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Separation of Human Breast Cancer and Epithelial Cells by Adhesion Difference in a Microfluidic Channel

  • Kwon, Keon-Woo (School of Mechanical and Aerospace Engineering, Seoul National University) ;
  • Choi, Sung-Sik (School of Life Sciences and Biotechnology, Korea University) ;
  • Kim, Byung-Kyu (School of Aerospace and Mechanical Engineering, Hankuk Aviation University) ;
  • Lee, Se-Na (School of Life Sciences and Biotechnology, Korea University) ;
  • Lee, Sang-Ho (School of Life Sciences and Biotechnology, Korea University) ;
  • Park, Min-Cheol (School of Mechanical and Aerospace Engineering, Seoul National University) ;
  • Kim, Pil-Nam (School of Mechanical and Aerospace Engineering, Seoul National University) ;
  • Park, Suk-Ho (Microsystem Research Center, Korea Institute of Science and Technology) ;
  • Kim, Young-Ho (School of Aerospace and Mechanical Engineering, Hankuk Aviation University) ;
  • Park, Jun-Gyul (Microsystem Research Center, Korea Institute of Science and Technology) ;
  • Suh, Kahp-Y. (School of Mechanical and Aerospace Engineering, Seoul National University)
  • 발행 : 2007.09.30

초록

A simple, label-free microfluidic cell purification method is presented for separation of cancer cells by exploiting difference in cell adhesion. To maximize the adhesion difference, three types of polymeric nanostructures (50nm pillars, 50nm perpendicular and 50nm parallel lines with respect to the direction of flow) were fabricated using UV-assisted capillary moulding and included inside a polydimethylsiloxane (PDMS) microfluidic channel bonded onto glass substrate. The adhesion force of human breast epithelial cells (MCF10A) and human breast carcinoma (MCF7) was measured independently by injecting each cell line into the microfluidic device followed by culture for a period of time (e.g., one, two, and three hours). Then, the cells bound to the floor of a microfluidic channel were detached by increasing the flow rate of medium in a stepwise fashion. It was found that the adhesion force of MCF10A was always higher than that of MCF cells regardless of culture time and surface nanotopography at all flow rates, resulting in a label-free detection and separation of cancer cells. For the cell types used in our study, the optimum separation was found for 2 hours culture on 50nm parallel line pattern followed by flow-induced detachment at a flow rate of $300{\mu}l/min$.

키워드

참고문헌

  1. A. M. Moriarty, H. Alexander, R. A. Lerner, and G. B. Thornton, 'Antibodies to Peptides Detect New Hepatitis-B Antigen - Serological Correlation with Hepatocellular-Carcinoma,' Science, vol. 227, pp. 429-433, 1985 https://doi.org/10.1126/science.2981434
  2. I. Tamm, I. Cardinale, T. Kikuchi, and J. G. Krueger, 'E-Cadherin Distribution in Interleukin 6-Induced Cell-Cell Separation of Ductal Breast- Carcinoma Cells,' Proceedings of the National Academy of Sciences of the United States of America, vol. 91, pp. 4338-4342, 1994
  3. N. Scholler, N. Fu, Y. Yang, Z. M. Ye, G. E. Goodman, K. E. Hellstrom, and I. Hellstrom, 'Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma,' Proceedings of the National Academy of Sciences of the United States of America, vol. 96, pp. 11531-11536, 1999
  4. J. H. Kim, J. S. Kim, H. Choi, S. M. Lee, B. H. Jun, K. N. Yu, E. Kuk, Y. K. Kim, D. H. Jeong, M. H. Cho, and Y. S. Lee, 'Nanoparticle probes with surface enhanced Raman spectroscopic tags for cellular cancer targeting,' Analytical Chemistry, vol. 78, pp. 6967-6973, 2006 https://doi.org/10.1021/ac0607663
  5. J. K. Herr, J. E. Smith, C. D. Medley, D. H. Shangguan, and W. H. Tan, 'Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells,' Analytical Chemistry, vol. 78, pp. 2918-2924, 2006 https://doi.org/10.1021/ac052015r
  6. D. Shangguan, Y. Li, Z. W. Tang, Z. H. C. Cao, H. W. Chen, P. Mallikaratchy, K. Sefah, C. Y. J. Yang, and W. H. Tan, 'Aptamers evolved from live cells as effective molecular probes for cancer study,' Proceedings of the National Academy of Sciences of the United States of America, vol. 103, pp. 11838-11843, 2006
  7. A. Higuchi and Y. Tsukamoto, 'Cell separation of hepatocytes and fibroblasts through surface-modified polyurethane membranes,' Journal of Biomedical Materials Research Part A, vol. 71A, pp. 470-479, 2004 https://doi.org/10.1002/jbm.a.30169
  8. Y. Ito and K. Shinomiya, 'A new continuous-flow cell separation method based on cell density: Principle, apparatus, and preliminary application to separation of human buffy coat,' Journal of Clinical Apheresis, vol. 16, pp. 186-191, 2001 https://doi.org/10.1002/jca.1032
  9. Z. Du, N. Colls, K. H. Cheng, M. W. Vaughn, and L. Gollahon, 'Microfluidic-based diagnostics for cervical cancer cells,' Biosensors & Bioelectronics, vol. 21, pp. 1991-1995, 2006 https://doi.org/10.1016/j.bios.2005.09.005
  10. W. C. Chang, L. P. Lee, and D. Liepmann, 'Biomimetic technique for adhesion-based collection and separation of cells in a microfluidic channel,' Lab on a Chip, vol. 5, pp. 64-73, 2005 https://doi.org/10.1039/b400455h
  11. A. Sin, S. K. Murthy, A. Revzin, R. G. Tompkins, and M. Toner, 'Enrichment using antibody-coated microfluidic chambers in shear flow: Model mixtures of human lymphocytes,' Biotechnology and Bioengineering, vol. 91, pp. 816-826, 2005 https://doi.org/10.1002/bit.20556
  12. F. F. Becker, X. B. Wang, Y. Huang, R. Pethig, J. Vykoukal, and P. R. C. Gascoyne, 'Separation of Human Breast-Cancer Cells from Blood by Differential Dielectric Affinity,' Proceedings of the National Academy of Sciences of the United States of America, vol. 92, pp. 860-864, 1995
  13. Y. Huang, S. Joo, M. Duhon, M. Heller, B. Wallace, and X. Xu, 'Dielectrophoretic cell separation and gene expression profiling on microelectronic chip arrays,' Analytical Chemistry, vol. 74, pp. 3362-3371, 2002 https://doi.org/10.1021/ac011273v
  14. C. M. Das, F. Becker, S. Vernon, J. Noshari, C. Joyce, and P. R. C. Gascoyne, 'Dielectrophoretic segregation of different human cell types on microscope slides,' Analytical Chemistry, vol. 77, pp. 2708-2719, 2005 https://doi.org/10.1021/ac048196z
  15. N. Sniadecki, R. A. Desai, S. A. Ruiz, and C. S. Chen, 'Nanotechnology for cell-substrate interactions,' Annals of Biomedical Engineering, vol. 34, pp. 59-74, 2006 https://doi.org/10.1007/s10439-005-9006-3
  16. A. I. Teixeira, G. A. Abrams, P. J. Bertics, C. J. Murphy, and P. F. Nealey, 'Epithelial contact guidance on well-defined micro- and nanostructured substrates,' Journal of Cell Science, vol. 116, pp. 1881-1892, 2003 https://doi.org/10.1242/jcs.00383
  17. R. Carbone, I. Marangi, A. Zanardi, L. Giorgetti, E. Chierici, G. Berlanda, A. Podesta, F. Fiorentini, G. Bongiorno, P. Piseri, P. G. Pelicci, and P. Milani, 'Biocompatibility of cluster-assembled nanostructured TiO2 with primary and cancer cells,' Biomaterials, vol. 27, pp. 3221-3229, 2006 https://doi.org/10.1016/j.biomaterials.2006.01.056
  18. D. H. Kim, P. Kim, I. Song, J. M. Cha, S. H. Lee, B. Kim, and K. Y. Suh, 'Guided three-dimensional growth of functional cardiomyocytes on polyethylene glycol nanostructures,' Langmuir, vol. 22, pp. 5419-5426, 2006 https://doi.org/10.1021/la060283u
  19. A. S. Goldstein and P. A. DiMilla, 'Application of fluid mechanic and kinetic models to characterize mammalian cell detachment in a radial-flow chamber,' Biotechnology and Bioengineering, vol. 55, pp. 616-629, 1997 https://doi.org/10.1002/(SICI)1097-0290(19970820)55:4<616::AID-BIT4>3.0.CO;2-K
  20. H. Lu, L. Y. Koo, W. C. M. Wang, D. A. Lauffenburger, L. G. Griffith, and K. F. Jensen, 'Microfluidic shear devices for quantitative analysis of cell adhesion,' Analytical Chemistry, vol. 76, pp. 5257-5264, 2004 https://doi.org/10.1021/ac049837t
  21. E. Martines, K. McGhee, C. Wilkinson, and A. Curtis, 'A parallel-plate flow chamber to study initial cell adhesion on a nanofeatured surface,' Ieee Transactions on Nanobioscience, vol. 3, pp. 90-95, 2004 https://doi.org/10.1109/TNB.2004.828268
  22. S. J. Choi, P. J. Yoo, S. J. Baek, T. W. Kim, and H. H. Lee, 'An ultraviolet-curable mold for sub-100-nm lithography,' Journal of the American Chemical Society, vol. 126, pp. 7744-7745, 2004 https://doi.org/10.1021/ja048972k
  23. K. Y. Suh, Y. S. Kim, and H. H. Lee, 'Capillary force lithography,' Advanced Materials, vol. 13, pp. 1386-1389, 2001 https://doi.org/10.1002/1521-4095(200109)13:18<1386::AID-ADMA1386>3.0.CO;2-X
  24. A. Khademhosseini, K. Y. Suh, S. Jon, G. Eng, J. Yeh, G. J. Chen, and R. Langer, 'A soft lithographic approach to fabricate patterned microfluidic channels,' Analytical Chemistry, vol. 76, pp. 3675-3681, 2004 https://doi.org/10.1021/ac035415s
  25. A. Khademhosseini, J. Yeh, G. Eng, J. Karp, H. Kaji, J. Borenstein, O. C. Farokhzad, and R. Langer, 'Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays,' Lab on a Chip, vol. 5, pp. 1380-1386, 2005 https://doi.org/10.1039/b508096g
  26. M. C. Park, J. Y. Hur, K. W. Kwon, S. H. Park, and K. Y. Suh, 'Pumpless, selective docking of yeast cells inside a microfluidic channel induced by receding meniscus,' Lab on a Chip, vol. 6, pp. 988-994, 2006 https://doi.org/10.1039/b602961b