Harnessing Microfluidics for Research and Development

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Harnessing Microfluidics for Research and
Development Nathaniel C. Cady Asst. Prof.
Nanobioscience College of Nanoscale Science
Engineering
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• Outline
• Fluid dynamics (for non-majors)
• Building microfluidic devices
• Examples of research devices

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Turbulent Flow
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Laminar Flow
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Flow regime is predictable!
Reynolds Number
Re (density) x (velocity) x (diameter)
(viscosity) If Re 3000 or higher
turbulent flow If 2000-3000 transitional
flow If less than 2000 laminar flow 2300
transition point
Microfluidic devices capitalize on small channel
sizes to control flow regime
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• Advantages of Microfluidic Devices
• Well-controlled fluid dynamics
• Diffusion-limited mixing
• Controllable fluid interactions
• Small fluid volume
• Less sample and reagent needed
• More samples per unit area (multiplexing)
• Microfluidics Lab-on-a-chip

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Device Fabrication
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• Fabrication of Microfluidic Devices
• Fabrication schemes range from simple to highly
  complex
• Primarily rely on micro / nanofabrication
  techniques
• Lithography (photo-, electron beam, imprint)
• Etching or molding of 3-D channels
• Capping or enclosure of channels

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Photolithography
Transfer Pattern
Develop Resist
Etch substrate
Remove Resist
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Making a Microfluidic Device
Direct
Indirect
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Fabrication is relatively easy
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Practical Applications Diagnostics
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Microchip-based DNA Biosensor

35mm
20 mm
Integrated DNA Purification Real-Time PCR
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DNA-based Diagnostics
EtOH (wash buffer)
GuSCN (lysis buffer)
dH2O (elution buffer)
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Micropillars for DNA Purification

10 microns
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Integrated Control System
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Detection Results
Cady et. al. (2005) Sensors Actuators B.
107(1) 332-341 Cady et. al. (2003) Biosensors
Bioelectronics. 19 59-66
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Practical Applications Micro Printing
Patterning
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Biomolecular Printing
30 microns
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Probing Neural Networks
Signaling ?
SiO2
Gold
Glass
With Dr. Bill Shain Dr. Matt Hynd Wadsworth
Center, NYS Dept. of Health
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Biomolecular Printing
Insert movie
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Printed Guidance for Neural Networks

• Microelectrode arrays (MEAs) coated with
  PEG-based hydrogel
• NeN used to pattern hydrogel with FITC-labeled
  bioactive peptides
• Successful printing of both spots and lines

200um
Microelectrode Array (MEA)
Hydrogel-coated MEA patterned with the laminin
peptide, biotin-IKVAV. The laminin peptide
biotin-IKVAV was printed onto using the automated
NanoEnabler bioprinter. Printed peptide was
arranged in a pattern consisting of orthogonal 2
mm-wide lines connecting 10 mm diameter node.
Courtesy of Matthew Hynd, PhD NYS DOH
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Neural Networks

• Printed MEAs seeded with primary hippocampal
  neurons
• Cells proliferated on the arrays and formed
  neural network on MEAs
• Results were comparable to studies using
  microcontact printing methods
  (Hynd, et. al., J. Neuroscience Methods, 2006)

200um
Patterned neuronal network at 2 weeks in vitro.
Primary hippocampal neurons were plated onto
patterned arrays at a density of 400 cells/mm2.
Scanning electron microscope image of patterned
neural network.
Courtesy of Matthew Hynd, PhD NYS DOH
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Cellular Printing
Slow, difficult
High acceleration / thermal exposure
potentially damaging to cells
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Direct Cell Printing

• Polymeric Surface Patterning Tool
• Developed at CNSE, UAlbany (Cady Lab)
• Designed to enable live cell printing directly
  onto solid surfaces
• Larger channels and cantilever allow for whole
  cells to be printed

Fluid Reservoir
Channel
Printing Tip
BioForce Silicon-based SPT
Polymeric SPT
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Bacterial Cell Printing
E. coli pET28A-GFP on polystyrene
20 µm
20 µm
20 µm
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Mammalian Cell Printing
Mouse MTLn3-GFP (diluted) printed on polystyrene
50 µm
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Practical Applications Cell Dynamics
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Biomimetic Device for Tumor Cell Dissemination
Studies
Weir Structures (Constrictions)
Collection Area
O2 Input
Output
Tumor Cell Input
1000µm
Cell
Weir Structures (Constrictions)
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Flow Cell Design
Device Filled with Dye
500µm
Fluid Flow Direction
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Fluid Dynamic Modeling
Fluid velocity vectors
Units (cm/sec)
500µm
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Device Testing
HEp3 Cells (Human Epidermal Carcinoma 3)
Fluid Flow
Cells were smaller than anticipated needed
different weir spacing!
100um
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Rapid Prototyping of New Device
Fluid Flow
100um
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Summary

• Microfluidic devices reduce sample volume and
  offer unique fluid dynamic environments
• Novel fluid dynamics can affect reaction rates,
  diffusion, biological processes
• Practical applications (like patterning) can be
  accomplised using microfluidics
• Novel fluid environments can be used for
  biomimetic studies

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Acknowledgements
University at Albany Mt. Sinai Dr. Robert
Geer Dr. Julio Aguirre-Ghiso Dr. Magnus
Bergkvist Dr. Alain Kaloyeros Research
Support UAlbany Startup Funds UAlbany FRAP AB
Awards BioForce Instruments CNSE / CAS
Challenge Grant