Introduction

Chapter
Part of the Springer Theses book series (Springer Theses)

Abstract

Microfluidic technology, also called “lab on a chip” (LOC), miniaturized the basic units of biological, chemical and medical laboratories using a chip with a size of only several square centimeters. This technology is rapidly developing in recent years. The manipulations of sample preparation, reaction, separation, and detection were integrated into micro-scale channels, in order to achieve a portable, automatic, rapid, and accurate analysis system. The concept of micro-total analysis systems (μTAS) was first defined by Manz [1] in 1990. During the last 30years, micro-fabricating techniques developed rapidly, as well as the separation and detection methods. Thus, the microfluidic devices fabrication was greatly improved. Micro-valves [2] and micro-reactors [3] were successfully integrated in the microfluidic devices, which provided the essential conditions for the integration and automation of microfluidic devices. As a fast developing analysis technique, μTAS was widely applied in various research fields, particularly in disease diagnosis, environment monitoring, immunoassays, and protein research [4].

Keywords

Matrix Assisted Laser Desorption Ionization Microfluidic Device Cell Analysis Microfluidic Chip Fluid Shear Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Manz A, Graber N, Widmer HM (1990) Miniaturized total chemical-analysis systems – a novel concept for chemical sensing. Sens Actuat B Chem 1:244–248Google Scholar
  2. 2.
    Emrich CA, Tian HJ, Medintz IL, Mathies RA (2002) Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis. Anal Chem 74:5076–5083Google Scholar
  3. 3.
    Thorsen T, Maerkl SJ, Quake SR (2002) Microfluidic large-scale integration. Science 298:580–584Google Scholar
  4. 4.
    Vilkner T, Janasek D, Manz A (2004) Micro total analysis systems. Recent developments. Anal Chem 76:3373–3385Google Scholar
  5. 5.
    Liang SL, Chan DW (2007) Enzymes and related proteins as cancer biomarkers: a proteomic approach. Clin Chim Acta 381:93–97Google Scholar
  6. 6.
    Huang CP, Lu J, Seon H, Lee AP, Flanagan LA, Kim HY, Putnam AJ, Jeon NL (2009) Engineering microscale cellular niches for three-dimensional multicellular co-cultures. Lab Chip 9:1740–1748Google Scholar
  7. 7.
    Sung JH, Shuler ML (2009) A micro cell culture analog (mu CCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs. Lab Chip 9:1385–1394Google Scholar
  8. 8.
    Chung S, Sudo R, Mack PJ, Wan CR, Vickerman V, Kamm RD (2009) Cell migration into scaffolds under co-culture conditions in a microfluidic platform. Lab Chip 9:269–275Google Scholar
  9. 9.
    Tourovskaia A, Figueroa-Masot X, Folch A (2005) Differentiation-on-a-chip: a microfluidic platform for long-term cell culture studies. Lab Chip 5:14–19Google Scholar
  10. 10.
    Yamada M, Hirano T, Yasuda M, Seki M (2006) A microfluidic flow distributor generating stepwise concentrations for high-throughput biochemical processing. Lab Chip 6:179–184Google Scholar
  11. 11.
    Paguirigan A, Beebe DJ (2006) Gelatin based microfluidic devices for cell culture. Lab Chip 6:407–413Google Scholar
  12. 12.
    Toh YC, Zhang C, Zhang J, Khong YM, Chang S, Samper VD, van Noort D, Hutmacher DW, Yu HR (2007) A novel 3D mammalian cell perfusion-culture system in microfluidic channels. Lab Chip 7:302–309Google Scholar
  13. 13.
    Gomez-Sjoberg R, Leyrat AA, Pirone DM, Chen CS, Quake SR (2007) Versatile, fully automated, microfluidic cell culture system. Anal Chem 79:8557–8563Google Scholar
  14. 14.
    Yao B, Luo GA, Feng X, Wang W, Chen LX, Wang YM (2004) A microfluidic device based on gravity and electric force driving for flow cytometry and fluorescence activated cell sorting. Lab Chip 4:603–607Google Scholar
  15. 15.
    Pamme N, Wilhelm C (2006) Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis. Lab Chip 6:974–980Google Scholar
  16. 16.
    Choi S, Song S, Choi C, Park JK (2009) Microfluidic self-sorting of mammalian cells to achieve cell cycle synchrony by hydrophoresis. Anal Chem 81:1964–1968Google Scholar
  17. 17.
    Wheeler AR, Throndset WR, Whelan RJ, Leach AM, Zare RN, Liao YH, Farrell K, Manger ID, Daridon A (2003) Microfluidic device for single-cell analysis. Anal Chem 75:3581–3586Google Scholar
  18. 18.
    Bailey RC, Kwong GA, Radu CG, Witte ON, Heath JR (2007) DNA-encoded antibody libraries: a unified platform for multiplexed cell sorting and detection of genes and proteins. J Am Chem Soc 129:1959–1967Google Scholar
  19. 19.
    McClain MA, Culbertson CT, Jacobson SC, Allbritton NL, Sims CE, Ramsey JM (2003) Microfluidic devices for the high-throughput chemical analysis of cells. Anal Chem 75:5646–5655Google Scholar
  20. 20.
    Lee JN, Jiang X, Ryan D, Whitesides GM (2004) Compatibility of mammalian cells on surfaces of poly(dimethylsiloxane). Langmuir 20:11684–11691Google Scholar
  21. 21.
    Piruska A, Nikcevic I, Lee SH, Ahn C, Heineman WR, Limbach PA, Seliskar CJ (2005) The autofluorescence of plastic materials and chips measured under laser irradiation. Lab Chip 5:1348–1354Google Scholar
  22. 22.
    Wu HK, Ren KN, Zhao YH, Su J, Ryan D (2010) Convenient method for modifying poly(dimethylsiloxane) to be airtight and resistive against absorption of small molecules. Anal Chem 82:5965–5971Google Scholar
  23. 23.
    Lai S, Wang SN, Luo J, Lee LJ, Yang ST, Madou MJ (2004) Design of a compact disk-like microfluidic platform for enzyme-linked immunosorbent assay. Anal Chem 76:1832–1837Google Scholar
  24. 24.
    Mehta G, Lee J, Cha W, Tung YC, Linderman JJ, Takayama S (2009) Hard Top soft bottom microfluidic devices for cell culture and chemical analysis. Anal Chem 81:3714–3722Google Scholar
  25. 25.
    Bettinger CJ, Weinberg EJ, Kulig KM, Vacanti JP, Wang YD, Borenstein JT, Langer R (2006) Three-dimensional microfluidic tissue-engineering scaffolds using a flexible biodegradable polymer. Adv Mater 18:165–169Google Scholar
  26. 26.
    Fidkowski C, Kaazempur-Mofrad MR, Borenstein J, Vacanti JP, Langer R, Wang YD (2005) Endothelialized microvasculature based on a biodegradable elastomer. Tissue Eng 11:302–309Google Scholar
  27. 27.
    Heo J, Thomas KJ, Seong GH, Crooks RM (2003) A microfluidic bioreactor based on hydrogel-entrapped E. coli: cell viability, lysis, and intracellular enzyme reactions. Anal Chem 75:22–26Google Scholar
  28. 28.
    Ling Y, Rubin J, Deng Y, Huang C, Demirci U, Karp JM, Khademhosseini A (2007) A cell-laden microfluidic hydrogel. Lab Chip 7:756–762Google Scholar
  29. 29.
    Liu MC, Ho D, Tai YC (2008) Monolithic fabrication of three-dimensional microfluidic networks for constructing cell culture array with an integrated combinatorial mixer. Sens Actuat B Chem 129:826–833Google Scholar
  30. 30.
    Kim MJ, Breuer KS (2008) Microfluidic pump powered by self-organizing bacteria. Small 4:111–120Google Scholar
  31. 31.
    Meyvantsson I, Warrick JW, Hayes S, Skoien A, Beebe DJ (2008) Automated cell culture in high density tubeless microfluidic device arrays. Lab Chip 8:717–724Google Scholar
  32. 32.
    Unger MA, Chou HP, Thorsen T, Scherer A, Quake SR (2000) Monolithic microfabricated valves and pumps by multilayer soft lithography. Science 288:113–116Google Scholar
  33. 33.
    Hulme SE, Shevkoplyas SS, Whitesides GM (2009) Incorporation of prefabricated screw, pneumatic, and solenoid valves into microfluidic devices. Lab Chip 9:79–86Google Scholar
  34. 34.
    King KR, Wang SH, Irimia D, Jayaraman A, Toner M, Yarmush ML (2007) A high-throughput microfluidic real-time gene expression living cell array. Lab Chip 7:77–85Google Scholar
  35. 35.
    Berger M, Castelino J, Huang R, Shah M, Austin RH (2001) Design of a microfabricated magnetic cell separator. Electrophoresis 22:3883–3892Google Scholar
  36. 36.
    Lee H, Purdon AM, Westervelt RM (2004) Manipulation of biological cells using a microelectromagnet matrix. Appl Phys Lett 85:1063–1065Google Scholar
  37. 37.
    Furdui VI, Harrison DJ (2004) Immunomagnetic T cell capture from blood for PCR analysis using microfluidic systems. Lab Chip 4:614–618Google Scholar
  38. 38.
    Umehara S, Wakamoto Y, Inoue I, Yasuda K (2003) On-chip single-cell microcultivation assay for monitoring environmental effects on isolated cells. Biochem Biophys Res Commun 305:534–540Google Scholar
  39. 39.
    Enger J, Goksor M, Ramser K, Hagberg P, Hanstorp D (2004) Optical tweezers applied to a microfluidic system. Lab Chip 4:196–200Google Scholar
  40. 40.
    Yang MS, Li CW, Yang J (2002) Cell docking and on-chip monitoring of cellular reactions with a controlled concentration gradient on a microfluidic device. Anal Chem 74:3991–4001Google Scholar
  41. 41.
    Valero A, Merino F, Wolbers F, Luttge R, Vermes I, Andersson H, van den Berg A (2005) Apoptotic cell death dynamics of HL60 cells studied using a microfluidic cell trap device. Lab Chip 5:49–55Google Scholar
  42. 42.
    Kobel S, Valero A, Latt J, Renaud P, Lutolf M (2010) Optimization of microfluidic single cell trapping for long-term on-chip culture. Lab Chip 10:857–863Google Scholar
  43. 43.
    Ogunniyi AO, Story CM, Papa E, Guillen E, Love JC (2009) Screening individual hybridomas by microengraving to discover monoclonal antibodies. Nat Protoc 4:767–782Google Scholar
  44. 44.
    Di Carlo D, Wu LY, Lee LP (2006) Dynamic single cell culture array. Lab Chip 6:1445–1449Google Scholar
  45. 45.
    Skelley AM, Kirak O, Suh H, Jaenisch R, Voldman J (2009) Microfluidic control of cell pairing and fusion. Nat Methods 6:147–152Google Scholar
  46. 46.
    Frimat JP, Becker M, Chiang YY, Marggraf U, Janasek D, Hengstler JG, Franzke J, West J (2011) A microfluidic array with cellular valving for single cell co-culture. Lab Chip 11:231–237Google Scholar
  47. 47.
    Liu CS, Liu JJ, Gao D, Ding MY, Lin JM (2010) Fabrication of microwell arrays based on two-dimensional ordered polystyrene microspheres for high-throughput single-cell analysis. Anal Chem 82:9418–9424Google Scholar
  48. 48.
    Lee SH, Jeong HE, Park MC, Hur JY, Cho HS, Park SH, Suh KY (2008) Fabrication of hollow polymeric microstructures for shear-protecting cell containers. Adv Mater 20:788–792Google Scholar
  49. 49.
    Khademhosseini A, Yeh J, Eng G, Karp J, Kaji H, Borenstein J, Farokhzad OC, Langer R (2005) Cell docking inside microwells within reversibly sealed microfluidic channels for fabricating multiphenotype cell arrays. Lab Chip 5:1380–1386Google Scholar
  50. 50.
    Rettig JR, Folch A (2005) Large-scale single-cell trapping and imaging using microwell arrays. Anal Chem 77:5628–5634Google Scholar
  51. 51.
    Park MC, Hur JY, Cho HS, Park SH, Suh KY (2011) High-throughput single-cell quantification using simple microwell-based cell docking and programmable time-course live-cell imaging. Lab Chip 11:79–86Google Scholar
  52. 52.
    Park MC, Hur JY, Kwon KW, Park SH, Suh KY (2006) Pumpless, selective docking of yeast cells inside a microfluidic channel induced by receding meniscus. Lab Chip 6:988–994Google Scholar
  53. 53.
    Anselme K, Davidson P, Popa AM, Giazzon M, Liley M, Ploux L (2010) The interaction of cells and bacteria with surfaces structured at the nanometre scale. Acta Biomater 6:3824–3846Google Scholar
  54. 54.
    Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE (1997) Geometric control of cell life and death. Science 276:1425–1428Google Scholar
  55. 55.
    Kim P, Kim DH, Kim B, Choi SK, Lee SH, Khademhosseini A, Langer R, Suh KY (2005) Fabrication of nanostructures of polyethylene glycol for applications to protein adsorption and cell adhesion. Nanotechnology 16:2420–2426Google Scholar
  56. 56.
    Barbulovic-Nad I, Au SH, Wheeler AR (2010) A microfluidic platform for complete mammalian cell culture. Lab Chip 10:1536–1542Google Scholar
  57. 57.
    Abdelgawad M, Wheeler AR (2009) The digital revolution: a new paradigm for microfluidics. Adv Mater 21:920–925Google Scholar
  58. 58.
    Au SH, Shih SCC, Wheeler AR (2011) Integrated microbioreactor for culture and analysis of bacteria, algae and yeast. Biomed Microdevices 13:41–50Google Scholar
  59. 59.
    Yang J, Li CW, Yang MS (2004) Hydrodynamic simulation of cell docking in microfluidic channels with different dam structures. Lab Chip 4:53–59Google Scholar
  60. 60.
    Huang LR, Cox EC, Austin RH, Sturm JC (2004) Continuous particle separation through deterministic lateral displacement. Science 304:987–990Google Scholar
  61. 61.
    Chronis N, Lee LP (2005) Electrothermally activated SU-8 microgripper for single cell manipulation in solution. J Microelectromech Syst 14:857–863Google Scholar
  62. 62.
    Revzin A, Sekine K, Sin A, Tompkins RG, Toner M (2005) Development of a microfabricated cytometry platform for characterization and sorting of individual leukocytes. Lab Chip 5:30–37Google Scholar
  63. 63.
    Murthy SK, Sin A, Tompkins RG, Toner M (2004) Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers. Langmuir 20:11649–11655Google Scholar
  64. 64.
    Xu Y, Phillips JA, Yan JL, Li QG, Fan ZH, Tan WH (2009) Aptamer-based microfluidic device for enrichment, sorting, and detection of multiple cancer cells. Anal Chem 81:7436–7442Google Scholar
  65. 65.
    Phillips JA, Xu Y, Xia Z, Fan ZH, Tan WH (2009) Enrichment of cancer cells using aptamers immobilized on a microfluidic channel. Anal Chem 81:1033–1039Google Scholar
  66. 66.
    Wei HB, Li HF, Gao D, Lin JM (2010) Multi-channel microfluidic devices combined with electrospray ionization quadrupole time-of-flight mass spectrometry applied to the monitoring of glutamate release from neuronal cells. Analyst 135:2043–2050Google Scholar
  67. 67.
    Camelliti P, McCulloch AD, Kohl P (2005) Microstructured cocultures of cardiac myocytes and fibroblasts: a two-dimensional in vitro model of cardiac tissue. Microsc Microanal 11:249–259Google Scholar
  68. 68.
    Park ES, Brown AC, DiFeo MA, Barker TH, Lu H (2010) Continuously perfused, non-cross-contaminating microfluidic chamber array for studying cellular responses to orthogonal combinations of matrix and soluble signals. Lab Chip 10:571–580Google Scholar
  69. 69.
    Tsang VL, Bhatia SN (2004) Three-dimensional tissue fabrication. Adv Drug Deliv Rev 56:1635–1647Google Scholar
  70. 70.
    Tan JL, Tien J, Pirone DM, Gray DS, Bhadriraju K, Chen CS (2003) Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc Natl Acad Sci USA 100:1484–1489Google Scholar
  71. 71.
    Kunze A, Giugliano M, Valero A, Renaud P (2011) Micropatterning neural cell cultures in 3D with a multi-layered scaffold. Biomaterials 32:2088–2098Google Scholar
  72. 72.
    Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328:1662–1668Google Scholar
  73. 73.
    Walsh CL, Babin BM, Kasinskas RW, Foster JA, McGarry MJ, Forbes NS (2009) A multipurpose microfluidic device designed to mimic microenvironment gradients and develop targeted cancer therapeutics. Lab Chip 9:545–554Google Scholar
  74. 74.
    Cheng SY, Heilman S, Wasserman M, Archer S, Shuler ML, Wu MM (2007) A hydrogel-based microfluidic device for the studies of directed cell migration. Lab Chip 7:763–769Google Scholar
  75. 75.
    Glawdel T, Elbuken C, Lee LEJ, Ren CL (2009) Microfluidic system with integrated electroosmotic pumps, concentration gradient generator and fish cell line (RTgill-W1)-towards water toxicity testing. Lab Chip 9:3243–3250Google Scholar
  76. 76.
    Hung PJ, Lee PJ, Sabounchi P, Lin R, Lee LP (2005) Continuous perfusion microfluidic cell culture array for high-throughput cell-based assays. Biotechnol Bioeng 89:1–8Google Scholar
  77. 77.
    Chung BG, Flanagan LA, Rhee SW, Schwartz PH, Lee AP, Monuki ES, Jeon NL (2005) Human neural stem cell growth and differentiation in a gradient-generating microfluidic device. Lab Chip 5:401–406Google Scholar
  78. 78.
    Sundararaghavan HG, Monteiro GA, Firestein BL, Shreiber DI (2009) Neurite growth in 3D collagen gels with gradients of mechanical properties. Biotechnol Bioeng 102:632–643Google Scholar
  79. 79.
    Huang GS, Mei YF, Thurmer DJ, Coric E, Schmidt OG (2009) Rolled-up transparent microtubes as two-dimensionally confined culture scaffolds of individual yeast cells. Lab Chip 9:263–268Google Scholar
  80. 80.
    Jung JH, Choi CH, Chung S, Chung YM, Lee CS (2009) Microfluidic synthesis of a cell adhesive Janus polyurethane microfiber. Lab Chip 9:2596–2602Google Scholar
  81. 81.
    Fu AY, Chou HP, Spence C, Arnold FH, Quake SR (2002) An integrated microfabricated cell sorter. Anal Chem 74:2451–2457Google Scholar
  82. 82.
    Wang MM, Tu E, Raymond DE, Yang JM, Zhang HC, Hagen N, Dees B, Mercer EM, Forster AH, Kariv I, Marchand PJ, Butler WF (2005) Microfluidic sorting of mammalian cells by optical force switching. Nat Biotechnol 23:83–87Google Scholar
  83. 83.
    Liu YJ, Guo SS, Zhang ZL, Huang WH, Baigl D, Xie M, Chen Y, Pang DW (2007) A micropillar-integrated smart microfluidic device for specific capture and sorting of cells. Electrophoresis 28:4713–4722Google Scholar
  84. 84.
    Zheng S, Lin H, Liu JQ, Balic M, Datar R, Cote RJ, Tai YC (2007) Membrane microfilter device for selective capture, electrolysis and genomic analysis of human circulating tumor cells. J Chromatogr A 1162:154–161Google Scholar
  85. 85.
    Andersen KB, Levinsen S, Svendsen WE, Okkels F (2009) A generalized theoretical model for “continuous particle separation in a microchannel having asymmetrically arranged multiple branches”. Lab Chip 9:1638–1639Google Scholar
  86. 86.
    Yamada M, Kano K, Tsuda Y, Kobayashi J, Yamato M, Seki M, Okano T (2007) Microfluidic devices for size-dependent separation of liver cells. Biomed Microdevices 9:637–645Google Scholar
  87. 87.
    Kuntaegowdanahalli SS, Bhagat AAS, Kumar G, Papautsky I (2009) Inertial microfluidics for continuous particle separation in spiral microchannels. Lab Chip 9:2973–2980Google Scholar
  88. 88.
    Wu ZG, Willing B, Bjerketorp J, Jansson JK, Hjort K (2009) Soft inertial microfluidics for high throughput separation of bacteria from human blood cells. Lab Chip 9:1193–1199Google Scholar
  89. 89.
    Huh D, Bahng JH, Ling YB, Wei HH, Kripfgans OD, Fowlkes JB, Grotberg JB, Takayama S (2007) Gravity-driven microfluidic particle sorting device with hydrodynamic separation amplification. Anal Chem 79:1369–1376Google Scholar
  90. 90.
    Shevkoplyas SS, Yoshida T, Munn LL, Bitensky MW (2005) Biomimetic autoseparation of leukocytes from whole blood in a microfluidic device. Anal Chem 77:933–937Google Scholar
  91. 91.
    Huang R, Barber TA, Schmidt MA, Tompkins RG, Toner M, Bianchi DW, Kapur R, Flejter WL (2008) A microfluidics approach for the isolation of nucleated red blood cells (NRBCs) from the peripheral blood of pregnant women. Prenat Diagn 28:892–899Google Scholar
  92. 92.
    SooHoo JR, Walker GM (2009) Microfluidic aqueous two phase system for leukocyte concentration from whole blood. Biomed Microdevices 11:323–329Google Scholar
  93. 93.
    Lenshof A, Ahmad-Tajudin A, Jaras K, Sward-Nilsson AM, Aberg L, Marko-Varga G, Malm J, Lilja H, Laurell T (2009) Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray diagnostics. Anal Chem 81:6030–6037Google Scholar
  94. 94.
    Vahey MD, Voldman J (2008) An equilibrium method for continuous-flow cell sorting using dielectrophoresis. Anal Chem 80:3135–3143Google Scholar
  95. 95.
    Gossett DR, Weaver WM, Mach AJ, Hur SC, Kwong Tse HT, Lee W, Amini H, Di Carlo D (2010) Label-free cell separation and sorting in microfluidic systems. Anal Bioanal Chem 397:3249–3267Google Scholar
  96. 96.
    Yamada M, Seki M (2006) Microfluidic particle sorter employing flow splitting and recombining. Anal Chem 78:1357–1362Google Scholar
  97. 97.
    Ji HM, Samper V, Chen Y, Heng CK, Lim TM, Yobas L (2008) Silicon-based microfilters for whole blood cell separation. Biomed Microdevices 10:251–257Google Scholar
  98. 98.
    Evron E, Dooley WC, Umbricht CB, Rosenthal D, Sacchi N, Gabrielson E, Soito AB, Hung DT, Ljung BM, Davidson NE, Sukumar S (2001) Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR. Lancet 357:1335–1336Google Scholar
  99. 99.
    Fuqua SAW, Wiltschke C, Zhang QX, Borg A, Castles CG, Friedrichs WE, Hopp T, Hilsenbeck S, Mohsin S, O’Connell P, Allred DC (2000) A hypersensitive estrogen receptor-alpha mutation in premalignant breast lesions. Cancer Res 60:4026–4029Google Scholar
  100. 100.
    Du Z, Cheng KH, Vaughn MW, Collie NL, Gollahon LS (2007) Recognition and capture of breast cancer cells using an antibody-based platform in a microelectromechanical systems device. Biomed Microdevices 9:35–42Google Scholar
  101. 101.
    Plouffe BD, Njoka DN, Harris J, Liao JH, Horick NK, Radisic M, Murthy SK (2007) Peptide-mediated selective adhesion of smooth muscle and endothelial cells in microfluidic shear flow. Langmuir 23:5050–5055Google Scholar
  102. 102.
    Hasenbein ME, Andersen TT, Bizios R (2002) Micropatterned surfaces modified with select peptides promote exclusive interactions with osteoblasts. Biomaterials 23:3937–3942Google Scholar
  103. 103.
    Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment – RNA ligands to bacteriophage-T4 DNA-polymerase. Science 249:505–510Google Scholar
  104. 104.
    Ellington AD, Szostak JW (1990) Invitro Selection of RNA Molecules That Bind Specific Ligands. Nature 346:818–822Google Scholar
  105. 105.
    Neryl AA, Wrenger C, Ulrich H (2009) Recognition of biomarkers and cell-specific molecular signatures: aptamers as capture agents. J Sep Sci 32:1523–1530Google Scholar
  106. 106.
    Chang WC, Lee LP, Liepmann D (2005) Biomimetic technique for adhesion-based collection and separation of cells in a microfluidic channel. Lab Chip 5:64–73Google Scholar
  107. 107.
    Morris KN, Jensen KB, Julin CM, Weil M, Gold L (1998) High affinity ligands from in vitro selection: complex targets. Proc Natl Acad Sci USA 95:2902–2907Google Scholar
  108. 108.
    Lien KY, Chuang YH, Hung LY, Hsu KF, Lai WW, Ho CL, Chou CY, Lee GB (2010) Rapid isolation and detection of cancer cells by utilizing integrated microfluidic systems. Lab Chip 10:2875–2886Google Scholar
  109. 109.
    Herr JK, Smith JE, Medley CD, Shangguan DH, Tan WH (2006) Aptamer-conjugated nanoparticles for selective collection and detection of cancer cells. Anal Chem 78:2918–2924Google Scholar
  110. 110.
    Shangguan D, Cao ZH, Meng L, Mallikaratchy P, Sefah K, Wang H, Li Y, Tan WH (2008) Cell-specific aptamer probes for membrane protein elucidation in cancer cells. J Proteome Res 7:2133–2139Google Scholar
  111. 111.
    Mayer G, Ahmed MSL, Dolf A, Endl E, Knolle PA, Famulok M (2010) Fluorescence-activated cell sorting for aptamer SELEX with cell mixtures. Nat Protoc 5:1993–2004Google Scholar
  112. 112.
    Guo KT, Schafer R, Paul A, Gerber A, Ziemer G, Wendel HP (2006) A new technique for the isolation and surface immobilization of mesenchymal stem cells from whole bone marrow using high-specific DNA aptamers. Stem Cells 24:2220–2231Google Scholar
  113. 113.
    Cerchia L, de Franciscis V (2010) Targeting cancer cells with nucleic acid aptamers. Trends Biotechnol 28:517–525Google Scholar
  114. 114.
    Jeon NL, Baskaran H, Dertinger SKW, Whitesides GM, Van de Water L, Toner M (2002) Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat Biotechnol 20:826–830Google Scholar
  115. 115.
    Takayama S, Ostuni E, LeDuc P, Naruse K, Ingber DE, Whitesides GM (2001) Laminar flows – Subcellular positioning of small molecules. Nature 411:1016–1016Google Scholar
  116. 116.
    Kim M, Kim T (2010) Diffusion-based and long-range concentration gradients of multiple chemicals for bacterial chemotaxis assays. Anal Chem 82:9401–9409Google Scholar
  117. 117.
    Walker GM, Sai JQ, Richmond A, Stremler M, Chung CY, Wikswo JP (2005) Effects of flow and diffusion on chemotaxis studies in a microfabricated gradient generator. Lab Chip 5:611–618Google Scholar
  118. 118.
    Powers MJ, Domansky K, Kaazempur-Mofrad MR, Kalezi A, Capitano A, Upadhyaya A, Kurzawski P, Wack KE, Stolz DB, Kamm R, Griffith LG (2002) A microfabricated array bioreactor for perfused 3D liver culture. Biotechnol Bioeng 78:257–269Google Scholar
  119. 119.
    Leclerc E, David B, Griscom L, Lepioufle B, Fujii T, Layrolle P, Legallaisa C (2006) Study of osteoblastic cells in a microfluidic environment. Biomaterials 27:586–595Google Scholar
  120. 120.
    Lucchetta EM, Lee JH, Fu LA, Patel NH, Ismagilov RF (2005) Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics. Nature 434:1134–1138Google Scholar
  121. 121.
    El-Ali J, Gaudet S, Gunther A, Sorger PK, Jensen KF (2005) Cell stimulus and lysis in a microfluidic device with segmented gas–liquid flow. Anal Chem 77:3629–3636Google Scholar
  122. 122.
    Gilleland CL, Rohde CB, Zeng F, Yanik MF (2010) Microfluidic immobilization of physiologically active Caenorhabditis elegans. Nat Protoc 5:1888–1902Google Scholar
  123. 123.
    Easley CJ, Rocheleau JV, Head WS, Piston DW (2009) Quantitative measurement of zinc secretion from pancreatic islets with high temporal resolution using droplet-based microfluidics. Anal Chem 81:9086–9095Google Scholar
  124. 124.
    Gao D, Liu JJ, Wei HB, Li HF, Guo GS, Lin JM (2010) A microfluidic approach for anticancer drug analysis based on hydrogel encapsulated tumor cells. Anal Chim Acta 665:7–14Google Scholar
  125. 125.
    Lion N, Rohner TC, Dayon L, Arnaud IL, Damoc E, Youhnovski N, Wu ZY, Roussel C, Josserand J, Jensen H, Rossier JS, Przybylski M, Girault HH (2003) Microfluidic systems in proteomics. Electrophoresis 24:3533–3562Google Scholar
  126. 126.
    Sato K, Yamanaka M, Takahashi H, Tokeshi M, Kimura H, Kitamori T (2002) Microchip-based immunoassay system with branching multichannels for simultaneous determination of interferon-gamma. Electrophoresis 23:734–739Google Scholar
  127. 127.
    Kim A, Ah CS, Park CW, Yang J-H, Kim T, Ahn C-G, Park SH, Sung GY (2010) Direct label-free electrical immunodetection in human serum using a flow-through-apparatus approach with integrated field-effect transistors. Biosens Bioelectron 25:1767–1773Google Scholar
  128. 128.
    Chen C, Skog J, Hsu CH, Lessard RT, Balaj L, Wurdinger T, Carter BS, Breakefield XO, Toner M, Irimia D (2010) Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip 10:505–511Google Scholar
  129. 129.
    Dishinger JF, Reid KR, Kennedy RT (2009) Quantitative monitoring of insulin secretion from single islets of Langerhans in parallel on a microfluidic chip. Anal Chem 81:3119–3127Google Scholar
  130. 130.
    Gruner G (2006) Carbon nanotube transistors for biosensing applications. Anal Bioanal Chem 384:322–335Google Scholar
  131. 131.
    Zheng GF, Patolsky F, Cui Y, Wang WU, Lieber CM (2005) Multiplexed electrical detection of cancer markers with nanowire sensor arrays. Nat Biotechnol 23:1294–1301Google Scholar
  132. 132.
    Gustafsson M, Hirschberg D, Palmberg C, Jornvall H, Bergman T (2004) Integrated sample preparation and MALDI mass spectrometry on a microfluidic compact disk. Anal Chem 76:345–350Google Scholar
  133. 133.
    Liu HH, Felten C, Xue QF, Zhang BL, Jedrzejewski P, Karger BL, Foret F (2000) Development of multichannel devices with an array of electrospray tips far high-throughput mass spectrometry. Anal Chem 72:3303–3310Google Scholar
  134. 134.
    Bings NH, Wang C, Skinner CD, Colyer CL, Thibault P, Harrison DJ (1999) Microfluidic devises connected to fused-silica capillaries with minimal dead volume. Anal Chem 71:3292–3296Google Scholar
  135. 135.
    Lazar IM, Grym J, Foret F (2006) Microfabricated devices: a new sample introduction approach to mass spectrometry. Mass Spectrom Rev 25:573–594Google Scholar
  136. 136.
    Wang C, Oleschuk R, Ouchen F, Li JJ, Thibault P, Harrison DJ (2000) Integration of immobilized trypsin bead beds for protein digestion within a microfluidic chip incorporating capillary electrophoresis separations and an electrospray mass spectrometry interface. Rapid Commun Mass Spectrom 14:1377–1383Google Scholar
  137. 137.
    Benetton S, Kameoka J, Tan AM, Wachs T, Craighead H, Henion JD (2003) Chip-based P450 drug metabolism coupled to electrospray ionization-mass spectrometry detection. Anal Chem 75:6430–6436Google Scholar
  138. 138.
    Ma B, Zhang GH, Qin JH, Lin BC (2009) Characterization of drug metabolites and cytotoxicity assay simultaneously using an integrated microfluidic device. Lab Chip 9:232–238Google Scholar
  139. 139.
    Xue QF, Foret F, Dunayevskiy YM, Zavracky PM, McGruer NE, Karger BL (1997) Multichannel microchip electrospray mass spectrometry. Anal Chem 69:426–430Google Scholar
  140. 140.
    Ramsey RS, Ramsey JM (1997) Generating electrospray from microchip devices using electroosmotic pumping. Anal Chem 69(13):2617–2617, 69(6):1174–1174Google Scholar
  141. 141.
    Huikko K, Ostman P, Grigoras K, Tuomikoski S, Tiainen VM, Soininen A, Puolanne K, Manz A, Franssila S, Kostiainen R, Kotiaho T (2003) Poly(dimethylsiloxane) electrospray devices fabricated with diamond-like carbon-poly(dimethylsiloxane) coated SU-8 masters. Lab Chip 3:67–72Google Scholar
  142. 142.
    Rohner TC, Rossier JS, Girault HH (2001) Polymer microspray with an integrated thick-film microelectrode. Anal Chem 73:5353–5357Google Scholar
  143. 143.
    Sainiemi L, Nissila T, Jokinen V, Sikanen T, Kotiaho T, Kostiainen R, Ketola RA, Franssila S (2008) Fabrication and fluidic characterization of silicon micropillar array electrospray ionization chip. Sens Actuat B Chem 132:380–387Google Scholar
  144. 144.
    Dethy JM, Ackermann BL, Delatour C, Henion JD, Schultz GA (2003) Demonstration of direct bioanalysis of drugs in plasma using nanoelectrospray infusion from a silicon chip coupled with tandem mass spectrometry. Anal Chem 75:805–811Google Scholar
  145. 145.
    Arscott S, Le Gac S, Rolando C (2005) A polysilicon nanoelectrospray-mass spectrometry source based on a microfluidic capillary slot. Sens Actuat B Chem 106:741–749Google Scholar
  146. 146.
    Hoffmann P, Hausig U, Schulze P, Belder D (2007) Microfluidic glass chips with an integrated nanospray emitter for coupling to a mass spectrometer. Angew Chem Int Ed 46:4913–4916Google Scholar
  147. 147.
    Zheng YF, Li HF, Guo ZH, Lin JM, Cai ZW (2007) Chip-based CE coupled to a quadrupole TOF mass spectrometer for the analysis of a glycopeptide. Electrophoresis 28:1305–1311Google Scholar
  148. 148.
    Mao XL, Chu IK, Lin BC (2006) A sheath-flow nanoelectrospray interface of microchip electrophoresis MS for glycoprotein and glycopeptide analysis. Electrophoresis 27:5059–5067Google Scholar
  149. 149.
    Kameoka J, Orth R, Ilic B, Czaplewski D, Wachs T, Craighead HG (2002) An electrospray ionization source for integration with microfluidics. Anal Chem 74:5897–5901Google Scholar
  150. 150.
    Li FA, Wang CH, Her GR (2007) A sheathless poly(methyl methacrylate) chip-CE/MS interface fabricated using a wire-assisted epoxy-fixing method. Electrophoresis 28:1265–1273Google Scholar
  151. 151.
    Zhang BL, Foret F, Karger BL (2000) A microdevice with integrated liquid junction for facile peptide and protein analysis by capillary electrophoresis/electrospray mass spectrometry. Anal Chem 72:1015–1022Google Scholar
  152. 152.
    Razunguzwa TT, Lenke J, Timperman AT (2005) An electrokinetic/hydrodynamic flow microfluidic CE-ESI-MS interface utilizing a hydrodynamic flow restrictor for delivery of samples under low EOF conditions. Lab Chip 5:851–855Google Scholar
  153. 153.
    Xie J, Miao YN, Shih J, Tai YC, Lee TD (2005) Microfluidic platform for liquid chromatography-tandem mass spectrometry analyses of complex peptide mixtures. Anal Chem 77:6947–6953Google Scholar
  154. 154.
    Vollmer M, Horth P, Rozing G, Coute Y, Grimm R, Hochstrasser D, Sanchez JC (2006) Multi-dimensional HPLC/MS of the nucleolar proteome using HPLC-chip/MS. J Sep Sci 29:499–509Google Scholar
  155. 155.
    Tan AM, Benetton S, Henion JD (2003) Chip-based solid-phase extraction pretreatment for direct electrospray mass spectrometry analysis using an array of monolithic columns in a polymeric substrate. Anal Chem 75:5504–5511Google Scholar
  156. 156.
    Jo K, Heien ML, Thompson LB, Zhong M, Nuzzo RG, Sweedler JV (2007) Mass spectrometric imaging of peptide release from neuronal cells within microfluidic devices. Lab Chip 7:1454–1460Google Scholar
  157. 157.
    Willis RC (2006) Challenges for clinical diagnostic devices. Anal Chem 78:5261–5265Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Beijing Research Institute of Chemical Industry, SINOPECBeijingChina

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