PROCESS ANALYTICAL RESPONSE TO THE DEMANDS OF HIGH THROUGHPUT EXPERIMENTATION

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PROCESS ANALYTICAL RESPONSE TO THE DEMANDS OF
HIGH THROUGHPUT EXPERIMENTATION

• MEL KOCH
• CPAC
• UNIVERSITY OF WASHINGTON

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NEW DIRECTIONSIN INDUSTRY
? GLOBALIZATION OF BUSINESSES
? CONSOLIDATION OF INDUSTRIES ? CONSTRICTED
RESOURCES
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THE DRIVERS
? PRODUCTIVITY ? QUALITY ? ENVIRONMENTAL
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THE DRIVERS ALLREQUIRE RESEARCH
YET RESOURCES ARE
S H R I N K I N G
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EFFECTIVE PARTNERINGIS NEEDED
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PARTNERING
? WITHIN AN ORGANIZATION ? ACROSS INDUSTRY ?
INDUSTRY - UNIVERSITY (GOVERNMENT) ?
INDUSTRY - GOVERNMENT - UNIVERSITY
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CENTER FOR PROCESS ANALYTICAL CHEMISTRY
UNIVERSITY OF WASHINGTON,
SEATTLE
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Real-time Data Acquisition . . .

• . . . provides researchers with a video of a
  chemical process.
• Deliverables
• Composition
• Unknown Identification
• Reaction Pathways Kinetics
• Chemical Topography
• Emission Monitoring
• Process Hardware Integrity
• Reactive Chemical Issues
• On-line Feasibility Studies

H2 Monomer C2H6
Gas-Phase Reactor On-line MS
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Short-term On-line Analytical Measurements ...
Catalysis RD On-line MS, GC, FTIR

• . . . maximize the investment of capital,
  hardware, staff by. . .
• Shortening development time,
• Increasing productivity, and
• Maximizes asset utilization unattended data
  collected 24 hours a day. Allows process
  parameters to be tweaked in real time to link
  cause and effect.
• Making better decisions.
• Evaluate methods and instrumentation for
  permanent applications before committing capital.

MS
GC
High-Flow Reactor
FTIR
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Allows On-line Concepts to be Developed

• Over 190 materials evaluated in 5 reactors 1st
  year.
• Each run at
• 12 different combinations of T P.
• Steady-state conditions for 3-6 hours.
• 3 days to complete typical evaluation.
• Potential for 605 catalysts/year.
• 12X improvement in sample throughput.

Tube Reactors in Fluidized Bed
On-line GC/MS Direct MS
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CPAC is a Consortium of Industrial Sponsors,
National Laboratories and Government Agencies
? Established in 1984, the Objective of the
Center is to Address Challenges in Real-Time and
Continuous Process Monitoring and Control
? Provides a Forum for Multidisciplinary
Participation in Process Analytical Technology
Definition, Creation, and Utilization
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BENEFITS OF CONSORTIA MEMBERSHIP
New Technology
Peer Communication
Students
Deliverables
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PEER COMMUNICATION
? BENCHMARKING ? CLEARING HOUSE ? FOCUS GROUPS
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Sponsor Focus Groups
? Oil Petrochemicals ? Chemicals Materials ?
Food Consumer Products ? Bio Tech /
Pharmaceuticals ? National Labs Agencies ?
Instrument Companies
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CPAC Industrial Sponsors
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CPAC Government Sponsors

• Environmental Protection Agency
• Los Alamos National Laboratory
• National Institute of Standards Technology
• Pacific Northwest National Labs
• Sandia National Laboratory
• Westinghouse Savannah River Co.

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Core Research Areas
? Chemometrics ? Sensors ? Spectroscopy /
Imaging ? Chromatography ? Flow Injection
Analysis ? Process Control
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Multidisciplinary
? Chemistry ? Chemical Engineering ? Electrical
Engineering ? Bioengineering ? Applied Physics ?
Forestry ? Mechanical Engineering ? Food Science
Engineering ? Health Sciences
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OTHER UNIVERSITY PARTNERING
University of Minnesota University of
Arkansas University of Alberta Clarkson
University University of Delaware Texas Tech
University University of Michigan Arizona State
University University of California
Davis University of Colorado
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INDUSTRY NEEDS

• ? MIXING EFFICIENCY
• ? CLEANING VALIDATION
• ? PARTICLE SIZING
• ? CHEMICAL COMPOSITION (molecular, spatial)
• ? COATING CONSISTENCY
• ? VAPOR CHARACTERIZATION
• ? VISCOSITY / RHEOMETRICS
• MOISTURE CONCENTRATION
• BIOASSAY

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CPAC STRATEGIC PLATFORMS

• ? SURFACE AND INTERFACIAL CHARACTERIZATION AND
  CONTROL
• MULTICOMPONENT MATERIALS CHARACTERIZATION AND
  CONTROL
• VERSATILE MICROANALYTICAL SYSTEMS
• ? PROCESS MONITORING, MODELING AND CONTROL

PROBLEMS
SYSTEMS
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•  
• Sensors
• Grating Light Reflection Spectroscopy
•  
• High Precision Reflectometer
•  
• Fast Versatile Microfabricated Moisture Sensors
•  
• Vapochromic Detection and Identification of
  Volatile Organic Compounds
• Advanced Surface Plasmon Resonance Sensors
•  
• In-Situ Evaluation of Physical Sensor Health
  and Output Signal Validity
• Dynamic Surface Tension Detector

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Relevance ofOptical Low Coherence Reflectometry
(OLCR)

• Q What do the following things have in common?
• airplanes
• pharmaceutical tablets
• plastic food wrappers
• beverage bottles

A

• All of them have surface layers (i.e., films or
  coatings) that give
• products desired properties.
• Surface layers need to be deposited and tested
  rapidly in industrial
• processes.
• Industry needs fast, sensitive, reliable,
  non-contact measurement
• methods for these processes.

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Multiple Layer Polymer Materials
Scattering materials
Drug delivery patch
Distance in micrometers
Distance in micrometers
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Photo of new OLCR
Power supplies
Fiber optic interferometer
Delay line for setting end face reflection
location
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Spectroscopy/Imaging Evaluating Raman
Spectroscopy to Improve Process Monitoring and
Materials Characterization Development and
Application of On-Line Particle Analyzers
Non-destructive Measurement of Moisture
Distribution with Fringing Electric Field Sensors
Application of MRI for Analysis
of Mixing   Development of a Micro NMR
System   Ultrasonic Sensor for Viscosity and
Microstructural Measurements
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Raman Microscope w/ Waveguide Flow Cell
spectrograph/detector
Raman microscope
laser
beam splitter
CCD
filter
microscope objective
Purge
HPLC pump
Waste
waveguide
injection valve
column
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HPLC/Raman Analysis of Aromatic Compounds
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Raman Immersion Ball Probe Design
Probe barrel when used with collimated
laser length is not an issue.
Probe Tip O-ring sealed and threaded to barrel
Ball sapphire ball lens (focal point is on face
of lens)
Ball Fastener threads into tip and pressure
seals ball into a fluoroelastomer seal and the
probe tip
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Monitoring Protein in a Separation Process _at_
Cargill-Memphis

• Raman ball probe inserted directly
• into flowing stream
• Analysis performed 20 meters from
• instrument
• Analysis performed under moderate
• process conditions (temp. and flow)

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Future Applications of RamanBall Probe
Proposed use of a ball probe(s) in a V-blender
fiber to probe(s)
optical interface

• use of fibers has the potential of
• coupling multiple probes to one blender

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CPAC INITIATIVES

• NEW SAMPLING AND SENSOR INITIATIVE
• CONNECTIVITY INTIATIVE
• INSTRUMENTATION FOR MICRO REACTORS INITIATIVE
• FERMENTATION MONITORING AND CONTROL INITIATIVE
• CHEMOMETRICS ON-LINE INITIATIVE
• RAW MATERIAL QUALITY RELATED TO FINAL PRODUCT
  PROPERTIES

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NEW RESEARCH INITIATIVE

• INSTRUMENTATION FOR MICROREACTORS

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THE DRIVER IS THE NEED FOR HIGH THROUGHPUT
EXPERIMENTAION

• DISCOVERY
• SCREENING
• PROCESS DEVELOPMENT
• PROCESS CONTROL

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DISCOVERY TO COMMERCIALIZATION
DESIGN OF EXPERIMENTS
REACTOR
DATA EVALUATION
ANALYZE
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CPAC CHEMOMETRIC RESEARCH PROJECTS

• Chemometrics for Smart Sensors
•  
• Novel Classification Tools Combining Data
  Mining and Statistical Inferencing Techniques
• New Approaches to Transfer and Maintenance of
  Multivariate Calibrations
•  
• Genetic Algorithms that Emulate Human Pattern
  Recognition through Machine Learning for Data
  Mining and Knowledge Discovery
•  
• Incorporating Raw Material Variation into
  Process Chemometric Models
•  

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REVOLUTIONARY ADVANCES THAT ARE AFFECTING
CHEMICAL MEASUREMENTS

• MEASUREMENT INFORMATION PROCESSING
• MINIATURIZATION
• ENGINEERED MATERIALS
• ELECTRO-OPTICS

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Developed and Fabricated Miniature Preconcentrato
rs, Gas Chromatographic (GC) Columns and Surface
Acoustic Wave (SAW) Arrays
Preconcentrator/ Thermal Desorber
4 SAW Array
One Meter GC Column
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Gas analysis components are integrated on novel
electrical/fluidic circuit board
Preconcentrator
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A fully autonomous hand-held microanalyzer

Containing Multiple coated/packed GC columns
w/multiple coated SAW detectors
and Multiple LC columns with fluorescence
electrochemical detection
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Double Focusing Mass Spectrometer University
of Minnesota Proof-of-Concept Mass range
1-200amu Resolving Power 150
Detector
Mass Analyzer
Ionizer

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The ILD-50 Industrial Leak Detector
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Air, He, Ar, and Carbon Dioxide CS-50
7e-9
6e-9
5e-9
4e-9
Intensity
3e-9
2e-9
1e-9
0
-1e-9
0
10
20
30
40
50
60
m/z
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Development of a Micro NMR System

• UCD NMR Facility
• MicroInstruments and Systems Laboratory
• Department of Electrical and Computer Engineering
• Department of Biological and Agricultural
  Engineering
• University of California, Davis

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Initial Results
NMR spectrum of a 3 microliter water sample using
the RF microcoil shown on the right.
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CPAC Micro-Reactor Platform Initiative-
Argonaut Technologies Quest parallel reactor

• 10 simultaneous reactions
• Select temperatures from
• 40 oC to 130 oC
• Multitude of mixing speeds
• Amenable for spectroscopic monitoring

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• Microfluidics Enables Integrated Chemical and
  Cellular Analysis in a Single Disposable Fluidics
  Module

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CPC SELECTO A commercially available modular
microreaction system

• Broad applicability
• Demanding chemistry

• Flexible and easy to use
• High operational safety

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Reactor Module
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Raman Ball Probe on Outlet of CPC System
Real-time Reaction Monitoring
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MICRO REACTOR TOPICS

• BATCH - PARALLEL
• CONTINUOUS / MICRO FLUIDIC
• ELECTROTHERMAL
• ACOUSTICAL
• CALIBRATION / STANDARDIZATON
• MONITORING / CONTROL

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CHALLENGES TO USING MICROREACTORS

• INTERFACING MODULAR UNITS
• SAMPLING AND SCREENING
• ANALTYICAL CHARACTERIZATION
• DATA HANDLING
• PROCESS MODELING AND FEED BACK CONTROL

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SOME RELEVANT CURRENT CPAC RESEARCH EFFORTS

• MICRO-LC
• SURFACE TENSION DETECTION
• GCxGC
• FRINGE FIELD SENSORS
• VAPOCHROMIC SENSORS
• RAMAN
• GRATED LIGHT REFLECTIVE SPECTROSCOPY
• REFLECTOMETRY
• FLOW-THROUGH PARTICLE ANALYZER
• SURFACE PLASMON RESONANCE
• MINI-MASS SPECTROMETER
• DATA HANDLING

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ADVANCES IN SENSORS AND CONTROLSHIGHLIGHT THE
NEED FOR IMPROVED SAMPLING AND DATA HANDLING
TECHNOLOGIES
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SAMPLING

• ? Most systems today are unique
• But they could be Modularized
• Smart Systems are Needed
• NeSSI has appeared

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Response to CPAC RFPsSwagelok

• Complies with SP76
• Metallic C seal design now
• Elastomer seals later
• 3 channels
• 1.5 blocks downmounts
• Lego? like assembly
• IGC II technology
• highly engineered
• Investigating flow X-proofing solutions

Courtesy of Swagelok
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Response to CPAC RFPsAutoflow

• Fully compliant with SP76
• TFE loaded elastomer seals
• 3 channels
• 1.5 blocks
• Division 1 cartridge heating
• Div. 2 thermal flow meter, flow switches
• Utilizing current electrical X-proofing concepts

Courtesy of Autoflow
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Response to CPAC RFPs Rosemount-Swagelok

• Field mounted chromatograph with a
  miniature/modular sample system

Courtesy of Rosemount Swagelok
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NeSSI with Analyzer on board and Wireless
SensorManager(I/OController)
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CPAC FermentationInitiative

• Goal to improve process control of fermentation
  processes through the use of both commercial and
  newly developed analytical tools

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FERMENTATION CONTROL INITIATIVE

• Set up a test bed that is maintained and operated
  by visiting scientists
• Form a steering team from the 20 interested
  member organizations
• Communicate project planning and results via
  sponsors only section of web site

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SOME RELEVANT CURRENT CPAC RESEARCH EFFORTS
MICRO-LC DYNAMIC SURFACE TENSION GCxGC LAB-ON-A-VA
LVE FRINGE FIELD SENSORS VAPOCHROMIC
SENSORS RAMAN GLRS REFLECTOMETRY SPR MINI-MS DATA
HANDLING
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CPAC Sponsor Support
Kaiser Optical Systems Kraft Foods Los Alamos
Natl Lab Merck Pharma. Novozymes Pharmacia
Procter and Gamble Rosemount Analytical Sandia
Natl Lab Swagelok
Agilent Amgen Aventis Pharma. Baxter
Bristol-Myers Squibb Cargill Dow Chemical DuPont
Genentech Honeywell
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CENTERS ENHANCEACADEMIC PROGRAMS
? MULTIDISCIPLINARY ? SHOWCASE EMERGING
TECHNOLOGIES ? PROVIDE PRACTICAL FOCUS ? COMPETE
WELL FOR SCARCE RESOURCES