Parametric control of collision rates and capture rates in geometrically enhanced differential immunocapture (GEDI) microfluidic devices for rare cell capture
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The enrichment and isolation of rare cells from complex samples, such as circulating tumor cells (CTCs) from whole blood, is an important engineering problem with widespread clinical applications. One approach uses a microfluidic obstacle array with an antibody surface functionalization to both guide cells into contact with the capture surface and to facilitate adhesion; geometrically enhanced differential immunocapture is a design strategy in which the array is designed to promote target cell–obstacle contact and minimize other interactions (Gleghorn et al. 2010; Kirby et al. 2012). We present a simulation that uses capture experiments in a simple Hele-Shaw geometry (Santana et al. 2012) to inform a target-cell-specific capture model that can predict capture probability in immunocapture microdevices of any arbitrary complex geometry. We show that capture performance is strongly dependent on the array geometry, and that it is possible to select an obstacle array geometry that maximizes capture efficiency (by creating combinations of frequent target cell–obstacle collisions and shear stress low enough to support capture), while simultaneously enhancing purity by minimizing non-specific adhesion of both smaller contaminant cells (with infrequent cell–obstacle collisions) and larger contaminant cells (by focusing those collisions into regions of high shear stress).
KeywordsImmunocapture Rare cell capture Circulating tumor cell CTC LNCaP Prostate cancer GEDI Microfluidic Microdevice
The work described was partially supported by the Cornell Center on the Microenvironment & Metastasis through Award Number U54CA143876 from the National Cancer Institute, Sanofi U.S., the National Science Foundation Graduate Research Fellowship Program (T.L.), the Cornell NSF GK-12 program (S.S.), and the Cornell Sloan Fellowship (S.S.).
- G.K. Batchelor, An Introduction to Fluid Dynamics (Cambridge, 1967)Google Scholar
- B. Das, P. Johnson, A. Popel, Computational fluid dynamic studies of leukocyte adhesion effects on non-Newtonian blood flow through microvessels. Biorheol. 37(3), 239–258 (2000)Google Scholar
- M. Dembo, D.C. Torney, K. Saxman, D. Hammer, The reaction-limited kinetics of membrane-to-surface adhesion. Philos. Trans. R. Soc. London. Biol. 234(1274), 55–83 (1988)Google Scholar
- J.P. Gleghorn, J.P. Smith, B.J. Kirby, Transport and collision dynamics in periodic asymmetric obstacle arrays: Rational design of microfluidic rare-cell immunocapture devices. Phys. Rev. E. (in press)Google Scholar
- J.P. Gleghorn, E.D. Pratt, D. Denning, H. Liu, N.H. Bander, S.T. Tagawa, D.M. Nanus, P.A. Giannakakou, B.J. Kirby, Capture of circulating tumor cells from whole blood of prostate cancer patients using geometrically enhanced differential immunocapture (gedi) and a prostate-specific antibody. Lab. Chip. 10, 27–29 (2010)CrossRefGoogle Scholar
- B.J. Kirby, M. Jodari, M.S. Loftus, G. Gakhar, E.D. Pratt, C. Chanel-Vos, J.P. Gleghorn, S.M. Santana, H. Liu, J.P. Smith, V.N. Navarro, S.T. Tagawa, N.H. Bander, D.M. Nanus, P. Giannakakou, Functional characterization of circulating tumor cells with a prostate-cancer-specific microfluidic device. PLoS ONE. 7(4), e35,976 (2012)CrossRefGoogle Scholar
- S. Nagrath, L.V. Sequist, S. Maheswaran, D.W. Bell, D. Irimia, L. Ulkus, M. Smith, E.L. Kwak, S. Digurmarthy, A. Muzikansky, P. Ryan, U. Balis, R.G. Tompkins, D.A. Haber, M. Toner, Isolation of rare circulating tumor cells in cancer patients by microchip technology. Nature. 450, 1235–1239 (2007)CrossRefGoogle Scholar
- D. Saintillan, E. Darve, E.S.G. Shaqfeh, A smooth particle-mesh ewald algorithm for stokes suspension simulations. The sedimentation of fibers. Phys. Fluids 17. 033(3), 301 (2005)Google Scholar
- S.L. Stott, R.J. Lee, S. Nagrath, M. Yu, D.T. Miyamoto, L. Ulkus, E.J. Inserra, M. Ulman, S. Springer, Z. Nakamura, A.L. Moore, D.I. Tsukrov, M.E. Kempner, D.M. Dahl, C.L. Wu, A.J. Iafrate, M.R. Smith, R.G. Tompkins, L.V. Sequist, M. Toner, D.A. Haber, S. Maheswaran, Isolation and characterization of circulating tumor cells from patients with localized and metastatic prostate cancer, Sci. Trans. Med. (2010)Google Scholar
- A.H. Talasaz, A.A. Powell, D.E. Huber, J.G. Berbee, K.H. Roh, W. Yu, W. Xiao, M.M. Davis, R.F. Pease, M.N. Mindrinos, S.S. Jeffrey, R.W. Davis, Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device. Proc. Natl. Acad Sci. USA. 106(10), 3970–3975 (2009)CrossRefGoogle Scholar
- Zhu, B., J.P. Smith, M.L. Yarmush, Y. Nahmias, B.J. Kirby, S.K. Murthy, Microfluidic enrichment of mouse epidermal stem cells and validation of stem cell proliferation in vitro. Tissue Eng. C (2013)Google Scholar