CPAC Webinar Feb. 2009 Process Spectroscopy and Optical Sensing

1. CPAC Webinar Feb. 2009 Process Spectroscopy and Optical Sensing Brian Marquardt Ph.D. Director – Applied Optical Sensing Lab Applied Physics Lab University of Washington Seattle, Washington 98105

2. Process Raman Applications • Pharmaceuticals • Food quality and safety • Polymers/coatings • Fermentation/biotech • Cellular/tissue • Oil/fuels/petrochemicals • Oceanography/environment • Challenges • Reproducible sampling • Fluorescence

3. Quantitative Raman = Effective Sampling • no moving parts • sapphire spherical lens • constant focal length and sample volume • probe is ALWAYS aligned when in • contact with sample • effective sampling of liquids, slurries, • powders, pastes and solids • high sampling precision allows it to • be used effectively to monitor dynamic • mixing systems (powder/slurry/particle) • improved measurement precision leads to robust multivariate calibration of process Raman data CPAC developed, patented and licensed Raman ballprobe

4. Analysis of a Batch Fermentation Process Real-time Fermentation Monitoring Yeast Fermentation Process Image from Purves et al., Life: The Science of Biology, 4th Edition

5. Raw Raman Data for Fermentation Batch Reaction (8 day run) Fluorescence

6. Raman Data After Fluorescence Correction Algorithm Applied

7. 3D Plot of fluorescence corrected Raman fermentation data

8. Raman Analysis and Optical Trapping of Single Cells Raman Microscope and Instrument Raman Microscope and Microchip

9. Micro-reactors and Raman lead to improved understanding and control 2,4-dinitrotoluene 2,6-dinitrotoluene 2-nitrotoluene 3-nitrotoluene 4-nitrotoluene nitric acid sulfuric acid toluene 500 1000 2000 1500 Raman Shift (cm-1)

10. PCA Analysis on data after mixing: 1st PCA scores  Increase in reaction yield after each temperature step • without residence time module • flow rate: 0.89 ml/min (residence time ~ 5 min) Real-time Understanding and Control

11. CPAC/FDA/Corning MicroReactor • Goal: to improve reaction development and optimization through the use of continuous glass microreactors, NeSSI and analytics • Funded by the FDA to demonstrate the benefits of improved reactor design, effective sampling and online analytics to increase process understanding (QbD) • QbD Project began November 2008

12. 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 interfaces • Standard platform formicro analytics

13. What does NeSSI Provide • Simple “Lego-like” assembly • Easy to re-configure • No special tools or skills required • Standardized flow components • “Mix-and-match” compatibility between vendors • Growing list of components • Standardized electrical and comm. (Gen II) • “Plug-and-play” integration of multiple devices • Simplified interface for programmatic I/O and control • Advanced analytics (Gen III) • Micro-analyzers • Integrated analysis or “smart” systems

14. NeSSI Gas Generation System Mass Flow Controllers Mixed Gases O2 N2 Fully automated gas generation system for sensor calibration: 4 Stage dilution, able to produce and maintain gas concentrations of 100% to 0.1%(1000 ppm) from standard bottle gas Fully calibrated, automated system with set and forget capability Automated Circor NeSSI Gas/Vapor System

15. Small Optical Sensors Oxygen Moisture Ammonia Hydrogen Common Solvents Alcohols Esters Amines Chlorinated Organics Organic Hydrocarbons (BTEX) Carbon Dioxide (in development) Hydrogen Sulfide (in development) • vapochromic chemistry • optical response to analytes • 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

16. Vapochromic Humidity Sensor - Measurment time – 100 ms - 3 reps per concentration

17. Sensor response to O2 Gas 120 20 replicates at each concentration Concentration range: 0 -100% Oxygen 100 R2 = 0.990, 3 PC RMSEC = 1.0744 80 Predicted O2 % 60 0% 40 Intensity (counts) 20 100 % Wavelength (nm) 0 0 10 20 30 40 50 60 70 80 90 100 Calculated O2 %

18. Low Concentration Dissolved O2 Calibration 39 5 replicates at each concentration Concentration range: 1 μmol/L - 39 μmol/L 1 μmol /L 31 R2=0.997, 2 PCs, RMSEC= 0.67861 24 Predicted [O2] (μmol/L) Intensity (counts) 16 9 5 2 39 μmol/L 1 1 μmol/L = 32.5 ppb Measured [O2] (μmol/L) Wavelength (nm)

19. 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

20. Potential Applications • Analysis of metal complexes in food, cellulosic biomass, pharmaceuticals and fermentation apps. • Determination of ionic and inorganic species in a variety of chemical/production processes • Glasses, ceramics, zeolites, alloys, corrosion analysis • Quantitative analysis of catalyst composition for screening and development • Couple with vibrational techniques to develop a hyphenated technique (Raman/LIBS) to define both organic and inorganic analytes in a process system

21. Acknowledgements CPAC Washington Tech. Center National Science Foundation National Institute of Health, Charlie Branham and Wes Thompson Many current and past CPAC sponsors