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SP.718 Special Topics at Edgerton Center: D-Lab Health: Medical Technologies for the Developing WorldSpring 2009

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Colorimetric Diagnostic Assay for the Measurement of Blood Glucose

Dlab

Health

1

Deepali Ravel, Yi Wang, and anonymous students AL, ML and DR

Background

Prevalence of Diabetes in Central America

•

One glucometer

is shared

between 15 clinics in the

Nicaraguan province of Estelí.

•

Test strips are proprietary and

expensive

•

Poor distribution of test strips

and glucometers

–

leads to a

mismatch in supply at hospitals

Deaths AttributableMales –

10.4% (2007)

Females –

18.2% (2007)

Nicaragua Diabetes Statistics:National Prevalence

7.6% (2007)9.4% (2025)

2

Courtesy of the International Diabetes Federation. Used with permission.

Diabetes Management

•

When a patient has diabetes, their body cannot effectively regulate glucose levels.

•

It is dangerous if glucose concentrations fall outside normal range

•

Goal: Glycemic

control

–

Keep within normal values of 70-130 mg/dl

–

Poor glycemic

control –

200-500 mg/dl over months

•

Measure blood glucose levels 4 –

5 times a day

–

Allow patients to act quickly to correct for swings in their glucose concentrations, by either injecting a dose of insulin or consuming glucose pills.

3

Diabetes in the Developing World

Why is it a problem?

•

Has reached epidemic proportions-

Due to rapid cultural changes, increasing urbanization, dietary

changes

•

Currently affects 246 million people, 6% of world’s adult population-

Contributes to 19.7 million DALYs-

By 2025, 80% of all new cases will appear in developing countries

•

6 million people develop diabetes each year-

Less than half the people with diabetes in developing countries

are diagnosed

•

Diabetes causes 3.5 million deaths each year-

Two-thirds of deaths caused by diabetes occur in developing countries

The burden of the disease increasingly falls on developing countries

4

Diabetes Prevalence in 2007

5

Courtesy of the International Diabetes Federation. Used with permission.

Diabetes Prevalence in 2025

6

Courtesy of the International Diabetes Federation. Used with permission.

Problem Statement

“In order to control their disease, diabetes patients must monitor their blood glucose level on a regular basis. In the region of Estelí, in Nicaragua , one glucometer

is shared between 15 clinics, meaning that the vast majority of patients are not receiving daily monitoring. Glucose testing is so infrequent

because test strips are proprietary and expensive.

Our challenge is to design a fast, cheap, safe and reliable way of measuring glucose levels that can be used widely by diabetes patients, even in poor resource settings.”

-

Team GlucoTank

7

Current Glucometers

Drop a prick of blood onto a test strip, which the

glucometer

than reads to measure glucose levels,

through an electrochemical assay.

8

Source: Wikipedia (public domain)

Design SpecificationsCharacteristic Current Our PrototypeSample Volume 0.3ul to 10ul 10ul

Accuracy 10-15% UnknownRange Be able to measure healthy glucose

range: 70-130 mg/dl100-200 mg/dl

Processing Time 3-60 seconds 30-60 seconds

Testing Site Mostly fingertips FingertipTesting Frequency Up to 10-12 times per day SameReader Size Around 8cm x 5cm x 3cm (palm size) 20cm x 6cm x 2.5cmReader Price $25 to $100. Some companies offer free

monitors, but sell test stripsVery low

Test Strip Price $1.00-$2.00 <$0.20Units US preference is mg/dl. Canada and

Europe preference is mmol/l

(x/18)mg/dl

Other Qualities Allow data storage/ monitoring None

9

Design Ideas I: Telemedicine

A. Use Camera Phone to take image of test strip

B. Transfer image to computer in off-

site lab/hospital

C. Use imaging software such as Photoshop to convert image to grayscale

D. Read out the mean intensity and use “key”

to translate value to Glucose level

•

Create colorimetric test strips, and a phone (or computer) application that, when a picture of the strip is loaded, it converts it to gray scale and measures the average light intensity-

translating that to a glucose level. • However:

-

Cell phones that have computer power to do this are quite expensive (idea not able to adapt to single user level)-

Similar idea being pursued by Diagnostics for All

10

Design Ideas II: Glucophone

•

More expensive technology than the telemedicine idea.

•

Uses cell phone to display, power, and store data–

Data can be sent to a central database for remote patient monitoring

•

However: –

Expensive to develop

–

Technologically challenging?–

Company already doing this

–

Would be difficult designing component attachable to all phones

11

Image remove due to copyright restrictions.

Photos of the GlucoPhone, from http://www.glucophone.com.

Pugh ChartDesign Goals Status Quo Design 1 Design 2 Design 3 Design 4

DesignParameters

Weights (1-3)

Current glucometers

are expensive and

proprietary.

Microfluidic

glucose test system

Current Glucometer

with non-proprietary

strips

Paper diagnostic-

only colorimetric

strip-

no meter

New, Local Glucometer

with Locally Built Test

Strips

Long-term Effectiveness 3 -1 1 -1 1 1Speed of Use 2 1 1 1 1 1Reliability 3 1 1 1 -1 1Accuracy 3 1 0 1 -1 1Economy 3 0 -1 1 1 1Accessibility 2 1 1 1 1 1Usability 2 1 0 1 1 1Simplicity 2 1 0 1 1 1Practicality 2 0 0 1 1 1Maintainability 3 0 1 0 1 1Aesthetic Appeal 1 1 1 1 1 -1Environmental Friendliness 1 0 1 0 1 0Safety 3 1 1 1 1 1Versatility 2 1 1 1 1 0Efficiency 2 1 1 1 1 1Marketability 2 0 0 -1 1 1Ease of Integration 1 0 1 0 1 1Total 9 10 10 13 13Weighted Total 19 20 22 25 32

12

Pugh Chart

13

Design Goals Weights (1-3) Status Quo Design 1 Design 2 Design 3 Design 4 Current

glucometers

are expensive and

proprietary.

Microfluidic

glucose test system

Current Glucometer

with non-proprietary

strips

Paper diagnostic-

only colorimetric

strip-

no meter

New, Local Glucometer

with Locally Built Test

Strips

Long-term Effectiveness 3 -1 1 -1 1 1

Reliability 3 1 1 1 -1 1Accuracy 3 1 0 1 -1 1Economy 3 0 -1 1 1 1

Maintainability 3 0 1 0 1 1

Safety 3 1 1 1 1 1

Total 2 3 3 2 6Weighted Total 6 9 9 6 18

Our Proposed Solution: Colorimetric Strips

14

The reagents for theglucose assay are placedon a Filter Paper Test Strip.10ul of the glucose solution(blood) are deposited onstrip. Color change fromclear to blue is witnessed.

Our Proposed Solution: Reader

15

Battery-operated hand-held readerLEDs

indicate blood glucose-level within set ranges

Costs

16

Paper Test Strips: Reagents per strip : 1.5 centsPackaging: approximately 5 cents per strip -Packaging constraints: must protect the strips from light, since some reagents are light-sensitive. Solution: use aluminum coated paper.

Reader: Approximately $10 or less per reader-

Cost of electrical components is very low.

Testing and Validation

17

Test strips: Tested different concentrations of glucose

• Fasting levels, normal levels, and high levels all give different dye intensity.

•Tested different reagent deposition orders

Future work: test time/light sensitivity of reagents, inkjet printing of reagents

Testing and Validation

18

Reader:

•

Tested device with “calibration strips”

and our strips

-

Sensitive to white and three increasing intensities of blue on calibration strips

•

Tested device in normal room lighting and within device housing (dark) Future work: Test device with specific glucose concentrations, actual strips and

smaller ranges of concentration

Manufacturing and Regulatory Pathways

19

Our design is simple and cheap to produce:• Local diagnostic company• Local materials

Distribution:Follow the distribution system currently used in Nicaragua, and spread to Polyclinics.3-4 for use in clinic at first, but eventually 1 glucometer

per

Diabetes patient. Regulation:

• 510(k) pathway• Predicate device-

colorimetric glucose assay, optic technology

Medical Device Compass Chart

Glucophone

Cost

Effe

ctiv

enes

s

Standard Glucometer

Advanced Glucometer

Lab-Intensive Glucose Assay

Colorimetric Test Strips

Urinanalysis

Strips

Our Goal

Colorimetric test strips were abandoned around 10 years ago for the electrochemical test strips, since there was no appropriate reader at that time. The electrochemical assay is more expensive, but also more accurate.

Our Current

Prototype

20

Future Work

21

Developing the Test Strip:

•

Double layer strip idea, with a top layer that is able to filter

the blood cells allowing just the serum to pass through to reagents.

Developing the Reader:

•

Creating a more sensitive reader with more LED indicator lights, so we can inform of patients their glucose levels more accurately.

Questions?

22