Brian Marquardt and Dave Veltkamp Applied Physics Laboratory

1. Brian Marquardt and Dave Veltkamp Applied Physics Laboratory / Center for Process Analytical Chemistry University of Washington Seattle, WA 98105 Combining Analytical Sensors and NeSSI to Improve Process Understanding

2. Project Goals and Objectives Establish research platforms integrating microreactors, NeSSI, and analytical monitoring for the multidisciplinary investigation of bio-processing and bio-fuels related processes. These systems will be used to support other CPAC and University projects investigating bio-processing, provide opportunities for student education, and allow development of additional instrumentation and techniques for monitoring bio-processes.

3. Project Research Plan Task 1: integrate the microreactors with the NeSSI� fluidics system and the analytical monitoring instruments. Task 2: characterize the systems so their properties (i.e., flow, mixing, heat transfer, residence time, etc.) are well understood. Task 3: development of the on-line analytical to monitor the key operational parameters and reaction progress. Task 4: development of strategies and implementations for automation and control of the system. Software and hardware for data and control communication interfaces (hopefully utilizing a Gen II NeSSI�-bus network) will need to be developed and tested.

4. Benefits of Being NeSSI� Your condition space is constrained Volumes, flow rates, pressures, and viscosities inherently bounded by architecture Your interfaces are defined Electrical power, communication, and sample are all available in a standard way Power budget could be main driver to miniaturize Your 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

5. Where Does NeSSI� Fit in the Lab Instrument/Sensor Interfaces Design standards make development simpler Reduced toolset to be mastered Reduced sample variability to account for Calibration/validation built-in Consistent physical environment for measurement Stream switching and/or mixing allow generation of standards to match analytical requirements Reaction monitoring Microreactors and continuous flow reactors Batch reactors (with fast loop) Sample Preparation Gas handling (mixing, generation, delivery) Liquid handling (mixing, dilution, conditioning, etc.)

6. NeSSI with an Array of Micro-Analytical Techniques will Impact Many Industries Process Control Process Optimization Product Development

7. Sensing Technologies Gas Chromatography Thermal Desorption (?) Dielectric (v) Spectroscopies IR (+), NIR (+) UV- Vis (+) Raman (v) Fluorescence (+) Impedance (+) Conductivity (v) Refractive Index (v)

8. Corning Microreactor + NeSSI

9. Interfacing NeSSI� to ASI microFast GC� Complete gas/vapor sensing test platform on the bench top Gas delivery, vapor generation, and blending in NeSSI� Real time verification of composition using GC and EP-IR Easily extended to include other analytical and sample treatments

10. NeSSI Ballprobe - Raman/NIR/UV

11. Agilent NeSSI Dielectric Sensor

12. Liquid Chromatography for NeSSI� Scott Gilbert, CPAC Visiting ScholarCrystal Vision Microsystems LLCAtofluidic Technologies, LLC Split flow approach to sampling m-fluidic LC Chip for On-line Sample Pretreatment Pulsed electrochemical detection (on-chip)

13. NeSSI Gas Generation System

14. Vapochromic NeSSI Sensor Design simple design reversible response low power inexpensive NeSSI compatible fast response times high quantum efficiency long term sensor stability sensitive to a variety of analytes large number of available vapochromic compounds (selectivity)

15. Vapochromic NeSSI Sensor Design

17. NeSSI Gas Permeation Apparatus

18. Other potential commercial analyzers for NeSSI/microreactor project

19. C2V fast micro-GC

20. At-Line GC�s with NeSSI Compat.

21. Applied Analytics Inc. Diode Array OMA-300 A� Fiber-optics-diode-array process analyzer For on-line concentration monitoring

22. Applied Analytics Microspec IR FEATURES Ideal for monitoring PPM level WATER in various solvents In stream quantitative measurements Contains no moving parts and Extremely robust allowing for installations in process stream environments Replaces analyzers such as process spectrometers in the process plant.

23. NeSSI� IR Gas Cell

24. NeSSI Compatible Spectroscopic Cell Axiom Analytical, Inc. Currently Available FFV Series Transmission Cells (Near-IR, UV-Visible) FNL-120 UV-Visible ATR Cell In Development Raman Cells (Single- and Multi-pass) Possible Development Diffuse Reflectance Cells (For turbid liquids) Mid-IR ATR Cells

25. NeSSI Project Deliverables Integrate NeSSI, microreactors and analytics Develop and publish the NeSSI Gen III specification Continue development of interfaces for analytical instrumentation liquid sample vaporizer using nanoliter volume inkjet-type injectors and heated carrier stream Direct liquid injection to GC Direct liquid injection to Mass spec Likely will need to generalize Scott Gilbert�s dilution stream device On-board dilutant (solvent) storage reservoirs Pneumatic pumping (piston/syringe pump) The main goal for this year is to publish the Gen III Spec we want to avoid some of the problems encountered in the Gen II spec (which was too focused on how to accomplish a goal rather than just stating the desired functional goal for the system, and letting the developer figure out how to meet that goal). At the same time, we do not want to wait too long before publishing some guidance or roadmap for those wishing to develop or commercialize NeSSI analytical devices. The secondary goal is to continue to look at what analytical interfaces are missing or not widely available on NeSSI and work to investigate, demonstrate, or develop the needed interfaces. This year we will focus on liquid sample streams and analytically getting part of that sample into the vapor phase for injection onto a GC or into a mass spec. We are currently looking at inkjet-type injection pumps (Lee Company) that can inject very small droplets (20-50 nanoliter droplets) into a heated carrier stream � coupled with the trap and purge injector of the ASI microFAST GC alliviates many of the constriants on the liquid injection.The main goal for this year is to publish the Gen III Spec we want to avoid some of the problems encountered in the Gen II spec (which was too focused on how to accomplish a goal rather than just stating the desired functional goal for the system, and letting the developer figure out how to meet that goal). At the same time, we do not want to wait too long before publishing some guidance or roadmap for those wishing to develop or commercialize NeSSI analytical devices. The secondary goal is to continue to look at what analytical interfaces are missing or not widely available on NeSSI and work to investigate, demonstrate, or develop the needed interfaces. This year we will focus on liquid sample streams and analytically getting part of that sample into the vapor phase for injection onto a GC or into a mass spec. We are currently looking at inkjet-type injection pumps (Lee Company) that can inject very small droplets (20-50 nanoliter droplets) into a heated carrier stream � coupled with the trap and purge injector of the ASI microFAST GC alliviates many of the constriants on the liquid injection.

26. Analytical-on-NeSSI Gen III Spec. Work with Sponsors, Vendors, End-users Draft at Fall 2008 CPAC Meeting Final at Spring 2009 CPAC Meeting Goal is to provide analytical developers with a clear idea of what they must design to and what they can expect from NeSSI Compendium of parameters Example reference systems Generally useful to extend application base of NeSSI Developing and publishing the Gen III specification would be a collaborative sheaperded by CPAC � iterative set of drafts and revisions In the end, we want to give the potential developer of analytical a clear idea of what they can expect (range of conditions their sensor must tolerate), how they can restrict the conditions (by specifying sample conditioning components that must be present on the NeSSI system), and how they can interact with the NeSSI system (draw power, communicate data, alarms, status, etc) This would help others deploying NeSSI as sampling systems, fluidic systems (as in microreactor), or as analytical systems � all leading to more and easier deploymentsDeveloping and publishing the Gen III specification would be a collaborative sheaperded by CPAC � iterative set of drafts and revisions In the end, we want to give the potential developer of analytical a clear idea of what they can expect (range of conditions their sensor must tolerate), how they can restrict the conditions (by specifying sample conditioning components that must be present on the NeSSI system), and how they can interact with the NeSSI system (draw power, communicate data, alarms, status, etc) This would help others deploying NeSSI as sampling systems, fluidic systems (as in microreactor), or as analytical systems � all leading to more and easier deployments

27. Typical info for the Gen lll Spec Application operational setting ranges Available sample conditioning options Power budget limits and example calculation Communication protocols, messages, and rates Much of this work will be performed with the help of Bruce Finlayson's senior project students and from our work at CPAC This is representative of what kind of information we want for the specThis is representative of what kind of information we want for the spec

28. Acknowledgments Center for Process Analytical Chemistry CPAC Post-doc � Tom Dearing Students � Charles Branham and Wes Thompson, UW Vendors who provided slides Professor Kent Mann, Univ. of Minnesota Scott Gilbert � UW Visiting scholar Swagelok, Parker and Circor ABB, Agilent, Aspectrics, Honeywell, ExxonMobil