gloves and proper protective clothing. Safety glasses are recommended. Good ventilation in the work area isrecommended. Minimize the potential for production of aerosols.

Accidental Spillage and DisposalAbsorb spilled material in vermiculite or other suitable absorbents; sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least 30minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.

First AidInhalation - Remove to fresh air. Seek medical advice. Skin - Wash skin after each contact with plenty of soap and water. Getmedical attention if skin is cut or punctured. Eye - Immediately flush eyes with plenty of water for at least 15 minutes and getmedical attention. Ingestion - Drink 1-2 glasses of water. Seek medical advice.




INSTRUCTIONS FOR USEReconstitution

ReconstitutionNOTE; Each bottle of control has a corresponding diluent labeled by number. Use the

appropriate diluent in the reconstitution of the lyophilate.

Storage

1. Materials should be at room temperature before reconstitution. Vials should sit out approximately 60 minutes at roomtemperature when taken from freezer storage.

2. Slowly invert the diluent bottle several times to mix the contents thoroughly. DO NOT SHAKE.3. Gently tap the lyophilate vial on the counter several times to dislodge any material adhering to the stopper.4. Remove the seal and stopper from each bottle just prior to the addition of the diluent. Do not leave vials unstoppered.5. Add exactly 3.0 ml_ of the appropriate diluent to each vial. Use a clean, dry pipette for each vial. A Class A volumetric

pipette, or an automated pipette of equivalent accuracy, is recommended because of the importance of this reconstitutionprocedure to the accuracy of the results. Discard any remaining diluent.

6. Replace stopper and hold it firmly in place. Invert the vial gently. DO NOT SHAKE. Reconstitution time is less than 10minutes using a rotator or rocker. Manual reconstitution, with occasional inversion, may take up to 30 minutes.Visually verify that all freeze-dried material is dissolved prior to use.

7. Keep all control fluids tightly stoppered when not in use. At the time of reconstitution, it is recommended that the operatordate and initial the vial.


Storage and Stability for DT Isoenzyme ControlDT Isoenzyme ControlUnopenedReconstituted

Storage ConditionFrozen <-18°C(<0°F)Refrigerated 2°-8°C (36°-46°F)

StabilityUntil expiration date<5 days if tightly stoppered

Refer to the Assay Sheet for analyte-specific stability information.Exposure to light must be minimized to preserve creatine kinase activity.

Materials Provided12 vials of lyophilized control.12 vials of diluent containing 5 ml_ each.


Test ProcedureAfter reconstitution, the control serum should be assayed in the same manner as a patient sample. The reported values canthen be compared with those given on the assay sheet.

NOTE: Be sure to use components from the same kit lot number.

1. Remove reconstituted material stored in the refrigerator.2. Mix vial thoroughly by gently inverting several times. DO NOT SHAKE.3. Place a portion of fluid in a cup and cap the cup.4. Restopper the vial and immediately return it to the refrigerator.5. Bring the cup to room temperature before analysis (approximately 15 minutes).6. Analyze according to instructions found in the Operator's Manual.7. Discard any unused portion in the cup following testing.8. Discard reconstituted control after 5 days.

Assay Values• Obtained values should fall within the published values for the lot number in use. Be sure the lot number on the assay

sheet is the same as the lot number printed on the label of the vial being used.• If separate generation-specific assay ranges are listed, use the appropriate range given for the generation of slides being

used. Generation-specific assay ranges are attributed to differences between freeze-dried materials and fresh specimens.They do not indicate a change in the accuracy of patient results.


[•I ViTRIINSTRUCTIONS FOR USEReferences DT Isoenzyme Control

• Each range has been determined on a number of VITROS DT Chemistry Systems in a single laboratory. If your results donot fall within the published ranges specified on the assay sheet, you should investigate reconstitution error (e.g., pipettingwrong volume of diluent, or loss of freeze-dried material during reconstitution).

• Additional performance information can be found in the appropriate Instructions for Use sheet in the Operator's Manual.

References1. NCCLS. Protection of Laboratory Workers from Instrument Biohazards and Infectious Diseases Transmitted by Blood, Body Fluids and Tissue;



Glossary of Symbols

Do Not Reuse


Lot Number

Serial Number



Manufacturer

t.1X




Store At or Below

Store At or Above

Store Between


It


Keep Dry

This end up

Irritant


Revision History


2003-03-21

Version2.0

1.0 (905601 h)

Description of Technical Changes*New format, technically equivalent to 905601 h with the following minorchanges:• Updated Glossary of Symbols table

• Clarified product use and assay value acceptability• Added reference to NCCLS• Reworded Precautions to match carton• Reworded title to Test Procedure• Added Note to Reconstitution and Test Procedure• Further defined Materials Required but Not Provided• Added Glossary of symbols, Revision History, signature block, CE mark,








C€

EC I REPOrtho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom


Ortho-Clinical Diagnosticsm, company



I Products

viTRmsChemistry I

INSTRUCTIONS FOR USEVITROS Chemistry Products DT Reference Fluid DT Reference Fluid

Intended UseFor in vitro diagnostic use only.VITROS DT Reference Fluid is used in the potentiometric measurement of sodium (Na+), potassium (K*), chloride (Cl~), andcarbon dioxide (CO2) on VITROS DT Chemistry Systems.

ReagentsVITROS DT Reference Fluid is an aqueous solution of electrolytes and a polymer agent. An inert green dye has been addedfor better visibility in the pipette tip.

Reactive Ingredients4.5 mM potassium chloride, 9.0 mM sodium acetate, 25.0 mM sodium bicarbonate, 0.05 mM sodium bromide and 103.5 mMsodium chloride.

Other IngredientsDye, polyvinylpyrrolidone, preservative, and sodium hydroxide.

Warnings and PrecautionsFor in vitro diagnostic use only.This product is low hazard for usual handling.


Accidental Spillage and DisposalFlush to sewer with large amounts of water.

First AidInhalation - Remove to fresh air. Seek medical advice. Skin - Wash skin after each contact with soap and plenty of water for atleast 15 minutes. If symptoms are present'after washing, seek medical advice. Eye - Immediately flush eyes, including underthe eyelids, with plenty of water for at least 15 minutes. Seek medical advice. Ingestion -Seek medical advice, if needed.


StorageIMPORTANT; Do Not Freeze.

Fluid Storage and Stability for DT Reference FluidReference

Unopened

Opened

Fluid StorageRefrigeratedRoom temperatureRefrigerated

Condition2°-8°C18°-282°-8°C

(36°-46°F)°C (64°-82°F)(36°-46°F)

StabilityUntil expiration date<8 hours<1 month if tightly stoppered


INSTRUCf IONS FOR USEDT Reference Fluid Materials Provided

Materials Provided4 bottles of VITROS DT Reference Fluid containing 10 mL each.

Materials Required, But Not ProvidedLaboratory wipes.

Test ProcedureThe fluid must be allowed to reach room temperature before use. A minimum period of 15 minutes is recommended forrefrigerated fluid.1. Gently invert bottle of VITROS DT Reference Fluid several times in order to mix the fluid. DO NOT SHAKE.2. Remove the cap and squeeze at least 4 drops into the small well of the dual-sample cup placed in the sample holder on the

analyzer.3. Before recapping the bottle, gently wipe off any residual reference fluid from the tip with laboratory wipes.4. At the time of initial use, it is recommended the operator date and initial the bottle.5. Refer to the Operator's Manual for additional instructions on sample analysis.6. Discard any unused portion in the dual-sample cup after analysis.7. Return the bottle of VITROS DT Reference Fluid to refrigerator storage.8. Discard any unused portion in the bottle after 1 month.

Glossary of SymbolsThe Glossary of Symbols table defines the symbols used on the VITROS DT Chemistry Products packaging and on theVITROS DT Chemistry Products Assay Sheets.

Glossary of Symbols

Ne pas reutiliser

A utiliser avant la datede peremption(Annee-mois-jour)

Nutnero de lot

Numero de serie

Reference catalogueou code produit

Attention: Consulter lemode d'emploi.

Fabricant

IXX

Representant autorise dansI'Union europeenne

Suffisant pour "n" dosages

Pour diagnostic in vitro

Conserver a une temperatureinferieure ou egale a

Conserver a une temperaturesuperieure ou egale a

Conserver a une temperaturecomprise entre

Consultez la notice d'utilisation

I

i

t)

Attention, fragile.

Tenir au sec

Haut

Irritant

Le fabricant suit desprocedures de gestion deI'emballage


(3 VITR^S

INSTRUCTIONS FOR USERevision History DT Reference Fluid

Revision History


2003-03-28

Version2.0

1.0

Description of Technical Changes*New format, technically equivalent to 906089k with the following minorchanges:• Updated Glossary of Symbols table

• Reworded Intended Use.• Added Reagents section.• Reworded title to Test Procedure.• Added mixing instructions to Test Procedures.• Added introductory sentences to the Test Procedure.• Added Glossary of Symbols, Revision History, signature block, CE mark,






INSTRUCTIONS FOR USEDT Reference Fluid Revision History

C€

I EC REP IOrtho-Clinical DiagnosticsJohnson & Johnson50-100 Holmers Farm WayHigh WycombeBuckinghamshireHP12 4DPUnited Kingdom





Chemistry

INSTRUCTIONS FOR USEVITROS Chemistry Products 7% BSA 7% BSA

Intended UseFor in vitro diagnostic use only.VITROS 7% BSA is used to dilute samples when assay values exceed the reportable (dynamic) range.

ReagentsVITROS 7% BSA is an aqueous solution of bovine serum, inorganic salts, and preservatives.

Reactive IngredientsI None

Other Ingredients7% bovine serum albumin, inorganic salts and preservatives

PrecautionsFor in vitro diagnostic use only.While these products are bovine in origin, they should be handled using the same precautions as with any other blood or blood-derived product.

The packaging (vial stopper) of this product contains dry natural rubber, whichmay cause allergic reactions in some individuals.


Accidental Spillage and DisposalAbsorb spilled material in vermiculite or other suitable absorbents, sweep up and dispose of with clinical waste. Disinfect areawith a 5.25% sodium hypochlorite solution (household bleach) diluted with 9 parts water and leave undisturbed for at least30 minutes. Excess or unwanted materials and packaging for this product should be disposed of with other clinical waste.

First Aid• Inhalation - Remove to fresh air. Seek medical advice.• Skin -Wash skin after each contact with soap and plenty of water. If symptoms are present after washing, seek medical

advice.• Eye - Immediately flush eyes, including under the eyelids, with plenty of water for at least 15 minutes. Seek medical advice.• Ingestion - Drink 1-2 glasses of water. Seek medical advice.


Version 2.0 Pub. No. J11460

7% BSA

N/ITFJCpEB 0

INSTRUCTIONS FOR USEStorage

StorageFluid Storage and Stability for 7% BSA7% BSA

Unopened

Opened

Storage ConditionFrozen <-18°C (<0°F)Refrigerated 2°-8°C (36°-46°F)Refrigerated 2°-8°C (36°-46°F)On-analyzer*

StabilityUntil expiration dateUntil expiration date<28 days if tightly stoppered<7 days

* VITROS 250 System only.

For additional information and instructions, refer to the operator's manual for your VITROS Chemistry System.

Materials Provided• 12 vials (5 ml_ each) of VITROS 7% BSA (CAT No. 826 2487)

Materials Required, But Not Provided• An accurate pipette for performing dilutions

Test Procedure1. Warm fluid to room temperature, 18°-28°C (64°-82°F), prior to use (approximately 30 minutes when taken from the "

refrigerator, 60 minutes from the freezer).2. Mix thoroughly by gentle inversion. DO NOT SHAKE.3. After thorough mixing, remove the seal and stopper from each bottle just prior to use. Keep all fluids tightly stoppered when

not in use. At the time of initial use, it is recommended the operator date and initial the bottle.4. Refer to the Instructions for Use for the appropriate VITROS slides for dilution directions.5. Analyze the specimen as instructed in the VITROS Operator's Manual.6. Store the tightly stoppered bottle of VITROS 7% BSA in the refrigerator.7. Discard any unused portion in the cup following testing.


Glossary of Symbols

SN

Do Not Reuse


Lot Number


Q—— Catalog Number orKCI - Product Code


ft

Manufacturer




Store At or Below

Store At or Above

X

I

i

Store Between



Keep Dry

This end up

Pub. No. J11460 Version 2.0

INSTRUCTIONS FOR USERevision History 7% BSA

Revision HistoryDate of Revision2003-07-28

2002APR19

Version2.0

1.0- English only


• New organization and sections consistent with IVD Directive• Reactive Ingredients - removed 7% bovine serum albumin• Precautions - added the warningNew format, technically equivalent to 2000MAR27.




Version 2.0 Pub. No. J11460

INSTRUCTIONS FOR USE7% BSA Revision History

C€



'Ortho-Clinical DiagnosticsofctMm company


Pub. No. J11460 Version 2.0


September 19, 2005

IMPORTANT NOTIFICATIONNew CDM PROM 0136 and Updated DT Control Assay Sheets for

VITROS® DT60/DT60II Chemistry Systems

Dear Customer,

This notification contains updated information for your VITROS® DT60/DT60II ChemistrySystem including:

Calibration Data Module (CDM PROM) 0136

CDM 0136 contains data that allows you to use new lot numbers of VITROS® DT Slides andVITROS DT Calibrator Kits.

Install this CDM in your VITROS DT60 or DT60 H System at your earliestconvenience. You will not lose calibration for any tests that are currentlycalibrated and are within expiration dates. Be sure to power off your analyzerbefore you install the CDM. Refer to Section 2.3.3 of your operator's manual forcomplete instructions for installing the CDM.

Updated Control Assay Sheets

The enclosed control assay sheets, revised 2005-08-22, contain ranges for all current generationsof VITROS DT Slides supported on CDM 0136. Revisions to the control ranges are alwaysflagged with a change bar ( |) . The control ranges for VITROS Chemistry Products CK DTSlides have been updated for the following:

. VITROS CK DT GEN 60 and GEN 61:o LOT V5856o LOT W5858

Select the assay sheets for the lot numbers of controls you are using or have in stock.Replace any previous versions of control assay sheets with a revised sheet. Be sure toreplace the sheets packed inside any control boxes. Use these updated control ranges forany tests you run.

Ref. CD05-135_xUSFH Page 1 of 1New CDM PROM 0136 and Updated DT Control Assay Sheets for



We thank you for your continued use of VITROS DT Chemistry Systems. If you have anyquestions, please do not hesitate to call our Hotline Support Center.

Please distribute this info to all relevant persons. We only have sent this to your attention.

Sincerely,

Annemie Dries

' J1'Jj)

Customer and CommercialServices Manager

Ref. CD05-135_xUS_V2_draft Page 1 of 1New CDM PROM 0130 and Updated DT Control Assay Sheets for


I Products

VITRCpS1

Chemistry IAssay Summary

1 12

igMTROS DTCalibratorsSS

M.. :.:B6tila|fe!SE';beoriweritipnat IMfift

*:.Ml I)'

•IMVI ul

I- • J! •, SIIM

• M ! . asma (except Ammonia Heparin)

t

v

m | Bilirubin, Neonatal

'«" . Bilirubin, Total

5"C !

«* ! Cholesterol

I"

HDL Cholesterolfr i Micro HDL

Cholesterol KU_ __

Creatinine

Glucose

Lactate

Magnesium

Phosphorous

Total Protein

NBILDT

TBD-DT

CHOL DT

HDLCDT

CRBA DT

GLUDT

LAC DT

MgDT

PIIOSDT

TPDT

Serum or Heparin plasma (Samples frompatients other than newboms are notrecommended)

Serum or Heparin plasma



Serum, HDI'A plasma, Heparin plasma(except Ammonia Hep?.i in)

Scrum, Heparin/iiDTA plasma, Sodium' Fluoride/Potassium Oxalate, plasma

Fluoride (Xaldte plasma Ileparsn plasma*



Serum orllepdrin plasma

! Triglyceri.de

Urea Nitrogen

I Uric Acid

TRIGDT | Serum, Heparin plasma*

DT Calibrator Kit

DT Calibrator Kit

j DT Calibrator Kit

DT Calibrator Kit

! DT Calibrator Kit

! DT Calibrator Kit{Do not pre-treat

^calibrators)

DT Calibiatoi Kit

DT Calibrator Kit

DTCaliljiatorKit

DT Calibrator Kit

DI Calibrator Kit

DT Calibrator Kit

I. DT Calibrator Kit

1.2 3, &4

1,2,&3

1,2, & 3

1,2, & 3

1, 2, & 3

1, 2, & 4

1.2,1, &4

I.2.&.!

1,2, &.;

I .2 .&3

1.2, &4

1,2. & 3

1, 2, & 3

1 - 500 umol/L

5 - 900 L7L

0.1-20 mg/dL

0 I 20 mg/dl.

50 - 325 mg/dL

1-llOrmj'dL

OOl-lSmg'dl

20- 450 mg/dL

0 5 12 mmol I.

0 2 - 7 0 mg/dL

0 5 - 1 3 0 mil dL

2 0 -11 0g/dL

1 - 500 umol/L

5-900U/L

Isotonic saline or reagent grade water

Refer to AMYL DT TFU* Patient sera withlow amyiase activiiy or Tsotonic saline

2-342umol/L |VITROS7%BSA

9-30timol-'L

30-HOL7L.

1.0-10.5 mg/dL

2 -342 umol/L

1.3-8.4mmol/L

0.03- 2.84 mmol/L

1 1326nmol'l-

l.l-25mmoI.'L

0 5~12 0mmol-L

0 1 - 2 9 mmof/L

C 16-4 20mmoM.

200-110 0g/L

V1TROS 7% BSA or reagent-grade water

i Isotonic salirfe or reagent-grade water

VITROS HDI,C Sample Diluent*

VITROS "% BSA or reagent-grade water

Isotonic saline or reagent-grade watv'r

Isotonic saline or leagent-grade water

Isotonic salme or reagent-giadc water

Isotonic saline or reagent-grade water


15-400mg/dL j 0.17-4.52mmol/L I VITROS 7% BSA, Isotonic saline ori reagent-grade water

0 2 - 1 3mg,dL

Desirable < 200 mg<'dLBorder line 200 - 239 ma'dl

High >240 mg/dL "

Low <40 mgldLHigh S60 mg/dL

M 0 8 - 1 5mg,dLF 0 7 - 1 2 ,ng/JL

Fasting Adults 74-I06mg,'dL

0 7 - 2 1 mmol L

1 0 - 2 3 mg/'dL

2 S - 4 5 mg'dL

63-S2g/dI.

Normal: <150 mg/dLBorderline high: 150-199 mg/dL

High: 200-499 mg/dLVery High: >500 mg/dL

BUN'UREA DT

Serum, Hepann plasma or EDTA plasma

URIC DT I Serum or Heparin plasma

' DT Calibrator Kit

I DT Calibrator Kit

1.2.&3

1, 2, & 3

1 100 mg/dL

j 0.3-16 mg/dL

0 4 - 3 5 7mmol/L

18-952 nmo!/L



M: 9 - 2 0 mg/dLf 7 - 1 7 mg/dL

M: 3.5-8.5 mg/dLF: 2.5 - 6.2 mg/dL

9 - 30 umol L

J0- I10U/L

17-180nmol/L

3 - 2 2 umol'L

' ^ 2 mmol 'L5 2 - 6 2 mmol L

>6 2 mmol I

<1 Ommol/L>1.6mmol;L

7 1 - 13>(imoli62 -10C-union

4 1-5 Qmrnol/L

0""-2 1 mmol.'l.

0 7 10 mrtol/L

u S1 - 1 4> mmol.L

63 - 82 g/L

<1.69 mmol/L1.69-2.25 mmol/L2.26-5.64 mmol/L

__ >_5.65 mmol/L

Tf-*7 1 mmoi'L2 5 - 6 J mmolCL

208 -506 umoi/L149 - 369 Mmol/L

Carbon Dioxide

Chloride

Potassium

Sodium

CO; DT Serum or Heparin . •

O DT Serum or Heparin piasma

! Serum or Heparin plasma

I ' i I- •

ui i anbrator Kit

; DT Calibrator Kit

DT Calibrator Kit

1&2

1&2

to - JwmmoL'L

1,0 -11 mmol/L

95 - 21S mrnol/LMA^ DT Serum, [leparin plasma*

|"-" Upper limits of temperature for refrigerate jj' - Upper limit of temperature fc:1 freeze

This information was current as of the publication date. The Instructions For Use are the authorized source for information about VITROS assays.

©Ortho-Clinical Diagnostics, Inc., 2005 • VITROS is a trademark of Ortho-Clinical Diagnostics, Inc. • 100 Indigo Creek Drive • Rochester, NY 14626-5101

- 11 11 Do not dilute

w - i4u mrnof/i- Donoi dilute

1.0-11 mmol/L f Do not dilute

95 - 215 mmol/L Do not dilute

22-30 mmol 1

98- 107 mmol/L

3 5 - 5 1 mmol/L - serumPlasma range 0 1 -07 mmol 'L

lower than serum range

137- 145minol.t.

22 - 30 mmol 'L

98- I07mmoI'I.

3 5 - 5 1 minol'l. - seiiiin'lasma :<tnge 0 i - 'J 7 mmol.L

lower than serum ranee

137- 145 mmol/L

NOTE: this chart applies to the VITROS DT60/DT60 II Chemistry Systems, VITROS DTE/DTE II modules, and VITROSDTSC/DTSC II modules.

* IFJ - Instructions For Use. For details on IFU, refer to www.orthoclinical.com

Pub. No. J234Q7 EN 2005-08-12 ?Ortho-Clinicai Diagnosticsa (joJm*cn-<|}efttt*OK company

VITRChemistry

Products

Assay Summary2 / 2

i ;:;. 1 1 . - 1 •

lr..n

I I I . I I .I K. l l .i ' I). ..-• LI

1i

I I III I

I i d I 1 ) 1 V I I I I I " I • I . 1 1 )

k 1)1 Siii'ii .-i 11.-:cin | . o .

I I ) I 111 S l . l - l , I- 'I . , ' . T

H i ' * 1 ) 1 v i m . - ' ! l i - , - . i . P ' J M - I

I '1)1 V mi I. .. I 1)1 •

i •i

i{••

i( •

4 ~i •

Aianinej Aminotransferase

• ' i < i , i

, ' i . , . . ..-

I'Z'.f", ,1a.,,.

I ' l l

C I ; . ' 11. .liM*"*

i i n ,i k u < *

Ml!

- . . M . i l i u -

I Mi'. I re-iuiim.-

ALTDT

MM 111

'- kl1 1)1

•\M 1)1

I i l H

1 li> 1)1

I k HT

• 'KMHDI

( KM Hi

l.rCRl)i

Serum,

N i P .

"•» 11 1

Sirurr •

S 111 I

- -

vi. ,"

l)l-i-i.i

Hepann, or EDTA piasma

.... . - , „ . -1

i I.-, . .M ! j » - u

1

,-• i ~ - . i i i'<*-.:- j

• • • I . , - . •

• 1. i i | i

I ' i . n l l ,-.i . . : • ! - . ' • s

i DT Calibrator Kit

;>i . ii

, i -

1)1 i „: -,

1)1 • 1

IJI S.-U.I.

[ i n "

Dl 1... i.1 .ir-: ...

1). 1 .

I l l (.ill '

h i '

i r .

... K..-

. k

•llv

i k '

. .1 , ,

ku

O. k . -

BpttteNosset Cojwentional Unit*5Recommended Diluent*

I

A 4

.) i i • 11 i k ~ .:.

IJI ( 'n..., I, kll I 2 A. 4

i)i c ii, - . Kii i : A. -i

1)1 I . ••i.-iili- Kit 1 2 i. ••

( ,i".Vi'kn ' " A '

3 - 950 U/L : VITROS 7% BSA or Isotonic saline

V k I l».'|i !-l dl I L .1 IL^J.11. J".'..l ' * , it

II •. I I K - x . - . ' , I , . - ,

i - ' - l i 1 \ I !'<()•> UHu N.l'i.i -.''i-i.

1 I ' I I ' - I- 'I I \llko-. .is ,

i ' >i.. i i !••• i i \ n n u i - JU-)\ • ,ivw.m-.. . i n .

-i . - . i II \ I I R ( A • . | - \ i I i i . i .

H.I.I 0 I k 111 • Kl , . l i . ' ! " -> ' l t r

I : . - - , • II \ I i l ^ h s \ I . i-i . I .

]• - ; ' ' i i j . l h - - ' l ' no 1 l-.-.-'u. r.ji). it ' .h. -i -M

I •- I - I I . . — I I \ : list)-. - u . , s \ . I i . , '!iii

1" - : . . . . i I. 1-. -:•:„• I I l » ' u i i * i i . i i t . » :-i!r<.,. n t u

I \ i .i.li

I t U O D I ^ : : iniolli. ,n ,,.„„,- M i t | I H ( K | i 1 _.*., 1 ,.-!,.»..,

. . i f . i i r N O T E l - _ i d . " - J [ - j j ' i e v l I , . . L ' U L - l e C ! K ~ ' » i i i . ! y ^ , j e — . i , " P . - o . . i - T T E ' I •», j s s a - d . l T P - o

4 U^^er ,J:JL =! temperaue fjr rtf-3e."te i Lpper l..:.i. . f „ . . . - . a j i _ ._: . :_ -s DTSC/DTSC II modules.

j This information was current as of the publication date. The Instructions For Use are the authorized source for information about VITROS assays.

Adult 13-69 U/LM. 21-72 U/L .F:9-52U/L !

1321

9

-69 U/L-72 U/L-52 U/L

• I I . .

" I - • I . II

v - - . : : : i -. i

I ! (•" 1. H 11.1

>i - I " I I

' • • - I • • . 1 I

i • :••> i i

i

i

K-l. • .1 k\1'> 1 I

M - I I

^ I . ••>. I

• I - " I I

I . ; I

M • ! ' - s . . . 1

• ' • ' ' . I

- ' . - - I * . 1 I

: i - » . i i

i : i . ^ i

- » I II I

. . I- 1, -.- I_ 1 , , 1 .'

©Ortho-Clinical Diagnostics, Inc., 2005 • VITROS is a trademark of Ortho-Clinical Diagnostics, Inc. • 100 Indigo Creek Drive • Rochester, NY 14626-5101 Pub. No. J23407 EN 2005-08-12''Ortho-Clinical Diagnostics

VITROS DT Isoenzyme Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Folha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <t>uAAo avaAuCTEOJv via Ta auaTrjuaTa VITROS DT KCU DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

GEN

CK 6061

CKMB 71727374

CONV

16314220192216

133-193112-17215-2514-2417-2711 -21

U/L

U/L

SI

16314220192216

133-193112-17215-2514-2417-2711-21

U/L

U/L

EnglishReconstituted StabilityWhen stored at 2-8°C (36-46-F):

• Stable for 5 days.

• 3 ImportantMinimize room temperature exposure of freeze-dried control or reconstituted control fluid.

FrancaisStabilite ReconstitueConservation a 2-S°C (36-46°F):

• Stable pendant 5 jours.

CH ImportantLimiter 1'exposition a la temperature ambiante de I'echantillon de contrfile lyophilise ou du liquide de contrflle reconstitue.

DeutschStabilitat nach der RekonstitutionBei Lagerung zwischen 2 und 8 °C:

• Stabil fur 5 Tage.

03 WichtigGefriergetrocknete Kontrolle oder rekonstituierte Kontrollflussigkeit moglichst kurz der Raumtemperatur aussetzen.

EspafiolEstabilidad de la ReconstitucionCuando se conserva a 2-8°C (36-46°F):

• Estable durante 5 d(as.

Q3 ImportanteReducir al mlnimo la exposicion a temperaturas ambiente del control liofilizado o del llquido de control reconstituido.

PortuguSsEstabilidade apos ReconstituicaoQuando conservado a uma temperatura entre 2 e 8°C:

• Estavel durante 5 dias.

• 3 IMPORTANTEMinimizar a exposicSo do Itquido de controlo liofilizado ou reconstituido a temperatura ambiente.

ItalianoStabilita Dopo La RicostituzioneConservato a 2-8°C (36-46°F):

• Stabile per 5 giorni.

Q3 ImportanteLimitare al minimo I'esposizione a temperatura ambiente del controllo. liofilizzato o del fluido di controllo ricostituito.

DanskRekonstitutionsstabilitetVed opbevaring ved 2-8° C:

• Stabil i 5 dage.

• 3 VigtigtS0rg for, at frysetgrret kontrol eller rekonstitueret kontrolvasske kun eksponeres minimalt for stuetemperatur,

814 6003

N5555

2005-10-31

2005-08-22

2005-03-14

I CONV I Conventional • Unites' ' Ponderales • KonvenBonelleEinheiten • Convencional •Convencional • Convenzionale •Konventionel • Konventionellaenheter • EUU(3CITIK£C; • Konvansiyonel

|—o j—I s l * U n i t e s s l • Sl-Einheiten •1 ' SI • SI • SI • SI • Sl-enheter •

Movdoc; SI • SI

t value • Resultat • V\fert •» » > ¥ * i Valor-Valor-valore-Vserdi • Varde • T\\if\ • Dejjer

,, „ Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet Intervalle. •Messbereich. Der mit demAnalysegerSt erhaltene Wat sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del anaiizador debeestardentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vasrdi skal iiggeinden for dette omrade. • Intervall.Analysinstrumentets varde bor liggainom detta omrade. • EOpoc TIUOOV.H Tiurj TOU avaAuTii Trpeirei va eunlnrciat OUT6 TO zupoq TIJJUW. • Aralik.

Analizorun degeri bu aralikta olmalidir.

jrv»_ Revised-Mise a jour d u -M l Revidiert • Revisifin •I f f l Revisto a • Aggiornato al •

Revideret • Reviderad • Ava8tupi<i8r)K£• Revize edildi

^ ^ 4 _ Supersedes • Remplace laI ^B^ f f l l v e r s ' o n d u ' Ersetzt •l ^ a f f l J Substituye• Segue-sea•Sostituisce la versione del • Erstatter •Ersatter • YTrtpioxuei • Yerine gecer

AIIU/mLandU/Lat37°C. • Lesactivites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L nan sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid 37°C. • OAE; OI U/mL KOI U/LOTOU? 37°C. • 37 °C'de turn U/mLve U/L.

f Ortho-ainkal DiagrosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 1(2)

V1TR0S DT Isoenzyme Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Folha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <J>uAAo avaAuaEwv yia ra auaTrjuaia VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

REF 814 6003

SvenskaStabilitet efter rekonstitutionForvaring vid 2-8°C (36-46T):

• Stabil i 5 dagar.

• 3 Viktigt!Minimera exponering av frystorkad tontroll eller rekonstituerad kontrollvatska for rumstemperatur.

Diav crrroenKEOtiai at etpuoKpaofa 2-8°C (36-46°F):Iia6ep6 yia 5

CBx

avaauora&l.irjv htBiar\ at tepuoKpaakx Suuailou IOU uypoO tAfyxou, TTOU tyti UTroaitl ^pavon uioio y<J£,q<; f\ TTOU X£I

Sulandinlmi§ Halde Stabilite2-8 "C'de saklandigjinda:

• 5 gun stabildir.

B OnemliLliyofilize kontrolOn veya sulandinlmis kontrol sivisinin oda sicakliQina maruziyetini en aza indirin.

N55552005-10-31

2005-08-22

2005-03-14

^Or t to -gn jca l DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(2)

VITROS DT Isoenzyme Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Folha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • cpuAAo avaAuuEWV yia TO auorriuciTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

GEN

CK 6061

CKMB 71727374

CONV

13213015151911

102-162100-16010-2010-2014-246-16

U/L

U/L

SI

13213015151911

102-162100-16010-2010-2014-246-16

U/L

U/L

EnglishReconstituted StabilityWhen stored at 2-8°C (36-46°F):


03 ImportantMinimize room temperature exposure of freeze-dried control or reconstituted control fluid.

FrancaisStabilite ReconstitueConservation a 2-8°C (36-46°F):


LTD ImportantLImiter rexposition a la temperature ambiante de I'echantillon de controle lyophilise ou du liquide de controle reconstitue.


• Stabil for 5 Tage.

• 3 WichtigGefriergetrocknete Kontrolle Oder rekonstituierte Kontrollflussigkeit moglichst kurz der Raumtemperatur aussetzen.

EspaftoiEstabilidad de la ReconstitucionCuando se conserva a 2-8°C (36-46°F):

• Estable durante 5 dlas.

03 ImportanteReducir al mlnimo la exposicion a temperaturas ambiente del control liofilizado o del Ifquido de control reconstituido.

PortuguesEstabilidade apos ReconstituicaoQuando conservado a uma temperatura entre 2 e 8°C:


03 IMPORTANTEMinimizara exposicao do llquido de controlo liofilizado ou reconstitutdo a temperatura ambiente.

Italia noStabilita Dopo La Ricostituzione

' Conservato a 2-8°C (36-46°F):• Stabile per 5 giorni.

03 ImportanteLimitare al minimo I'esposizione a temperatura ambiente del controllo. liofilizzato o del fluido di controllo ricostituito.



03 VigtigtS0rg for, at fryseterret kontrol eller rekonstitueret kontrolvasske kun eksponeres minimalt for stuetemperatur.

REF 814 6003

LOT P5854

2006-10-31

2005-08-22

2005-03-14

I C O N V I Conventional • Unites' Ponderales • Konventionelle

Einheiten • Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • ZuppaTiKt; • Konvansiyonel

SI-Unites SI-Sl-Einheiten •SI-SI-SI-SI-SI-enheter>Movdoe? SI • SI

'i Value • Resultat • Wfert •**am valor-Valor-Valore •Vasrdi-Varde-Tiurj-DegerI, w Range. The analyzer value

should fall within this range.• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. -Messbereich. Der mit demAnalysegerat erhaltene Wfert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vaerdi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bor liggainom detta omrade. • Eupo? Tipciiv.H Tiun, TOU avaAuTii TrpeTrei va cuTrnrneiat OUT6 TO tupa; Tiutuv. • Aralik.Analizorun degeri bu aralikta olmalidir.

ft. Revised • Mise a jour du •Wm Revidiert • Revisi6n •i ^ J Revisto a • Aggiomato al •

Revideret • Reviderad • Ava6E(opr}6r|KE• Revize edildl

n g f c f t v Supersedes • Remplace laH K E S ] version du • Ersetzt •i S r f f l l Substituye-Segue-sea-Sostituisce la versione del • Erstatter •Ersatter • YirrepioxuEi • Yerine geger

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L nan sidocalculados a 37°C. • Todas U/mL eU/L a 37-C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/I ved 37° C. • Alia U/mL och U/Lvid 37"C. • OAEC OI U/mL Kdi U/Lorou? 37"C. • 37 °C'de turn U/mLve U/L.

^OrfogQinical Diagnost'csVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 1(2)

VITROS DT Isoenzyme Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sjstemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <t>uAAo avaAOaewv via m auaTnuaTa VITROS DT KQ\ DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

814 6003

SvenskaStabilitet efter rekonstitutionFOrvaring vid 2-B°C (36-46T):


03 Viktigt!Minimera exponering av frystorkad kontroll eller rekonstituerad kontrollvatska Tor rumstemperatur.

EAAn,viK<S

Diav OTT09r|K£i5eTai at 6epuoKpaola 2-8°C (36-46°F):£ia6Ep6 yia 5 riu£p«;.

CBEAaxioiOTroiriaiE iqv tK6tar\ at eepuoKpaofa Siouarfou IOU uypoO tAiyxou, TTOU £X« UTrooicf ^pavor) piaw i(iO5n? f\ TTOU t%aavaouoiaetl.

Sulandir i lmi ; Halde Stabilite2-8 °C'de saklandiginda:

• 5 gOn stabildir.

QD OnemliLliyofflize kontrolon veya sulandinlmis kontrol sivismin oda sicakhQina maruziyetini en aza indirin.

LOT P58542006-10-31

2005-08-22

2005-03-14

tprtho-ClJnicalVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(2)

VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fiir VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAuatcov yia Ta auaTqijaTa VITROS DT KOI DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

ALB

ALKPALT

AMYLAST

UN/UREACa

CHE

CHOL

CK

Cl-

CO2

CREACRSC

Fe

GT

GLU

HDLC

K+

LAC

LDH

Li

LIPA

GEN

545555

5758597558

54

69707172735153575859606153

52

51

5457565755575354555655565751

596061596052535758

2.42.290

383436358940

18

9.09.29.39.09.23.623.4214615015214616481

23.71.1

1.11.184827175818282893332342.8

1.41.41.4

4414351.01.2200188

CONV

2.1-2.71.9-2.576-10426-5022-4624-4823-4764-11421 -59

g/dL

U/L

U/L

U/L

U/L

15-21 mg/dL8.4 - 9.68.6 - 9.88.7 - 9.98.4 - 9.68.6 - 9.8

3.02 - 4.222.82 - 4.02133-159137-163139-165114-178132-19676-86

18.7-28.70.8-1.40.9-1.30.9-1.368 - 10066-9859-8363-8770-9271 -9371 -9378-10022-4421 -4323-452.5-3.11.1-1.71.1-1.71.1-1.7

393 - 489387 - 4830.6-1.40.8-1.6182-218170-206

mg/dL

U/mL

mg/dL

U/L

mmol/Lmmol/Lmg/dLmg/dL

U/L

mg/dL

mg/dL

mmol/Lmmol/L

U/L

mmol/L

U/L

SI

242290

3834363589

40

6.4

2.252.302.322.252.30362034203.83.93.914616481

23.797

9797

15.014.771754.54.64.64.90.850.830.882.8

1.41.41.44414351.01.2200188

2119

•27• 2 5

76-10426-22-24-23-

50464847

64-11421 -595.4 - 7.5

2.10-2.15-2.17-2.10-2.15-

2.402.452.472.402.45

3020-2820-

42204020

3.4-3.5-3.6-

4.14.24.3

114-132-

178196

76-8618.7-28.771 -12480-80-

115115

12.2-11.8 •

17.917.5

59-63-

8387

3.9-3.9-3:9-4.3-

5.15.25.25.6

0.57-0.54-0.59-

1.141.111.16

2.5-3.11.11.11.1

1.71.71.7

393-387-

489483

0.60.8

• 1 . 4

• 1 . 6

182-170-

218206

U/L

U/L

U/L

U/L

mmol/Lmmol/L

U/L

mmol/L

U/L

mmol/Lmmol/Lpmol/L(jmol/L

|Jmol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

U/L

mmol/L

U/L

REF 842 0317

LOT Q5480

2005-09-30

2005-08-22

2005-03-14

Conventional • UnitesPonderales • Konventionelle

Einheiten • Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • luupcrriKfc; • Konvansiyonel

SI • Unites SI • Sl-Einheiten •SI • SI • SI • SI • Sl-enheter •Movd6£?SI-SI

* Value • Resultat • Wfert •M-fr-—! valor -V&lor- Valore -Vaerdi-Varde-Tiuii-Deger

I, H Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnaiysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets veerdi skai liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bor liggainom detta omrade. • EOpo? Tiutuv.H Tiuri TOU avaAuni Trpnrei va EUTriTrraat auTO TO EOpo; TIUUV. • Arahk.Analizorun degeri bu aralikta olmalidir.

.?%-* Revised-Mise a jour du*Ifffflj Revidiert • Revisi6n •ISSil Revisto a • Aggiomato al •

Revideret- Reviderad -AvaBEioprlSriKE• Revize edildi

. A ^ Supersedes • Remplace laH w M i | version du • Ersetzt •

\miim] Substituye• Segue-sea•Sostituisce la versione del • Erstatter •Ersatter • YTTEPIOXUEI • Yerine ge?er

All U/mL and U/L at 37°C. • Lesactlvites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 "C gemessen. • Todoslos valores de U/mL y U/L nan sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodetemninati a 37"C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid 37°C. • OAE? OI U/mL rai U/L

orou? 37°C. • 37 "C'de tilm U/mLve U/L.

VITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 1(4)

VITROS DT Control 1Assay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROSDT II • Datenblatt fur VITROS DT und DT II Systemey DT II • Foiha do Ensaio para os Sistemas VITROS

DTet• Hoja de ensayo para los Sistemas VITROS DTDT e DT II • Foglietto di dosaggio per Sistemi

VITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAua£U)v Yia Ta ouaTi]|jaTa VITROS DT KCJI DT 1Test Sayfasi

GEN

Mg 5859

Na+ 52NBIL 64

65NH3 54

55PHOS 58

59"BIL 74

7576

THEO 62TP 62

6364

TRIG 60URIC 54

55

•As2.12.2118

1.01.277773.63.61.51.3

1.512.13.63.74.0108

4.03.8

EnglishQg Pretreatment Required

. HDLC

Reconstituted StabilityWhen stored at 2-8°C (36-46°F):


• Stable for 3 days: ALKP, Ca, CK, NBIL, TBIL.

• Stable for up to 8 hours: NH3

FrangaisH[i] Pretraitement necessaire, • HDLC

Stabilite ReconstitueConservation a 2-8°C (36-46°F):


. Stable pendant 3 jours: ALKP, Ca, CK, NBIL, TBIL.

• Stable pendant 8 heures apres le pretraitement: NH3.

DeutschQi] Vorbehandlung erforderlich

. HDLC

Stabil i tat nach der RekonstitutionBei Lagerung zwischen 2 und 8 °C:


. Stabil fur 3 Tage: ALKP, Ca, CK, NBIL, TBIL.

• Bis zu 8 Stunden nach der Vorbehandlung stabil: NH3

I • VITROS DT ve DT

CONV

1.8-1.9-113-0.3-0.5-4 2 -4 2 -3.0-3.0-1.0-0.8-1.0-

8.8-3.1-3.2-3.5-9 3 -

3.6-3.4-

—H

2.42.5123

1.71.9

1121124.24.22.01.82.015.44.14.24.5123

4.44.2

mg/dL

mmol/Lmg/dL

umol/L

mg/dL

mg/dL

ug/mLg/dL

mg/dLmg/dL

0.860.91118

17217777

1.161.1626222667

363740

1.22238226

II Sistemleri icin

SI

«

0.740.78113

5 -9 -

42 -42 -

0.970.97

17141749

313235

1.05214202

I—H

-0.99-1.03-1232932112112

-1.36-1.36-34-31-34-85

-41-42-45-1.39-262-250

mmol/L

mmol/Lpmol/L

|jmol/L

mmol/L

|jmol/L

umol/L

g/L

mmol/Lpmol/L

REF 842 0317

LOT Q5480

2005-09-30

2005-08-22

2005-03-14

^Ortho-qinkal DiafflosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(4)

VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • (MAAo avaAucr£U)v yia Ta auarrJijaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

REF 842 0317

Espanol[Jij Se requiere tratamiento previo

. HDLC

Estabilidad de la ReconstitucionCuando se consetva a 2-8°C (36-46°F):

• Estable durante 7 dfas.

• Estable durante 3 dfas: ALKP, Ca, CK, NBIL, TBIL

• Estable durante 8 horas despuSs de tratamiento previo: NH3.

Port ug uesQiJ Necessario Tratamento Previo

• HDLC

Estabilidade apos ReconstituicaoQuando oonservado a uma temperature entre 2 e 8°C:


• Estavel durante 3 dias: ALKP, Ca, CK, NBIL, TBIL.

• Estavel durante 8 horas depois do tratamento previo: NH3.

ItalianoQi] £ richiesto il pretrattamento

• HDLC

Stabilita Dopo La RicostituzioneConservato a 2-8°C (36-46°F):


• Stabile per 3 giorni: ALKP, Ca, CK, NBIL, TBIL.

• Stabile per 8 ore dopo il pretrattamento: NH3.

DanskQV| Forbehandling pakraevet

. HDLC

RekonstitutionsstabilitetVed opbevaring ved 2-8° C:


• Stabil i 3 dage: ALKP, Ca, CK, NBIL, TBIL

• Stabil i 8 timer efter forbehandling: NH3.

SvenskaQT| Forbehandling kravs

• HDLC

Stabilitet efter rekonstitutionForvaring vid 2-8°C (36-46°F):

• Stabil i 7 dagar. -

• Stabil i 3 dagar: ALKP, Ca, CK, NBIL, TBIL.

• Stabil i 8 timmar efter forbehandling: NH3.

EAAr]ViKdQT]

• HDLC

lTa9EpoTr|Ta avacruoraan,?Drav arro9nKe0eiai at 6£puoKpaofa 2-8°C (36-46°F):

• Zia8£p6 yict 7 rptptc;.

Sia6£p6 y«a 3 HM^P^: ALKP, Ca, CK, NBIL, TBIL,

IiaSepo Yia 8 (ipec; ptra rnv TTpo£TT£|£pYaofa: NH3.

LOT Q5480

2005-09-30

2005-08-22

2005-03-14


VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt filr VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II * Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • ct>uAAo avaAuaoov via TO auarrJuaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

REF 842 0317

TUrkgeQi] Gereken 6ni§lem

• HDLC

Sulandinlmi? Halde Stabilite2-S "C'de saklandiijinda:

• 7 gtin stabildir.

• 3 gone kadar stabil: ALKP, Ca, CK, NBIL, TBIL

• 6n if lemden sonra 8 gQne kadar stabil: NH3.

Q54802005-09-30

2005-08-22

2005-03-14


VITROS DT Isoenzyme Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Folha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <t>uAAo avaAucrewv yia Ta auaTrjuaTa VITROS DT KOI DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

GEN

CK 60

61

CKMB 71

72

73

74

132

127

15

16

15

12

CONV

102-162

97-157

10-20

11 -21

10-20

7-17

U/L

U/L

SI

132

127

15

16

15

12

102-162

97-157

10-20

11-21

10-20

7-17

U/L

U/L

EnglishReconstituted StabilityWhen stored at 2-8°C (36-46°F):


dS ImportantMinimize room temperature exposure of freeze-dried control or reconstituted control fluid.

FrancaisStabilite ReconstituteConservation a 2-8°C (36-46°F):


OS ImportantLimiter rexposition a la temperature ambiante de I'echantillon de controle lyophilise ou du liquide de contrOle reconstitufe



OB WichtigGefriergetrocknete Kontrolle oder rekonstituierte Kontrollflussigkeit moglichst kurz der Raumtemperatur aussetzen.

EspaftolEstabilidad de la ReconstitucionCuando se conserva a 2-8°C (36-46°F):

• Estable durante 5 dfas.

Q3 ImportanteReducir al mtnimo la exposici6n a temperaturas ambiente del control liofilizado o del Hquido de control reconstituido.

PortuguisEstabilidade apos Reconstitui^aoQuando conservado a uma temperatura entre 2 e 8°C:


CB IMPORTANTEMinimizar a exposigao do Hquido de controlo liofilizado ou reconstituido a temperatura ambiente.

ItalianoStabilita Dopo La RicostituzioneConservato a 2-8°C (36-46°F):


C0 ImportanteLimitare al minimo I'esposizione a temperatura ambiente del controllo. liofilizzato o del fluido di controllo ricostituito.



• 3 VigtigtSarg for, at fryset0rret kontrol eller rekonstitueret kontrolvaaske kun eksponeres minirnalt for stuetemperatur.

REF 814 6003

LOT Q6001

2007-03-31

2005-08-22

2005-04-19


Einheiten • Conventional •Conventional • Convenzionale •Konventionel • Konvenfionellaenheter • luuftariKi; • Konvansiyonel

I—gj—I SI -Unites SI - Sl-Einheiten •1 ' SI • SI • SI • SI • Sl-enheter •

MovdOE? SI • SI

i Value • Resultat • Wert •mmmiiM valor • Valor • valore •Vserdi-Varde-Tp^Deger

h H Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. DermitdemAnalysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del anatizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intetvallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vaardi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bor liggainom detta omrade. • EOpcx; Tiuiiw.H Ti|jrj TOU avaAuiii npiirei va Eutriin£iat auTo TO tCipo; TIUUV. • Aralik.Analizfiriin degeri bu aralikta olmalidir.

t Revised • Mise a jour du •Revidiert • Revision •Revisto a • Aggiornato al •

Revideret • Reviderad • Ava8£(jopii8r|KE• Revize edildi

^ i v Supersedes • Remplace la• M B ] version du • Ersetzt •M H l f f l l Substituye • Segue-se a •Sostituisce la versione del • Erstatter •Ersatter • YTTEPIOXUEI • Yerine gecer

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminees a 37"C. • Enzymaktivitaenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37° C. -Alia U/mL och U/Lvid 37°C. • OAE; OI U/mL KOI U/LOTOU? 37"C. • 37 °C'de turn U/mLve U/L.


VITROS DT Isoenzyme Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Folha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAucjEuov via TCI ovcnf\\iana VITROS DT KCII DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

REF 814 6003

SvenskaStabilitet efter rekonstitutionForvaring vid 2-8°C (36-46°F):

• Stabll i 5 clagar.

OH Viktigt!Minlmera exponering avfrystorkad kontroll eller rekonstituerad kontrollvatska for rumstemperatur.

EAAn.viKd

Oiav orrroeriKEOeiai os 6ep(jOKpaafa 2-8°C (36-46°F):Iia6£p6 via 5 nu£p£?.

OSavaauoia9El.

oiE iny £K9EOT| oe etp^joKpaofa Swuailou IOU uypoO £A£YX°U, TTOU 4XEI UTTOOTEI pavon, |j£aco i O n,? i TTOU txz\

Sulandinlmi§ Halde Stabilite2-8 °C'de saklandiginda:5 gun stabildir.

OnemliLliyofilize kontrolQn veya sulandirilmi? kontrol sivisinin oda sicakhgina maruziyetini en aza indirin.

LOT Q6001

2007-03-31

2005-08-22

2005-04-19


VITROS DT Control IAssay Sheet for VITROS DT and DT I! Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAuaewv yia m auorrjuaTo; VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

ALB

ALKPALT

AMYL

AST

BUN/UREACa

CHE

CHOL

CK

Cl-CO2CREACRSC

GGT

GLU

HDLC

K+LAC

LDH

Li

GEN

545555

5657585960757658

54

69707172735153575859606153

52

5154575657555758535455565556

_5751596061596052

CONV

2.52.388

263331313210811236

19

9.19.19.29.09.13.983.7915315315620022281

23.41.3

1.11.1103105737875899292983131322.8

1.41.41.44264081.1

2.2-2.82.0-2.674-10214-3821-4519-4319-4320-4483-13387-13717-55

16-22

8.5 - 9.78.5 - 9.78.6-9.88.4 - 9.68.5-9.7

3.38-4.583.19-4.39140-166140-166143-169168-232190-25476-86

18.4-28.4

1.0-1.6

0.9-1.30.9-1.387-11989-12161 -8566-9063-87

78-10081-10381 - 10387-10920-4220-4221-432.5-3.11.1-1.71.1-1.71.1-1.7

378 - 474360 - 4560.7-1.5

g/dL

U/L

U/L

U/L

U/L

mg/dLmg/dL

U/mL

mg/dL

U/L


U/L

mg/dL

mg/dL

mmol/Lmmol/L

U/L

mmol/L

SI

252388

263331313210811236

22-20-

2826

74-10214-21-19-19-20-

3845434344

83-87-

133137

17-556.8 5.7-7.92.272.272.302.252.27398037904.04.04.020022281

23.4115

9797

18.418.87378754.95.15.15.40.800.800.832.8

1.41.41.4426408

2.12-2.12-2.15-2.10-2.12-

2.422.422.452.402.42

3380-3190-

45804390

3.6-3.6-3.7-

4.34.34.4

168-190-

232254

76-8618.4-28.488 - 14180-80-

115115

15.6-15.9-

21.321.7

616663

•85

•90

-874.3-4.5-4.5-4.8-

5.65.75.76.1

0.52-0.52-0.54-

1.091.091.11

2.5-3.11.11.11.1

1.71.71.7

378-360-

474456

1.1 0.7-1.5

g/L

U/L

U/L

U/L

U/L

mmol/Lmmol/L

U/L

mmol/L

U/L

mmol/Lmmol/L|jmol/L(jmol/L

Mmol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

U/L

mmol/L

REF 842 0317

LOT[ T56522006-04-30

2005-08-22

2005-03-14

I CONV I Conventional • Unites' Ponderales • Konventionelle

Einheiten • Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • luupariKfc • Konvansiyonel

SI -Unites SI - Sl-Einheiten •SI • SI • SI • SI • Sl-enheter •

SI

J Value • Resultat • Wert •l g a t B S M Valor-Valor • Valore-Vaardi • VaYde • Tun, • De§er

K ri Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnalysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstnjmentets vsrdi skal llggeinden for dette omra"de. • Intervall.Analysinstrumentets varde bor liggainom delta omrade. • EOpo? TIU&V.H nun, TOU avaXuTrj TTPEWEI va EiJTrimEiot auTO TO Edpos HJJUIV. > Aralik.Analizorun degeri bu aralikta olmalidir.

t Revised • Mise a jour du •Revidiert-Revisi6n-Revisto a • Aggiornato al •

Revideret • Reviderad • Ava8£U)pti6r|K£• Revize edildi

BBt£VM Supersedes • Remplace la^^ESffll version du • Ersetzt •^• ra f f i j Substituye-Segue-sea-Sostituisce la versione del • Erstatter •Ersatter • YmpicrxuEi • Yerine gecer

Ail U/mL and U/L at 37°C. • Lesactivites enzymatjques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37" C. • Alia U/mL och U/Lvid 37°C. - O A E ; 01 U/mL rai U/LOTOUC 37°C. • 37 °C'de turn U/mLve U/L.

Ortho-Clinkal PagnostiesVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 1(4)

VITROS DT Control 1Assay Sheet for VITROS DT andDT II • Datenblatl fur VITROS DT

DT II Systems • Fiche de controle pour les Systemes VITROSund DT II Systeme • Hoja de ensayo para los!

DTetBistemas VITROS DT

y DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS tDT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAu0£U)v yia Ta ouoTi uaTa VITROS DT Kai DT 1Test Sayfasi

GEN

...Li 53LIPA 57

5859

Mg 5859

Na+ 52NBIL 64

6566

NH3 5455

PHOS 5859

TBIL 747576

THEO 6263

TP 626364

TRIG 60URIC 54

55

EnglishQI] Pretreatment Required

• HDLC



• Stable for 3 days: ALKP, Ca, CK, NBIL,


FrancaisQi] Pretraitement necessaire

. HDLC



. Stable pendant 3 jours: ALKP, Ca, CK,

I • VITROS DT ve DT II Sistemleri icin

L CONV |

1.1

2652472712.02.1117

1.11.11.51141083.63.51.51.51.511.39.23.73.84.11054.14.0

TBIL.

NBIL, TBIL.


N M

0.7-1.5247 - 283229 - 265253 - 2891.7-2.31.8-2.4112-1220.4-1.80.4-1.80.8 - 2.279 - 14973 - 1433.0-4.22.9-4.11.0-2.01.0-2.01.0-2.0

8.0-14.65.9-12.53.2 - 4.23.3-4.33.6-4.690-1203.7 - 4.53.6 - 4.4

mmol/LU/L

mg/dL

mmol/Lmg/dL

umol/L

mg/dL

mg/dL

ug/mL

g/dL

mg/dTT1

mg/dL

1.1

2652472710.820.86117

1919261141081.161.132626266351373841

1.19244238

SI

H H

0.7-1.5247 - 283229 - 265253 - 2890.70-0.950.74 - 0.99112-122

7-317-3114-38

79-14973 - 143

0.97-1.360.94-1.32

17-3417-3417-3444-8133-6932-4233-4336-46

1.02-1.36220 - 268214-262

mmol/LU/L

mmol/L

mmol/Lumol/L

umol/L

mmol/L

umol/L

Mmol/L

9/L

mmol/Lumol/L

842 0317

LOT T5652

2006-04-30

2005-08-22

2005-03-14

Ortho-Clnical DJagnosfcs»flBhww«ffil«w company VITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(4)

VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • 0uMo avaAuCTEWv yia ra aucmpaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

REF 842 0317

DeutschQT) Vorbehandlung erforderlich

• HDLC

Stabilitat nach der RekonstitutionBei Lagerung zwischen 2 und 8 °C:

• Statail far 7 Tage.

• Stabil far 3 Tage: ALKP, Ca, CK, NBIL, TBIL.

• Bis zu 8 Stunden nach der Vorbehandlung stabil: NH3.

EspafiolQlij Se requiere tratamiento previo

• HDLC

Estabilidad de la ReconstitucionCuando se conserva a 2-8°C (36-^)6°F):


• Estable durante 3 dfas: ALKP, Ca, CK, NBIL, TBIL.

• Estable durante 8 horas despues de tratamiento previo: NH3.

Portugues[Ji] Necessario Tratamento Previo

• HDLCEstabilidade apos ReconstituicaoQuando conservado a uma temperatura entre 2 e 8°C:


. Estavel durante 3 dias: ALKP, Ca, CK, NBIL, TBIL.


ItalianoQij E richiesto il pretrattamento

• HDLCStabilita Dopo La RicostituzioneConservato a 2-8°C (36-46°F):




DanskQij Forbehandling pakraevet

. HDLC



• Stabil i 3 dage: ALKP, Ca, CK, NBIL, TBIL


SvenskaQg Forbehandling kravs

• HDLC

Stabilitet efter rekonstitutionFOrvaring vid 2-8°C (36-46°F):


. Stabil i 3 dagar: ALKP, Ca, CK, NBIL, TBIL.


T5652

2006-04-30

2005-08-22

2005-03-14


VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OOAAo avaAuaEWV yia TO auaTrj|jaTa VITROS DT KOI DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

842 0317

EAAr|ViKci

HDLC

Ta avaauonraansDiav arroSniaOtTai at 9£p(JOKpaota 2-8°C (36-46°F):Iia8£p6 yia 7 wtpt<;.

IiaOtpo yia 3 mitpa;: ALKP, Ca, CK, NBIL, TBIL.

: NH3.

TUrkge[Ji] Gereken Oni§lem

• HDLC

Sulandinlmif Halde Stabilite2-8 °C'de saklandiginda:

• 7 gan stabildir.

. 3 gQne kadar stabil: ALKP, Ca, CK, NBIL, TBIL.

• On i§lemden sonra 8 gQne kadar stabil: NH3.

LOT T56522006-04-30

2005-08-22

2005-03-14

Ortho-CIJnScal DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 4(4)

VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • 0uAAo avaAuaEcov yia TO auorrJLiaTa VITROS DT KCII DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

ALB

ALKPALT

AMYL

AST

BUN/UREACa

CHE

CHOL

CK

Cl-CO2

CREACRSC

GGT

GLU

HDLC

K+

LAC

LDH

Li

GEN

54555556575859607576585469707172735153575859606153

5251545756575557585354555655565751

5960615960

2.62.5103

31343637409910736

19

8.89.08.98.99.1

4.214.1216716516718817878

24.61.31.11.18690707572858784923838372.9

1.51.51.5415398

52 1.1

CONV

2.3 - 2.92.2-2.889-11719-4322-4624-4825-4928-5274-12482 -13217-55

16-22

8.2 - 9.48.4 - 9.68.3 - 9.58.3 - 9.58.5-9.7

3.61 -4.813.52 - 4.72154-180152-178154-180156-220146-21073-83

19.6-29.6

1.0-1.6

0.9-1.30.9-1.370-10274-10658-8263-8760-84

74-9676-9873-9581 -10327-4927-4926-482.6-3.21.2-1.81.2-1.81.2-1.8

367 - 463350 - 4460.7-1.5

g/dL

U/L

U/L

U/L

U/L

mg/dLmg/dL

U/mL

mg/dL

U/L


U/L

mg/dL

mg/dL

mmol/Lmmol/L

U/L

SI

262510331343637409910736

6.8

2.202.252.222.222.27421041204.34.34.318817878

24.6115

9797

15.416.17075724.74.84.75.10.980.980.962.9

1.51.51.5415398

23-22-

2928

89-11719-22-24-25-28-

4346484952

74-82-

124132

17-555.7-7.9

2.05-2.10-2.07-2.07-2.12-

2.352.402.372.372.42

3610-3520-

48104720

4.0-3.9-4.0-

4.74.64.7

156-146-

220210

73-83

80-80-

115115

12.5-13.2

18.319.0

58-63-60-

828784

4 . 1 •

4.2-4.1-4.5-

5.35.45.35.7

0.70-0.70-0.67-

1.271.271.24

2.6 - 3.21.2-1.2-1.2-

1.81.81.8

367-350-

463446

mmol/L| 1T 0.7-1.5

9/L

U/L

U/L

U/L

U/L

mmol/Lmmol/L

U/L

mmol/L

U/L

mmol/L19.6-29.6 mmol/L88-141 |jjmol/L

Mmol/L

umol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

U/L

mmol/L

REF 842 0317

LOT V5856

2006-12-31

2005-08-22

2005-03-14

I CONV I Conventional • Unites' Ponderales • Konventionelle

Einheiten • Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • IUUPCITIKE'S • Konvansiyonel

I—5—I SI • Unites SI • Sl-Einheiten •1 ' Sl-SI-SI-SI-SI-enheter-

Mov<Soe;SI-SI

Value • Resultat • Wtert •Valor-Valor-Valore•

Vserdi-Varde-Tiuri'Deger

n rt Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnalysegerSt erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vaerdi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bor llggainom detta omrade. • EOpoc TIUCOV.H Tipq TOU ovaAuirj TrpETrei va EMTrrrrraat auTo TO Eupo? TIUWV. • Aralik.Analizorun degeri bu aralikta olmalidir.

t Revised• Mise a jour du •Revidiert • Revisi6n •Revisto a • Aggiornato al •

Revideret • Reviderad • Ava8£(jjpner|K£• Revize edildi

, > j _ Supersedes • Remplace laW c W l version du • Ersetzt •Baarrai Substituye-Segue-sea-Sostituisce la versione del • Erstatter •Ersatter • Yntpioxuei • Yerine ge?er

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37-C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid 37"C. • OAE? oi U/mL KCII U/LOTOUC 37°C. • 37 °C'de turn U/mLve U/L.

Ortho-Clinical DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 1(4)

VITROS DT Control 1Assay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • ct>OAAo avaAuaeujv yra Ta ouorrjuaTa VITROS DT m DT II • VITROS DT ve DT II Sistemleri i?inTest Sayfasi

GEN... Li 53L1PA 57

5859

Mg 5859

| CONV

miU,1.1

2272142311.91.9

Na+ 52 | 116NBIL 64

6566

NH3 5455

PHOS 5859

TBIL 747576

THEO 6263

TP 626364

TRIG 60URIC 54

55

1.01.11.3102943.73.61.41.31.3

10.49.34.03.94.091

4.24.1

H H

0.7-1.5209 - 245196-232213-2491.6-2.21.6-2.2

111-1210.3-1.70.4-1.80.6-2.067 -13759-1293.1 -4.33.0-4.20.9-1.90.8-1.80.8-1.87.1-13.76.0-12.63.5-4.53.4-4.43.5-4.576 -1063.8-4.63.7-4.5

mmol/LU/L

mg/dL

mmol/Lmg/dL

umol/L

mg/dL

mg/dL

ug/mL

g/dL

mg/dLmg/dL

I SI

1.12272142310.780.78

| ^ W\

0.7-1.5209 - 245196-232213-2490.66-0.910.66 - 0.91

116 | 111-12117192210294

1.191.162422225852403940

1.03250244

5-297-3110-34

67-13759-129

1.00-1.390.97-1.36

15-3214-3114-3139-7633-7035-4534-4435-45

0.86-1.20226 - 274220 - 268

mmol/LU/L

mmol/L

mmol/Lumol/L

umol/L

mmol/L

umol/L

umol/L

g/L

mmol/Lpmol/L

EnglishQi] Pretreatment Required

• HDLC





FrangaisQTJ Pretraitement necessaire

. HDLC

Stabilite ReconstituteConservation a 2-8°C (36-46°F):


. Stable pendant 3 jours: ALKP, Ca, CK, NBIL, TBIL.


REF 842 0317

LOT V58562006-12-31

2005-08-22

2005-03-14

Ortho-Clinical Diagnosticscompany VITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(4)

VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAucFEOJV yia ia auaTtipaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

REF 842 0317

LOT V58562006-12-31

2005-08-22

Deutsch[]1] Vorbehandlung erforderlich

• HDLC





EspaholQi] Se requiere tratamiento previo

• HDLC

Estabilidad de la ReconstitucionCuando se conserva a 2-8°C (36-46°F):

• Estable durante 7 d(as.

• Estable durante 3 dfas: ALKP, Ca, CK, NBIL, TBIL.


PortuguesQi] Necessario Tratamento Previo

. HDLC

Estabilidade apos ReconstituicaoQuando conservado a uma temperatura entre 2 e 8°C:


. Estavel durante 3 dias: ALKP, Ca, CK, NBIL, TBIL.


ItalianoQ|| E richiesto il pretrattamento

• HDLC

Stabilita Dopo La RicostituzioneConservato a 2-8°C (36-46cF):

a Stabile per 7 giorni.

• Stabile per 3 giorni: ALKP, Ca, CK, NBIL, TBIL


Dansk[Jij Forbehandling pakraevet

• HDLC

RekonstitutionsstabilitetVed opbevaring ved 2-8° G:


• Stabil i 3 dage: ALKP, Ca, CK, NBIL, TBIL.


SvenskaQij Forbehandling kravs

• HDLC

Stabilitet efter rekonstitutionFOrvaring vid 2-8°C (36-46°F):




2005-03-14


VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAucjEUJV via Ta ouaTii(jaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

REF 842 0317

EAAnviKdQi]

• HDLC

Diav aTTO9r|KE0£iai at SEppoKpaofa 2-8°C (36-46°F):

• IiaespO yia 7 t)\itpt<;.

• Zia8£p6 yia 3 (]\itpt<;: ALKP, Ca, CK, NBIL, TBIL.

a: NH3.

TUrkge[JiJ Gereken Oni§lem

• HDLC

Sulandinlmi? Halde Stabilite2-8 °C'de saklandiginda:

• 7 gfln stabildir.

• 3 gone kadar stabil: ALKP, Ca, CK, NBIL, TBIL.

• On i§lemden sonra 8 gone kadar stabil: NH3.

V5856

2006-12-31

2005-08-22

2005-03-14


VITROS DT Control 1Assay Sheet for VITROS DTandDT II • Datenblatt fur VITROS DTy DT II • Foiha do Ensaio para os

DT II Systems • Fiche de controle pour les Systemes VITROSund DT II Systeme • Hoja de ensayo para los

DTetSistemas VITROS DT

Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • KontrollbladDT II • OuAAo avaAucTEUJv yia Ta auaTrjuciTa VITROS DT Kai DT 1Test Sayfasi

ALB

ALKP

ALT

AMYL

AST

BUN/UREA

Ca

CHE

CHOL

CK

Cl-

CO2

CREA

CRSC

e

GGT

GLU

HDLC

K+LAC

LDH

Li

GEN

545555

5657585960757658

54

69707172735153575859606153

52

51

5457565755575853545556565751

59606159605253

2.52.5105

272529273410910838

19

9.19.09.29.19.13.803.7815716115916715780

23.91.1

1.21.185927377758886859231302.8

1.41.41.44344251.11.2

CONVj

I • VITROS DT ve

H H

2.2-2.82.2-2.891-11915-3913-3717-4115-3922-4684-13483-13319-5716-228.5-9.78.4 - 9.68.6 - 9.88.5 - 9.78.5-9.7

3.20 - 4.403.18-4.38144-170148-174146-172135-199125-18975-85

18.9-28.90.8-1.41.0-1.40.9-1.369-10176-10861 -8565-8963-8777-9975-9774-9681 - 10320-4219-41

2.5-3.11.1-1.71.1-1.71.1-1.7

386 - 482377 - 4730.7-1.50.8-1.6

g/dL

U/L

U/L

U/L

U/L

mg/dL

mg/dL

U/mL

mg/dL

U/L

mmol/L

mmol/L

mg/dL

mg/dL

MQ/dL

U/L

mg/dL

mg/dL

mmol/L

mmol/L

U/L

mmol/L

2525105

272529273410910838

6.8

2.272.252.302.272.27380037804.14.24.116715780

23.997

10697

15.216.57377754.94.84.75.10.800.782.8

1.41.41.44344251.11.2

for VITROS DTochDT II Sistemleri icin

SI |

H H

22-2822-2891-11915-3913-3717-4115-3922-4684-13483-13319-57

5.7 - 7.92.12-2.422.10-2.402.15-2.452.12-2.422.12-2.423200 - 44003180-4380

3.7-4.43.8-4.53.8-4.4135-199125-18975-85

18.9-28.971 - 12488-12480-115

12.4-18.113.6-19.3

61 -8565 - 8963-874.3-5.54.2 - 5.44.1 -5.34.5-5.7

0.52-1.090.49-1.062.5-3.11.1-1.71.1-1.71.1-1.7

386 - 482377 - 4730.7-1.50.8-1.6

g/L

U/L

U/L

U/L

U/L

mmol/Lmmol/L

U/L

mmol/L

U/L

mmol/Lmmol/L(jmol/Lumol/L

umol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

U/L

mmol/L

842 0317

X6041

2007-04-30

2005-08-22

2005-06-10

Conventional • UnitesPonderales • KonvenSonelle

Einheiten • Convencional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • IUU|3CITIK£'; • Konvansiyonel

| — g j — | SI • Unites SI • Sl-Einheiten •1 ' SI • SI • SI • SI • SLenheter •

Movd5£? SI • SI

* Value • Resultat • Wsrt •wmmsa Valor -Valor -Valore •Vjerdi 'Varde-TiurrDefier

l< , ^ Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de Panalyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnalysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeester dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vaerdi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bflr liggainom detta omrade. • EOfxx; TIU&V.H Tiuri TOU ccvaAurfi Trptrra va EUTrnnEias auTo TO Eupo<; tipiiw. • Aralik.Analizorun degeri bu aralikta olmahdir.

t Revised • Mise a jour du •Revidiert • Revision •Revisto a • Aggiomato al •

Revideret • Reviderad • Ava9EU)pn,8n,KE• Revize edildi

_ _ * " j ~ Supersedes • Remplace laIBSf f l l version du-Ersetzt-

i f f l n ™ ! Substituye • Segue-se a •Sostituisce la versione del • Erstatter •ErsStter • YrrEpiox UEI • Yerine geosr

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L nan sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37-C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid 37"C. • OAE? OI U/mL mi U/L

OTOUS 37°C. • 37 °C'de tiirn U/mLve U/L.

^Or tho -a in i ca l DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 1(4)

VITROS DT Control 1Assay Sheet for VITROS DT andDT II • Datenblatt fur VITROS DTy DT II • Foiha do Ensaio para os

DT II Systems • Fiche de controle pour les Systemes VITROS DTetund DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTSistemas VITROS DT e DT II • Foglietto di dosaggio per Sistemi

VITROS DT e DT II • Kontrolark til VITROS [3T og DT II Systems • Kontrollblad iDT II • cpuAAo avaAucreiJdv yia Ta auaTquaTa VITROS DT KCII DTTest Sayfasi

GEN

LIPA 575859

Mg 5859

Na+ 52NBIL 64

6566

H3 5455

PHOS 5859

TBIL 7576

THEO 6263

TP 626364

TRIG 60URIC 54

55

English[Jjj Pretreatment Required

• HDLG

Reconstituted StabilityWhen stored at 2-8°C (36-46T):




FrangaisQiJ Pretraitement necessaire

. HDLC

Stabilite ReconstitueConservation a 2-8°C (36-46T):


• Stable pendant 3 jours: ALKP, Ca, CK,

2272162322.01.9117

1.31.31.797913.23.21.71.611.59.53.93.94.0111

4.03.9

TBIL

NBIL, TBIL


or VITROS DT ochI • VITROS DT ve DT II Sistemleri i

CONV J

N H

209 - 245198 - 234214 - 2501.7-2.31.6-2.2112-1220.6-2.00.6-2.01.0-2.462-13256-1262.6 - 3.82.6-3.81.2-2.21.1 -2.1

8.2-14.86.2-12.83.4 - 4.43.4 - 4.43.5-4.596-1263.6 - 4.43.5 - 4.3

U/L

mg/dL

mmol/Lmg/dL

umol/L

mg/dL

mg/dL

Mg/mL

g/dL

mg/dLmg/dL

tJam2272162320.820.78117

2222299791

1.031.0329276453393940

1.25238232

SI

r ™

209 - 245198-234214-2500.70 - 0.950.66 - 0.91112-12210-3410-3417-41

62-13256-126

0.84-1.230.84-1.23

21 -3819-3646-8234-7134-4434-4435-45

1.08-1.42214-262208 - 256

cin

U/L

mmol/L

mmol/Lumol/L

umol/L

mmol/L

umol/L

umol/L

g/L

mmol/Lumol/L

REF 842 0317

LOT X6041

2007-04-30

2005-08-22

2005-06-10


VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II» Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAuCTEWv via Ta ouaTiiucna VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

REF 842 0317

LOT X6041

2007-04-30

2005-08-22

DeutschQi] Vorbehandlung erforderlich

. HDLC



• Stabil fdr 3 Tage: ALKP, Ca, CK, NBIL, TBIL.


EspaftolQij Se requiere tratamiento previo

. HDLC

Estabilidad de la ReconstitucionCuando se conserva a 2-8°C (36-46T):

ym Estable durante 7 dias.

• Estable durante 3 dias: ALKP, Ca, CK, NBIL, TBIL.



• HDLC

Estabilidade apos Reconstitui?aoQuando conservado a uma temperatura entre 2 e 8"C:




ItalianoQg E- richiesto il pretrattamento

• HDLC

Stabilita Dopo La RicostituzioneConservato a 2-8°C (36^16°F):




Dansk[j i] Forbehandling pakraevet

• HDLC





Svenskarjg Forbehandling kravs

• HDLC





2005-06-10

Ortho-Qinkal DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 3(4)

VITROS DT Control IAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • 0uAAo avaAuCTEiov yia Ta 0uaTrj|jaTa VITROS DT KCII DT II • VITROS DT ve DT 11 Sisternleri iginTest Sayfasi

842 0317

HDLC

Orav aTro6r)K£taai at StppoKpacrfa 2-8°C (36-46°F):

• IiaSepo yia 3 r\\itpt<;: ALKP, Ca, CK, NBIL, TBIL

• lTa9tp6 yia 8 lOpec; (Jtid tnv TTpo£TTE5£PYao'a: NH3.

TUrkgeQl| Gereken dni§lem

• HDLC

Sulandinlmi? Halde Stabilite2-8 °C'de saklandiginda:

• 7 gQn stabildir.

• 3 gone kadarstabil: ALKP, Ca, CK, NBIL, TBIL.

• On iflemden sonra 8 gQne kadar stabil: NH3.

X60412007-04-30

2005-08-22

2005-06-10

Ortho-ClinicalBVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 4(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • 4>uAAo avaAucrecov yia TO ouCTTrj|jaTa VITROS DT KCII DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

ALB

ALKPALT

AMYLAST

UN/UREACa

CHE

CHOL

CK

Cl-CO2CREACRSC

Fe

GT

GLU

HDLC

K+LAC

LDH

Li

LIPA

GEN54555556575859755854

6970717273515357585960615352515457565755575354555655565751596061596052535758

CONV

4.54.4427

196197197196324

209

4912.212.612.312.212.57.697.6124924624287196310815.95.16.26.22452414715063033022993155751555.53.84.14.0

146413672.32.4705671

4.0-3.9-

5.04.9

337-5171 7 1 •

172-172-171 -

221222222221

274 - 374184-23443-55

11.411.811.511.411.7

•13.0•13.4•13.1•13.0•13.3

6.796.71

-8.59-8.51

227-224-220-

271268264

745837-

-9971089

103-11310.9-20.94.1-6.15.7-5.7-

6.76.7

219-215-

271267

438-473-

504539

282281278294

•324•323• 320• 336

43-37-4 1 •

716569

5.2-5.83.33.63.5

•4.3

• 4.6

•4.513251228

• 1603

•1506

1.71.8

• 2.9

3.0641-607-

769735

g/dL

U/LU/L

U/LU/L

mg/dLmg/dL

U/mL

mg/dL

U/L


U/L

mg/dL

mg/dL

mmol/Lmmol/L

U/L

mmol/L

U/L

SI

4544

40-39-

5049

427 337-51719619719719632420917.53.043.143.073.043.12769076106.46.46.387196310815.945154854843.943.147150616.816.816.617.51.471.321.425.5

3.84.14.0

146413672.32.4705671

171 -172-172-171 -

221222222221

274 - 374184-23415.3-19.62.84-2.94-2.87 •2.84-2.92-

3.243.343.273.243.32

6790-6710-

85908510

5.9-5.8-5.7-

7.06.96.8

745837-

•9971089

10.9-20.9362 - 539504-504-

592592

39.2-38.5-

48.547.8

438-473-

504539

15.7-15.6-15.4-16.3-

18.017.917.818.7

1 . 1 1 •

0.96-1.06-

1.841.681.78

5.2-5.83.3-3.6-3.5 •

4.34.64.5

1325-1228-

16031506

1.7-1.8-

2.93.0

641 •

607-769735

g/L

U/LU/L

U/LU/L

mmol/Lmmol/L

U/L

mmol/L

U/L

103-113 mmol/Lmmol/LMmol/LMmol/L

Mmol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

•U/L

mmol/L

U/L

REF 144 8042

LOT R5482

2005-09-30

2005-08-22

2005-03-14J

I CONV I Conventional • Unites' ' Ponderales • KonventionelleEinheiten • Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • Iuu|3ariK££ • Konvansiyonel

|—Sj—i SI • Unites SI • Sl-Einheiten •' ' SI • SI • SI • SI • Sl-enheter •

• SI

. . _ * _ Value • Resultat • Wert •" * " Valor -Valor -Valore-Vasrdi • Varde • Tiun. • Deger

h M Range. The analyzer valueshould tell within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. -Messbereich. Der mit demAnalysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omr&de.Analyseinstrumentets vasrdi skal liggeinden fbrdette omrade. • Intervall.Analysinstrumentets varde bor liggainom detta omrade. • EOpo? TIUOOV.H Tiprj TOU avoAuTii TTPETTEI va £|jTrim£iat auro TO tupcx; Tipuw. • Aralik.Analizorun degeri bu aralikta olmalidir.


Revideret • Reviderad • Ava6EU)pr|er|K£• Revize edildi

if%-~ Supersedes • Remplace la• 9 version du • Ersetzt •fflfflTt™I Substituye-Segue-sea-Sostituisce la versione del • Erstatter •Ersatter • Ympioxuti • Yerine gecer

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdetermineesaST-C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid 37"C. • Otes oi U/mL KCII U/L

crrou? 37°C. • 37 "C'de turn U/mLve U/L.


VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAuaewv yia Ta aucniiuaTa VITROS DT KCH DT II • VITROS DT ve DT II Sistemleri iginTestSayfasi

GEN

Mg 5859

Na+ 52NBIL 64

65NH3 54

55PHOS 58

59BIL 74

7576

THEO 62

TP 626364

TRIG 60URIC 54

55

CONV

4.74.813714.014.92252116.66.612.812.812.922.97.06.87.023210.610.3

4.2-5.24.3 - 5.3131-14312.4-15.613.3-16.5150-300136-2865.4-7.85.4 - 7.8

11.2-14.411.2-14.411.3-14.518.7-27.16.5-7.56.3 - 7.36.5-7.5

208 - 2569.8-11.49.5-11.1

mg/dL

mmol/Lmg/dL

umol/L

mg/dL

mg/dL

ug/mLg/dL

mg/dLmg/dL

1.931.97137

2392552252112.132.13219219221127706870

2.62630613

EnglishQIJ Pretreatment Required

• HDLC





FrancjaisTj] Pretraitement necessaire

. HDLC

Stabilite ReconstitueConservation a 2-8°C (36~46°F):


. Stable pendant 3 Jours: ALKP, Ca, CK, NBIL, TBIL.

• Stable pendant 8 heures apres le pretraitement: NH3..

DeutschOg Vorbehandlung erforderlich

• HDLC

Stabilitat nach der RekonstitutionBei Lagerung zwisohen 2 und 8 °C:




SI

1.73-1.77-

2.142.18

131-143212-227-

267282

150-136-

300286

1.74-1.74-

2.522.52

192-192-193-

246246248

104-15065-63-65-

757375

2.35 - 2.89583-565-

678660

mmol/L

mmol/Lumol/L

umol/L

mmol/L

pmol/L

(jmol/L

g/L

mmol/Lumol/L

REF 144 8042

R5482

2005-09-30

2005-08-22

2005-03-14


VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de contr6le pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • ct>uAAo avaAuCTEtov yia TO aucnriiJaTa VITROS DT xai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

144 8042

LOT R5482

2005-09-30

2005-08-22

Espaflol[] i j Se requiere tratamiento previo

• HDLC



• Estable durante 3 dlas: ALKP, Ca, CK, NBIL, TBIL.


PortuguesQTj Necessario Tratamento Previo

• HDLC

Estabilidade apos Reconstitui?aoQuando oonservado a uma temperatura entre 2 e 8°C:




ItalianoQjJ £ richiesto il pretrattamento

• HDLC

Stabilita Dopo La RicostituzioneConservato a 2-S°C (36-46°F):





• HDLC





SvenskaQT] Forbehandling kravs

• HDLC

Stabilitet efter rekonstitutionFotvaring vid 2-8°C (36-46°F):




I ATraiTErrai Trpo£Tr£$£pY<rcna

HDLC

ETa8EpoTr|Ta ava<?uo~Tao~r|£Diav arro9r|K£0£iai O£ 6£puoKpaola 2-8°C (36-46°F):Im0£p6 yia 7 r\\itpzt;.

Iia8£p6 yia 3 r]\itpt<;: ALKP, Ca, CK, NBIL, TBIL.

:NH3.

2005-03-14

ny VITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 3(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAOaEiDV yia la ouoTiifjaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

REF 144 8042

TUrkcerjg Gereken Oni§lem

• HDLC

Sulandinlmis. Halde Stabilite2-8 "C'de saklandiQinda:

• 7 gGn stabildir.


• On isjemden sonra 8 gUne kadar stabil: NH3.

R5482

2005-09-30

2005-08-22

2005-03-14

tOrthoClinkal DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 4(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaACiCTEWV yia ra auoTfjuciTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

GEN

ALB 5455

ALKP 55ALT 56

57585960

AMYL 7576

AST 58BUN/UREA 54Ca 69

70717273

CHE 5153

CHOL 575859

CK 6061

Cl- 53CO2 52CREA 51CRSC 54

57e 56

57GGT 55

5758

GLU 53545556

HDLC 555657

K+ 51LAC 59

6061

LDH 5960

Li 52

LCONV j

•iUi4.44.2413

205208212208208354361204

50

11.711.711.811.812.07.317.13252241238914986111

17.45.0

6.06.22772664184404603053022953095959595.5

3.84.13.9

143913502.4

[ ^ ^ 1

3.9 - 4.93.7 - 4.7

323 - 503180-230183-233187-237183-233183-233304 - 404311-411179-22944-56

10.9-12.510.9-12.511.0-12.611.0-12.611.2-12.86.41 - 8.216.23 - 8.03230 - 274219-263216-260

788-1040860-1112

g/dL

U/L

U/L

U/L

U/L

mg/dLmg/dL

U/mL

mg/dL

U/L

106-116 mmol/L12.4-22.4 |mmol/L

4.0 - 6.05.5 - 6.55.7-6.7

251 - 303240 - 292385 - 451407-473427 - 493284 - 326281 - 323274-316288 - 33045-7345-7345-735.2 - 5.83.3 - 4.33.6 - 4.63.4 - 4.4

1300-15781211 -1489

1.8-3.0

mg/dLmg/dL

Mg/dL

U/L

mg/dL

mg/dL

mmol/Lmmol/L

U/L

mmol/L

I SI

BiUs4442

413

205208212208208354361204

17.82.922.922.942.942.99731071306.56.26.2914986111

17.4442

53054849.647.641844046016.916.816.417.21.531.531.535.53.84.13.9

143913502.4

1 ^ ^1| ^ W\

39-4937-47

323 - 503180-230183-233187-237183-233183-233304 - 404311-411179-22915.7-20.02.72-3.122.72-3.122.74-3.142.74-3.142.79-3.196410-82106230-8030

5.9 - 7.15.7-6.85.6-6.7

788 - 1040 -860-1112106-11612.4-22.4354 - 530486 - 575504 - 592

44.9-54.243.0 - 52.3385 - 451407 - 473427 - 49315.8-18.115.6-17.915.2-17.516.0-18.31.16-1.891.16-1.891.16-1.895.2 - 5.83.3-4.33.6-4.63.4 - 4.4

1300-15781211-1489

1.8-3.0

g/L

U/L

U/L

U/L

U/L

mmol/Lmmol/L

U/L

mmol/L

U/L

mmol/Lmmol/LMmol/Lpmol/L

Mmol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

U/L

mmol/L

REF 144 8042

U5654

2006-04-30

2005-08-22

2005-03-14

I CONV I Conventional • Unites' ' Ponderales • KonventionelleEinheiten«Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • IUUPOTIK£C, • Konvansiyonel

| — s T H SI-Unites SI-Sl-Einheiten-' ' Sl -SI-SI-SI-SI-enheter-

MovdOEC, SI • SI

* Value • Resultat • Wtert •iwMBimi valor-Valor • Valore-Vasrdi-Varde-TiurrDeger

n H Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnalysegerat erhaltene Wfert sollte Etchinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vaerdi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets vSrde bor liggainom detta omrade. • Eupor, nuciiv.H Tiurj TOU ovaAurrj TTPSTTEI va euTriTrreiat auTo TO Eupoc, uutfiv. • Aralik.Analizorun degeri bu aralikta olmalidir.

A . Revised -Mise a jour du-M j l Revidiert • Revisibn •ISSJ Revisto a • Aggiomato al •

Revideret • Reviderad • AvaSEU)pii9r|KE• Revize edildi

_ J V Supersedes• RemplacelaBlKf f l l version du • Ersetzt •

w T f f l J Substituye • Segue-se a •Sostituisce la versione del • Erstatter •Ersatter • Ympioxuei • Yerine gecer

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid37°C. -OAEC-oiU/mLKaiU/LOTOUC, 37°C. • 37 "C'de turn U/mLve U/L.


VITROS DT Control IIAssay Sheet for VITROS DT andDT II • Datenblatt fur VITROS DTy DT II • Foiha do Ensaio para os

DT II Systems • Fiche de controle pour les Systemes VITROSund DT II Systeme • Hoja de ensayo para los 5

DTetSistemas VITROS DT

Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <t>GAAo avaAucjEwv yia m auaTrjuaTa VITROS DT Kai DT 1Test Sayfasi

GEN... Li 53LIPA 57

5859

Mg 5859

Na+ 52NBIL 64

6566

NH3 5455

PHOS 5859

TBIL 747576

THEO 6263

TP 626364

TRIG 60URIC 54

55

2.47867537974.74.814114.314.614.82282297.16.913.113.012.521.317.96.76.76.922610.710.5

CONV

I • VITROS DT ve DT II Sistemleri igin

N M

1.8-3.0722 - 850689-817733 - 8614.2-5.24.3 - 5.3135 -14712.7-15.913.0-16.213.2-16.4153-303154-3045.9 - 8.35.7-8.1

11.5-14.711.4-14.610.9-14.117.1 -25.513.7-22.16.2 - 7.26.2 - 7.26.4 - 7.4

202 - 2509.9-11.59.7-11.3

mmol/LU/L

mg/dL

mmol/Lmg/dL

umol/L

mg/dL

mg/dL

ug/mL

g/dL

mg/dLmg/dL

I si

2.47867537971.931.971412452502532282292.292.2322422221411899676769

2.55636625

[^ W\

1.8-3.0722 - 850689-817733 - 8611.73-2.141.77-2.18135-147217-272222 - 277226 - 280153-303154-3041.91-2.681.84-2.62197-251195-250186-24195-14276-12362-7262-7264-74

2.28 - 2.83589 - 684577 - 672

mmol/LU/L

mmol/L

mmol/L(jmol/L

|jmol/L

mmol/L

Mmol/L

pmol/L

g/L

mmol/Lumol/L

EnglishQg Pretreatment Required

• HDLC



. Stable for 3 days: ALKP, Ca, CK, NBIL,


FrangaisQTJ Pretraitement necessaire

. HDLC



. Stable pendant 3 jours: ALKP, Ca, CK,

TBIL

NBIL, TBIL.


144 8042

LOT U56542006-04-30

2005-08-22

2005-03-14


VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <DuAAo avaAuaewv yia Ta aucrrrjuaTa VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

REF 144 8042

DeutschQT| Vorbehandlung erforderlich

• HDLC


• StabilfCir7Tage.

• Stabil ft)r3 Tage: ALKP, Ca, CK, NBIL, TBIL.


Espanol[Ji| Se requiere tratamiento previo

• HDLC

Estabilidad de la ReconstitucionCuando se oonserva a 2-8°C (36-46°F):


. Estable durante 3 dfas: ALKP, Ca, CK, NBIL, TBIL.


PortuguSs[ Jij Necessario Tratamento Previo

• HDLC

Estabilidade apos Reconstitute)Quando conservado a uma temperatura entre 2 e 8°C:




ItalianoQiJ E richiesto il pretrattamento

. HDLC





DanskQT| Forbehandling pakraevet

• HDLC





SvenskaQ7J Forbehandling kravs

. HDLC





LOT U5654

2006-04-30

2005-08-22

2005-03-14

tOrtrK>Clinic3lDiagTostbVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 3(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAuaaov via Ta auaTrj|JciTa VITROS DT KOI DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

144 8042

Ql] ATfaiTEITOI Trp0ETT£$£pYCI0ic(

. HDLC

iTaetpoTriTa avaoruoraansOiav orrroSriKECiEiai at SepiJOKpaafa 2-8°C (36-46°F):

• Ira8jp6 yia 7 n^P£C-

. Iraetpo yia 3 r)[itpz<;: ALKP, Ca, CK, NBIL, TBIL.

• Iia9£p6 Yia 8 oDpt? jjttcS inv TTpOETTE§EpYaa!a: NH3.

TUrkgeQiJ Qereken Oni§lem

• HDLC

Sulandinlmi? Halde Stabilite2-8 "C'desaklandiginda:

• 7 gCin stabildir.


• On iflemden sonra.8 gQne kadar stabil: NH3.

LOT U5654

2006-04-30

2005-08-22

2005-03-14

Ortho-qnical DiagnostisVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 4(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • <t>GAAo avaAuaECDV yia TO auaTrjuaTct VITROS DT KCII DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

GEN

ALB 5455

ALKP 55ALT 56

57585960

AMYL 7576

AST 58BUN/UREA 54Ca 69

70717273

CHE 5153

CHOL 575859

CK • 60• 61

Cl- 53CO2 52CREA 51CRSC 54

57e 56

57GGT 55

5758

GLU 53545556

HDLC 555657

K+ 51LAC 59

6061

LDH 5960

Li 52

•An.4.44.1448

184187188184181357369209

53

12.112.512.212.212.57.107.1424723323410661018114

16.55.1

6.06.32432494554765013053022983126060595.3

3.84.13.9

145013852.4

CONV J

H M

3.9 - 4.93.6-4.6

358 - 538159-209162-212163-213159-209156 - 206307 - 407319-419184-23447-59

11.3-12.911.7-13.311.4-13.011.4-13.011.7-13.36.20 - 8.006.24 - 8.04225 - 269211 -255212-256940-1192892-1144109-11911.5-21.54.1 -6.15.5-6.55.8-6.8

217-269223 - 275422 - 488443 - 509468 - 534284 - 326281 - 323277-319291 - 33346-7446-7445-735.0-5.63.3-4.33.6-4.63.4 - 4.4

1311 -15891246-1524

1.8-3.0

g/dL

U/L

U/L

U/L

U/L

mg/dLmg/dL

U/mL

mg/dL

U/L

mmol/L

4441

448

184187188184181357369209

18.93.023.123.043.043.12710071406.46.06.1

10661018114

mmol/L 16.5mg/dLmg/dL

Mg/dL

U/L

mg/dL

mg/dL

mmol/Lmmol/L

U/L

mmol/L

451

53055743.544.645547650116.916.816.517.31.551.551.535.3

3.84.13.9

145013852.4

SI I

J«- H39-4936-46

358 - 538159-209162-212163-213159-209156-206307 - 407319-419184-23416.8-21.12.82 - 3.222.92 - 3.322.84 - 3.242.84 - 3.242.92 - 3.326200 - 80006240 - 8040

5.8 - 7.05.5-6.65.5 - 6.6

940-1192892-1144109-11911.5-21.5362 - 539486 - 575513-601

38.8 - 48.239.9 - 49.2422 - 488443 - 509468 - 53415.8-18.115.6-17.915.4-17.716.2-18.51.19-1.911.19-1.911.16-1.895.0-5.63.3-4.33.6-4.63.4-4.4

1311-15891246-1524

1.8-3.0

g/L

U/L

U/L

U/L

U/L

mmol/Lmmol/L

U/L

mmol/L

U/L

mmol/Lmmol/Lpmol/LMmol/L

Mmol/L

U/L

mmol/L

mmol/L

mmol/Lmmol/L

U/L

mmol/L

REF 144 8042

LOT W5858

2006-12-31

2005-08-22

2005-03-14

i C O N V I Conventional • Unites' ' Ponderales • KonventionelleBnheiten • Conventional •Conventional • Convenzionale •Konventionel • Konventionellaenheter • IUUJ3OTIK£C; • Konvansiyonel

SI • Unites SI • Sl-Einheiten •SI • SI • SI • SI • Sl-enheter •Mova5£? SI • SI

. * Value • Resultat • Wert •VZZm valor-Valor-Valore-Veerdi-Varde-TiprrDeger

n rt Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnalysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestardentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valorsottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentetsvaerdi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bb'r liggainom detta omrade. • Eiipoc. Tiutiw.H Tipri TOU avaAuTfi TTpEtrei va £|jTTfirraat OUT6 TO Eupoc; TIUUV. • Aralik.

Analizorun degeri bu aralikta olmalidir.

t Revised• Mise a jour du •Revidiert • Revision •Revisto a • Aggiornato al •

Revideret • Reviderad • Ava8EU)pii6r|icE• Revize edildi

_ _ > V , Supersedes • Remplaoe laI B M j J i version du • Ersetzt •BansSJ Substituye-Segue-sea-Sostituisce la versione del • Erstatter •Ersatter • Ynepioxua • Yerine gecer

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminees a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37° C. • Alia U/mL och U/Lvid 37°C. • OAt? OI U/mL m\ U/LOTOU? 37°C. • 37 °C'de turn U/mLve U/L.


VITROS DT Control IIAssay Sheet for VITROS DT andDT II • Datenblatt fur VITROS DTy DT II • Foiha do Ensaio para os

DT II Systems • Fiche de controle pour les Systemes VITROS DT etund DT II Systeme • Hoja de ensayo para los.Sistemas VITROS DTSistemas VITROS DT e DT II • Foglietto di dosaggio per Sistemi

VITROS DT e DT II • Kontrolark lil VITROS DT og DT II Systems • Kontrollblad 1DT II • OuAAo avaAuaewv yia Ta auorrj|jaTa VITROS DT KOI DT 1Test Sayfasi

GEN

... Li 53

LIPA 575859

Mg 5859

Na+ 52NBIL 64

6566

NH3 5455

PHOS 5859

TBIL 747576

THEO 6263

TP 626364

TRIG 60URIC 54

55

EnglishQT| Pretreatment Required

« HDLC





Francjais

QT| Pretraitement necessaire• HDLC

Stabilite Reconstitute- - Conservation a 2-8 °C (36-46 °F):


• Stable pendant 3 jours: ALKP, Ca, CK

• A .2.4

8708548744.64.8142

14.114.014.32302197.27.112.812.612.022.620.26.86.46.6223

10.210.1

TBIL.

NBIL, TBIL.


or VITROS DTochI • VITROS DT ve DT II Sistemleri icin

CONV |

(^ W\

1.8-3.0806 - 934790-918810-9384.1-5.14.3 - 5.3136-14812.5-15.712.4-15.612.7-15.9155-305144-2946.0 - 8.45.9-8.3

11.2-14.411.0-14.210.4-13.618.4-26.816.0-24.46.3 - 7.35.9 - 6.96.1-7.1199-2479.4-11.09.3-10.9

mmol/LU/L

mg/dL

mmol/Lmg/dL

pmol/L

mg/dL

mg/dL

jjg/mL

g/dL

mg/dLmg/dL

. U s2.4

8708548741.891.97142

2412392452302192.322.29219215205125112686466

2.52607601

SI

H H1.8-3.0

806 - 934790-918810-9381.69-2.101.77-2.18136-148214-268212-267217-272155-305144-2941.94-2.711.91-2.68192-246188-243178-233102 - 14989-13563-7359-6961-71

2.25 - 2.79559 - 654553-648

mmol/LU/L

mmol/L

mmol/LMmol/L

pmol/L

mmol/L

umol/L

umol/L

g/L

mmol/L|jmol/L

REF 144 8042

W5858

2006-12-31

2005-08-22

2005-03-14

Ortho-Clnical DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fiir VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAuaewv via TCI auaTrjuaTa VITROS DT KCII DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

REF 144 8042

Deutsch[JiJ Vorbehandlung erforderlich

. HDLC



• Stabil fQr 3 Tage: ALKP, Ca, CK, NBIL, TBIL.


EspanolQYj Se requiere tratamiento previo

• HDLC



. Estable durante 3 dfas: ALKP, Ca, CK, NBIL, TBIL.



• HDLC

Estabilidade apos ReconstituigaoQuando conservado a uma temperatura entre 2 e 8°C:




ItalianoQiJ £ richiesto il pretrattamento

• HDLC

Stabilita Dopo La RicostituzioneConservato a 2-8°C (36-46T):


. Stabile per 3 giorni: ALKP, Ca, CK, NBIL, TBIL.



• HDLC




• Stabil i 8 timer efter forbehandling: NH3. .

SvenskaQI) Forbehandling kravs

• HDLC





W58582006-12-31

2005-08-22

2005-03-14

Ortho-Clinical DJagrxsticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 3(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • cDuAAo avaAuaewv via Ta auaTrj|jaTa VITROS DT KOI DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

144 8042

Qi]HDLC

ETCtBepoTrvra avaauaTaan?Diav cnroOriKEGEiai at. Qcp^oKpaola 2-8°C (36-46°F):Sia9cp6 yia 7 r\ytpts-

Iia6£p6 yia 3 r\\itpa;: ALKP, Ca, CK, NBIL, TBIL.

Iia8Ep6 Yia 8 (Spec; ptia ir|V TTpOETC^EPYaafa: NH3.

TOrkgeQHJ Gereken Oni§lem

• HDLC

Sulandinlmi§ Halde Stabilite2-8 °C'de saklandiginda:

• 7 gOn stabildir.

• 3 gQne kadar stabil: ALKP, Ca, CK, NBIL, TBIL.

• On i§lemden sonra 8 gCine kadar stabil: NH3.

W5858

2006-12-31

2005-08-22

2005-03-14

tOrthodinkal DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 4(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuAAo avaAucrEwv yia TO auaTnucna VITROS DT KCII DT II • VITROS DT ve DT II Sistemleri icinTestSayfasi

GEN

ALB 5455

ALKP 55ALT 56

57585960

CONV

4.54.4447

AMYL 7576

AST 58BUN/UREA 54

Ca 6970717273

CHE 5153

CHOL 575859

CK 6061

Cl-CO2~

53

52

182185186181184361361209

4912.312.412.412.412.47.38

242231232930906109

16.9

4.0-5.03.9 - 4.9357 - 537157-207160-210161-211156-206159-209311-411311-411184 - 234

g/dL

SI

45

~44T

40-39-

5049

357 - 537U/L

U/L

U/L43-55 mg/dL

11.5-13.111.6-13.211.6-13.211.6-13.211.6-13.26.48 - 8.286.37-8.17220 - 264209 - 253210-254

804-1056780 - 1032

mg/dL

U/mL

mg/dL

U/L

104-114 mmol/L

CREA 51 5.0

11.9-21.9 mmol/L4.0 - 6.0

CRSC

•e

54575657

GGT 555758

6.36.2242254471482513

5.8-6.85.7 - 6.7

216-268228 - 280438 - 504449-515480 - 546

mg/dLmg/dL

ug/dL

~U7LT

182185186181184

361361209

17.5

3.093.093.09

738072706.36.0

930906109

16.9442

557_548_43.345.5

157-160-161 -156-159-

207210211206

311311

411411

U/LU/L

U/L

184-234 U/L

15.3-19.62.87-2.89-2.89-2.89-2.89-

3.293.293.293.29

6480-6370-

82808170

5.7-5.4-5.4-

6.86.56.6

804-780-

10561032

mmol/Lmmol/L

U/L

mmol/L

U/L

104^114 |mmol/L

11.9-21.9354 - 530513-504-

601592

471482513

38.7-40.8-

48.050.1

438-449-480-

504515546

mmol/Lumol/Lumol/L

umol/L

U/L

REF 144 8042

Y6043

2007-04-30

2005-08-22

2005-06-10


Einheiten • Convencional •Convencional • Convenzionale •Konventionei • Konventionellaenheter • EuupcrriKEi; • Konvansiyonel

SI • Unites SI • Sl-Bnheiten •ShSI 'SI-SI-SI-enheter-Movdot; SI • SI

i Value • Resultat • V\fert •• — « " — Valor- Valor- Valore-Vaerdi • Varde • Tiun, • Deger

H M Range. The analyzer valueshould fall within this range.

• Tolerance. La valeur de I'analyseurdoit se trouver dans cet intervalle. •Messbereich. Der mit demAnalysegerat erhaltene Wert sollte sichinnerhalb dieses Bereichs bewegen. •Intervalo. El valor del analizador debeestar dentro del rango. • Intervalo. Ovalor do analisador devera estar dentrodeste intervalo. • Intervallo. II valoreottenuto sull'analizzatore dovrebberientrare in questo intervallo. • Omrade.Analyseinstrumentets vasrdi skal liggeinden for dette omrade. • Intervall.Analysinstrumentets varde bor liggainom detta omrade. • Eupo? TIUUJV.H Tiurl TOU avaAuTr\ TrpETrti va t|jTrlTn£iOE auTO TO EOpo? Tiuuv. • Aralik.AnalizorUn degeri bu aralikta olmalidir.


Revideret • Reviderad • AvaSEUpfienKE• Revize edildi

, . ry. Supersedes • Remplace laji juSHj]] version du • Ersetzt •™ r i M l SubsBtuye • Segue-se a •Sostituisce la versione del • Erstatter •Ersatter • YTTEPIOXUEI • Yerine ge?er

All U/mL and U/L at 37°C. • Lesactivites enzymatiques sontdeterminess a 37°C. • Enzymaktivitatenwerden bei 37 °C gemessen. • Todoslos valores de U/mL y U/L han sidocalculados a 37°C. • Todas U/mL eU/L a 37°C. • I valori U/ml e U/L sonodeterminati a 37°C. • Alle U/ml ogU/l ved 37" C. • Alia U/mL och U/Lvid 37°C. • DAEC OI U/mL mi U/Lorous 37°C. • 37 °C'de turn U/mLve U/L.


VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontroiark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • cMMo avaAuaEUw yia TO auaTipcna VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri iginTest Sayfasi

GENLIPA 57

5859

Mg 5859

Na+ 52NBIL 64

6566

6946707084.8

139

15.015.315.6

630 - 758606 - 734644 - 772

630 - 758606 - 734644 - 772

229 - 284234 - 289239 - 294

13.4-16.613.7-16.914.0-17.2

EnglishQi) Pretreatment Required

. HDLC





FrangaisQi] Pretraitement necessaire

. HDLC



• Stable pendant 3 jours: ALKP, Ca, CK, NBIL, TBIL.


umol/L

SI

REF 144 8042

LOT Y6043

2007-04-30

2005-08-22

2005-06-10

tgrtho-ainical DiagriastfcsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 2(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fUr VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Foiha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OuMo avaAuaewv yia ra auaTitycna VITROS DT KOI DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

144 8042

DeutschQg Vorbehandlung erforderlich

• HDLC

Stabilitat nach der RekonstitutionBei Lagerung zwisohen 2 und 8 °C:


• Stabil fQr 3 Tage: ALKP, Ca, CK, NBIL, TBIL.

• Bis zu 8 Stunden naeh der Vorbehandlung stabil: NH3.

EspanolQg Se requiere tratamiento previo

• HDLC



• Estable durante 3 dlas: ALKP, Ca, CK, NBIL, TBIL.


PortuguSs['Jij Necessario Tratamento Previo

• HDLCEstabilidade apos ReconstituigaoQuando conservado a uma temperatura entre 2 e 8°C:




ItalianoQi) £ richiesto il pretrattamento

• HDLC





DanskQi] Forbehandling pakrasvet

. HDLC




• Stabil i 8.timer efter forbehandling: NH3.

SvenskaQJ] Forbehandling kravs

. HDLC





LOT Y6043

2007-04-30

2005-08-22

2005-06-10

Crtho-ginical DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 3(4)

VITROS DT Control IIAssay Sheet for VITROS DT and DT II Systems • Fiche de controle pour les Systemes VITROS DT etDT II • Datenblatt fur VITROS DT und DT II Systeme • Hoja de ensayo para los Sistemas VITROS DTy DT II • Folha do Ensaio para os Sistemas VITROS DT e DT II • Foglietto di dosaggio per SistemiVITROS DT e DT II • Kontrolark til VITROS DT og DT II Systems • Kontrollblad for VITROS DT ochDT II • OGMo avaXucjEOJV yia TO ouoTrnjaia VITROS DT Kai DT II • VITROS DT ve DT II Sistemleri icinTest Sayfasi

144 8042

Qi] ATTCtiTEncii •tTpoETrt^

• HDLC

iTaSepoTriTa avaauaTaan?Oiav aTTo9riK£Ci£iai oe etppoKpaata 2-8°C (36-46°F):

• Iia8ep6 yia 7 HM P5?-

• Xiaetpo yia 3 r\\Apc^. ALKP, Ca, CK, NBIL, TBIL.

a: NH3.

TUrk?efji) Gereken 6ni§lem

• HDLC

Sulandinlmif Halde Stabilite2-8 °C'de saklandiginda:

• 7 gon stabildir.


• On i§lemden sonra 8 gone kadar stabil: NH3.

LOT Y6043

2007-04-30

2005-08-22

2005-06-10

j t OrthcvQircal DiagnosticsVITROS is a trademark of Ortho-Clinical Diagnostics, Inc. www.orthoclinical.com 4(4)


100 Indigo Creek DriveRochester, NY 14626-5101

DECLARATION OF CONFORMITYManufacturer: Ortho-Clinical Diagnostics, Inc.

100 Indigo Creek DriveRochesterNew York 14626-5101USA

Authorized Current From January 2004

Representative: Ortho-Clinical Diagnostics Ortho-Clinical DiagnosticsMandeville House Johnson & Johnson62 The Broadway Amersham 50 - 100 Holmers Farm WayBuckinghamshire HP7 0HJ High WycombeUnited Kingdom Buckinghamshire HP 12 4DP

United Kingdom

Ortho-Clinical Diagnostics is declaring that the in vitro diagnostic medicaldevices below comply with the provisions of Directive 98/79/EC on In VitroDiagnostic Medical Devices and the UK Medical Devices Regulations 2002.

Standards Applied:ISO 13485:1996 Quality Systems - Medical devices- Supplementary requirements to ISO 9001ISO 14971 Medical Devices- Application of risk management to medical devices.EN 591 Instructions for use for in vitro diagnostic instruments for professional useEN 980 Graphical symbols for the use in the labeling of medical devices.EN 13612 Performance evaluations of in vitro diagnostic medical devicesEN 61326-1 Electrical equipment for measurement, control, and laboratory use - EMC

requirements

EMC: EN55011 EN61000-4-2 EN61000-4-5EN61000-3-2 EN61000-4-3 EN61000-4-6EN61000-3-3 EN61000-4-4 EN61000-4-11

Safety: IEC 61010-1IEC 61010-2-101

Product Name: VITROS DT60 II Chemistry SystemProduct Code: 842 2172

Applies to Serial Numbers Greater than 60034380

Product Name: VITROS DTSC II ModuleProduct Code: 824 7355


Product Name: VITROS DTE II ModuleProduct Codes: 183 5727


Classification: Non-Annex II

Page 1 of2

The following

Product Name: VITROS DT60 II Chemistry SystemProduct Code: 842 2172

Applies to Serial Numbers Less than 60034381

Product Name: VITROS DTSC II ModuleProduct Code: 824 7355

Applies to Serial Numbers Below: 62022389

Product Name: VITROS DTE II ModuleProduct Codes: 183 5727

Applies to Serial Numbers Below: 61022526

bear the CE mark indicating conformity to the following product specifications:

Application of Council Directive: 1) EMC Directive 89/336/EEC amendments

2) Low Voltage Directive 73/23/EEC

and standards:

EMC: EN5OO81-1 (Emissions) FCC Part 15 Class AF.N55O11 Class A Radiated and ConductedEN50082-1 (Immunity) ICES-003 Class A

IEC 801 -2 Radiated and ConductedIEC 801-3IEC 8014 VCCI Class!

EN 605 5 5 -2 Powerline Harmonics

Safety: IEC 1010-1UL3101-1CSAC22.2No. 1010.1

Patricia O'Brien (year/month/day)Site Director, RochesterQuality Regulatory Compliance

Page 2 of2

manual vitros dtii

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