The capture and subsequent analysis of rare cells, such as circulating tumor cells from a peripheral blood sample, has the potential to advance our understanding and treatment of a wide range of diseases. There is a particular need for high purity (i.e., high specificity) techniques to isolate these cells, reducing the time and cost required for single-cell genetic analyses by decreasing the number of contaminating cells analyzed. Previous work has shown that antibody-based immunocapture can be combined with dielectrophoresis (DEP) to differentially isolate cancer cells from leukocytes in a characterization device. Here, we build on that work by developing numerical simulations that identify microfluidic obstacle array geometries where DEP–immunocapture can be used to maximize the capture of target rare cells, while minimizing the capture of contaminating cells. We consider geometries with electrodes offset from the array and parallel to the fluid flow, maximizing the magnitude of the resulting electric field at the obstacles' leading and trailing edges, and minimizing it at the obstacles' shoulders. This configuration attracts cells with a positive DEP (pDEP) response to the leading edge, where the shear stress is low and residence time is long, resulting in a high capture probability; although these cells are also repelled from the shoulder region, the high local fluid velocity at the shoulder minimizes the impact on the overall transport and capture. Likewise, cells undergoing negative DEP (nDEP) are repelled from regions of high capture probability and attracted to regions where capture is unlikely. These simulations predict that DEP can be used to reduce the probability of capturing contaminating peripheral blood mononuclear cells (using nDEP) from 0.16 to 0.01 while simultaneously increasing the capture of several pancreatic cancer cell lines from 0.03–0.10 to 0.14–0.55, laying the groundwork for the experimental study of hybrid DEP–immunocapture obstacle array microdevices.
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January 2015
Research Article|
February 10 2015
Enhancing sensitivity and specificity in rare cell capture microdevices with dielectrophoresis
James P. Smith;
James P. Smith
a)
1Sibley School of Mechanical and Aerospace Engineering,
Cornell University
, Ithaca, New York 14853, USA
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Chao Huang;
Chao Huang
b)
2Department of Biomedical Engineering,
Cornell University
, Ithaca, New York 14853, USA
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Brian J. Kirby
Brian J. Kirby
c)
1Sibley School of Mechanical and Aerospace Engineering,
Cornell University
, Ithaca, New York 14853, USA
3Division of Hematology and Medical Oncology, Department of Medicine,
Weill Cornell Medical College
, New York, New York 10065, USA
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a)
Present address: Massachusetts Institute of Technology Lincoln Laboratory, Lexington, Massachusetts 02420, USA.
b)
Present address: Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
c)
Author to whom correspondence should be addressed. Electronic mail: kirby@cornell.edu
Biomicrofluidics 9, 014116 (2015)
Article history
Received:
December 08 2014
Accepted:
February 02 2015
Citation
James P. Smith, Chao Huang, Brian J. Kirby; Enhancing sensitivity and specificity in rare cell capture microdevices with dielectrophoresis. Biomicrofluidics 1 January 2015; 9 (1): 014116. https://doi.org/10.1063/1.4908049
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