Biomedical Microdevices

, Volume 16, Issue 1, pp 143–151 | Cite as

Parametric control of collision rates and capture rates in geometrically enhanced differential immunocapture (GEDI) microfluidic devices for rare cell capture

  • James P. Smith
  • Timothy B. Lannin
  • Yusef A. Syed
  • Steven M. Santana
  • Brian J. Kirby
Article

Abstract

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).

Keywords

Immunocapture Rare cell capture Circulating tumor cell CTC LNCaP Prostate cancer GEDI Microfluidic Microdevice 

References

  1. T. Baier, S. Mohanty, K.S. Drese, F. Rampf, J. Kim, F. Schoenfeld, Modelling immunomagnetic cell capture in CFD. Microfluid. Nanofluid. 7(2), 205–216 (2009)CrossRefGoogle Scholar
  2. G.K. Batchelor, An Introduction to Fluid Dynamics (Cambridge, 1967)Google Scholar
  3. G.I. Bell, M. Dembo, P. Bongrand, Cell adhesion competition between nonspecific repulsion and specific bonding. Biophys. J. 45(6), 1051–1064 (1984)CrossRefGoogle Scholar
  4. 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
  5. J. Davis, D. Inglis, K. Morton, D. Lawrence, L. Huang, S. Chou, J. Sturm, R. Austin, Deterministic hydrodynamics: Taking blood apart. Proc. Natl. Acad. Sci. USA 103(40), 14,779–14,784 (2006)CrossRefGoogle Scholar
  6. P. Decuzzi, M. Ferrari, The adhesive strength of non-spherical particles mediated by specific interactions. Biomater. 27(30), 5307–5314 (2006)CrossRefGoogle Scholar
  7. 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
  8. C. Dong, X.X. Lei, Biomechanics of cell rolling: shear flow, cell-surface adhesion, and cell deformability. J. Biomech. 33(1), 35–43 (2000)CrossRefGoogle Scholar
  9. M.L. Dustin, L.M. Ferguson, P.Y. Chan, T.A. Springer, D.E. Golan, Visualization of cd2 interaction with lfa-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area. J. Cell. Biol. 132(3), 465–74 (1996)CrossRefGoogle Scholar
  10. J. Frechette, G. Drazer, Directional locking and deterministic separation in periodic arrays. J. Fluid. Mech. 627, 379–401 (2009)CrossRefMATHGoogle Scholar
  11. 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
  12. 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
  13. A. Hatch, G. Hansmann, S.K. Murthy, Engineered alginate hydrogels for effective microfluidic capture and release of endothelial progenitor cells from whole blood. Langmuir. 27(7), 4257–4264 (2011)CrossRefGoogle Scholar
  14. H.B. Hsieh, D. Marrinucci, K. Bethel, D.N. Curry, M. Humphrey, R.T. Krivacic, J. Kroener, L. Kroener, A. Ladanyi, N. Lazarus, P. Kuhn, R.H. Bruce, J. Nieva, High speed detection of circulating tumor cells. Biosens. Bioelectron. 21(10), 1893–1899 (2006)CrossRefGoogle Scholar
  15. D. Inglis, J. Davis, R. Austin, J. Sturm, Critical particle size for fractionation by deterministic lateral displacement. Lab. Chip. 6(5), 655–658 (2006)CrossRefGoogle Scholar
  16. 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
  17. M.B. Lawrence, T.A. Springer, Leukocytes roll on a selectin at physiologic flow rates: Distinction from and prerequisite for adhesion through integrins. Cell. 65(5), 859–873 (1991)CrossRefGoogle Scholar
  18. H.K. Lin, S. Zheng, A.J. Williams, M. Balic, S. Groshen, H.I. Scher, M. Fleisher, W. Stadler, R.H. Datar, Y.C. Tai, R.J. Cote, Portable filter-based microdevice for detection and characterization of circulating tumor cells. Clin. Cancer. Res. 16(20), 5011–5018 (2010)CrossRefGoogle Scholar
  19. K. Loutherback, K.S. Chou, J. Newman, J. Puchalla, R.H. Austin, J.C. Sturm, Improved performance of deterministic lateral displacement arrays with triangular posts. Microfluid. Nanofluid. 9, 1143–1149 (2010)CrossRefGoogle Scholar
  20. Z.Y. Luo, F. Xu, T.J. Lu, B.F. Bai, Direct numerical simulation of detachment of single captured leukocyte under different flow conditions. J. Mech. Med. Biol. 11(2), 273–284 (2011)CrossRefGoogle Scholar
  21. 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
  22. N. N’Dri, W. Shyy, R. Tran-Soy-Tay, Computational modeling of cell adhesion and movement using a continuum-kinetics approach. Biophys. J. 85(4), 2273–2286 (2003)CrossRefGoogle Scholar
  23. C. Orsello, D. Lauffenburger, D. Hammer, Molecular properties in cell adhesion: a physical and engineering perspective. Trends. Biotech. 19(8), 310–316 (2001)CrossRefGoogle Scholar
  24. E.D. Pratt, C. Huang, B.G. Hawkins, J.P. Gleghorn, B.J. Kirby, Rare cell capture in microfluidic devices. Chem. Eng. Sci. 66(7), 1508–1522 (2011)CrossRefGoogle Scholar
  25. Y. Saad, M.H. Schultz, Gmres: a generalized minimal residual algorithm for solving nonsymmetric linear systems. SIAM. J. Sci. Stat. Comp. 7(3), 856–869 (1986)CrossRefMATHMathSciNetGoogle Scholar
  26. 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
  27. S.M. Santana, H. Liu, N.H. Bander, J.P. Gleghorn, B.J. Kirby, Immunocapture of prostate cancer cells by use of anti-psma antibodies in microdevices. Biomed. Microdev. 14, 401–407 (2012)CrossRefGoogle Scholar
  28. J.P. Smith, A.C. Barbati, S.M. Santana, J.P. Gleghorn, B.J. Kirby, Microfluidic transport in microdevices for rare cell capture. Electrophor. 33(21), 3133–3142 (2012)CrossRefGoogle Scholar
  29. 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
  30. 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
  31. Y. Wan, J. Tan, W. Asghar, Y.t. Kim, Y. Liu, S.M. Iqbal, Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices. J. Phys. Chem. B. 115(47), 13,891–13,896 (2011)CrossRefGoogle Scholar
  32. Z. Wu, B. Willing, J. Bjerketorp, J.K. Jansson, K. Hjort, Soft inertial microfluidics for high throughput separation of bacteria from human blood cells. Lab. Chip. 9, 1193–1199 (2009)CrossRefGoogle Scholar
  33. S. Zheng, H. Lin, J.Q. Liu, M. Balic, R. Datar, R.J. Cote, Y.C. Tai, Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells. J. Chromatogr. A. 1162(2), 154–161 (2007)CrossRefGoogle Scholar
  34. 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
  35. C. Zhu, G. Bao, N. Wang, Cell mechancis: mechanical response, cell adhesion, and molecular deformation. Ann. Rev. Biomed. Eng. 2(1), 189 (2000)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • James P. Smith
    • 1
  • Timothy B. Lannin
    • 1
  • Yusef A. Syed
    • 1
  • Steven M. Santana
    • 1
  • Brian J. Kirby
    • 1
    • 2
  1. 1.Sibley School of Mechanical and Aerospace EngineeringCornell UniversityIthacaUSA
  2. 2.Division of Hematology and Medical OncologyDepartment of Medicine, Weill Medical College of Cornell UniversityNew YorkUSA

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