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• 综述与评论 •

微流控芯片测定单细胞内化学组分的进展

郝丽1, 徐春秀2, 程和勇2, 刘金华1, 殷学锋*1,2   

  1. 1. 杭州师范大学材料与化学化工学院 杭州 310036;
    2. 浙江大学化学系微分析系统研究所 杭州 310027
  • 收稿日期:2011-10-01 修回日期:2011-12-01 出版日期:2012-08-24 发布日期:2012-08-06
  • 通讯作者: 殷学锋 E-mail:yinxf@zju.edu.cn
  • 基金资助:

    国家自然科学基金项目(No.21075110,20890020)和杭州钱江特聘学者基金项目(No.HZ 2010-41)资助

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导出 被引次数 ( 6 | 5 )

Recent Advances in the Determination of Intracellular Contents in Individual Cells Using Microfluidic Devices

Hao Li1, Xu Chunxiu2, Cheng Heyong2, Liu Jinhua1, Yin Xuefeng1,2   

  1. 1. College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036, China;
    2. Institute of Microanalytical Systems, Department of Chemistry, Zhejiang University, Hangzhou 310027, China
  • Received:2011-10-01 Revised:2011-12-01 Online:2012-08-24 Published:2012-08-06
细胞是生命的基本单元。由于细胞的个体差异,传统分析群体细胞的方法难以得到单细胞的重要信息。准确可靠地测定单细胞内化学组分的含量能大大提高从正常细胞中辨别不正常细胞的能力,为进一步研究和发展生物化学、医学和临床检验等领域奠定基础。近年来,用微流控芯片进行单细胞分析已引起广泛的兴趣。微流控芯片可以集成单细胞进样、溶膜、电泳分离胞内化学组分和高灵敏度测定等一系列操作步骤,为分析单细胞内的化学组分提供了新的技术平台。本文主要综述了近年来微流控芯片测定单细胞内化学组分的进展。重点在于利用电渗流、压力结合电渗流和激光镊子等技术操控单细胞在微流控芯片上完成单细胞进样、溶膜、细胞内化学组分的电泳分离和高灵敏度测定等一系列操作步骤。对在微流控芯片上的衍生技术也做了较为详细的阐述。
关键词： 单细胞分析, 微流控芯片, 芯片上操控单细胞, 细胞内化学组分的测定
Cells are the fundamental unit of life. Owing to cellular heterogeneity, traditional biochemical assays which analyze cells in bulk often overlook the rich information available when single cells are studied. Accurate and reliable determination of the chemical composition in individual cells would greatly improve the probability of discriminating infected cells from healthy ones and provide a solid foundation on study and development in various fields including biochemistry, medicine, and pathology clinic. Microfluidic chip system for single-cell analysis is now attracting broad interests. The ability of integrating the whole process on one microfluidic chip, including single cell injection, lysis, separation and detection of cellular constituents by chip-based CE, offers a new technical platform for single cell analysis. This article provides a review on recent advances in determining intracellular contents in individual cells using microfluidic devices. Focus areas include on-chip single cell manipulation by means of electroosmotic flow (EOF), pressure-driven flow combined with EOF and optical tweezer (OT) to perform sequentially single cell injection, lysis, separation and detection of cellular constituents by chip-based CE with highly sensitive detection. The approaches on on-chip derivatization are also addressed. Contents 1 Introduction
2 On-chip single cell manipulation by means of electroosmotic flow (EOF)
3 On-chip single cell manipulation by means of pressure-driven flow combined with EOF
4 On-chip single cell manipulation by optical tweezer
5 On-chip cells derivatization
6 Conclusions and outlook
Key words: single-cell analysis, microfluidic chip, on-chip single cell manipulation, determination of intracellular contents

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[1] Zare R N, Kim S. Annu. Rev. Biomed. Eng., 2010, 12: 187-201
[2] Sims C E, Allbritton N L. Lab Chip, 2007, 7: 423-440
[3] Cohen D, Dickerson J A, Whitmore C D, Turner E H, Palcic M M, Hindsgaul O, Dovichi N J. Annu. Rev. Anal. Chem., 2008, 1: 165-190
[4] Borland L M, Kottegoda S, Phillips K S, Allbritton N L. Annu. Rev. Anal. Chem., 2008, 1: 191-227
[5] Huang W H, Ai F, Wang Z L, Cheng J K. J. Chromatogr. B, 2008, 866: 104-122
[6] 邓彬(Deng B), 徐见容(Xu J R), 汪志明(Wang Z M), 肖玉秀(Xiao Y X). 化学进展(Progress in Chemistry), 2010, 22: 2215-2223
[7] 程介克(Cheng J K). 单细胞分析(Single-Cell Analysis). 北京: 科学出版社(Beijing: Science Press), 2005
[8] Lin Y Q, Trouillon R, Safina G, Ewing A G. Anal. Chem., 2011, 83: 4369-4392
[9] El-Ali J, Sorger P K, Jensen K F. Nature, 2006, 442: 403-411
[10] Yi C Q, Li C W, Ji S L, Yang M S. Anal. Chim. Acta, 2006, 560: 1-23
[11] Yi C Q, Zhang Q, Li C W, Yang J, Zhao J L, Yang M S. Anal. Bioanal. Chem., 2006, 384: 1259-1268
[12] Li P C H, Harrison D J. Anal. Chem., 1997, 69: 1564-1568
[13] Xia F Q, Jin W R, Yin X F, Fang Z L. J. Chromatogr. A, 2005, 1063: 227-233
[14] Shi B X, Huang W H, Cheng J K. Electrophoresis, 2007, 28: 1595-1600
[15] Cheng H, Huang W H, Chen R S, Wang Z L, Cheng J K. Electrophoresis, 2007, 28: 1579-1586
[16] Mellors J S, Jorabchi K, Smith L M, Ramsey J M. Anal. Chem., 2010, 82: 967-973
[17] Chen Z Z, Li Q L, Wang X, Wang Z Y, Zhang R R, Yin M, Yin L L, Xu K H, Tang B. Anal. Chem., 2010, 82: 2006-2012.
[18] McClain M A, Culbertson C T, Jacobson S C, Allbritton N L, Sims C E, Ramsey J M. Anal. Chem., 2003, 75: 5646-5655
[19] Phillips K S, Lai H H, Johnson E, Sims C E, Allbritton N L. Lab Chip, 2011, 11: 1333-1341
[20] Klepárník K, Horky M. Electrophoresis, 2003, 24: 3778-3783
[21] Gao J, Yin X F, Fang Z L. Lab Chip, 2004, 4: 47-52
[22] Ling Y Y, Yin X F, Fang Z L. Electrophoresis, 2005, 26: 4759-4766
[23] Sun Y, Yin X F. J. Chromatogr. A, 2006, 1117: 228-233
[24] Zhu L L, Lu M, Yin X F. Talanta, 2008, 75: 1227-1233
[25] Yu L F, Huang H Q, Dong X L, Wu D P, Qin J H, Lin B C. Electrophoresis, 2008, 29: 5055-5060
[26] Xu C X, Yin X F. J. Chromatogr. A, 2011, 1218: 726-732
[27] Xu C X, Wang M, Yin X F. Analyst, 2011, 136: 3877-3883
[28] Wang H Y, Lu C. Chem. Commun., 2006, 3528-3530
[29] Munce N R, Li J Z, Herman P R, Lilge L. Anal. Chem., 2004, 76: 4983-4989
[30] Hellmich W, Pelargus C, Leffhalm K, Ros A, Anselmetti D. Electrophoresis, 2005, 26: 3689-3696
[31] Ros A, Hellmich W, Regtmeier J, Duong T T, Anselmetti D. Electrophoresis, 2006, 27: 2651-2658
[32] Hellmich W, Greif D, Pelargus C, Anselmetti D, Ros A. J. Chromatogr. A, 2006, 1130: 195-200
[33] Greif D, Galla L, Ros A, Anselmetti D. J. Chromatogr. A, 2008, 1206: 83-88
[34] Hogan B L, Yeung E S. Anal. Chem., 1992, 64: 284l-2845
[35] Wu H K, Wheeler A, Zare R N. Proc. Natl. Acad. Sci. USA, 2004, 101: 12809-12813
[36] Huang B, Wu H K, Bhaya D, Grossman A, Granier S, Kobilka B K, Zare R N. Science, 2007, 315: 81-84
[37] Zhao S L, Li X T, Liu Y M. Anal. Chem., 2009, 81: 3873-3878
[38] Zhao S L, Huang Y, Shi M, Liu R J, Liu Y M. Anal. Chem., 2010, 82: 2036-2041
[39] Zhao S L, Huang Y, Liu Y M. J. Chromatogr. A, 2009, 1216: 6746-6751
[40] Ye F G, Huang Y, Xu Q, Shi M, Zhao S L. Electrophoresis, 2010, 31: 1630-1636
[41] Zhao S L, Huang Y, Ye F G, Shi M, Liu Y M. J. Chromatogr. A, 2010, 1217: 5732-5736
[42] Dishinger J F, Reid K R, Kennedy R T. Anal. Chem., 2009, 81: 3119-3127
[43] Reid K R, Kennedy R T. Anal. Chem., 2009, 81: 6837-6842
[44] Godwin L A, Pilkerton M E, Deal K S, Wanders D, Judd R L, Easley C J. Anal. Chem., 2011, 83: 7166-7172
[45] Ottesen E A, Hong J W, Quake S R, Leadbetter J R. Science, 2006, 314: 1464-1467
[46] Jiang D C, Sims C E, Allbritton N L. Electrophoresis, 2010, 31: 2558-2565
[47] Marc P J, Sims C E, Bachman M, Li G P, Allbritton N L. Lab Chip, 2008, 8: 710-716
[48] Boardman A, Chang T, Folch A, Dovichi N J. Anal. Chem., 2010, 82: 9959-9961
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