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

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.

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. Software and hardware for data and control communication interfaces (hopefully utilizing a Gen II NeSSI™-bus network) will need to be developed and tested.

Benefits of Being NeSSI™ Your condition space is constrained Volumes, flow rates, pressures, and viscosities inherently bounded by architecture 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 Electrical power, communication, and sample are all available in a standard way Power budget could be main driver to miniaturize 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) 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 Lab Instrument/Sensor Interfaces Design standards make development simpler Design standards make development simpler Reduced toolset to be mastered Reduced sample variability to account for Calibration/validation built-in 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 Microreactors and continuous flow reactors Batch reactors (with fast loop) Batch reactors (with fast loop) Sample Preparation Gas handling (mixing, generation, delivery) Gas handling (mixing, generation, delivery) Liquid handling (mixing, dilution, conditioning, etc.) Liquid handling (mixing, dilution, conditioning, etc.)

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

Sensing Technologies Gas Chromatography Thermal Desorption (?) Thermal Desorption (?) Dielectric (√) Spectroscopies IR (+), NIR (+) IR (+), NIR (+) UV- Vis (+) UV- Vis (+) Raman (√) Raman (√) Fluorescence (+) Fluorescence (+) Impedance (+) Conductivity (√) Refractive Index (√) Vapochromic Sensors (+) GLRS (+) Particle Sizing Light scattering (?) Light scattering (?) Turbidity (+) pH (√) RGA (+) Mass Spectrometry (√) LC, SEC, IC (+) Terrahertz (?)

Corning Microreactor + NeSSI

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 Vapochromic sensor optical cell GC sipper port EP-IR gas cell

NeSSI Ballprobe - Raman/NIR/UV

Agilent NeSSI Dielectric Sensor Cable 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

Liquid Chromatography for NeSSI™ micromixer diluent in column mobile phase in sample in Scott Gilbert, CPAC Visiting Scholar Crystal Vision Microsystems LLC Atofluidic Technologies, LLC Split flow approach to sampling  -fluidic LC Chip for On-line Sample Pretreatment Pulsed electrochemical detection (on-chip) Liters per minute microliters per minute nanoliters per minute

NeSSI Gas Generation System Features of Circor NeSSI System : 1.4 State dilution, able to produce and maintain gas concentrations in ppb range 2.Fully automated system, set and forget capability Automated Circor NeSSI Gas/Vapor System N2N2 O2O2 Mixed Gases Mass Flow Controllers

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)

Vapochromic NeSSI Sensor Design Fiber optic cable to Ocean Optics Spectrometer Swagelok 2-Port Valve Base Fiber- optic Probe(405 nm LED) Inner Body O-ring (inside) Outer Body Exploded View Close up of Outer Body Tip VapochromicT ip

Development of a Micro-NMR System NMR spectrum of a 3 micro liter water sample using a RF micro-coil M. McCarthy, UC Davis

NeSSI Gas Permeation Apparatus

Other potential commercial analyzers for NeSSI/microreactor project

C2V fast micro-GC

At-Line GC’s with NeSSI Compat. ABB Natural GC Siemens microSAM Agilent 3000 Micro GC

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

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.

NeSSI™ IR Gas Cell

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 Courtesy of Mike Doyle Axiom Analytical, Inc.

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 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 Likely will need to generalize Scott Gilbert’s dilution stream device On-board dilutant (solvent) storage reservoirs Pneumatic pumping (piston/syringe pump)

Analytical-on-NeSSI Gen III Spec. Work with Sponsors, Vendors, End-users Draft at Fall 2008 CPAC Meeting Draft at Fall 2008 CPAC Meeting Final at Spring 2009 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 Compendium of parameters Example reference systems Example reference systems Generally useful to extend application base of NeSSI

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 Much of this work will be performed with the help of Bruce Finlayson's senior project students and from our work at CPAC

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