Biomedical Microdevices

, Volume 11, Issue 4, pp 883–892 | Cite as

Microdevice for the isolation and enumeration of cancer cells from blood

  • Swee Jin Tan
  • Levent Yobas
  • Gabriel Yew Hoe Lee
  • Choon Nam Ong
  • Chwee Teck LimEmail author


Cancer metastasis is the main attribute to cancer-related deaths. Furthermore, clinical reports have shown a strong correlation between the disease development and number of circulating tumor cells (CTCs) in the peripheral blood of cancer patients. Here, we present a label-free microdevice capable of isolating cancer cells from whole blood via their distinctively different physical properties such as deformability and size. The isolation efficiency is at least 80% for tests performed on breast and colon cancer cells. Viable isolated cells are also obtained which may give further insights to the understanding of the metastatic process. Contrasting with conventional biochemical techniques, the uniqueness of this microdevice lies in the mechanistic and efficient means of isolating viable cancer cells in blood. The microdevice has the potential to be used for routine monitoring of cancer development and cancer therapy in a clinical setting.


Circulating tumor cells (CTCs) Microfluidic device Cancer cell isolation Metastasis Physical separation Biomechanical properties Cell mechanics 



The equipment support provided by the Global Enterprise for Micro Mechanics and Molecular Medicine (GEM4) Laboratory at the National University of Singapore is gratefully acknowledged.

Supplementary material

Movie 1 (MPG 2.4 mb)

Movie 2 (MPG 2.3 mb)

Movie 3 (MPG 2.17 mb)

Movie 4 (MPG 5.14 mb)


  1. W.J. Allard, J. Matera, M.C. Miller, M. Repollet, M.C. Connelly, C. Rao, A.G. Tibbe, J.W. Uhr, L.W. Terstappen, Clin. Cancer Res. 10, 6897 (2004). doi: 10.1158/1078-0432.CCR-04-0378 CrossRefGoogle Scholar
  2. P.A. Baeuerle, O. Gires, Br. J. Cancer 96, 417 (2007). doi: 10.1038/sj.bjc.6603494 CrossRefGoogle Scholar
  3. M. Balic, N. Dandachi, G. Hofmann, H. Samonigg, H. Loibner, A. Obwaller, A. van der Kooi, A.G. Tibbe, G.V. Doyle, L.W. Terstappen, T. Bauernhofer, Cytometry B Clin. Cytom. 68, 25 (2005). doi: 10.1002/cyto.b.20065 Google Scholar
  4. P.D. Beitsch, E. Clifford, Am. J. Surg. 180, 446 (2000). doi: 10.1016/S0002-9610(00)00518-3 CrossRefGoogle Scholar
  5. G.T. Budd, M. Cristofanilli, M.J. Ellis, A. Stopeck, E. Borden, M.C. Miller, J. Matera, M. Repollet, G.V. Doyle, L.W. Terstappen, D.F. Hayes, Clin. Cancer Res. 12, 6403 (2006). doi: 10.1158/1078-0432.CCR-05-1769 CrossRefGoogle Scholar
  6. S.F. Chang, C.A. Chang, D.Y. Lee, P.L. Lee, Y.M. Yeh, C.R. Yeh, C.K. Cheng, S. Chien, J.J. Chiu, Proc. Natl. Acad. Sci. USA 105, 3927 (2008). doi: 10.1073/pnas.0712353105 CrossRefGoogle Scholar
  7. P.Y. Chiou, A.T. Ohta, M.C. Wu, Nature 436, 370–372 (2005). doi: 10.1038/nature03831 CrossRefGoogle Scholar
  8. M. Cristofanilli, K.R. Broglio, V. Guarneri, S. Jackson, H.A. Fritsche, R. Islam, S. Dawood, J.M. Reuben, S.W. Kau, J.M. Lara, S. Krishnamurthy, N.T. Ueno, G.N. Hortobagyi, V. Valero, Clin. Breast Cancer 7, 471 (2007). doi: 10.3816/CBC.2007.n.004 CrossRefGoogle Scholar
  9. M. Cristofanilli, G.T. Budd, M.J. Ellis, A. Stopeck, J. Matera, M.C. Miller, J.M. Reuben, G.V. Doyle, W.J. Allard, L.W. Terstappen, D.F. Hayes, N. Engl. J. Med. 351, 781 (2004)CrossRefGoogle Scholar
  10. S. Dawood, K. Broglio, V. Valero, J. Reuben, B. Handy, R. Islam, S. Jackson, G.N. Hortobagyi, H. Fritsche, M. Cristofanilli, Cancer 113, 2422 (2008). doi: 10.1002/cncr.23852 CrossRefGoogle Scholar
  11. D. Di Carlo, L.Y. Wu, L.P. Lee, Lab. Chip. 6, 1445 (2006). doi: 10.1039/b605937f CrossRefGoogle Scholar
  12. D. Flieger, A.S. Hoff, T. Sauerbruch, I.G. Schmidt-Wolf, Clin. Exp. Immunol. 123, 9–14 (2001). doi: 10.1046/j.1365-2249.2001.01435.x CrossRefGoogle Scholar
  13. H. Gogas, G. Kefala, D. Bafaloukos, K. Frangia, A. Polyzos, D. Pectasides, D. Tsoutsos, P. Panagiotou, J. Ioannovich, D. Loukopoulos, Br. J. Cancer 87, 181 (2002). doi: 10.1038/sj.bjc.6600419 CrossRefGoogle Scholar
  14. D.S. Gray, J.L. Tan, J. Voldman, C.S. Chen, Biosens. Bioelectron. 19, 1765–1774 (2004)CrossRefGoogle Scholar
  15. G.P. Gupta, J. Massague, Cell 127, 679–695 (2006). doi: 10.1016/j.cell.2006.11.001 CrossRefGoogle Scholar
  16. D.F. Hayes, M. Cristofanilli, G.T. Budd, M.J. Ellis, A. Stopeck, M.C. Miller, J. Matera, W.J. Allard, G.V. Doyle, L.W. Terstappen, Clin. Cancer Res. 12, 4218 (2006). doi: 10.1158/1078-0432.CCR-05-2821 CrossRefGoogle Scholar
  17. D.S. Hoon, Nat. Clin. Pract. Oncol. 1, 74 (2004). doi: 10.1038/ncponc0041 CrossRefGoogle Scholar
  18. H.J. Kahn, A. Presta, L.Y. Yang, J. Blondal, M. Trudeau, L. Lickley, C. Holloway, D.R. McCready, D. Maclean, A. Marks, Breast Cancer Res. Treat. 86, 237 (2004). doi: 10.1023/B:BREA.0000036897.92513.72 CrossRefGoogle Scholar
  19. R.T. Krivacic, A. Ladanyi, D.N. Curry, H.B. Hsieh, P. Kuhn, D.E. Bergsrud, J.F. Kepros, T. Barbera, M.Y. Ho, L.B. Chen, R.A. Lerner, R.H. Bruce, Proc. Natl. Acad. Sci. USA 101, 10501 (2004). doi: 10.1073/pnas.0404036101 CrossRefGoogle Scholar
  20. O. Lara, X. Tong, M. Zborowski, J.J. Chalmers, Exp. Hematol. 32, 891 (2004). doi: 10.1016/j.exphem.2004.07.007 CrossRefGoogle Scholar
  21. J.E. Losanoff, W. Zhu, W. Qin, F. Mannello, E.R. Sauter, Breast 17, 540 (2008). doi: 10.1016/j.breast.2008.04.005 CrossRefGoogle Scholar
  22. A.M. Malek, S.L. Alper, S. Izumo, JAMA 282, 2035 (1999). doi: 10.1001/jama.282.21.2035 CrossRefGoogle Scholar
  23. L.A. Mattano Jr., T.J. Moss, S.G. Emerson, Cancer Res. 52, 4701 (1992)Google Scholar
  24. J.C. McDonald, G.M. Whitesides, Acc. Chem. Res 35, 491–499(2002). doi: 10.1021/ar010110q CrossRefGoogle Scholar
  25. S. Mocellin, D. Hoon, A. Ambrosi, D. Nitti, C.R. Rossi, Clin. Cancer Res. 12, 4605 (2006). doi: 10.1158/1078-0432.CCR-06-0823 CrossRefGoogle Scholar
  26. H. Mohamed, L.D. McCurdy, D.H. Szarowski, S. Duva, J.N. Turner, M. Caggana, IEEE Trans. Nanobioscience 3, 251 (2004). doi: 10.1109/TNB.2004.837903 CrossRefGoogle Scholar
  27. J.G. Moreno, S.M. O’Hara, S. Gross, G. Doyle, H. Fritsche, L.G. Gomella, L.W. Terstappen, Urology 58, 386 (2001). doi: 10.1016/S0090-4295(01)01191-8 CrossRefGoogle Scholar
  28. S. Nagrath, L.V. Sequist, S. Maheswaran, D.W. Bell, D. Irimia, L. Ulkus, M.R. Smith, E.L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U.J. Balis, R.G. Tompkins, D.A. Haber, M. Toner, Nature 450, 1235 (2007). doi: 10.1038/nature06385 CrossRefGoogle Scholar
  29. F. Nole, E. Munzone, L. Zorzino, I. Minchella, M. Salvatici, E. Botteri, M. Medici, E. Verri, L. Adamoli, N. Rotmensz, A. Goldhirsch, M.T. Sandri, Ann. Oncol. 19, 891 (2007). doi: 10.1093/annonc/mdm558 CrossRefGoogle Scholar
  30. F. Nole, E. Munzone, L. Zorzino, I. Minchella, M. Salvatici, E. Botteri, M. Medici, E. Verri, L. Adamoli, N. Rotmensz, A. Goldhirsch, M.T. Sandri. Ann. Oncol. 19, 891–897 (2008) doi: 10.1093/annonc/mdm558 Google Scholar
  31. W.A. Osta, Y. Chen, K. Mikhitarian, M. Mitas, M. Salem, Y.A. Hannun, D.J. Cole, W.E. Gillanders, Cancer Res. 64, 5818 (2004). doi: 10.1158/0008-5472.CAN-04-0754 CrossRefGoogle Scholar
  32. N. Pamme, Lab Chip 7, 1644 (2007). doi: 10.1039/b712784g CrossRefGoogle Scholar
  33. K. Pantel, R.H. Brakenhoff, B. Brandt, Nat. Rev. Cancer 8, 329 (2008). doi: 10.1038/nrc2375 CrossRefGoogle Scholar
  34. J.M. Reuben, S. Krishnamurthy, W. Woodward, M. Cristofanilli, Expert Opin. Med. Diagnostics 2, 339 (2008). doi: 10.1517/17530059.2.4.339 CrossRefGoogle Scholar
  35. A. Rolle, R. Gunzel, U. Pachmann, B. Willen, K. Hoffken, K. Pachmann, World J. Surg. Oncol. 3, 18 (2005). doi: 10.1186/1477-7819-3-18 CrossRefGoogle Scholar
  36. A. Rosenthal, J. Voldman, Biophys. J. 88, 2193–2205 (2005). doi: 10.1529/biophysj.104.049684 CrossRefGoogle Scholar
  37. C.P. Schroder, M.H. Ruiters, S. de Jong, A.T. Tiebosch, J. Wesseling, R. Veenstra, J. de Vries, H.J. Hoekstra, L.F. de Leij, E.G. de Vries, Int. J. Cancer 106, 611 (2003). doi: 10.1002/ijc.11295 CrossRefGoogle Scholar
  38. J.P. Shelby, J. White, K. Ganesan, P.K. Rathod, and D.T. Chiu, 100, (2003)Google Scholar
  39. D.A. Smirnov, D.R. Zweitzig, B.W. Foulk, M.C. Miller, G.V. Doyle, K.J. Pienta, N.J. Meropol, L.M. Weiner, S.J. Cohen, J.G. Moreno, M.C. Connelly, L.W. Terstappen, S.M. O'Hara, Cancer Res. 65, 4993 (2005). doi: 10.1158/0008-5472.CAN-04-4330 CrossRefGoogle Scholar
  40. P.S. Steeg. Nat. Med. 12, 895–904 (2006) doi:10.1038/nm1469Google Scholar
  41. S. Steen, J. Nemunaitis, T. Fisher, J. Kuhn. Proc 21, 127 (2008). Bayl Univ Med CentGoogle Scholar
  42. R. Szatanek, G. Drabik, J. Baran, P. Kolodziejczyk, J. Kulig, J. Stachura, M. Zembala. Oncol. Rep. 19, 1055 (2008)Google Scholar
  43. S.J. Tan, L. Yobas, G.Y.H. Lee, C.N. Ong, C.T. Lim, International Conference on Biocomputation, Bioinformatics, and Biomedical Technologies, 2008. BIOTECHNO '08. (2008)Google Scholar
  44. S. Urtishak, R.K. Alpaugh, L.M. Weiner, R.F. Swaby, Biomarkers Med. 2, 137 (2008). doi: 10.2217/17520363.2.2.137 CrossRefGoogle Scholar
  45. J. Voldman, Curr Opin Biotechnol 17, (2006)Google Scholar
  46. L. Weiss, Adv Cancer Res 54, (1990)Google Scholar
  47. L. Weiss, D.S. Dimitrov, Cell Biophys. 6, 9 (1984)Google Scholar
  48. L. Weiss, D.S. Dimitrov, J. Theor. Biol. 121, 307 (1986)CrossRefGoogle Scholar
  49. G. Wiedswang, B. Naume, Nat. Clin. Pract. Oncol. 4, 154 (2007)CrossRefGoogle Scholar
  50. C.S. Wong, M.T. Cheung, B.B. Ma, E. Pun Hui, A.C. Chan, C.K. Chan, K.C. Lee, W. Cheuk, M.Y. Lam, M.C. Wong, C.M. Chan, J.K. Chan, and A.T. Chan, Int. J. Surg. Pathol. 16, (2008)Google Scholar
  51. H. Yagata, S. Nakamura, M. Toi, H. Bando, S. Ohno, A. Kataoka, Int J Clin Oncol 13, 252 (2008)CrossRefGoogle Scholar
  52. B. Yap, and R.D. Kamm, J. Appl. Physiol. 98, (2005)Google Scholar
  53. V. Zieglschmid, C. Hollmann, O. Bocher, Crit. Rev. Clin. Lab. Sci. 42, 155 (2005)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Swee Jin Tan
    • 1
    • 2
  • Levent Yobas
    • 1
  • Gabriel Yew Hoe Lee
    • 3
  • Choon Nam Ong
    • 4
  • Chwee Teck Lim
    • 2
    • 3
    • 5
    Email author
  1. 1.Institute of MicroelectronicsA*STAR (Agency for Science, Technology and Research)SingaporeSingapore
  2. 2.Graduate School for Integrative Sciences and EngineeringNational University of SingaporeSingaporeSingapore
  3. 3.Singapore-MIT AllianceSingaporeSingapore
  4. 4.Department of Epidemiology and Public HealthNational University of SingaporeSingaporeSingapore
  5. 5.Division of Bioengineering and Department of Mechanical EngineeringNational University of SingaporeSingaporeSingapore

Personalised recommendations