Skip to main content
SpringerLink
Log in

Single-cell Analysis with Microfluidic Devices

  • Reviews
  • Published:
Analytical Sciences Aims and scope Submit manuscript

Abstract

A microfluidic device as a pivotal research tool in chemistry and life science is now widely recognized. Indeed, microfluidic techniques have made significant advancements in fundamental research, such as the inherent heterogeneity of single-cells studies in cell populations, which would be helpful in understanding cellular molecular mechanisms and clinical diagnosis of major diseases. Single-cell analyses on microdevices have shown great potential for precise fluid control, cell manipulation, and signal output with rapid and high throughput. Moreover, miniaturized devices also have open functions such as integrating with traditional detection methods, for example, optical, electrochemical or mass spectrometry for single-cell analysis. In this review, we summarized recent advances of single-cell analysis based on various microfluidic approaches from different dimensions, such as in vitro, ex vivo, and in vivo analysis of single cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. L. M. Zahn, Science, 2017, 358, 57.

    Article  Google Scholar 

  2. Y. Guo, Z. Li, W. Su, L. Wang, Y. Zhu, and J. Qin, Artif. Organs., 2018, 42, 1196.

    Article  CAS  PubMed  Google Scholar 

  3. D. Cohen, J. A. Dickerson, C. D. Whitmore, E. H. Turner, M. M. Palcic, O. Hindsgaul, and N. J. Dovichi, Annu. Rev. Anal. Chem., 2008, 1, 165.

    Article  CAS  Google Scholar 

  4. X. Zhang, Q. Qiu, H. Jiang, F. Zhang, Y. Liu, C. Amatore, and W. Huang, Angew. Chem., Int. Ed., 2017, 129, 13177.

    Article  Google Scholar 

  5. Y. Song, T. Tian, Y. Shi, W. Liu, Y. Zou, T. Khajvand, S. Wang, Z. Zhu, and C. Yang, Chem. Sci., 2017, 8, 1736.

    Article  CAS  PubMed  Google Scholar 

  6. Y. Wang, H. Wang, P. Deng, W. Chen, Y. Guo, T. Tao, and J. Qin, Lab Chip, 2018, 18, 3606.

    Article  CAS  PubMed  Google Scholar 

  7. C. L. Brown, V. Fleischauer, and J. Heo, Anal. Sci., 2017, 33, 525.

    Article  CAS  PubMed  Google Scholar 

  8. J. Nakanishi, T. Takarada, K. Yamaguchi, and M. Makea, Anal. Sci., 2008, 24, 67.

    Article  CAS  PubMed  Google Scholar 

  9. Y. Pei, X. Wang, W. Huang, P. Liu, and L. Zhang, Cellulose, 2013, 20, 1897.

    Article  CAS  Google Scholar 

  10. F. Fan, H. Shen, G. Zhang, X. Jiang, and X. Kang, Clin. Chim. Acta, 2014, 431, 113.

    Article  CAS  PubMed  Google Scholar 

  11. N. Ye, M. Wang, J. Qin, and B. Lin, Biomed. Microdevices, 2010, 12, 513.

    Article  CAS  PubMed  Google Scholar 

  12. L. T. H. Kao, L. Shankar, T. G. Kang, G. Zhang, G. K. I. Tay, S. R. M. Rafei, and C. W. H. Lee, Biosens. Bioelectron., 2011, 26, 2006.

    Article  CAS  PubMed  Google Scholar 

  13. A. Hibara, M. Fukuyama, M. Chung, C. Priest, and M. A. Proskurnin, Anal. Sci., 2016, 32, 11.

    Article  CAS  PubMed  Google Scholar 

  14. S. Lo and D. Yao, Int. J. Mol. Sci., 2015, 16, 16763.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. X. Feng, B. F. Liu, J. Li, and X. Liu, Mass. Spectrom. Rev., 2015, 34, 535.

    Article  CAS  PubMed  Google Scholar 

  16. Z. Wang, M. Gerstein, and M. Snyder, Nat. Rev. Genet., 2009, 10, 57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. L. He, A. Kniss, A. San-Miguel, T. Rouse, M. L. Kemp, and H. Lu, Lab Chip, 2015, 15, 1497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. T. H. Ong, D. J. Kissick, E. T. Jansson, T. J. Comi, E. V. Romanova, S. S. Rubakhin, and J. V. Sweedler, Anal. Chem., 2015, 87, 7036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Y. Sakuta, I. Takehara, K. Tsunoda, and K. Sato, Anal. Sci., 2018, 34, 1073.

    Article  CAS  PubMed  Google Scholar 

  20. M. K. Alam, E. Koomson, H. Zou, C. Yi, C. Li, T. Xu, and M. Yang, Anal. Chim. Acta, 2018, 1044, 29.

    Article  CAS  PubMed  Google Scholar 

  21. H. Zhang, X. Cui, J. Bi, S. Dai, and H. Ye, Eng. Life Sci., 2015, 15, 582.

    Article  CAS  Google Scholar 

  22. A. Giulietti, L. Overbergh, D. Valckx, B. Decallonne, R. Bouillon, and C. Mathieu, Methods, 2001, 25, 386.

    Article  CAS  PubMed  Google Scholar 

  23. T. Kalisky, S. Oriel, T. H. B. Lev, N. B. Haim, A. Trink, Y. Wineberg, I. Kanter, S. Gilad, and S. Pyne, Brief. Funct. Genomics, 2018, 17, 64.

    Article  CAS  PubMed  Google Scholar 

  24. M. Hosokawa, Y. Nishikawa, M. Kogawa, and H. Takeyama, Sci. Rep—UK, 2017, 7, 5199.

    Article  Google Scholar 

  25. M. M. Kiss, L. O. Donnelly, N. R. Beer, J. Warner, C. G. Bailey, B. W. Colston, J. M. Rothberg, D. R. Link, and J. H. Leamon, Anal. Chem., 2008, 80, 8975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. K. A. Heyries, C. Tropini, M. VanInsberghe, C. Doolin, O. I. Petriv, A. Singhal, K. Leung, C. B. Hughesman, and C. L. Hansen, Nat. Methods, 2011, 8, 649.

    Article  CAS  PubMed  Google Scholar 

  27. S. Karra and W. Gorski, Anal. Chem., 2013, 85, 10573.

    Article  CAS  PubMed  Google Scholar 

  28. T. X. Hu, X. H. Zhang, L. Zhang, W. Wen, and S. F. Wang, Biosens. Bioelectron., 2016, 77, 451.

    Article  CAS  PubMed  Google Scholar 

  29. N. Tsuyama, H. Mizuno, and T. Masujima, Anal. Sci., 2011, 27, 163.

    Article  CAS  PubMed  Google Scholar 

  30. K. Sato, Anal. Sci., 2015, 31, 867.

    Article  CAS  PubMed  Google Scholar 

  31. Z. Wang, M. Gerstein, and M. Snyder, Nat. Rev. Genet., 2009, 10, 57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. F. Tang, C. Barbacioru, Y. Wang, E. Nordman, C. Lee, N. Xu, X. Wang, J. Bodeau, B. B. Tuch, A. Siddiqui, K. Lao, and M. A. Surani, Nat. Methods, 2009, 6, 377.

    Article  CAS  PubMed  Google Scholar 

  33. F. Tang, C. Barbacioru, E. Nordman, B. Li, N. Xu, V. I. Bashkirov, K. Lao, and M. A. Surani, Nat. Protoc., 2010, 5, 516.

    Article  CAS  PubMed  Google Scholar 

  34. A. M. Streets, X. Zhang, C. Cao, Y. Pang, X. Wu, L. Xiong, L. Yang, Y. Fu, L. Zhao, F. Tang, and Y. Huang, Proc. Natl. Acad. Sci. U. S. A., 2014, 111, 7048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. L. Huang, F. Ma, A. Chapman, S. Lu, and X. S. Xie, Annu. Rev. Genomics Hum. Genet., 2015, 16, 79.

    Article  CAS  PubMed  Google Scholar 

  36. H. C. Fan, G. Fu, and S. P. Fodor, Science, 2015, 347, 1258367.

    Article  PubMed  Google Scholar 

  37. S. M. Prakadan, A. K. Shalek, ans D. A. Weitz, Nat. Rev. Genet., 2017, 18, 345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. A. M. Klein, L. Mazutis, I. Akartuna, N. Tallapragada, A. Veres, V. Li, L. Peshkin, D. A. Weitz, and M. W. Kirschner, Cell, 2015, 161, 1187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. M. Wu and A. K. Singh, Curr. Opin. Biotech., 2012, 23, 83.

    Article  CAS  PubMed  Google Scholar 

  40. S. Hu, D. A. Michels, M. A. Fazal, C. Ratisoontorn, M. L. Cunningham, and N. J. Dovichi, Anal. Chem., 2004, 76, 4044.

    Article  CAS  PubMed  Google Scholar 

  41. J. M. Irish, R. Hovland, P. O. Krutzik, O. D. Perez, O. Bruserud, B. T. Gjertsen, and G. P. Nolan, Cell, 2004, 118, 217.

    Article  CAS  PubMed  Google Scholar 

  42. N. J. Dovichi and S. Hu, Curr. Opin. Chem. Biol., 2003, 7, 603.

    Article  CAS  PubMed  Google Scholar 

  43. J. R. Newman, S. Ghaemmaghami, J. Ihmels, D. K. Breslow, M. Noble, J. L. DeRisi, and J. S. Weissman, Nature, 2006, 441, 840.

    Article  CAS  PubMed  Google Scholar 

  44. B. Huang, H. Wu, D. Bhaya, A. Grossman, S. Granier, B. K. Kobilka, and R. N. Zare, Science, 2007, 315, 87.

    Article  Google Scholar 

  45. A. J. Hughes, D. P. Spelke, Z. Xu, C. C. Kang, D. V. Schaffer, and A. E. Herr, Nat. Methods, 2014, 11, 749.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. F. Xu, H. Zhao, X. Feng, L. Chen, D. Chen, Y. Zhang, F. Nan, J. Liu, and B. Liu, Angew. Chem. Int. Ed., 2014, 53, 6730.

    Article  CAS  Google Scholar 

  47. D. Chen, F. Fan, X. Zhao, F. Xu, P. Chen, J. Wang, L. Ban, Z. Liu, X. Feng, Y. Zhang, and B. Liu, Anal. Chem., 2016, 88, 2466.

    Article  CAS  PubMed  Google Scholar 

  48. Z. Li, M. Huang, X. Wang, Y. Zhu, J. Li, C. C. L. Wong, and Q. Fang, Anal. Chem., 2018, 90, 5430.

    Article  CAS  PubMed  Google Scholar 

  49. Q. Han, E. M. Bradshaw, B. Nilsson, D. A. Hafler, and J. C. Love, Lab Chip., 2010, 10, 1391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. J. Choi, K. R. Love, Y. Gong, T. M. Gierahn, and J. C. Love, Anal. Chem., 2011, 83, 6890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Q. Han, N. Bagheri, E. M. Bradshaw, D. A. Hafler, D. A. Lauffenburger, and J. C. Love, Proc. Natl. Acad. Sci. U. S. A., 2012, 109, 1607.

    Article  CAS  PubMed  Google Scholar 

  52. Q. Han, E. M. Bradshaw, B. Nilsson, D. A. Hafler, and J. C. Love, Lab Chip., 2010, 10, 1391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. G. B. Salieb-Beugelaar, G. Simone, A. Arora, A. Philippi, and A. Manz, Anal. Chem., 2010, 82, 4848.

    Article  CAS  PubMed  Google Scholar 

  54. J. P. Urbanski, M. T. Johnson, D. D. Craig, D. L. Potter, D. K. Gardner, and T. Thorsen, Anal. Chem., 2008, 80, 6500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Y. S. Heo, L. M. Cabrera, C. L. Bormann, G. D. Smith, and S. Takayama, Lab Chip, 2012, 12, 2240.

    Article  CAS  PubMed  Google Scholar 

  56. M. Jie, H. Lin, Z. He, H. Liu, H. Li, and J. Lin, Sci. China Chem., 2018, 61, 236.

    Article  CAS  Google Scholar 

  57. Q. Huang, S. Mao, M. Khan, and J. Lin, Analyst, 2019, 144, 808.

    Article  CAS  PubMed  Google Scholar 

  58. M. Khan, S. Mao, W. Li, and J. Lin, Chem.—Eur J., 2018, 24, 15398.

    Article  CAS  PubMed  Google Scholar 

  59. F. Chen, L. Lin, J. Zhang, Z. He, K. Uchiyama, and J. Lin, Anal. Chem., 2016, 88, 4354.

    Article  CAS  PubMed  Google Scholar 

  60. Q. Wu, D. Gao, J. Wei, F. Jin, W. Xie, Y. Jiang, and H. Liu, Chem. Commun., 2014, 50, 2762.

    Article  CAS  Google Scholar 

  61. C. R. Pestana, A. C. Urbaczek, J. V. Alberici, G. J. Rodrigues, and E. Carrilho, Life. Sci., 2017, 172, 42.

    Article  CAS  PubMed  Google Scholar 

  62. P. Chen, S. Yan, J. Wang, Y. Guo, Y. Dong, X. Feng, X. Zeng, Y. Li, W. Du, and B. Liu, Anal. Chem., 2019, 91, 1619.

    Article  CAS  PubMed  Google Scholar 

  63. Y. Li, D. Chen, Y. Zhang, C. Liu, P. Chen, Y. Wang, X. Feng, W. Du, and B. Liu, Sens. Actuators, B, 2016, 225, 563.

    Article  CAS  Google Scholar 

  64. P. Chen, Y. Guo, X. Feng, S. Yan, J. Wang, Y. Li, W. Du, and B. Liu, Anal. Chem., 2017, 89, 9209.

    Article  CAS  PubMed  Google Scholar 

  65. P. Chen, X. Feng, S. Yan, Y. Guo, J. Wang, Y. Li, D. Chen,W. Du, and B. Liu, Sens. Actuators, B, 2018, 263, 281.

    Article  CAS  Google Scholar 

  66. L. Li, Q. Wang, J. Feng, L. Tong, and B. Tang, Anal. Chem., 2014, 86, 5101.

    Article  CAS  PubMed  Google Scholar 

  67. S. Casabella, P. Scully, N. Goddard, and P. Gardner, Analyst, 2016, 141, 689.

    Article  CAS  PubMed  Google Scholar 

  68. B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, ACS Nano, 2015, 9, 11849.

    Article  CAS  PubMed  Google Scholar 

  69. B. Agnarsson, H. K. Wayment-Steele, F. Höök, and A. Kunze, Nanoscale, 2016, 8, 19219.

    Article  CAS  PubMed  Google Scholar 

  70. I. StojanoviC, T. J. G. vander Velden, H. W. Mulder, R. B. M. Schasfoort, and L. W. M. M. Terstappen, Anal. Biochem., 2015, 485, 112.

    Article  CAS  PubMed  Google Scholar 

  71. S. Yan, X. Zhang, X. Dai, X. Feng, W. Du, and B. Liu, Sens. Actuators, B, 2016, 8, 33457.

    CAS  Google Scholar 

  72. S. Yan, P. Chen, X. Zeng, X. Zhang, Y. Li, Y. Xia, J. Wang, X. Dai, X. Feng, W. Du, and B. Liu, Anal. Chem., 2017, 89, 12039.

    Article  CAS  PubMed  Google Scholar 

  73. T. S. Safaei, R. M. Mohamadi, E. H. Sargent, and S. O. Kelley, ACS Appi. Mater Inter., 2015, 7, 14165.

    Article  CAS  Google Scholar 

  74. Y. Liu, M. Li, F. Zhang, A. Zhu, and G. Shi, Anal. Chem., 2015, 87, 5531.

    Article  CAS  PubMed  Google Scholar 

  75. X. L. Guo, R. Zhu, and X. L. Zong, Analyst, 2015, 140, 6571.

    Article  CAS  PubMed  Google Scholar 

  76. L. Lin, K. Mawatari, K. Morikawa, and T. Kitamori, Anal. Sci., 2016, 32, 75.

    Article  CAS  PubMed  Google Scholar 

  77. X. Zhao, F. Xu, L. Tang, W. Du, X. Feng, and B. Liu, Biosens. Bioelectron., 2013, 50, 28.

    Article  PubMed  Google Scholar 

  78. L. Hu, A. Ge, X. Wang, S. Wang, X. Yue, J. Wang, X. Feng, W. Du, and B. Liu, Biosens. Bioelectron., 2018, 110, 233.

    Article  CAS  PubMed  Google Scholar 

  79. L. Hu, J. Ye, H. Tan, A. Ge, L. Tang, X. Feng, W. Du, and B. Liu, Anal. Chim. Acta, 2015, 887, 155.

    Article  CAS  PubMed  Google Scholar 

  80. X. Wang, L. Tang, Y. Xia, L. Hu, X. Feng, W. Du, and B. Liu, Integr Biol., 2013, 5, 728.

    Article  CAS  Google Scholar 

  81. S. S. Bosari, J. Huayta, and A. S. Miguel, Lab Chip, 2018, 18, 3090.

    Article  PubMed Central  Google Scholar 

  82. Z. Zhu, W. Chen, B. Tian, Y. Luo, J. Lan, D. Wu, D. Chen, Z. Wang, and D. Pan, Sens. Actuators, B, 2018, 275, 470.

    Article  CAS  Google Scholar 

  83. A. R. Peimani, G. Zoidl, and P. Rezai, Biomicrofluidics, 2018, 12, 14113.

    Article  Google Scholar 

  84. T. J. Levario, C. Zhao, T. Rouse, S. Y. Shvartsman, and H. Lu, Sci. Rep—UK, 2016, 6, 21366.

    Article  CAS  Google Scholar 

  85. R. Ghaemi, P. Arefi, A. Stosic, M. Acker, Q. Raza, J. J. Roger, and P. R. Selvaganapathy, Lab Chip, 2017, 17, 3898.

    Article  CAS  PubMed  Google Scholar 

  86. R. Ghaemi, P. Rezai, F. R. Nejad, and P. R. Selvaganapathy, Biomicrofluidics, 2017, 11, 34113.

    Article  Google Scholar 

Download references

Acknowledgments

This work is supported by the National Natural Science Foundation of China (31870856, 31870854, 21775049 and 31700746), the National Key R&D Program of China (2016YFF0100801 and 2017YFA0700403) and China Postdoctoral Science Foundation funded project (2018T110753 and 2018M630847).

Author information

Authors and Affiliations

  1. The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics' Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Xiaowen Ou, Peng Chen & Bi-Feng Liu

Authors
  1. Xiaowen Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bi-Feng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bi-Feng Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ou, X., Chen, P. & Liu, BF. Single-cell Analysis with Microfluidic Devices. ANAL. SCI. 35, 609–618 (2019). https://doi.org/10.2116/analsci.19R001

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2116/analsci.19R001

Keywords

Search

Navigation