Immunomagnetic nanoscreening of circulating tumor cells with a motion controlled microfluidic system
- 1.1k Downloads
Combining the power of immunomagnetic assay and microfluidic microchip operations, we successfully detected rare CTCs from clinical blood samples. The microfluidic system is operated in a flip-flop mode, where a computer-controlled rotational holder with an array of microfluidic chips inverts the microchannels. We have demonstrated both theoretically and experimentally that the direction of red blood cell (RBC) sedimentation with regards to the magnetic force required for cell separation is important for capture efficiency, throughput, and purity. The flip-flop operation reduces the stagnation of RBCs and non-specific binding on the capture surface by alternating the direction of the magnetic field with respect to gravity. The developed immunomagnetic microchip-based screening system exhibits high capture rates (more than 90%) for SkBr3, PC3, and Colo205 cell lines in spiked screening experiments and successfully isolates CTCs from patient blood samples. The proposed motion controlled microchip-based immunomagnetic system shows great promise as a clinical tool for cancer diagnosis and prognosis.
KeywordsCirculating tumor cells (CTCs) Immunomagnetic assay Microfluidic chip Gravity Capture efficiency Purity Fluorescent imaging
We thank Dr. Hirofumi Tanaka of the University of Texas at Austin for his help in the measurements of blood viscosities and Dr. Rodney S. Ruoff’s laboratory of the University of Texas at Austin for his help in the COMSOL simulation. We also want to thank Microelectronics Research Center (MRC) and Center for Nano- and Molecular Science (CNM) at UT Austin for providing facilities for microchip fabrication. We are grateful for the financial support from National Institute of Health (NIH) National Cancer Institute (NCI) Cancer Diagnosis Program under the grant 1R01CA139070.
- T. Fehm, A. Sagalowsky, E. Clifford, P. Beitsch, H. Saboorian, D. Euhus, S. Meng, L. Morrison, T. Tucker, N. Lane, B.M. Ghadimi, K. Heselmeyer-Haddad, T. Ried, C. Rao, J.W. Uhr, Clin. Cancer Res. 8, 2073–2084 (2002)Google Scholar
- P. Paterlini-Brechot, N.L. Benali, Science 253, 180–204 (2007)Google Scholar
- 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 and M. Toner, 450, pp. 1235–1239 (2007)Google Scholar
- S.L. Stott, C.H. Hsu, D.I. Tsukrov, M. Yu, D.T. Miyamoto, B.A. Waltman, S.M. Rothenberg, A.M. Shah, M.E. Smas, G.K. Korir, F.P. Floyd Jr., A.J. Gilman, J.B. Lord, D. Winokur, S. Springer, D. Irimia, S. Nagrath, L.V. Sequist, R.J. Lee, K.J. Isselbacher, S. Maheswaranc, D.A. Haber, M. Toner, PNAS 107, 18392–18397 (2010)CrossRefGoogle Scholar
- J. Sun, M. Li, C. Liu, Y. Zhang, D. Liu, W. Liu, G. Hu, X. Jiang, Lab on a Chip (2012)Google Scholar
- S. Zhang, H.K. Lin, and B. Lu, Biomed Microdevices, pp. 203–213 (2011)Google Scholar
- T. Zhu, R. Cheng, S.A. Lee, E. Rajaraman, M.A. Eiteman, T.D. Querec, E.R. Unger, L. Mao, Microfluid Nnaofluid (2012)Google Scholar