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Harnessing gravitational, hydrodynamic and negative dielectrophoretic forces for higher throughput cell sorting

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Abstract

We present a negative dielectrophoretic (n-DEP) force based high throughput cell sorting system integrating a cantilever-type electrode array in a vertical macro channel to leverage gravity driven flow and eliminate the need for external pumps. The system comprises a macro-sized channel to increase throughput, a cantilever electrode array (L×W×H=150 μm ×500 μm×10 μm) to achieve n-DEP force and high throughput, and a flow regulator to precisely control hydrodynamic force. The hydrodynamic force and the n-DEP force acting on the target cell are evaluated theoretically. In addition, optimal separation conditions are investigated using computational models. Separation conditions are experimentally investigated based on simulation results. Finally, to demonstrate the separation performance of the sorting system, we performed the separation of the human breast cancer cells (MCF 7) from diluted red blood cells (RBCs) under conditions of low voltage (7Vp-p with 500 kHz) and flow rate of 5 μL·min−1. The system can separate MCF 7 cell with 71% separation efficiency in case of the ratio of 1: 60000 (MCF 7: RBCs).

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References

  1. Tsutsui, H. & Ho, C.M. Cell separation by non-inertial force fields in microfluidic systems. Mech. Res. Commun. 36, 92–103 (2009).

    Article  Google Scholar 

  2. Kersaudy-Kerhoas, M., Dhariwal, R. & Desmulliez, M.P.Y. Recent advances in microparticle continuous separation. IET Nanobiotechnol. 2, 1–13 (2008).

    Article  CAS  Google Scholar 

  3. Thomas, A.F. & Achim, W. Microfluidics for miniaturized laboratories on a chip. Chem. Phys. Chem. 9, 2140–2156 (2008).

    Article  Google Scholar 

  4. Huh, D., Gu, W., Kamotani, Y., Grotberg, J.B. & Takayama, S. Microfluidics for flow cytometric analysis of cells and particles. Physiol. Meas 26, R 73–98 (2005).

    Article  Google Scholar 

  5. Radisic, M., Lyer, R.K. & Murthy, S.K. Micro- and nanotechnology in cell separation. Int. J. Nanomedicine 1, 3–14 (2006).

    Article  CAS  Google Scholar 

  6. Bonner, W.A., Sweet, R.G., Hulett, H.R. & Herzenberg, L.A. Fluorescence activated cell sorting. Rev. Sci. Instrum. 43, 404–409 (1972).

    Article  CAS  Google Scholar 

  7. Applegate, R.W., Squire, J., Vestad, T. & Oakey, J. Microfluidic sorting system based on optical waveguide integration and diode laser bar trapping. Lab. Chip 6, 422–426 (2006).

    Article  CAS  Google Scholar 

  8. Pamme, N. & Manz, A. On-chip free-flow magnetophoresis: continuous flow separation of magnetic particles and agglomerates. Anal. Chem. 76, 7250–7256 (2004).

    Article  CAS  Google Scholar 

  9. Kim, Y. et al. Novel platform for minimizing cell loss on separation process: Droplet-based magnetically activated cell separator. Rev. Sci. Instrum. 78, 074301–074307 (2007).

    Article  Google Scholar 

  10. Talary, M.S., Mills, K.I., Hoy, T., Burnett, A.K. & Pethig, R. Dielectrophoretic separation and enrichment of CD34+ cell subpopulation from bone marrow and peripheral blood stem cells. Med. Biol. Eng. Comp. 33, 235–237 (1995).

    Article  CAS  Google Scholar 

  11. Stephens, M., Talary, M.S., Pethig, R., Burnett, A.K., & Mills, K.I. The dielectrophoresis enrichment of CD34+ cells from peripheral blood stem cell harvests. Bone Marrow Transpl. 18, 777–782 (1996).

    CAS  Google Scholar 

  12. Vykoukal, J., Vykoukal, D.M., Freyberg, S., Alt, E.U. & Gascoyne, P.R.C. Enrichment of putative stem cells from adipose tissue using dielectrophoretic field-flow fractionation. Lab. Chip 8, 1386–1393 (2008).

    Article  CAS  Google Scholar 

  13. Dholakia, K., Reece, P. & Gu, M. Optical micromanipulation. Chem. Soc. Rev. 37, 42–55 (2008).

    Article  CAS  Google Scholar 

  14. Wang, M. et al. “Microfluidic drifting”-implementing three-dimensional hydrodynamic focusing with a single-layer planar microfluidic device. Nat. Biotechnol. 23, 83–87 (2005).

    Article  CAS  Google Scholar 

  15. Lin, A. et al. Formation of high electromagnetic gradients through a particle-based microfluidic approach. J. Micromech. Microeng. 17, 1299–1306 (2007).

    Article  CAS  Google Scholar 

  16. Petersson, F., Nilsson, A., Holm, C., Jonsson, H. & Laurell, T. Separation of lipids from blood utilizing ultrasonic standing waves in microfluidic channels. Analyst 129, 938–943 (2004).

    Article  CAS  Google Scholar 

  17. Petersson, F., Nilsson, A., Holm, C., Jonsson, H. & Laurell, T. Continuous separation of lipid particles from erythrocytes by means of laminar flow and acoustic standing wave forces. Lab. Chip 5, 20–22 (2005).

    Article  CAS  Google Scholar 

  18. Petersson, F., Aberg, L., Sward-Nilsson, M. & Laurell, T. Free flow acoustophoresis: microfluidic-based mode of particle and cell separation. Anal. Chem. 79, 5117–5123 (2007).

    Article  CAS  Google Scholar 

  19. Nagrath, S., Sequist, L.V., Maheswaran, S., Bell, D.W. & Irimia, D. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450, 1235–1239 (2007).

    Article  CAS  Google Scholar 

  20. Klimanskaya, I., Chung, Y., Becker, S., Lu, S. & Lanza, R. Human embryonic stem cell lines derived from single blastomeres. Nature 444, 481–485 (2006).

    Article  CAS  Google Scholar 

  21. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006).

    Article  CAS  Google Scholar 

  22. An, J., Lee, J., Lee, S.H., Park, J. & Kim, B. Separation of malignant human breast cancer epithelial cells from healthy epithelial cells using an advanced dielectrophoresis-activated cell sorter (DACS). Anal. Bioanal. Chem. 394, 801–809 (2009).

    Article  CAS  Google Scholar 

  23. Herbert, A.P. & Joe, S.C. Dielectrophoresis of cells. Biophys. J. 11, 711–727 (1971).

    Article  Google Scholar 

  24. Pommer, M.S. et al. Dielectrophoretic separation of platelets from diluted whole blood in microfluidic channels. Electrophoresis 29, 1213–1218 (2008).

    Article  CAS  Google Scholar 

  25. Kim, U. & Soh, H.T. Simultaneous sorting of multiple bacterial targets using integrated Dielectrophoretic-Magnetic Activated Cell Sorter. Lab. Chip 9, 2313–2318 (2009).

    Article  CAS  Google Scholar 

  26. Boettcher, M. et al. Gravitation-driven stress-reduced cell handling. Anal. Bioanal. Chem. 390, 857–863 (2008).

    Article  CAS  Google Scholar 

  27. Han, K.H. & Frazier, A.B. Lateral-driven continuous dielectrophoretic microseparators for blood cells suspended in a highly conductive medium. Lab. Chip 8, 1079–1086 (2008).

    Article  CAS  Google Scholar 

  28. Chin, H.K., Yee, C.L., Isabel, R., Chun, Y. & Kamal, Y.T. Cell motion model for moving dielectrophoresis. Anal. Chem. 80, 5454–5461 (2008).

    Article  Google Scholar 

  29. Unyoung, K., Jiangrong, Q., Sophia, A.K., Patrick, S.D. & Tom, H.S. Multitarget dielectrophoresis activated cell sorter. Anal. Chem. 80, 8656–8661 (2008).

    Article  Google Scholar 

  30. Morgan, H. & Green, N.G. AC Electrokinetics: Colloids and Nanoparticles (Baldock: Research Studies Press) (2003).

    Google Scholar 

  31. Nuttawut, L., Kumaravel, K., Chun, Y., Volodymyr, I. & Roman, S. Microfluidic characterization and continuous separation of cells and particles using conducting poly(dimethyl siloxane) electrode induced alternating current-dielectrophoresis. Anal. Chem. 83, 9579–9585 (2011).

    Article  Google Scholar 

  32. Seungkyung, P., Mehti, K. & Ali, B. Particle trapping in high-conductivity media with electrothermally enhanced negative dielectrophoresis. Anal. Chem. 81, 2303–2310 (2009).

    Article  Google Scholar 

  33. Guck, J., Schinkinger, S., Lincoln, B. & Wottawah, F. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys. J. 88, 3689–3698 (2005).

    Article  CAS  Google Scholar 

  34. Helen, C., Fatima, L., Hilary, T. & Michael, H. Biophysical characterization of MDR breast cancer cell lines reveals the cytoplasm is critical in determining drug sensitivity. Biochinica et Biophysica Acta 1770, 601–608 (2006).

    Google Scholar 

  35. Kim, Y., Lee, J., Kim, Y., Shin, S. & Kim, B. Cantilever-type electrode array-based high-throughput microparticle sorting platform driven by gravitation and negative dielectrophoretic force. J. Micromech. Microeng. 21, 015015 (2011).

    Article  Google Scholar 

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Authors and Affiliations

  1. School of Aerospace and Mechanical Engineering, Korea Aerospace University, Goyang, Gyeonggi-do, 412-791, Korea

    Junghun Lee, Youngwoong Kim & Byungkyu Kim

  2. Department of Biomedical Engineering, Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, WI, USA

    David J. Beebe

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  1. Junghun Lee
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  2. Youngwoong Kim
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  3. David J. Beebe
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  4. Byungkyu Kim
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Correspondence to Byungkyu Kim.

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Lee, J., Kim, Y., Beebe, D.J. et al. Harnessing gravitational, hydrodynamic and negative dielectrophoretic forces for higher throughput cell sorting. BioChip J 6, 229–239 (2012). https://doi.org/10.1007/s13206-012-6305-2

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  • DOI: https://doi.org/10.1007/s13206-012-6305-2

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