Lab-on-a-chip%20Devices%20for%20Cell%20Separation%20and%20Identification

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Lab-on-a-chip Devices for Cell Separation and
Identification
Feb 2008

• A PhD project at Macquarie University under the
  guidance of Dr. David Inglis and Prof. Ewa Goldys.

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Microbes, cells and small organisms come in a
wide array of shapes and sizes

• Yeast

Blood Cells
Photo Credit H.D.A Lindquist, U.S. EPA
cryptosporidium
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Microfluidic or Lab-on-a-chip Devices can be used
to separate different cell types

• Various blood cell separations have been
  demonstrated
• J. A. Davis, D. W. Inglis, K. M. Morton, D. A.
  Lawrence, L. R. Huang, S. Y. Chou, J. C. Sturm,
  and R. H. Austin, Deterministic hydrodynamics
  taking blood apart, Proc. Nat. Acad. Sci. (USA),
  vol. 103, pp. 14779-14784, 2006.

• D. W. Inglis, J. A. Davis, T. J. Zieziulewicz, D.
  A. Lawrence, R. H. Austin, and J. C. Sturm,
  Determining blood cell size using micro?uidic
  hydrodynamics, J. Immunol. Meth., vol. 329, pp.
  151-156, 2008.
• D. W. Inglis, K. J. Morton, J. A. Davis, T. J.
  Zieziulewicz, D. A. Lawrence, R. H. Austin, and
  J. C. Sturm, Microfluidic device for label-free
  measurement of platelet activation, Submitted to
  Lab on a Chip, Jan 08.
• But no work yet with microorganisms!

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This project will lead to publications which
demonstrate the separation of microorganisms on
portable inexpensive polymer microfluidic devices.

• Such devices may have applications in
• early detection of human diseases such as sepsis
  and various parasitic diseases
• as well as management of swimming pool and
  drinking water quality.

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What is Micro-Fluidics
Fabrication Process

• Microfluidics microfabricated structures for
  fluid handling
• Engineers know how to microfabricate and build
  integrated systems
• mTAS Micro Total Analysis System
• Integrate microfluidic components into a useful
  device, a Lab on a Chip
• development and application of micro- and
  nanofabricated devices and systems for chemical
  and biochemical measurements. The technology
  encompasses extensive areas of application in
  clinical diagnostics, genomics and proteomics,
  environmental assays, separation science,
  cellular analysis or drug discovery. From
  Micralyne.com
• Interdisciplinary Physics, Chemistry, Biology

Photolithography
Reactive Ion Etching
Drill access holes
Seal with cover slip
Fluid goes in
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High Resolution Separation with Size - Position
Correlation

• Peak width 10 nm
• No known method fractionates with such resolution.

Can include chirp to fractionate over a range of
sizes by varying g or ?
Huang et al, Science 2004
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Cell Separation by Size
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White blood cells come in different sizes and can
be differentiated

Cancerous Lymphocytes
Healthy Lymphocytes
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Human platelets change size in response to
chemical and temperature stimulus
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Proposed Device

• Use the technique described above to create a
  simple to use high throughput cell concentrator.
• Parallel channels for separation and
  concentration on a glass slide. A second layer
  distributes fluid to the channels and collects
  their output.
• Structures will be molded PDMS.
• Master mold will be lithographically defined SU-8
  polymer.

20-micron PDMS pillars