, Volume 2, Issue 4, pp 277–286 | Cite as

Applications of Microfluidics in Stem Cell Biology

  • Qiucen ZhangEmail author
  • Robert H. Austin


Stem cell research can significantly benefit from recent advances of microfluidics technology. In a rationally designed microfluidic device, analyses of stem cells can be done in a much deeper and wider way than in a conventional tissue culture dish. Miniaturization makes analyses operated in a high-throughput fashion, while controls of fluids help to reconstruct the physiological environments. Through integration with present characterization tools like fluorescent microscope, microfluidics offers a systematic way to study the decision-making process of stem cells, which has attractive medical applications. In this paper, recent progress of microfluidic devices on stem cell research are discussed. The purpose of this review is to highlight some key features of microfluidics for stem cell biologists, as well as provide physicists/engineers an overview of how microfluidics has been and could be used for stem cell research.


Microfluidics Stem cells Cancer 



This work was supported by NSF grant NSF0750323 and National Cancer Institute grant U54CA143803. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.


  1. 1.
    Whitesides, G. (2006). The origins and the future of microfluidics. Nature, 442(7101), 368.CrossRefGoogle Scholar
  2. 2.
    El-Ali, J., Sorger, P., Jensen, K. (2006). Cells on chips. Nature, 442(7101), 403.CrossRefGoogle Scholar
  3. 3.
    Austin, R., Tung, C., Lambert, G., Liao, D., Gong, X. (2010). An introduction to micro-ecology patches. Chemical Society Reviews, 39(3), 1049.CrossRefGoogle Scholar
  4. 4.
    Weissman, I. (2000). Stem cells: units of development, review Units of regeneration, and units in evolution. Cell, 100, 157.CrossRefGoogle Scholar
  5. 5.
    Thomson, J., Itskovitz-Eldor, J., Shapiro, S., Waknitz, M., Swiergiel, J., Marshall, V., Jones, J. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282(5391), 1145.CrossRefGoogle Scholar
  6. 6.
    Fuchs, E., & Segre, J. (2000). Stem cells: review a new lease on life. Cell, 100, 143.CrossRefGoogle Scholar
  7. 7.
    Nichols, J., Zevnik, B., Anastassiadis, K., Niwa, H., Klewe-Nebenius, D., Chambers, I., Scholer, H., Smith, A. (1998). Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell, 95(3), 379.CrossRefGoogle Scholar
  8. 8.
    Brignier, A., & Gewirtz, A. (2010). Embryonic and adult stem cell therapy. Journal of Allergy and Clinical Immunology, 125(2), S336.CrossRefGoogle Scholar
  9. 9.
    Yamanaka, S. (2007). Strategies and new developments in the generation of patient-specific pluripotent stem cells. Cell Stem Cell, 1(1), 39.CrossRefGoogle Scholar
  10. 10.
    Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4), 663.CrossRefGoogle Scholar
  11. 11.
    Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., Yamanaka, S. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131(5), 861.CrossRefGoogle Scholar
  12. 12.
    Johansson, C., Momma, S., Clarke, D., Risling, M., Lendahl, U., Frisén, J. (1999). Identification of a neural stem cell in the adult mammalian central nervous system. Cell, 96(1), 25.CrossRefGoogle Scholar
  13. 13.
    Jiang, Y., Jahagirdar, B., Reinhardt, R., Schwartz, R., Keene, C., Ortiz-Gonzalez, X., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., et al. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 418(6893), 41.CrossRefGoogle Scholar
  14. 14.
    Potten, C., & Loeffler, M. (1990). Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. Development, 110(4), 1001.Google Scholar
  15. 15.
    Mery, E., Ricoul, F., Sarrut, N., Constantin, O., Delapierre, G., Garin, J., Vinet, F. (2008). A silicon microfluidic chip integrating an ordered micropillar array separation column and a nano-electrospray emitter for LC/MS analysis of peptides. Sensors and Actuators B: Chemical, 134(2), 438.CrossRefGoogle Scholar
  16. 16.
    Kalkandjiev, K., Riegger, L., Kosse, D., Welsche, M., Gutzweiler, L., Zengerle, R., Koltay, P. (2011). Microfluidics in silicon/polymer technology as a cost-efficient alternative to silicon/glass. Journal of Micromechanics and Microengineering, 21, 025008.CrossRefGoogle Scholar
  17. 17.
    Lin, Y., Yang, C., Wang, C., Chang, F., Huang, K., Hsieh, W. (2012). An aluminum microfluidic chip fabrication using a convenient micromilling process for fluorescent poly (DL-lactide-co-glycolide) microparticle generation. Sensors, 12(2), 1455.CrossRefGoogle Scholar
  18. 18.
    Xia, Y., & Whitesides, G. (1998). Soft lithography. Annual Review of Materials Science, 28(1), 153.CrossRefGoogle Scholar
  19. 19.
    Unger, M., Chou, H., Thorsen, T., Scherer, A., Quake, S. (2000). Monolithic microfabricated valves and pumps by multilayer soft lithography. Science, 288(5463), 113.CrossRefGoogle Scholar
  20. 20.
    Yu, L., Li, C., Liu, Y., Gao, J., Wang, W., Gan, Y. (2009). Flow-through functionalized PDMS microfluidic channels with dextran derivative for ELISAs. Lab Chip, 9(9), 1243.CrossRefGoogle Scholar
  21. 21.
    Fiddes, L., Raz, N., Srigunapalan, S., Tumarkan, E., Simmons, C., Wheeler, A., Kumacheva, E. (2010). A circular cross-section PDMS microfluidics system for replication of cardiovascular flow conditions. Biomaterials, 31(13), 3459.CrossRefGoogle Scholar
  22. 22.
    Wang, M., Cui, D., Wang, L., Chen, X., Zhao, Q. (2011). Fabrication of microfluidic electrocontrolled chip in polydimethylsiloxane (PDMS). International Journal of Nonlinear Sciences and Numerical Simulation, 3(3–4), 207.Google Scholar
  23. 23.
    Knight, J., Vishwanath, A., Brody, J., Austin, R. (1998). Hydrodynamic focusing on a silicon chip: mixing nanoliters in microseconds. Physical Review Letters, 80(17), 3863.CrossRefGoogle Scholar
  24. 24.
    Loutherback, K., Puchalla, J., Austin, R., Sturm, J. (2009). Deterministic microfluidic ratchet. Physical Review Letters, 102(4), 45301.CrossRefGoogle Scholar
  25. 25.
    Loutherback, K., Chou, K., Newman, J., Puchalla, J., Austin, R., Sturm, J. (2010). Improved performance of deterministic lateral displacement arrays with triangular posts. Microfluidics and Nanofluidics, 9(6), 1143.CrossRefGoogle Scholar
  26. 26.
    Lambert, G., Liao, D., Austin, R. (2010). Collective escape of chemotactic swimmers through microscopic ratchets. Physical Review Letters, 104(16), 168102.CrossRefGoogle Scholar
  27. 27.
    Zhang, Q., Lambert, G., Liao, D., Kim, H., Robin, K., Tung, C., Pourmand, N., Austin, R. (2011). Acceleration of emergence of bacterial antibiotic resistance in connected microenvironments. Science, 333(6050), 1764.CrossRefGoogle Scholar
  28. 28.
    Hong, J., Quake, S., et al. (2003). Integrated nanoliter systems. Nature Biotechnology, 21(10), 1179.CrossRefGoogle Scholar
  29. 29.
    Mark, D., Weber, P., Lutz, S., Focke, M., Zengerle, R., von Stetten, F. (2011). Aliquoting on the centrifugal microfluidic platform based on centrifugo-pneumatic valves. Microfluidics and Nanofluidics, 10(6), 1279.CrossRefGoogle Scholar
  30. 30.
    Araci, I., & Quake, S. (2012). Microfluidic very large scale integration (mVLSI) with integrated micromechanical valves. Lab Chip, 12, 2803–2806. doi: 10.1039/C2LC40258K.CrossRefGoogle Scholar
  31. 31.
    Tsai, J., & Lin, L. (2002). Active microfluidic mixer and gas bubble filter driven by thermal bubble micropump. Sensors and Actuators A: Physical, 97, 665.CrossRefGoogle Scholar
  32. 32.
    Kannappan, K., Bogle, G., Travas-Sejdic, J., Williams, D. (2011). Computational design of mixers and pumps for microfluidic systems, based on electrochemically-active conducting polymers. Chemical Physics, 13(12), 5450.CrossRefGoogle Scholar
  33. 33.
    Lee, C., Chang, C., Wang, Y., Fu, L. (2011). Microfluidic mixing: a review. International Journal of Molecular Sciences, 12(5), 3263.CrossRefGoogle Scholar
  34. 34.
    Graydon, O. (2011). Microfluidics: laser-induced bubbles create valves and pumps. Nature Photonics, 5(5), 256.CrossRefGoogle Scholar
  35. 35.
    Kim, J., Kang, M., Jensen, E., Mathies, R. (2012). Lifting gate PDMS microvalves and pumps for microfluidic control. Analytical Chemistry doi: 10.1021/ac202934x.CrossRefGoogle Scholar
  36. 36.
    Morrison, S., & Spradling, A. (2008). Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell, 132(4), 598.CrossRefGoogle Scholar
  37. 37.
    Barker, N., Ridgway, R., van Es, J., M. van de Wetering, Begthel, H., M. van den Born, Danenberg, E., Clarke, A., Sansom, O., Clevers, H. (2008). Crypt stem cells as the cells-of-origin of intestinal cancer. Nature, 457(7229), 608.CrossRefGoogle Scholar
  38. 38.
    Aguiari, P., Leo, S., Zavan, B., Vindigni, V., Rimessi, A., Bianchi, K., Franzin, C., Cortivo, R., Rossato, M., Vettor, R., et al. (2008). High glucose induces adipogenic differentiation of muscle-derived stem cells. Science, 105(4), 1226.Google Scholar
  39. 39.
    Ivanovic, Z. (2009). Hypoxia or in situ normoxia: the stem cell paradigm. Journal of Cellular Physiology, 219(2), 271.MathSciNetCrossRefGoogle Scholar
  40. 40.
    De Filippis, L., & ZDelia, D. (2011). Hypoxia in the regulation of neural stem cells. Cellular and Molecular Life Sciences, 68(17), 2831–2844.CrossRefGoogle Scholar
  41. 41.
    Gómez-Sjöberg, R., Leyrat, A., Pirone, D., Chen, C., Stephen, R. (2007). Versatile, fully automated, microfluidic cell culture system. Analytical Chemistry, 79(22), 8557.CrossRefGoogle Scholar
  42. 42.
    Lecault, V., VanInsberghe, M., Sekulovic, S., Knapp, D., Wohrer, S., Bowden, W., Viel, F., McLaughlin, T., Jarandehei, A., Miller, M., et al. (2011). High-throughput analysis of single hematopoietic stem cell proliferation in microfluidic cell culture arrays. Nature Methods, 8(7), 581.CrossRefGoogle Scholar
  43. 43.
    Taylor, R., Falconnet, D., Niemistö, A., Ramsey, S., Prinz, S., Shmulevich, I., Galitski, T., Hansen, C. (2009). Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform. Proceedings of the National Academy of Sciences, 106(10), 3758.CrossRefGoogle Scholar
  44. 44.
    Wang, Z., Kim, M., Marquez, M., Thorsen, T. (2007). High-density microfluidic arrays for cell cytotoxicity analysis. Lab Chip, 7(6), 740.CrossRefGoogle Scholar
  45. 45.
    Tay, S., Hughey, J., Lee, T., Lipniacki, T., Quake, S., Covert, M. (2010). Single-cell NF-[kgr] B dynamics reveal digital activation and analogue information processing. Nature, 466(7303), 267.CrossRefGoogle Scholar
  46. 46.
    Chin, M., Mason, M., Xie, W., Volinia, S., Singer, M., Peterson, C., Ambartsumyan, G., Aimiuwu, O., Richter, L., Zhang, J., et al. (2009). Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell, 5(1), 111.CrossRefGoogle Scholar
  47. 47.
    Kenis, P., Ismagilov, R., Whitesides, G. (1999). Microfabrication inside capillaries using multiphase laminar flow patterning. Science, 285(5424), 83.CrossRefGoogle Scholar
  48. 48.
    Takayama, S., Ostuni, E., LeDuc, P., Naruse, K., Ingber, D., Whitesides, G., et al. (2001). Subcellular positioning of small molecules. Nature, 411(6841), 1016.CrossRefGoogle Scholar
  49. 49.
    Mark, D., Haeberle, S., Roth, G., Von Stetten, F., Zengerle, R. (2010). Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications. Chemical Society Reviews, 39(3), 1153.CrossRefGoogle Scholar
  50. 50.
    Oppegard, S., Nam, K., Carr, J., Skaalure, S., Eddington, D. (2009). Modulating temporal and spatial oxygenation over adherent cellular cultures. PLoS One, 4(9), e6891.CrossRefGoogle Scholar
  51. 51.
    Toley, B., Park, J., Kim, B., Venkatasubramanian, R., Maharbiz, M., Forbes, N. (2011). Micrometer-scale oxygen delivery rearranges cells and prevents necrosis in tumor tissue in vitro. Biotechnology Progress, 28(2), 515–525.CrossRefGoogle Scholar
  52. 52.
    Chung, B., Flanagan, L., Rhee, S., Schwartz, P., Lee, A., Monuki, E., Jeon, N. (2005). Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. Lab Chip, 5(4), 401.CrossRefGoogle Scholar
  53. 53.
    Lo, J., Sinkala, E., Eddington, D. (2010). Oxygen gradients for open well cellular cultures via microfluidic substrates. Lab Chip, 10(18), 2394.CrossRefGoogle Scholar
  54. 54.
    Lucchetta, E., Lee, J., Fu, L., Patel, N., Ismagilov, R. (2005). Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature, 434(7037), 1134.CrossRefGoogle Scholar
  55. 55.
    Houchmandzadeh, B., Wieschaus, E., Leibler, S., et al. (2002). Establishment of developmental precision and proportions in the early Drosophila embryo. Nature, 415, 798–801.CrossRefGoogle Scholar
  56. 56.
    Jaeger, J., Surkova, S., Blagov, M., Janssens, H., Kosman, D., Kozlov, K., et al. (2004). Dynamic control of positional information in the early Drosophila embryo. Nature, 430(6997), 368.CrossRefGoogle Scholar
  57. 57.
    Blagovic, K., Kim, L., Voldman, J. (2011). Microfluidic perfusion for regulating diffusible signaling in stem cells. PloS One, 6(8), e22892.CrossRefGoogle Scholar
  58. 58.
    Androutsellis-Theotokis, A., Leker, R., Soldner, F., Hoeppner, D., Ravin, R., Poser, S., Rueger, M., Bae, S., Kittappa, R., McKay, R. (2006). Notch signalling regulates stem cell numbers in vitro and in vivo. Nature, 442(7104), 823.CrossRefGoogle Scholar
  59. 59.
    Skelley, A., Kirak, O., Suh, H., Jaenisch, R., Voldman, J. (2009). Microfluidic control of cell pairing and fusion. Nature Methods, 6(2), 147.CrossRefGoogle Scholar
  60. 60.
    Park, J., Cho, C., Parashurama, N., Li, Y., Berthiaume, F., Toner, M., Tilles, A., Yarmush, M. (2007). Microfabrication-based modulation of embryonic stem cell differentiation. Lab Chip, 7(8), 1018.CrossRefGoogle Scholar
  61. 61.
    Justice, B., Badr, N., Felder, R. (2009). 3D cell culture opens new dimensions in cell-based assays. Drug Discovery Today, 14(1–2), 102.CrossRefGoogle Scholar
  62. 62.
    Haycock, J. (2011). 3D cell culture: a review of current approaches and techniques. Methods in Molecular Biology, 695, 1.CrossRefGoogle Scholar
  63. 63.
    Huh, D., Hamilton, G., Ingber, D. (2011). Trends in Cell Biology, 21(12), 745–754.CrossRefGoogle Scholar
  64. 64.
    Leclerc, E., Sakai, Y., Fujii, T. (2003). Cell culture in 3-dimensional microfluidic structure of PDMS (polydimethylsiloxane). Biomedical Microdevices, 5(2), 109.CrossRefGoogle Scholar
  65. 65.
    Albrecht, D., Underhill, G., Wassermann, T., Sah, R., Bhatia, S. (2006). Probing the role of multicellular organization in three-dimensional microenvironments. Nature Methods, 3(5), 369.CrossRefGoogle Scholar
  66. 66.
    Toh, Y., Zhang, C., Zhang, J., Khong, Y., Chang, S., Samper, V., van Noort, D., Hutmacher, D., Yu, H. (2007). A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip, 7(3), 302.CrossRefGoogle Scholar
  67. 67.
    Paguirigan, A., & Beebe, D. (2006). Gelatin-based microfluidic devices for cell culture. Lab Chip, 6(3), 407.CrossRefGoogle Scholar
  68. 68.
    Kim, M., Yeon, J., Park, J. (2007). A microfluidic platform for 3-dimensional cell culture and cell-based assays. Biomedical Microdevices, 9(1), 25.CrossRefGoogle Scholar
  69. 69.
    Ong, S., Zhang, C., Toh, Y., Kim, S., Foo, H., Tan, C., van Noort, D., Park, S., Yu, H. (2008). A gel-free 3D microfluidic cell culture system. Biomaterials, 29(22), 3237.CrossRefGoogle Scholar
  70. 70.
    Reya, T., Morrison, S., Clarke, M., Weissman, I. (2001). Stem cells, cancer, and cancer stem cells. Nature, 414, 105.CrossRefGoogle Scholar
  71. 71.
    Singh, S., Clarke, I., Hide, T., Dirks, P. (2004). Cancer stem cells in nervous system tumors. Oncogene, 23(43), 7267.CrossRefGoogle Scholar
  72. 72.
    Wang, J., & Dick, J. (2005). Cancer stem cells: lessons from leukemia. Trends in Cell Biology, 15(9), 494.CrossRefGoogle Scholar
  73. 73.
    Soltysova, A., Altanerova, V., Altaner, C., et al. (2005). Cancer stem cells. Neoplasma, 52(6), 435.Google Scholar
  74. 74.
    Jordan, C., Guzman, M., Noble, M. (2006). Cancer stem cells. New England Journal of Medicine, 355(12), 1253.CrossRefGoogle Scholar
  75. 75.
    Lugo, T., Pendergast, A., Muller, A., Witte, O. (1990). Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science, 247(4946), 1079.CrossRefGoogle Scholar
  76. 76.
    Rowley, J. (1973). A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by Quinacrine Fluorescence and Giemsa Staining. Nature, 243, 290.CrossRefGoogle Scholar
  77. 77.
    Faley, S., Copland, M., Wlodkowic, D., Kolch, W., Seale, K., Wikswo, J., Cooper, J. (2009). Microfluidic single cell arrays to interrogate signalling dynamics of individual, patient-derived hematopoietic stem cells. Lab Chip, 9(18), 2659.CrossRefGoogle Scholar
  78. 78.
    Zhang, Q., Robin, K., Liao, D., Lambert, G., Austin, R. (2011). The goldilocks principle and antibiotic resistance in bacteria. Molecular Pharmaceutics, 8(6), 2063–2068.CrossRefGoogle Scholar
  79. 79.
    Zhang, Q., & Austin, R. (2012). Physics of cancer: the impact of heterogeneity. Annual Review of Condensed Matter Physics, 3, 363–382.CrossRefGoogle Scholar
  80. 80.
    Lambert, G., Estévez-Salmeron, L., Oh, S., Liao, D., Emerson, B., Tlsty, T., Austin, R. (2011). An analogy between the evolution of drug resistance in bacterial communities and malignant tissues. Nature Reviews Cancer, 11(5), 375.CrossRefGoogle Scholar
  81. 81.
    Perez, O., & Nolan, G. (2006). Phospho-proteomic immune analysis by flow cytometry: from mechanism to translational medicine at the single-cell level. Immunological Reviews, 210(1), 208.CrossRefGoogle Scholar
  82. 82.
    Bøyum, A. (1974). Separation of blood leucocytes, granulocytes and lymphocytes. Tissue Antigens, 4(3), 269.CrossRefGoogle Scholar
  83. 83.
    Wachtel, S., Sammons, D., Manley, M., Wachtel, G., Twitty, G., Utermohlen, J., Phillips, O., Shulman, L., Taron, D., Müller, U., et al. (1996). Fetal cells in maternal blood: recovery by charge flow separation. Human Genetics, 98(2), 162.CrossRefGoogle Scholar
  84. 84.
    Baumgarth, N., & Roederer, M. (2000). A practical approach to multicolor flow cytometry for immunophenotyping. Journal of Immunological Methods, 243(1), 77.CrossRefGoogle Scholar
  85. 85.
    Dittrich, P., & Schwille, P. (2003). An integrated microfluidic system for reaction, high-sensitivity detection, and sorting of fluorescent cells and particles. Analytical Chemistry, 75(21), 5767.CrossRefGoogle Scholar
  86. 86.
    Pamme, N. (2006). Magnetism and microfluidics. Lab Chip, 6(1), 24.CrossRefGoogle Scholar
  87. 87.
    Chen, C., Cho, S., Tsai, F., Erten, A., Lo, Y. (2009). Microfluidic cell sorter with integrated piezoelectric actuator. Biomedical Microdevices, 11(6), 1223.CrossRefGoogle Scholar
  88. 88.
    Cho, S., Chen, C., Tsai, F., Godin, J., Lo, Y. (2010). Human mammalian cell sorting using a highly integrated micro-fabricated fluorescence-activated cell sorter (\(\upmu\)FACS). Lab Chip, 10(12), 1567.CrossRefGoogle Scholar
  89. 89.
    Baret, J., Miller, O., Taly, V., Ryckelynck, M., El-Harrak, A., Frenz, L., Rick, C., Samuels, M., Hutchison, J., Agresti, J., et al. (2009). Fluorescence-activated droplet sorting (FADS): efficient microfluidic cell sorting based on enzymatic activity. Lab Chip, 9(13), 1850.CrossRefGoogle Scholar
  90. 90.
    Franke, T., Braunmüller, S., Schmid, L., Wixforth, A., Weitz, D. (2010). Surface acoustic wave actuated cell sorting (SAWACS). Lab Chip, 10(6), 789.CrossRefGoogle Scholar
  91. 91.
    Huang, L., Cox, E., Austin, R., Sturm, J. (2004). Continuous particle separation through deterministic lateral displacement. Science, 304(5673), 987.CrossRefGoogle Scholar
  92. 92.
    Takagi, J., Yamada, M., Yasuda, M., Seki, M. (2005). Continuous particle separation in a microchannel having asymmetrically arranged multiple branches. Lab Chip, 5(7), 778.CrossRefGoogle Scholar
  93. 93.
    Hsu, C., Di, D., Carlo, Chen, C., Irimia, D., Toner, M. (2008). Microvortex for focusing, guiding and sorting of particles. Lab Chip, 8(12), 2128.CrossRefGoogle Scholar
  94. 94.
    Choi, S., Song, S., Choi, C., Park, J. (2007). Continuous blood cell separation by hydrophoretic filtration. Lab Chip, 7(11), 1532.CrossRefGoogle Scholar
  95. 95.
    Toner, M., & Irimia, D. (2005). Blood-on-a-chip. Annual Review of Biomedical Engineering, 7, 77.CrossRefGoogle Scholar
  96. 96.
    Vahey, M., & Voldman, J. (2008). An equilibrium method for continuous-flow cell sorting using dielectrophoresis. Analytical Chemistry, 80(9), 3135.CrossRefGoogle Scholar
  97. 97.
    Cheng, I., Froude, V., Zhu, Y., Chang, H., Chang, H. (2009). A continuous high-throughput bioparticle sorter based on 3D traveling-wave dielectrophoresis. Lab Chip, 9(22), 3193.CrossRefGoogle Scholar
  98. 98.
    Huang, R., Barber, T., Schmidt, M., Tompkins, R., Toner, M., Bianchi, D., Kapur, R., Flejter, W. (2008). A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women. Prenatal Diagnosis, 28(10), 892.CrossRefGoogle Scholar
  99. 99.
    Lau, A., Lee, L., Chan, J. (2008). An integrated optofluidic platform for Raman-activated cell sorting. Lab Chip, 8(7), 1116.CrossRefGoogle Scholar
  100. 100.
    Pamme, N. (2007). Continuous flow separations in microfluidic devices. Lab Chip, 7(12), 1644.CrossRefGoogle Scholar
  101. 101.
    Tsutsui, H., & Ho, C. (2009). Cell separation by non-inertial force fields in microfluidic systems. Mechanics Research Communications, 36(1), 92.CrossRefGoogle Scholar
  102. 102.
    Lenshof, A., & Laurell, T. (2010). Continuous separation of cells and particles in microfluidic systems. Chemical Society Reviews, 39(3), 1203.CrossRefGoogle Scholar
  103. 103.
    Gossett, D., Weaver, W., Mach, A., Hur, S., Tse, H., Lee, W., Amini, H., Di Carlo, D. (2010). Label-free cell separation and sorting in microfluidic systems. Analytical and Bioanalytical Chemistry, 397(8), 3249.CrossRefGoogle Scholar
  104. 104.
    Bonnet, D., & Dick, J. (1997). Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nature Medicine, 3(7), 730.CrossRefGoogle Scholar
  105. 105.
    Lapidot, T., Sirard, C., Vormoor, J., Murdoch, B., Hoang, T., Caceres-Cortes, J., Minden, M., Paterson, B., Caligiuri, M., Dick, J. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 367(6464), 645.CrossRefGoogle Scholar
  106. 106.
    Al-Hajj, M., Wicha, M., Benito-Hernandez, A., Morrison, S., Clarke, M. (2003). Prospective identification of tumorigenic breast cancer cells. Proceedings of the National Academy of Sciences, 100(7), 3983.CrossRefGoogle Scholar
  107. 107.
    Singh, S., Hawkins, C., Clarke, I., Squire, J., Bayani, J., Hide, T., Henkelman, R., Cusimano, M., Dirks, P. (2004). Identification of human brain tumour initiating cells. Nature, 432(7015), 396.CrossRefGoogle Scholar
  108. 108.
    Li, C., Heidt, D., Dalerba, P., Burant, C., Zhang, L., Adsay, V., Wicha, M., Clarke, M., Simeone, D. (2007). Identification of pancreatic cancer stem cells. Cancer Research, 67(3), 1030.CrossRefGoogle Scholar
  109. 109.
    Balic, M., Lin, H., Young, L., Hawes, D., Giuliano, A., McNamara, G., Datar, R., Cote, R. (2006). Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clinical Cancer Research, 12(19), 5615.CrossRefGoogle Scholar
  110. 110.
    Aktas, B., Tewes, M., Fehm, T., Hauch, S., Kimmig, R., Kasimir-Bauer, S., et al. (2009). Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Research, 11(4), R46.CrossRefGoogle Scholar
  111. 111.
    Nagrath, S., Sequist, L., Maheswaran, S., Bell, D., Irimia, D., Ulkus, L., Smith, M., Kwak, E., Digumarthy, S., Muzikansky, A., et al. (2007). Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature, 450(7173), 1235.CrossRefGoogle Scholar
  112. 112.
    Meng, S., Tripathy, D., Frenkel, E., Shete, S., Naftalis, E., Huth, J., Beitsch, P., Leitch, M., Hoover, S., Euhus, D., et al. (2004). Circulating tumor cells in patients with breast cancer dormancy. Clinical Cancer Research, 10(24), 8152.CrossRefGoogle Scholar
  113. 113.
    Lo utherback, K., D’Silva, J., Liu, L., Wu, A., Austin, R., Sturm, J. (2012). Deterministic separation of cancer cells from blood at 10 mL/min. Available from Nature Precedings. doi: 10101/npre.2012.6861.1.

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of PhysicsPrinceton UniversityPrincetonUSA

Personalised recommendations