Brian Marquardt Wes Thompson, Charles Branham, Lauren Hughs and Tom Dearing

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

Combining Analytical Sensors and NeSSI to Improve Efforts to Achieve Process Understanding

Analytical Sampling for Online Applications

Process Spectroscopy ApplicationsPharmaceuticalsFood quality and safetyPolymers/coatingsFermentation/biotechCellular/tissueOil/fuels/petrochemicalsOceanography/environmentChallenges

Reproducible samplingBackground interference

Why Use Process Sensors?

Real-time analysis for ..

Process characterizationProcess developmentProcess optimizationProcess controlProduction

Process Challenges

Analytical characterizationSampling and screeningData handling

Sensor fusing – talk tomorrowMulti-sensor modeling

Process modeling and feed back controlProcess optimization – move toward feed forward control????

Spectroscopic Analysis of a ProcessPossible problems with performing online spectroscopic measurements

Bubble formationSolid FormationPhase separationFouling, etching, …..Anything else that you could possibly imagine

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

NeSSI™ Modular Sampling SystemsNew Sampling/Sensor InitiativeSurface-mount modular component based gas and fluid handling and conditioning systems

ISA SP76 interface specificationElastomeric o-ring seals

Offer flexibility in design and implementationAllows for optimal positioning of analyzers in a process stream

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 componentsStandard 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

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

At-Line GC’s with NeSSI CompatibilityABB Natural GC

Siem

ens microS

AM

Agilent 3000 M

icro GC

Calidus fast GC from Falcon Analytical

Thermo/C2V Fast Micro-GC

http://www.c2v.nl/ as well as http://www.thermo.com

http://www.c2v.nl/http://www.c2v.nl/products/instrumentation/C2V-200_micro_gc_GCC-1000_cartridge.shtml

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

NeSSI Ballprobe - Raman/NIR/UV

Matrix Solutions: www.ballprobe.com

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

micrOptix

NeSSI UV-Vis/NIR Sensor

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

• Response time (T90) 

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 research and developments at CPAC

CPAC/FDA/Corning AF Reactor Project

Goal: to improve reaction development and optimization through the use of continuous glass flow reactors, NeSSI and analyticsPhase 1: Funded by the FDA to demonstrate the benefits of improved reactor design, effective sampling and online analytics to increase process understanding (QbD)Partners: FDA, Corning, CPAC, Kaiser, ParkerQbD Project began November 2008Process Reactions – June 2009

Corning® Advanced-FlowTM LFLow-Flow Capability (1-10 mL/min)

Low internal volume

High flexibility

Metal-free reaction path

Scalability

Compatibility with analytics

T, Flow and Pumping control

Corning has developed a reduced flow-rate reactor that retains the outstanding mixing and heat exchange performance of its Advance-FlowTM glass reactors while providing:

• LF platform will be the reactor platform for our Phase II FDA project

NeSSI Ballprobe - Raman/NIR/UV

Matrix Solutions: www.ballprobe.com

Ballprobe Specs.•Hastalloy c-276

Ti, SS, Monel•Sapphire optic•Std. temp range:

-40 – 350° C•Pressure:

0-350 Barr

NeSSI Sampling System for Reactor

Raman Probe

monitor

bypass

clean

Advanced Flow Reactor Images

Raman Probes

3D Plot of Raman Reaction Data

ChloroformateToluene

Toluene

Ch. 1GC Results (%)Test R-OH 2EHCF R-Cl Carbonate Dimer

1 1.17 0.00 0.26 96.17 2.402 2.16 45.84 0.32 51.42 0.59

Reaction Profiles for 2 DoE Steps

GC Results (%)

Test R-OH 2EHCF R-Cl Carbonate Dimer1 1.17 0.00 0.26 96.17 2.402 2.16 45.84 0.32 51.42 0.59

Test 1

Test 2

---- Carbonate---- Chloroformate

Reactor Feed 1

Reactor Feed 2

Product Stream

Real-timeCalibration

waste

prod

AnalyzerSuite

Pump 1

Pump 2

NESSI AF Reactor Sampling/Calibration

• Application of sampling systems and analytics to optimize and control AF reactor

NeSSI Gas/ Vapor System

NeSSI Gas/Vapor System

Permeation Tower

Aspectrics EPIR w/ glass cell

N2 Waste

NeSSI Flow Cell

ASI microFAST GC

NeSSI Calib. Gas Generation SystemFeatures of NeSSI System :• Fully digital• 4 Stage dilution,

able to produce and maintain gas concentrations in ppb range

• Fully automated system, set and forget capability

• Integrated C2V NeSSI compat. GC

• Calib, platform for gas sensor dev.

Gas Calib. System LabView Control Program• Perform automated DoE calibration runs• input and log sensor, reference, temperature and pressure feeds• System designed for full digital (plug and play) performance as h/w matures

Digital Gas Calibration System

Digital Gas Calibration System

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

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.

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

LIBS: Remote Elemental Analysis• Remote elemental

analysis with no sample preparation

• Fiber-optic delivery or long range delivery of laser by telescope for remote analysis

• Laser-induced plasma ablates and super heats samples to provide elemental spectral data

316 Stainless Steel

394 396 398 400 402 404

NFe

Fe Fe

0.625 nm

400 500 600 700 800 900300200Wavelength (nm)

Cr

Cr FeCrFe N

Selected spectra from database6061 Aluminum

316 Stainless Steel

Grade 2 Titanium

WD-40

Silicone lubricant

Calcium chloride

Potassium carbonate

Magnesium sulfate

Depth profiling of tablet easily accomplishedLaser readily absorbed by tabletBlackbody radiation decreases signal to noise

Ibuprofen Tablet

AcknowledgmentsCenter for Process Analytical ChemistryVendors who provided slidesParkerU.S. Food and Drug AdministrationCorning GlassKaiser Optical SystemsLa Maison Européenne des Procédés Innovants (MEPI )

Combining Analytical Sensors and NeSSI to Improve Efforts to Achieve Process UnderstandingAnalytical Sampling for Online ApplicationsProcess Spectroscopy ApplicationsWhy Use Process Sensors?Process ChallengesSpectroscopic Analysis of a ProcessNeSSI™ Modular Sampling SystemsWhat is NeSSI?What does NeSSI ProvideWhere Does NeSSI Fit in the LabNeSSI with an Array of Micro-Analytical Techniques will Impact Many IndustriesNeSSI Sensing TechnologiesNeSSI™: Enabler for MicroAnalyticalAt-Line GC’s with NeSSI CompatibilityCalidus fast GC from Falcon AnalyticalThermo/C2V Fast Micro-GCApplied Analytics Inc. Diode Array Applied Analytics Microspec IRSmall Diameter ATR-IR-Fiber Probes� Fiber Photonics Inc.NeSSI Ballprobe - Raman/NIR/UVNeSSI Raman Sampling BlockmicrOptixH2Scan Adaptation to NeSSITM PlatformAstute Sampling SystemAgilent NeSSI Dielectric SensorNeSSI™ IR Gas CellNeSSI Compatible Optical Cells �Axiom Analytical, Inc.Chevron NeSSI/Analytical UnitNeSSI based research and developments at CPACCPAC/FDA/Corning AF Reactor ProjectCorning® Advanced-FlowTM LF�Low-Flow Capability (1-10 mL/min)NeSSI Ballprobe - Raman/NIR/UVNeSSI Sampling System for ReactorAdvanced Flow Reactor Images3D Plot of Raman Reaction DataReaction Profiles for 2 DoE StepsNESSI AF Reactor Sampling/CalibrationNeSSI Gas/ Vapor SystemNeSSI Calib. Gas Generation SystemGas Calib. System LabView Control ProgramDigital Gas Calibration SystemSlide Number 42Design of Small Fiber Optic SensorsVapochromic Humidity SensorVapochromic Benzene SensorModular NeSSI Oxygen Gas SensorLIBS: Remote Elemental Analysis316 Stainless SteelSelected spectra from databaseIbuprofen TabletAcknowledgments