Microchip Devices for Bioanalysis

  • Anna C. Kinsella
  • Shelley D. Minteer
Part of the Springer Protocols Handbooks book series (SPH)

1. Introduction

Over the last two decades, microchip-based lab analysis systems have become more and more popular. These devices are typically called lab-on-a-chip devices or micro-TAS (micro total analysis systems), because they are designed to integrate an entire analytical instrument onto a small portable device. However, for the benefit of this chapter, we are going to refer to these devices as lab-on-a-chip devices, because this term is broader and includes both the analysis portion of the device, and also any other functions that the device might perform (i.e., microreactors, cell culturing, PCR, separations, etc.). Some of the devices are designed to be disposable and some are designed to be reuseable, but they are typically designed to be small portable, inexpensive devices that complete an entire chemical analysis.

The first lab-on-a-chip device was developed in 1979 when a gas chromato-graph was fabricated on a silicon wafer (1). Over the last 25 years, research has...


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  1. 1.
    Terry SC, Jerman JH, Angell JB (1979) A gas chromatograph air analyzer fabricated on a silicon wafer. IEEE Trans Electron Devices 26:1880–1886CrossRefGoogle Scholar
  2. 2.
    Manz A, Miyahara Y, Miura J, Watanabe Y, Miyagi H, Sato K (1990) Sens Actuators. Design of an open-tubular column liquid chromatograph using silicon chip technology. B1:249Google Scholar
  3. 3.
    Zeng Y, Chen H, Pang D, Wang Z, Cheng J (2002) Microchip capillary electro-phoresis with electrochemical detection. Anal Chem 74:2441–2445PubMedCrossRefGoogle Scholar
  4. 4.
    Jacobson SC, Moore AW, Ramsey JM (1995) Fused quartz substrates for microchip electrophoresis. Anal Chem 67:2059–2063CrossRefGoogle Scholar
  5. 5.
    Hatch A, Weigl BH, Zebert D, Yager P (1999) Microfluidic approaches to immu-noassays. Proc SPIE – Int Soc Opt Eng 3877:169–172Google Scholar
  6. 6.
    Chiem N, Harrison DJ (1997) Microchip-based capillary electrophoresis for immunoassays: analysis of monoclonal antibodies and theophylline. Anal Chem 69:373–378PubMedCrossRefGoogle Scholar
  7. 7.
    Oleschuk RD, Shultz-Lockyear LL, Ning Y, Harrison DJ (2000) Trapping of bead-based reagents within microfluidic systems: on-chip solid-phase extraction and electrochromatography. Anal Chem 72:585–590PubMedCrossRefGoogle Scholar
  8. 8.
    Choi JW, Ahn CH, Bhansali S, Henderson HT (2000) A new magnetic bead-based, filterless bioseparator with planar electromagnet surfaces for integrated biodetec-tion systems. Sens Actuators B68:34–39Google Scholar
  9. 9.
    Burns MA, Johnson BM, Brahmasandra SN et al (1998) An integrated nanoliter DNA analysis device. Science 280:1046–1048CrossRefGoogle Scholar
  10. 10.
    Kricka LJ, Wilding P (2003) Microchip PCR. Anal Bioanal Chem 277:820–825CrossRefGoogle Scholar
  11. 11.
    Li MW, Spence DM, Martin RS (2005) A microchip-based system for immobilizing PC 12 cells and amperometrically detecting catecholamines released after stimulation with calcium. Electroanalysis 17:1171–1180CrossRefGoogle Scholar
  12. 12.
    Woodruff GW (2004) Microfluidic channels in polymethylmethacrylate by optimizing aluminum adhesion. Proc Microelect Eng Conf 22:110–113Google Scholar
  13. 13.
    Srinivasan R (1982) Action of far ultraviolet-radiation on poly(ethylene-terphthalate) films – a method for controlled dry etching. Polymer 23:1863, 1864CrossRefGoogle Scholar
  14. 14.
    Harrison DJ, Fluri K, Seiler K, Fan Z, Effenhauser CS, Manz A (1993) Micromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science 261:895–897PubMedCrossRefGoogle Scholar
  15. 15.
    Jacobson SC, Koutny LB, Hergenroder R, Moore AW, Ramsey JM (1994) Microchip capillary electrophoresis wit an integrated postcolumn reactor. Anal Chem 66:3472–3476CrossRefGoogle Scholar
  16. 16.
    Fluri K, Fitzpatrick G, Chiem N, Harrison DJ (1996) Integrated capillary electro-phoresis devices with an efficient postcolumn reactor in planar quartz and glass chip. Anal Chem 68:4285–4290CrossRefGoogle Scholar
  17. 17.
    Liu Y, Foote RS, Jacobson SC, Ramsey RS, Ramsey JM (2000) Electrophoretic separation of proteins on a microchip with noncovalent, postcolumn labeling. Anal Chem 72:4608–4613PubMedCrossRefGoogle Scholar
  18. 18.
    Bousse L, Mouradian S, Minalla A, Yee H, Williams K, Dubrow R (2001) Protein sizing on a chip. Anal Chem 73:1207–1212PubMedCrossRefGoogle Scholar
  19. 19.
    Xue Q, Wainright A, Gangakhedkar S, Gibbons I (2001) Multiplexed enzyme assays in capillary electrophoretic single-use microfluidic devices. Electrophoresis 22:4000–4007PubMedCrossRefGoogle Scholar
  20. 20.
    Zugal SA, Burke BJ, Regnier FE, Lytle FE (2000) Electrophoretically mediated microanalysis of leucine aminopeptidase using two-photon excited fluorescence detection on a microchip. Anal Chem 72:5731–5735CrossRefGoogle Scholar
  21. 21.
    Abad-Villar EM, Tanyanyiwa J, Fernandez-Abedul MT, Costa-Gancia A, Hauser PC (2004) Detection of human immunoglubulin in microchip and conventional capillary electrophoresis with contactless conductivity measurements. Anal Chem 76:1282–1288PubMedCrossRefGoogle Scholar
  22. 22.
    Cheng SB, Skinner CD, Taylor J, Attiya S, Lee WE, Picelli G, Harrison DJ (2001) Development of a multichannel microfluidic analysis system employing affinity capillary electrophoresis for immunoassays. Anal Chem 73:1472–1479PubMedCrossRefGoogle Scholar
  23. 23.
    Chiem N, Harrison DJ (1997) Microchip-based capillary electrophoresis for immunoassays: analysis of monoclonal antibodies and theophylline. Anal Chem 69:373–378PubMedCrossRefGoogle Scholar
  24. 24.
    Wang J, Chatrathi MP, Tian B, Polsky R (2000) Microfabricated electrophoresis chips for simultaneous bioassays of glucose, uric acid, ascorbic acid, and acetomi-nophen. Anal Chem 72:2514–2518PubMedCrossRefGoogle Scholar
  25. 25.
    Garcia CD, Henry CS (2003) Direct determination of carbohydrates, amino acids, and antibiotics by microchip electrophoresis with pulsed amperometric detection. Anal Chem 75:4778–4783PubMedCrossRefGoogle Scholar
  26. 26.
    Wicks DA, Li PCH (2004) Separation of fluorescent derivatives of hydroxyl-containing small molecules on a microfluidic chip. Anal Chim Acta 507:107–114CrossRefGoogle Scholar
  27. 27.
    Wooley AT, Lao K, Lazer AN, Mathies RA (1998) Capillary electrophoresis chips with integrated electrochemical detection. Anal Chem 70:684–688CrossRefGoogle Scholar
  28. 28.
    Lapos JA, Manica DP, Ewing AG (2002) Dual fluorescence and electrochemical detection on an electrophoresis microchip. Anal Chem 74:3348–3353PubMedCrossRefGoogle Scholar
  29. 29.
    Gawron AJ, Martin RS, Lunte SM (2001) Fabrication and evaluation of a carbon-based dual electrode detector for poly(dimethylsiloxane) electrophoresis chips. Electrophoresis 22:242–248PubMedCrossRefGoogle Scholar
  30. 30.
    Jacobson SC, Ramsey JM (1996) Integrated microdevice for DNA restriction fragment analysis. Anal Chem 68:720–723CrossRefGoogle Scholar
  31. 31.
    Wooley AT, Mathies RA (1994) Ultra-high-speed DNA fragment separations using microfabricated capillary array electrophoresis chips. Proc Natl Acad Sci 91:11,348–11,352CrossRefGoogle Scholar
  32. 32.
    Xu F, Jabasini M, Baba Y (2002) DNA separation by microchip electrophoresis using low-viscosity hydroxypropylmethylcellulose-50 solutions enhanced by poly-hydroxy compounds. Electrophoresis 23:3608–3614PubMedCrossRefGoogle Scholar
  33. 33.
    Obeid PJ, Christopoulos TK, Crabtree HJ, Backhouse CJ (2003) Microfabricated device for DNA and RNA amplication by continuous-flow polymerase chain reaction and reverse transcription-polymerase chain reaction with cycle number selection. Anal Chem 75:288–295PubMedCrossRefGoogle Scholar
  34. 34.
    Rodriguez I, Lesaicherre M, Tie Y (2003) Practical integration of polymerase chain reaction amplification and electrophoretic analysis in microfluidic devices for genetic analysis. Electrophoresis 24:172–178PubMedCrossRefGoogle Scholar
  35. 35.
    Park N, Kim S, Hahn JH (2003) Cylindrical compact thermal-cycling device for continuous-flow polymerase chain reaction. Anal Chem 75:6029–6033PubMedCrossRefGoogle Scholar
  36. 36.
    Cho BS, Schuster TG, Zhu X, Chang D, Smith GD, Takayama S (2003) Passively driven integrated microfluidic system for separation of motile sperm. Anal Chem 75:4671–4675CrossRefGoogle Scholar
  37. 37.
    Schuster TG, Cho BS, Keller LM, Takayama S, Smith GD (2003) Isolation of motile spermatozoa from semen samples using microfluidics. Reprod Biomed Online 7:75–81PubMedCrossRefGoogle Scholar
  38. 38.
    Zini A, Finelli A, Phang D (2000) Influence of semen processing technique on human sperm DNA integrity. Urology 6:1081–1084CrossRefGoogle Scholar
  39. 39.
    Peterson ETK, Papautsky I (2006) Microtextured polydimethylsiloxane substrates for culturing mesenchymal stem cells. In: Shelley D. Minteer (ed) Methods in molecular biology, Humana Press in Totowa, New Jersey vol. 321, pp 179–197Google Scholar
  40. 40.
    Mata A, Boehm C, Fleischman AJJ, Muschler G, Roy S (2002) Analysis of connective tissue progenitor cell behavior on polydimethylsiloxane smooth and channel microtextures. Biomed Microdevices 4:267–275PubMedCrossRefGoogle Scholar
  41. 41.
    Borenstein JT, Terai H, King KR, Weinberg EJ, Kaazempur-Mofrad MR, Vacanti JP (2002) Microfabrication technology for vascularized tissue engineering. Biomed Microdevices 4:167–175CrossRefGoogle Scholar
  42. 42.
    Gray BL, Lieu DK, Collins SD, Smith RL, Barakat AI (2002) Microchannel platform for the study of endothelial cell shape and function. Biomed Microdevices 4:9–16CrossRefGoogle Scholar
  43. 43.
    Spence DM, Torrence NJ, Kovarik ML, Martin RS (2004) Amperometric determination of nitric oxide derived from pulmonary artery endothelial cells immobilized in a microchip channel. Analyst 129:995–1000PubMedCrossRefGoogle Scholar
  44. 44.
    Kaji H, Nishizawa M, Matsue T (2003) Localized chemical stimulation to micro-patterned cells using multiple laminar fluid flows. Labchip 3:208–211Google Scholar
  45. 45.
    Russo AP, Apoga D, Dowell N, Shain W, Turner AMP, Craighead HG, Hoch HC, Turner JN (2002) Microfabricated plastic devices from silicon using soft intermediates. Biomed Microdevices 4:277–283CrossRefGoogle Scholar
  46. 46.
    Chang WJ, Akin D, Sedlak M, Ladisch MR, Bashir R (2003) Poly(dimethylsiloxane and silicon hybrid biochip for bacterial culture. Biomed Microdevices 5:281–290CrossRefGoogle Scholar
  47. 47.
    Thiebaud P, Lauer L, Knoll W, Offenhausser A (2002) PDMS device for patterned application of microfluids to neuronal cells arranged by microcontact printing. Biosensors and Bioelectronics 17:87–93PubMedCrossRefGoogle Scholar
  48. 48.
    Li X, Li PCH (2006) Contraction study of a single cardiac muscle cell in a micro-fluidic chip. In: Shelley D. Minteer (ed) Methods in molecular biology, Humana Press in Totowa, New Jersey vol. 321, pp 199–225Google Scholar
  49. 49.
    Yang M, 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 74:3991–4001PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Anna C. Kinsella
    • 1
  • Shelley D. Minteer
    • 1
  1. 1.Department of ChemistrySaint Louis UniversitySt. Louis

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