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Biomedical Microdevices

, Volume 15, Issue 4, pp 611–616 | Cite as

Polymeric microfluidic devices exhibiting sufficient capture of cancer cell line for isolation of circulating tumor cells

  • Takashi OhnagaEmail author
  • Yutaka Shimada
  • Makoto Moriyama
  • Hiroyuki Kishi
  • Tsutomu Obata
  • Koji Takata
  • Tomoyuki Okumura
  • Takuya Nagata
  • Atsushi Muraguchi
  • Kazuhiro Tsukada
Article

Abstract

Here, we developed polymeric microfluidic devices for the isolation of circulating tumor cells. The devices, with more than 30,000 microposts in the channel, were produced successfully by a UV light-curing process lasting 3 min. The device surface was coated with anti-epithelial cell adhesion molecule antibody by just contacting the antibody solution, and a flow system including the device was established to send a cell suspension through it. We carried out flow tests for evaluation of the device’s ability to capture tumor cells using an esophageal cancer cell line, KYSE220, dispersed in phosphate-buffered saline or mononuclear cell separation from whole blood. After the suspension flowed through the chip, many cells were seen to be captured on the microposts coated with the antibody, whereas there were few cells in the device without the antibody. Owing to the transparency of the device, we could observe the intact and the stained cells captured on the microposts by transmitted light microscopy and phase contrast microscopy, in addition to fluorescent microscopy, which required fluorescence labeling. Cell capture efficiencies (i.e., recovery rates of the flowing cancer cells by capture with the microfluidic device) were measured. The resulting values were 0.88 and 0.95 for cell suspension in phosphate-buffered saline, and 0.85 for the suspension in the mononuclear cell separation, suggesting the sufficiency of this device for the isolation of circulating tumor cells. Therefore, our device may be useful for research and treatments that rely on investigation of circulating tumor cells in the blood of cancer patients.

Keywords

Circulating tumor cell Microfluidic device UV light-curable resin Cell surface marker Epithelial cell adhesion molecule Antibody 

Notes

Acknowledgments

This study was supported by Grant-in-Aid for Scientific Research (22500422).

Supplementary material

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References

  1. M. Alunni-Fabbroni, M.T. Sandri, Methods 50, 289 (2010)CrossRefGoogle Scholar
  2. I. Desitter, B.S. Guerrouahen, N. Benali-Furet, J. Wechsler, P.A. Janne, Y. Kuan, M. Yanagita, L. Wang, J.A. Berkowitz, R.J. Distel, Y.E. Cayre, Anticancer. Res. 31, 427 (2011)Google Scholar
  3. M.N. Dickson, P. Tsinberg, Z. Tang, F.Z. Bischoff, T. Wilson, E.F. Leonard, Biomicrofluidics 5, 034119 (2011)CrossRefGoogle Scholar
  4. E. Dotan, S.J. Cohen, K.R. Alpaugh, N.J. Meropol, Oncologist 14, 1070 (2009)CrossRefGoogle Scholar
  5. G.S. Fiorini, D.T. Chiu, Biotechniques 38, 429 (2005)CrossRefGoogle Scholar
  6. J. Hou, M.G. Krebs, L. Lancashire, R. Sloane, A. Backen, R.K. Swain, L.J.C. Priest, A. Greystoke, C. Zhou, K. Morris, T. Ward, F.H. Blackhall, C. Dive, J. Clin. Oncol. 30, 525 (2012)CrossRefGoogle Scholar
  7. M. Iwatsuki, K. Mimori, T. Yokobori, H. Ishi, T. Beppu, S. Nakamori, H. Baba, M. Mori, Cancer Sci. 101, 293 (2010)CrossRefGoogle Scholar
  8. J. Kaganoi, Y. Shimada, M. Kano, T. Okumura, G. Watanabe, M. Imamura, Br. J. Surg. 91, 1055 (2004)CrossRefGoogle Scholar
  9. H.K. Lin, S. Zheng, A.J. Williams, M. Balic, S. Groshen, H.I. Scher, M. Fleisher, W. Stadler, R.H. Datar, Y. Tai, R.J. Cote, Clin. Cancer Res. (2010). doi: 10.1158/1078-0432.CCR-10-1105
  10. 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 Lett. 450, 1235 (2007)CrossRefGoogle Scholar
  11. C.V. Pecot, F.Z. Bischoff, J.A. Mayer, K.L. Wong, T. Pham, J. Bottsford-Miller, R.L. Stone, Y.G. Lin, P. Jaladurgam, J.W. Roh, B.W. Goodman, W.M. Merritt, T.J. Pircher, S.D. Mikolajczyk, A.M. Nick, J. Celestino, C. Eng, L.M. Ellis, M.T. Deavers, A.K. Sood, Cancer Discov. 1, 580 (2011)CrossRefGoogle Scholar
  12. P. Pilati, S. Mocellin, L. Bertazza, F. Galdi, M. Briarava, E. Mammano, E. Tessari, G. Zavagno, D. Nitti, Ann. Surg. Oncol. 19, 402 (2012)CrossRefGoogle Scholar
  13. Y. Shimada, M. Imamura, T. Wagata, N. Yamaguchi, T. Tobe, Cancer 69, 277 (1992)CrossRefGoogle Scholar
  14. M. Takakura, S. Kyo, M. Nakamura, Y. Maida, Y. Mizumoto, Y. Bono, X. Zhang, Y. Hashimoto, Y. Urata, T. Fujiwara, M. Inoue, Br. J. Cancer 107, 448 (2012)CrossRefGoogle Scholar
  15. T. Xu, B. Lu, Y. Tai, A. Goldkorn, Cancer Res. 70, 6420 (2010)CrossRefGoogle Scholar
  16. H.K. Zheng, B. Lin, A. Lu, R. Williams, R.J. Datar, Y. Cote, Tai, Biomed Microdevices (2011). doi: 10.1007/s10544-010-9485-3

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Takashi Ohnaga
    • 1
    Email author
  • Yutaka Shimada
    • 2
  • Makoto Moriyama
    • 2
  • Hiroyuki Kishi
    • 3
  • Tsutomu Obata
    • 1
  • Koji Takata
    • 1
  • Tomoyuki Okumura
    • 2
  • Takuya Nagata
    • 2
  • Atsushi Muraguchi
    • 3
  • Kazuhiro Tsukada
    • 2
  1. 1.Central Research LaboratoriesToyama Industrial Technology CenterTakaokaJapan
  2. 2.Department of Surgery and Science, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
  3. 3.Department of Immunology, Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan

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