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Lab-on-Chip LC as a PAT Tool for Process
Monitoring
Scott GilbertCrystal Vision Microsystems LLCCPAC Visiting Scholar
CPAC Summer Institute July 15-17, 2008
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Requirements for an effective on-line HPLC analyzer
Small footprint, self-contained miniaturized HPLC unit for plant deploymentMinimally invasive – sub-ml sample sizeNear-real time analysis – 1 to 2 minutesZero sample cross talkEase of maintenance – minimize moving partsRobust
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Concept of a Modular LC Process Analyzer based on microfluidic Lab-on-Chip
NeSSI Generation III dream analyzer
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microLC NeSSI Configuration
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NeSSI microLC System
Full view of experimental modular LC prototype mounted on a Parker-Hannifin Intraflow™ pegboard with pressure control for fluid reservoirs. Sample circulation lines are connected to block.
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Details of NeSSI LC Sensor
Sampling technique takes advantage of pressure in sample loop
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Functional Integration of μ-fluidic LC Chip for On-line Sample Pretreatment
3 in
Electrical contact pads
mixer
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Monolithic continuous beds in microchannels -very fast baseline separations
Source: C. Ericson et al. Anal. Chem. 2000 72, 81-87.
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Sampling / Injection
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Chip under flow with two streams: fluorescent fluorescein dye tracer (green) and mobile phase (colorless) [video clip]
Detail of chromatographic injection of fluorescent dye tracer (video clip)
mixer
column
mobile phase
fluorescein dye
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Plug generation by flow-injection
20mm
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On-line sampling set-up
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Initial performance
Dilution performance at constant analyte concentrationSampling changing concentration of analyte at constant dilution
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Characteristics of μ−mixer for on-line dilution
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Simulation of reaction monitoring - standard addition of aliquots to reaction vessel
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Standard addition monitoring response data
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Integrated on-chip mixers and extractors for on-line sample conditioning
Performs functions:dilutionfiltrationpH conditioning
waste
diluentstreamsample stream
return micromixer
H-filter
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Considerations for on-line sampling of bioreactors
Big Issue is sample pretreatment of high solids slurries
Pre-dilution using micromixersPre-filtration using membrane filters (clogging?)On-chip liquid-liquid extraction using H-filterCleaning of sample lines
Can we use NeSSI as a sampling platform?Continuous flow can maintain cleanliness of Coating or growth of biomass possibility
We need your input!
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Future work at CPAC
New work in collaboration with Rob Synovec’s group
Chromatographic performance is being addressed presently Focus on small molecules initially
Eventually we will address the sampling issuesCollaboration will involve groups of Renata Bura and Clem Furlong for optimizing system
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Thank you for your attention!