中文
Announcement
More
Progress in Chemistry 2014, Vol. 26 Issue (06): 1050-1064 DOI: 10.7536/PC131115 Previous Articles   Next Articles

• Review •

Microfluidics-Based Single-Cell Biophysical Characterization

Tang Wenlai, Xiang Nan, Huang Di, Zhang Xinjie, Gu Xingzhong, Ni Zhonghua*   

  1. Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing 211189, China
  • Received: Revised: Online: Published:
  • Supported by:

    The work was supported by the National Basic Research Program of China (No.2011CB707601), the National Natural Science Foundation of China (No.91023024, 51375089), the Specialized Research Fund for the Doctoral Program of Higher Education (No.20110092110003) and the Natural Science Foundation of Jiangsu Province (No.BK2011336)

PDF ( 2787 ) Cited
Export

EndNote

Ris

BibTeX

Single-cell biophysical characterization has been widely employed for demonstrating the physiological activity and status of individual cells, or revealing the heterogeneity among various populations. It also plays an important role in the studies on cellular differentiation and pathology, as well as early clinical diagnosis and treatment. Compared to conventional biochemical schemes, the feature of scale compatibility between cell and microchannel makes microfluidics more suitable for precise microenvironment control, high-throughput manipulation, and multi-parameter label-free detection of individual cells. Therefore, microfluidics has become an important platform for single-cell characterization and analysis. This review covers the recent advances in microfluidics for characterizing the single-cell biophysical properties, and then focuses on the discussion of specific advantages, such as single-cell resolution level and high-throughput feature, offered by microfluidics. Finally, the challenges and future directions concerning the application of this scheme in clinical practices are also discussed, and a novel single-cell microdevice for multi-parameter characterization is proposed.

Contents
1 Introduction
2 Density(Mass) characterization
3 Electrical characterization
3.1 Microfluidic Coulter counter
3.2 Microfluidic impedance cytometer
4 Mechanical characterization
4.1 Optical stretcher
4.2 Electroporation-induced deformation
4.3 Structure-induced deformation
4.4 Fluid-induced deformation
5 Multi-parameter biophysical characterization
6 Conclusion and outlook

CLC Number: 

[1] Lee G Y H, Lim C T. Trends Biotechnol., 2007, 25: 111.
[2] Suresh S. Acta Biomater., 2007, 3: 413.
[3] Valero A, Braschler T, Renaud P. Lab Chip, 2010, 10: 2216.
[4] Di Carlo D. J. Lab. Autom., 2012, 17: 32.
[5] Cross S E, Jin Y S, Rao J, Gimzewski J K. Nat. Nanotechnol., 2007, 2: 780.
[6] Kuznetsova T G, Starodubtseva M N, Yegorenkov N I, Chizhik S A, Zhdanov R I. Micron, 2007, 38: 824.
[7] Hochmuth R M. J. Biomech., 2000, 33: 15.
[8] Shojaei-Baghini E, Zheng Y, Jewett M A S, Geddie W B, Sun Y. Appl. Phys. Lett., 2013, 102: 123704.
[9] Dao M, Lim C T, Suresh S. J. Mech. Phys. Solids, 2003, 51: 2259.
[10] Bausch A R, Ziemann F, Boulbitch A A, Jacobson K, Sackmann E. Biophys. J., 1998, 75: 2038.
[11] Hamill O P, Marty A, Neher E, Sakmann B, Sigworth F J. Pfluegers Arch., 1981, 391: 85.
[12] 杨频(Yang P),杜会枝(Du H Z),薛绍武(Xue S W). 化学进展(Progress in Chemistry), 2002, 14(4):251.
[13] Whitesides G M. Nature, 2006, 442: 368.
[14] Yin H B, Marshall D. Curr. Opin. Biotechnol., 2012, 23: 110.
[15] Zare R N, Kim S. Annu. Rev. Biomed. Eng., 2010, 12: 187.
[16] 王立凯(Wang L K),冯喜增(Feng X Z). 化学进展(Progress in Chemistry), 2005, 17(3): 482.
[17] 郝丽(Hao L),徐春秀(Xu C X),程和勇(Cheng H Y),刘金华(Liu J H),殷学锋(Yin X F). 化学进展(Progress in Chemistry), 2012, 24(8): 1544.
[18] 高健(Gao J),殷学锋(Yin X F),方肇伦(Fang Z L). 化学进展(Progress in Chemistry), 2004, 16(6): 975.
[19] Sun T, Morgan H. Microfluid. Nanofluid., 2010, 8: 423.
[20] Zheng Y, Sun Y. Micro Nano Lett., 2011, 6: 327.
[21] Mao X, Huang T J. Lab Chip, 2012, 12: 4006.
[22] Sha J, Hasan T, Milana S, Bertulli C, Bell N A W, Privitera G, Ni Z, Chen Y, Bonaccorso F, Ferrari A C, Keyser U F, Huang Y Y S. ACS Nano, 2013, 7: 8857.
[23] Zhang Y, Liu L, Sha J J, Ni Z H, Yi H, Chen Y F. Nanoscale Res. Lett., 2013, 8: 245.
[24] Chen K, Xiang N, Quan Y L, Zhu X L, Sun D K, Yi H, Ni Z H. Microfluid. Nanofluid., 2014, 16: 237.
[25] Zhu X L, Yi H, Ni Z H. Biomicrofluidics, 2010, 4: 013202.
[26] 朱晓璐(Zhu X L),倪中华(Ni Z H). 东南大学学报(自然科学版)Journal of Southeast University(Natural Science Edition), 2007, 37(5): 861.
[27] 项楠(Xiang N),朱晓璐(Zhu X L),倪中华(Ni Z H). 化学进展(Progress in Chemistry), 2011, 23(9): 1945.
[28] Xiang N, Chen K, Sun D K, Wang S F, Yi H, Ni Z H. Microfluid. Nanofluid., 2013, 14: 89.
[29] Xiang N, Yi H, Chen K, Sun D K, Jiang D, Dai Q, Ni Z H. Biomicrofluidics, 2013, 7: 044116.
[30] Maric D, Maric I, Barker J L. Methods, 1998, 16: 247.
[31] Martin S J, Bradley J G, Cotter T G. Clin. Exp. Immunol., 1990, 79: 448.
[32] Wyllie A H, Morris R G. Am. J. Pathol., 1982, 109: 78.
[33] Rodgers G P, Schechter A N, Noguchi C T. J. Lab. Clin. Med., 1985, 106: 30.
[34] Bosslet K, Ruffmann R, Altevogt P, Schirrmacher V. Br. J. Cancer., 1981, 44: 356.
[35] Burg T P, Godin M, Knudsen S M, Shen W, Carlson G, Foster J S, Babcock K, Manalis S R. Nature, 2007, 446: 1066.
[36] Godin M, Delgado F F, Son S M, Grover W H, Bryan A K, Tzur A, Jorgensen P, Payer K, Grossman A D, Kirschner M W, Manalis S R. Nat. Methods, 2010, 7: 387.
[37] Son S, Tzur A, Weng Y, Jorgensen P, Kim J, Kirschner M W, Manalis S R. Nat. Methods, 2012, 9: 910.
[38] Godin M, Bryan A K, Burg T P, Babcock K, Manalis S R. Appl. Phys. Lett., 2007, 91: 123121.
[39] Bryan A K, Goranov A, Amon A, Manalis S R. Proc. Natl. Acad. Sci. U. S. A., 2010, 107: 999.
[40] Grover W H, Bryan A K, Diez-Silva M, Suresh S, Higgins J M, Manalis S R. Proc. Natl. Acad. Sci. U. S. A., 2011, 108: 10992.
[41] Weng Y C, Delgado F F, Son S, Burg T P, Wasserman S C, Manalis S R. Lab Chip, 2011, 11: 4174.
[42] Huang Y, Wang X B, Holzel R, Becker F F, Gascoyne P R C. Phys. Med. Biol., 1995, 40: 1789.
[43] Dalton C, Goater A D, Burt J P H, Smith H V. J. Appl. Microbiol., 2004, 96: 24.
[44] Jang L S, Wang M H. Biomed. Microdevices, 2007, 9: 737.
[45] Kurz C V, Buth H, Sossalla A, Vermeersch V, Toncheva V, Dubruel P, Schacht E, Thielecke H. Biosens. Bioelectron., 2011, 26: 3405.
[46] Larsen U D, Blankenstein G, Branebjerg J. 1997 International Conference on Solid-State Sensors and Actuators. Chicago: IEEE, 1997. 1319.
[47] Saleh O A, Sohn L L. Rev. Sci. Instrum., 2001, 72: 4449.
[48] Saleh O A, Sohn L L. Nano Lett., 2003, 3: 37.
[49] Satake D, Ebi H, Oku N, Matsuda K, Takao H, Ashiki M, Ishida M. Sens. Actuators B, 2002, 83: 77.
[50] Zheng S Y, Liu M, Tai Y C. Biomed. Microdevices, 2008, 10: 221.
[51] Chun H G, Chung T D, Kim H C. Anal. Chem., 2005, 77: 2490.
[52] Kim K B, Chun H, Kim H C, Chun T D. Electrophoresis, 2009, 30: 1464.
[53] Choi H, Kim K B, Jeon C S, Hwang I, Lee S, Kim H K, Kim H C, Chung T D. Lab Chip, 2013, 13: 970.
[54] Deblois R W, Bean C P. Rev. Sci. Instrum., 1970, 41: 909.
[55] Nieuwenhuis J H, Kohl F, Bastemeijer J, Sarro P M, Vellekoop M J. Sens. Actuators B, 2004, 102: 44.
[56] Riordon J, Mirzaei M, Godin M. Lab Chip, 2012, 12: 3016.
[57] Jagtiani A V, Sawant R, Zhe J. J. Micromech. Microeng., 2006, 16: 1530.
[58] Zhe J, Jagtiani A, Dutta P, Hu J, Carletta J. J. Micromech. Microeng., 2007, 17: 304.
[59] Asghar W, Wan Y, Ilyas A, Bachoo R, Kim Y T, Iqbal S M. Lab Chip, 2012, 12: 2345.
[60] Pethig R, Kell D B. Phys. Med. Biol., 1987, 32: 933.
[61] Gawad S, Schild L, Renaud P. Lab Chip, 2001, 1: 76.
[62] Ayliffe H E, Frazier A B, Rabbitt R D. J. Microelectromech. Syst., 1999, 8: 50.
[63] Cheung K, Gawad S, Renaud P. Cytometry, Part A, 2005, 65A: 124.
[64] Sun T, Green N G, Gawad S, Morgan H. IET Nanobiotechnol., 2007, 1: 69.
[65] Schade-Kampmann G, Huwiler A, Hebeisen M, Hessler T, Di Berardino M. Cell Proliferation, 2008, 41: 830.
[66] Holmes D, Pettigrew D, Reccius C H, Gwyer J D, van Berkel C, Holloway J, Davies D E, Morgan H. Lab Chip, 2009, 9: 2881.
[67] van Berkel C, Gwyer J D, Deane S, Green N, Holloway J, Hollis V, Morgan H. Lab Chip, 2011, 11: 1249.
[68] Spencer D, Morgan H. Lab Chip, 2011, 11: 1234.
[69] Morgan H, Holmes D, Green N G. Curr. Appl. Phys., 2006, 6: 367.
[70] Watkins N, Venkatesan B M, Toner M, Rodriguez W, Bashir R. Lab Chip, 2009, 9: 3177.
[71] Mernier G, Duqi E, Renaud P. Lab Chip, 2012, 12: 4344.
[72] Evander M, Ricco A J, Morser J, Kovacs G T A, Leung L L K, Giovangrandi L. Lab Chip, 2013, 13: 722.
[73] Gou H L, Zhang X B, Bao N, Xu J J, Xia X H, Chen H Y. J. Chromatogr., A, 2011, 1218: 5725.
[74] Kang G, Yoo S K, Kim H I, Lee J H. IEEE Sens. J., 2012, 12: 1084.
[75] Barat D, Spencer D, Benazzi G, Mowlem M C, Morgan H. Lab Chip, 2012, 12: 118.
[76] Song H, Wang Y, Rosano J M, Prabhakarpandian B, Garson C, Pant K, Lai E. Lab Chip, 2013, 13: 2300.
[77] Lamontagne C A, Cuerrier C M, Grandbois M. Pfluegers Arch., 2008, 456: 61.
[78] Fletcher D A, Mullins D. Nature, 2010, 463: 485.
[79] Li Q S, Lee G Y H, Ong C N, Lim C T. Biochem. Biophys. Res. Commun., 2008, 374: 609.
[80] Barabino G A, Platt M O, Kaul D K. Annu. Rev. Biomed. Eng., 2010, 12: 345.
[81] Baskurt O K, Gelmont D, Meiselman H J. Am. J. Respir. Crit. Care Med., 1998, 157: 421.
[82] Bow H, Pivkin I V, Diez-Silva M, Goldfless S J, Dao M, Niles J C, Suresh S, Han J Y. Lab Chip, 2011, 11: 1065.
[83] Brown C D, Ghali H S, Zhao Z H, Thomas L L, Friedman E A. Kidney Int., 2005, 67: 295.
[84] Keymel S, Heiss C, Kleinbongard P, Kelm M, Lauer T. Horm. MeTab. Res., 2011, 43: 760.
[85] Ballas S K, Smith E D. Blood, 1992, 79: 2154.
[86] Doh I, Lee W C, Cho Y H, Pisano A P, Kuypers F A. Appl. Phys. Lett., 2012, 100: 173702.
[87] Polacheck W J, Li R, Uzel S G M, Kamm R D. Lab Chip, 2013, 13: 2252.
[88] Lin L A G, Liu A Q, Yu Y F, Zhang C, Lim C S, Ng S H, Yap P H, Gao H J. Appl. Phys. Lett., 2008, 92: 233901.
[89] Liang X M, Han S J, Reems J A, Gao D Y, Sniadecki N J. Lab Chip, 2010, 10: 991.
[90] Schoen I, Hu W, Klotzsch E, Vogel V. Nano Lett., 2010, 10: 1823.
[91] Guck J, Ananthakrishnan R, Moon T J, Cunningham C C, Kas J. Phys. Rev. Lett., 2000, 84: 5451.
[92] Guck J, Ananthakrishnan R, Mahmood H, Moon T J, Cunningham C C, Kas J. Biophys. J., 2001, 81: 767.
[93] Lincoln B, Erickson H M, Schinkinger S, Wottawah F, Mitchell D, Ulvick S, Bilby C, Guck J. Cytometry, Part A, 2004, 59A: 203.
[94] Guck J, Schinkinger S, Lincoln B, Wottawah F, Ebert S, Romeyke M, Lenz D, Erickson H M, Ananthakrishnan R, Mitchell D, Kas J, Ulvick S, Bilby C. Biophys. J., 2005, 88: 3689.
[95] Lai C W, Hsiung S K, Chen Y Q, Chiou A, Lee G B. J. Microelectromech. Syst., 2008, 17: 548.
[96] Bellini N, Vishnubhatla K C, Bragheri F, Ferrara L, Minzioni P, Ramponi R, Cristiani I, Osellame R. Opt. Express, 2010, 18: 4679.
[97] Lautenschlager F, Paschke S, Schinkinger S, Bruel A, Beil M, Guck J. Proc. Natl. Acad. Sci. U. S. A., 2009, 106: 15696.
[98] Wang M Y, Orwar O, Olofsson J, Weber S G. Anal. Bioanal. Chem., 2010, 397: 3235.
[99] Geng T, Lu C. Lab Chip, 2013, 13: 3803.
[100] Bao N, Zhan Y H, Lu C. Anal. Chem., 2008, 80: 7714.
[101] Bao N, Le T T, Cheng J X, Lu C. Integr. Biol., 2010, 2: 113.
[102] Bao N, Kodippili G C, Giger K M, Fowler V M, Low P S, Lu C. Lab Chip, 2011, 11: 3053.
[103] Henslee B E, Morss A, Hu X, Lafyatis G P, Lee L J. Anal. Chem., 2011, 83: 3998.
[104] Tsukada K, Sekizuka E, Oshio C, Minamitani H. Microvasc. Res., 2001, 61: 231.
[105] Shelby J P, White J, Ganesan K, Rathod P K, Chiu D T. Proc. Natl. Acad. Sci. U. S. A., 2003, 100: 14618.
[106] Rosenbluth M J, Lam W A, Fletcher D A. Lab Chip, 2008, 8: 1062.
[107] Hou H W, Li Q S, Lee G Y H, Kumar A P, Ong C N, Lim C T. Biomed. Microdevices, 2009, 11: 557.
[108] Guo Q, Reiling S J, Rohrbach P, Ma H S. Lab Chip, 2012, 12: 1143.
[109] Guo Q, Park S, Ma H. Lab Chip, 2012, 12: 2687.
[110] Huang S, Undisz A, Diez-Silva M, Bow H, Dao M, Han J Y. Integr. Biol., 2013, 5: 414.
[111] Lee W G, Bang H, Yun H, Lee J, Park J, Kim J K, Chung S, Cho K, Chung C, Han D C, Chang J K. Lab Chip, 2007, 7: 516.
[112] Adamo A, Sharei A, Adamo L, Lee B, Mao S, Jensen K F. Anal. Chem., 2012, 84: 6438.
[113] Guan G F, Chen P C Y, Peng W K, Bhagat A A, Ong C J, Han J Y. J. Micromech. Microeng., 2012, 22: 105037.
[114] Preira P, Valignat M P, Bico J, Theodoly O. Biomicrofluidics, 2013, 7: 024111.
[115] Gossett D R, Tse H T K, Lee S A, Ying Y, Lindgren A G, Yang O O, Rao J Y, Clark A T, Di Carlo D. Proc. Natl. Acad. Sci. U. S. A., 2012, 109: 7630.
[116] Dudani J S, Gossett D R, Tse H T K, Di Carlo D. Lab Chip, 2013, 13: 3728.
[117] Bransky A, Korin N, Nemirovski Y, Dinnar U. Biosens. Bioelectron., 2006, 22: 165.
[118] Forsyth A M, Wan J D, Ristenpart W D, Stone H A. Microvasc. Res., 2010, 80: 37.
[119] Lee S S, Yim Y, Ahn K H, Lee S J. Biomed. Microdevices, 2009, 11: 1021.
[120] Tomaiuolo G, Barra M, Preziosi V, Cassinese A, Rotoli B, Guido S. Lab Chip, 2011, 11: 449.
[121] Cha S, Shin T, Lee S S, Shim W, Lee G, Lee S J, Kim Y, Kim J M. Anal. Chem., 2012, 84: 10471.
[122] Zheng Y, Nguyen J, Wang C, Sun Y. Lab Chip, 2013, 13: 3275.
[123] Pang L, Chen H M, Freeman L M, Fainman Y. Lab Chip, 2012, 12: 3543.
[124] Katsumoto Y, Tatsumi K, Doi T, Nakabe K. Int. J. Heat Fluid Flow, 2010, 31: 985.
[125] Byun S, Son S, Amodei D, Cermak N, Shaw J, Kang J H, Hecht V C, Winslow M M, Jacks T, Mallick P, Manalis S R. Proc. Natl. Acad. Sci. U. S. A., 2013, 110: 7580.
[126] Cho Y H, Yamamoto T, Sakai Y, Fujii T, Kim B. J. Microelectromech. Syst., 2006, 15: 287.
[127] Chen J A, Zheng Y, Tan Q Y, Zhang Y L, Li J, Geddie W R, Jewett M A S, Sun Y. Biomicrofluidics, 2011, 5: 14113.
[128] Zheng Y, Shojaei-Baghini E, Azad A, Wang C, Sun Y. Lab Chip, 2012, 12: 2560.
[129] Sha J J, Ni Z H, Liu L, Yi H, Chen Y F. Nanotechnology, 2011, 22: 175304.
[130] Xiang N, Yi H, Chen K, Wang S F, Ni Z H. J. Micromech. Microeng., 2013, 23: 025016.
[131] Li J P, Zhang Y, Yang J K, Bi K D, Ni Z H, Li D Y, Chen Y F. Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys., 2013, 87: 062707.
[132] Sun D K, Wang Y, Jiang D, Xiang N, Chen K, Ni Z H. Appl. Phys. Lett., 2013, 103: 071905.

[1] Wei Li, Tiangui Liang, Yuanchuang Lin, Weixiong Wu, Song Li. Machine Learning Accelerated High-Throughput Computational Screening of Metal-Organic Frameworks [J]. Progress in Chemistry, 2022, 34(12): 2619-2637.
[2] Dandan Zhang, Qi Wu, Guangbo Qu, Jianbo Shi, Guibin Jiang. Quantitative Analysis of Metal Nanoparticles in Unicellular Aquatic Organisms [J]. Progress in Chemistry, 2022, 34(11): 2331-2339.
[3] Xiaohan Hou, Shengnan Liu, Qingzhi Gao. Application of Small-Molecule Fluorescent Probes in the Development of Green Pesticides [J]. Progress in Chemistry, 2021, 33(6): 1035-1043.
[4] Yifeng Chen, Cong Wang, Kefeng Ren, Jian Ji. Droplet Microarrays in Biomedical High-Throughput Research [J]. Progress in Chemistry, 2021, 33(4): 543-554.
[5] Di Feng, Guanghua Wang, Wenlai Tang, Jiquan Yang. Application of Microfluidic Impedance Cytometer in Single-Cell Detection [J]. Progress in Chemistry, 2021, 33(4): 555-567.
[6] Lesi Cai, Meng-Chan Xia, Zhanping Li, Sichun Zhang, Xinrong Zhang. Bioimaging By Secondary Ion Mass Spectrometry [J]. Progress in Chemistry, 2021, 33(1): 97-110.
[7] Chen Ni, Di Jiang, Youlin Xu, Wenlai Tang. Application of Viscoelastic Fluid in Passive Particle Manipulation Technologies [J]. Progress in Chemistry, 2020, 32(5): 519-535.
[8] Huitiao Li, Jianzhang Pan, Qun Fang. Development and Application of Digital PCR Technology [J]. Progress in Chemistry, 2020, 32(5): 581-593.
[9] Ping Liu, Jing Wang, Hongye Hao, Yunfan Xue, Junjie Huang, Jian Ji. Photochemical Surface Modification of Biomedical Materials [J]. Progress in Chemistry, 2019, 31(10): 1425-1439.
[10] Tianxi He, Qionglin Liang, Jiu Wang, Guoan Luo. Microfluidic Fabrication of Liposomes as Drug Carriers [J]. Progress in Chemistry, 2018, 30(11): 1734-1748.
[11] Deng Wangping, Wang Lihua, Song Shiping, Zuo Xiaolei. Biosensors in POCT Application [J]. Progress in Chemistry, 2016, 28(9): 1341-1350.
[12] Hao Li, Xu Chunxiu, Cheng Heyong, Liu Jinhua, Yin Xuefeng. Recent Advances in the Determination of Intracellular Contents in Individual Cells Using Microfluidic Devices [J]. Progress in Chemistry, 2012, 24(08): 1544-1553.
[13] . Recent Advances in Single-Cell Analysis Using Capillary Electrophoresis [J]. Progress in Chemistry, 2010, 22(11): 2215-2223.
[14] Shen Gangyi,Chen Yi,Zhang Yiming,Cui Jian. Surface Plasmon Resonance Imaging [J]. Progress in Chemistry, 2010, 22(08): 1648-1655.
[15] . Microfluidic Chip-Based Immunoassay [J]. Progress in Chemistry, 2009, 21(04): 687-695.