Brian Marquardt , Charles BranhamKent Mann – University of Minnesota

Applied Physics Laboratory /Center for Process Analytical ChemistryUniversity of WashingtonSeattle, WA 98105

Combining Analytical Sensors and NeSSI to Improve Process Understanding

Analytical Sampling for Online Applications

Why Use Microreactors?

High Throughput Experimentation For..

Discovery and screeningProcess optimizationProcess developmentProcess controlProduction?

Challenges To Using Microreactors

Analytical characterizationSampling and screeningData handlingProcess modeling and feed back control (particularly if they are used for production)Reaction optimization – move toward feed forward control????

FDA Micro-reactor Project - QbDCollaborative project between 4 entities to improve reaction development and optimization through the use of continuous micro-reactors, NeSSI and analytics

FDA/ Corning/Kaiser Optical Systtems/ CPACFunded by the FDA to demonstrate the benefits of improved reactor design, effective sampling and online analytics to increase process understandingProject started November 2008

Corning Microreactor + NeSSI

NeSSI Ballprobe - Raman/NIR/UV

Spectroscopic Analysis of ReactorPossible problems with performing online spectroscopic measurements

Bubble formation in sample linesdue to pressure dropsample degassing

Phase change between reactor and analyzerdue to temperature or pressure change

Most PAT problems are due to sampling not measurement deviceNeed better systems to sample processes

NeSSI Raman Sampling Block

• Parker Intraflow NeSSI substrate• Sample conditioning to induce backpressure to

reduce bubble formation and the heated substrate allows analysis at reactor conditions

What is NeSSI?• Industry-driven effort to

define and promote a new standardized alternative to sample conditioning systems for analyzers and sensors

Standard fluidic interface for modular surface-mount components Standard wiring and communications interfacesStandard platform formicro analytics

What does NeSSI ProvideSimple “Lego-like” assembly

Easy to re-configureNo special tools or skills required

Standardized flow components“Mix-and-match” compatibility between vendorsGrowing list of components

Standardized electrical and comm. (Gen II)“Plug-and-play” integration of multiple devicesSimplified interface for programmatic I/O and control

Advanced analytics (Gen III)Micro-analyzersIntegrated analysis or “smart” systems

Benefits of Being NeSSIYour condition space is constrained□ Volumes, flow rates, pressures, and viscosities inherently

bounded by architectureYour interfaces are defined□ Electrical power, communication, and sample are all available

in a standard way□ Power budget could be main driver to miniaturizeYour sample conditioning can be defined and controlled□ Specify up-stream and down-stream NeSSI components (and

verify)All this means your analytical can be more directed and focused

Where Does NeSSI Fit in the LabInstrument/Sensor Interfaces

Design standards make development simplerReduced toolset to be masteredReduced sample variability to account for

Calibration/validation built-inConsistent physical environment for measurementStream switching and/or mixing allow generation of standards to match analytical requirements

Reaction monitoringMicroreactors and continuous flow reactorsBatch reactors (with fast loop)

Sample PreparationGas handling (mixing, generation, delivery)Liquid handling (mixing, dilution, conditioning, etc.)

NeSSI with an Array of Micro-Analytical Techniques will Impact Many Industries

• Process Control• Process Optimization• Product Development

NeSSI Sensing TechnologiesGas Chromatography

Thermal DesorptionDielectricSpectroscopies

IR NIR UV- Vis Raman Fluorescence

Impedance Conductivity Refractive Index

Particle SizingLight scattering (?)

Turbidity pHRGAMass SpectrometryLC, SEC, ICTerahertz (?)

NeSSI™: Enabler for MicroAnalytical

(the “rail” concept)

Standard Mechanical Interface “Rail”

Standard Electrical (Digital) Interface “Rail”

Anyone’s Sensor Anyone’s Actuator

SAM*

Standard“hockey-puckPC”

PV

*Sensor/Actuator Manager

Standard“connectivity

”

What technologies are availableSuitability for modular sampling systems

C2V Fast Micro-GC

http://www.c2v.nl/

At-Line GC’s with NeSSI CompatibilityABB Natural GC

Siem

ens microS

AM

Agilent 3000 M

icro GC

Applied Analytics Inc. Diode Array OMA-300 A Fiber-optics-diode-array process analyzerFor on-line concentration monitoring

Applied Analytics Microspec IRFEATURES

Ideal for monitoring PPM level WATER in various solventsIn stream quantitative measurementsContains no moving parts andExtremely robust allowing for installations in process stream environmentsReplaces analyzers such as process spectrometers in the process plant.

Small Diameter ATR-IR-Fiber ProbesFiber Photonics Inc.

www.fibrephotonics.comDiamond ATR-IR-Fiber Probe of 2.7mm diameter in NeSSI

H2Scan Adaptation to NeSSITM Platform• Hydrogen specific: 0.5% H2 to 100% H2 v/v

• Response time (T90) < 30 sec

• In‐line, real‐time measurements in process gas streams up to 100OC

• Unique models for CO, H2S, wet CL2

• 4‐20mA, RS422 or RS232 serial connectivity

• Stable results 

• On‐site verification and calibration 

• Approved for hazardous locations– Intrinsically safe design– ATEX certificate granted; UL pending

• Cost effective to buy / install / maintain

• Field verification and calibration kit available

http://www.h2scan.com/

Astute Sampling System

GAS TREATMENT

COLUMN

Sampling + Sensors& micro-analyzers

Astute System with C2V Micro GC and H2Scan hydrogen analyzer Process

www.eif-filters.com

Agilent NeSSI Dielectric SensorCable to Agilent

Network Analyzer

Swagelok 2-Port

Valve Base

Dielectric Probe

Inner Body

O-ring (inside)

Outer Body

Exploded View

Close up of Coaxial

Probe Tip

NeSSI™ IR Gas Cell

NeSSI Compatible Optical Cells Axiom Analytical, Inc.

Courtesy of Mike DoyleAxiom Analytical, Inc.

Currently Available

FFV Series Transmission Cells (Near-IR, UV-Visible)FNL-120 UV-Visible ATR Cell

In DevelopmentRaman Cells (Single- and Multi-pass)

Possible DevelopmentDiffuse Reflectance CellsMid-IR ATR Cells

Chevron NeSSI/Analytical UnitSpecifications

ASI Microfast GCParker NeSSI gas handling/sampling systemCarrier gasMobility

NeSSI based Analytical Developments at CPAC

NeSSI Gas/ Vapor System

NeSSI Gas/Vapor System

Permeation Tower

Aspectrics EPIR w/ glass cell

N2 Waste

NeSSI Flow Cell

ASI microFAST GC

NeSSI Calibration Gas Generation System

Features of NeSSI System :• 4 Stage dilution, able to produce and maintain gas concentrations in ppb

range• Fully automated system, set and forget capability

Automated NeSSI Gas/Vapor System

N2

O2

Mixed Gases

Mass FlowControllers

Gas Mixing System LabView Control Program

Design of Small Fiber Optic SensorsOxygenMoistureAmmoniaHydrogenCommon Solvents

AlcoholsEstersAmines

Chlorinated OrganicsOrganic Hydrocarbons

(BTEX)Carbon Dioxide

(in development)Hydrogen Sulfide

(in development)

• vapochromic chemistry• optical response to analyte

• simple design• reversible response• low power• inexpensive• fast response times• high quantum efficiency• long term sensor stability• sensitive to a variety of analytes• wireless communication• battery powered

Modular NeSSI Oxygen Gas Sensor

Exploded View

1/16 in bifurcated fiber optic fiber

1/16 to 1/8 in Swagelok union

Agilent NeSSI Mount

Sensor Body

Close up of Outer Body Tip

Vapochromic Tip

Fiber optic ferrule with plastic housing

Vapochromic Humidity Sensor

0

20

40

60

80

100

0 20 40 60 80 100 humid meas, (Y-var, PC): (humid meas,2)

per10.Mas

per20.Mas

per30.Mas

per50.Mas

per70.Mas

per80.Mas

Elements:Slope:Offset:Correlation:RMSEC:SEC:Bias:

60.9998240.0075850.9999120.3423230.374996

-1.272e-06

Measured Y

Predicted Y

• 2 PC calibration model• humidity range: 10 – 80%• Ohmic feedback control

humidity generator used for reference stds.

- Measurment time – 100 ms- 3 reps per concentration

Vapochromic Benzene Sensor

Full spectrum response of the 0%, 10%, and 50% bubbler flow samples used to make the PLS model showing both the change in intensity and shift in peak maximum with changing benzene concentration.

Sensor response to O2

Pre

dict

ed O

2%

Calculated O2 %

R2 = 0.990, 3 PCRMSEC = 1.0744

20 replicates at each concentrationConcentration range: 0 -100% Oxygen

Inte

nsity

(cou

nts)

Wavelength (nm)

100 %

0%

120

100

80

60

40

20

01009080706050403020100

Future Miniature Oxygen SensorOxygen Sensor and probe Oxygen Sensing Tip

Liquid Chromatography for NeSSI™ Scott Gilbert, CPAC Visiting Scholar

Crystal Vision Microsystems LLCAtofluidic Technologies, LLC

• Split flow approach to sampling

• μ-fluidic LC Chip for On-line Sample Pretreatment

• Pulsed electrochemical detection (on-chip)

micromixer

diluent in

column

mobile phase in

sample in

Liters per minute

microliters per minute

nanoliters per minute

Development of a Micro-NMR System

M. McCarthy, UC Davis

AcknowledgmentsCenter for Process Analytical ChemistryStudents – Charles Branham and Wes Thompson, UWVendors who provided slidesProfessor Kent Mann’s Group, Univ. of MinnesotaScott Gilbert – UW Visiting scholarSwagelok, Parker and Circor ABB, Agilent, Aspectrics, Honeywell, ExxonMobil