Transcript Presentation 4

Instrumented NanoPhysiometer for
High Throughput Drug Screening
D. Michael Ackermann, Jon Payne,
Hilary Samples, James Wells
Overall Project Definition
Develop a miniaturized microfluidic-based cell
culture apparatus for high throughput
parallel drug screening with on-chip
monitoring of cell physiology.
Develop On-Board Drug Delivery Systems
To Achieve Desirable Low Flow Profiles
Using Peristaltic Pumping
Providing Ideal Parameters for Cell Viability
Big Picture
Applications:
A Research Tool
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Target Population:
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Protoype of research tool
Private research of BioMEMS group of VUSE BME
dept
Market Demand:
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Custom project for specific research
Future implications to broad market
High throughput screening
Pharmaceutical Testing
Toxicology
Motivation
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128 well plate assay technique
Limitations:
stationary state cell study
microliter reagent volumes
microliter scale studies
Nanophysiometer
Nanoliter Scale
Real Time Monitoring
Decrease:
Reagents (if any!)
Processing
Time
Project Goals
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Develop and Fabricate nanoliter sized cell culture
volumes with flow through perfusion
Design on-chip peristaltic pumps for low volume
perfusion and drug administration.
Design and incorporate thin film microelectrodes
in the inflow and outflow structures for
differential electrochemical monitoring of
various analytes such as pH, oxygen, glucose
and lactose in the media.
Optimize cell culture conditions to maintain cell
viability over long periods of time.
Develop a Labview based user interface for
mircofluidic control of the NanoPhysiometer
Nanoliter-sized Cell Culture
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** Nanophysiometer **
Accurate small-scale study of cell function
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Flow Through Perfusion
Continuous Media turn-over
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Cell Filters
300 um
STATUS: Mask came in on Friday
after 2 week delay!
500 um
Soft Lithography
STATUS: Made practice channels
and will make master on Tuesday
Peristaltic Pumps
Fluidics
Layer
STATUS:
Have pneumatic
controller and
pneumatic mask are
currently
programming the
Labview interface
Flexible PDMS Membrane
(Valve)
[1] S.R. Quake and A. Scherer, "From Micro to Nano Fabrication with Soft Materials", Science 290: 1536-40 (2000).
[2] M.A. Unger, H.-P. Chou, T. Thorsen, A. Scherer, and S.R. Quake, "Monolithic Microfabricated Valves and Pumps by Multilayer Soft Lithography", Science 288: 113116 (2000).
Electrochemical Monitoring
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Use integrated thin film microelectrodes to
monitor physiological parameters
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pH, glucose, etc.
Electrodes coated with a substrate specific
oxidase
Catalyze reaction producing H2O2
 H2O2 then detected
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STATUS: Will be integrated once cell lines are self
sustaining and fluidics/pneumatics are performing
Physiometer Mask Design
Electrodes
Microfluidics
Pneumatics
LabView programming
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User control of nanophysiometer system
Program Presets based on experimental needs
 Manual Control of Pumps and valves
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Measurements & Data acquisition
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Show parameter measurements
Time-Lapse Image Capture
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Qualitative analysis
STATUS: Developing pneumatic
controller interface code
Labview Control Panel
IMAGE
Schematic
Camera
LabView
Nanophysiometer
Electrode
D/A Converter
Pneumatic
Controller
Optimize Cell Culture Conditions
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Determine minimal
flow rates for
maintaining vitality
Allow for physiological
measurements
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Exp: pH differential as an
indicator of metabolic rate
STATUS: This week we are starting
our own cell culture line of
Fibroblasts from starter cells from
Evgeni in ChemE Department.
Atmospheric Cell Culture Conditions
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Maintain Temperature
and CO2/O2 levels
PDMS gas permeable
Plexiglas enclosure
Heated Microscope
stage
http://www.cyto.purdue.edu/flowcyt/educate/photos/confocal/images.htm
Timeline
JAN
Literature & Patent
Search
Define Goals & Project
Approach
Design Mask
Prototype/Device
Fabrication
Programming
Operation
Assessment &
Evaluation
Final Paper &
Presentation
FEB
MAR
APR
Budget
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Mask of device design- $600/mask
PDMS kit - $15
Cell culture supplies- $300/month
Tubing, wiring, etc.- ~$10
Electrodes- $500 (owned by lab)
References
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Unger, Quake, et. al. Monolithic Microfabricated Valves and
Pumps by Multilayer Soft Lithography. Science. Vol. 288. April
7, 2000
Ho, Chih-Ming. Fluidics – The Link Between Micro and Nano
Sciences and Technologies. 0-7803-5998-4/01. 2001 IEEE
Arik, Zurn, et. al. Design, Fabrication and ExperimentalNumerical Study of PZT Sensors. MSM 2000. Puerto Rico.
Gonzalez, Moussa. Simulation of MEMS Piezoelectric
Micropump for Biomedical Applications. 2002. Algor
Incorporated; Technical Document.
Bar-Cohen, Chang. Piezoelectrically Actuated Miniature
Peristaltic Pump. March 2000. Proceeding of 2000 SPIE Smart
Structures and Materials Symposium. No. 3992-103
Acknowledgements
 Dr.
Franz Baudenbacher
 David Schaffer
 Nanodelivery, Inc.