Advertisement

Abstract

The purpose of this chapter is threefold: introducing microfluidics to the general audience, describing in detail the polymerase chain reaction (a technique used for DNA amplification), and reviewing the state-of-the-art methods regarding the detection of pathogens by on-chip PCR. The first section gives a brief introduction to the field of microfluidics. Although the microfluidic technologies have been developed substantially since 1990, their existence and applications are still unknown from the general public. The history and the applications of miniaturized total analysis systems (μTAS) are therefore summarized in the first section (Microfluidics). Secondly, the polymerase chain reaction (PCR) is described in detail. The second section (DNA amplification) therefore covers a brief history of DNA and the applications, requirements, and processes of PCR. As a conclusion of this section, the different techniques available to perform PCR (namely conventional PCR, real-time PCR and on-chip PCR) are compared. Lastly a mini-review presents the state-of-the-art in terms of detection of pathogens by on-chip PCR. The polymerase chain reaction is becoming recognized by official administrations as an acceptable method for the detection of pathogens. It is therefore no surprise that the microfluidic community is also developing devices to support this transition. The last section (Minireview) provides a snapshot of the most exquisite techniques available for the on-chip detection and analysis of pathogens.

Keywords

Microfluidic Device Fluorescence Resonance Energy Transfer Conventional Polymerase Chain Reaction Internal Amplification Control Total Analysis System 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. Alberts B, Bray D, Johnson A, Lewis JA, Raff M, Roberts K, Walter P (1998) Essential cell biology - An introduction to the molecular biology of the cell. Garland Publishing, Inc., New York and LondonGoogle Scholar
  2. Auroux P-A (2005) Microfluidic devices used for shunting polymerase chain reactions. PhD thesis. Imperial College, London, UKGoogle Scholar
  3. Auroux P-A, Day P, Manz A (2003) Sample-shunting based PCR microfluidic device. Gordon Research Conference—Physics and Chemistry of Microfluidics. Big Sky Resort, Montana, USAGoogle Scholar
  4. Auroux P-A, Day PJ, Manz A (2005) Quantitative study of the adsorption of PCR reagents during on-chip bi-directional shunting PCR. International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) 283–285Google Scholar
  5. Auroux P-A, Day PJR, Niggli F, Manz A (2002) Microfluidic device for detection of low copy number nucleic acids. Nanotech 2002. Montreux, SwitzerlandGoogle Scholar
  6. Auroux P-A, Day PJR, Niggli F, Manz A (2003) PCR micro-volume device for detection of nucleic acids. The nanotechnology conference and trade show. San Francisco, CA, USA, p. 55.Google Scholar
  7. Auroux P-A, Koc Y, deMello AJ, Manz A, Day PJR (2004) Miniaturised nucleic acid analysis. Lab Chip 4:534–546CrossRefGoogle Scholar
  8. Baker J, Strachan M, Swartz K, Yurkovetsky Y, Rulison A, Brooks C, Kopf-Sill A (2003) Single molecule amplification in a continuous flow labchip device. International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) 1335Google Scholar
  9. Belgrader P, Benett W, Hadley D, Long G, Mariella RJ, Milanovich F, Nasarabadi S, Nelson W, Richards J, Stratton P (1998) Rapid pathogen detection using a microchip PCR array instrument. Clin Chem 44:2191–2194Google Scholar
  10. Belgrader P, Benett W, Hadley D, Long G, Mariella RJ, Milanovich F, Nasarabadi S, Nelson W, Richards J, Stratton P (1999) Infection disease: PCR detection of bacteria in seven minutes. Science 284:449CrossRefGoogle Scholar
  11. Belgrader P, Elkin CJ, Brown SB, Nasarabadi SN, Langlois RG, Milanovich FP, Colston BWJ, Marshall GD (2003) A reusable flow-through polymerase chain reaction instrument for continuous monitoring of infectious biological agents. Anal Chem 75:3114–3118CrossRefGoogle Scholar
  12. Bonnet G, Tyagi S, Libchaber A, Kramer FR (1999) Thermodynamics basis of the enhanced specificity of structured DNA probes. Proceedings of the National Academy of Science USA 96:6171–6176CrossRefGoogle Scholar
  13. Branebjerg J, Fabius B, Gravesen P (1994) Application of miniature analyzers - from microfluidic components to micro-TAS. International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) 141–151Google Scholar
  14. Bu MQ, Melvin T, Ensell G, Wilkinson JS, Evans AGR (2003) Design and theoretical evaluation of a novel microfluidic device to be used for PCR. J Micromech Microeng 13:S125–S130CrossRefGoogle Scholar
  15. Burns MA, Johnson BN, Brahmasandra SN, Handique K, Webster JR, Krishnan M, Sammarco TS, Man PM, Jones D, Heldsinger D, Mastrangelo CH, Burke DT (1998) An integrated nanoliter DNA analysis device. Science 282:484–487CrossRefGoogle Scholar
  16. Bustin SA (2002) Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J Mol Endocrinol 29:23–39CrossRefGoogle Scholar
  17. Caldarelli-Stefano R, Vago L, Bonetto S, Nebuloni M, Costanzi G (1999) Use of magnetic beads for tissue DNA extraction and IS6110 Mycobacterium tuberculosis PCR. Journal of Clinical Pathology: Molecular Pathology 52:158–163CrossRefGoogle Scholar
  18. Chalmers JJ, Zborowski M, Sun LP, Moore L (1998) Flow through, immunomagnetic cell separation. Biotechnol Prog 14:141–148CrossRefGoogle Scholar
  19. Chang YH, Lee GB, Huang FC, Chen YY, Lin JL (2006) Integrated polymerase chain reaction chips utilizing digital microfluidics. Biomedical Microdevices 8:215–225CrossRefGoogle Scholar
  20. Chaudhari AM, Woudenberg TM, Albin M, Goodson KE (1998) Transient liquid crystal thermometry of microfabricated PCR vessel arrays. J Microelectromech Syst 7:345–355CrossRefGoogle Scholar
  21. Cheng J, Shoffner MA, Hvichia GE, Kricka LJ, Wilding P (1996a) Chip PCR II. Investigation of different PCR amplification systems in microfabricated silicon-glass chips. Nucleic Acids Res 24:380–385Google Scholar
  22. Cheng J, Shoffner MA, Mitchelson KR, Kricka LJ, Wilding P (1996b) Analysis of ligase chain reaction products amplified in a silicon-glass chip using capillary electrophoresis. J Chromatogr A 732:151–158CrossRefGoogle Scholar
  23. Chien A, Edgar DB, Trela JM (1976) Deoxyribonucleic acid polymerase from the extreme thermophile Thermus Aquaticus. Journal of Bacteriology 127:1550–1557Google Scholar
  24. Chiou J, Matsudaira P, Sonin A, Ehrlich D (2001) A Closed-Cycle Capillary Polymerase Chain Reaction Machine. Anal Chem 2018–2021Google Scholar
  25. Chronis N, Lam W, Lee L (2001) A microfabricated bio-magnetic separator based on continuous hydrodynamic parallel flow. International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) 497–498Google Scholar
  26. Connors E, Lundregan T, Miller N, McEwen T (1996) Convicted by juries, exonerated by science: case studies in the use of DNA evidence to establish innocence after trial. National Institute of JusticeGoogle Scholar
  27. de Mello AJ (2001) DNA amplification: does ‘small’ really mean ‘efficient’? Lab on a Chip 1:24NCrossRefGoogle Scholar
  28. de Mello AJ, Wootton RCR (2002) But what is it good for? Applications of microreactor technology for the fine chemical industry. Lab on a Chip 1:7NCrossRefGoogle Scholar
  29. Deisingh AK, Thompson M (2004) Strategies for the detection of Escherichia coli O157 : H7 in foods. Journal of Applied Microbiology 96:419–429CrossRefGoogle Scholar
  30. Deng T, Whitesides GM, Radhakrishnan M, Zabow G, Prentiss M (2001) Manipulation of magnetic microbeads in suspension using micromagnetic systems fabricated with soft lithography. Appl Phys Lett 78:1775–1777CrossRefGoogle Scholar
  31. Derzelle S, Dilasser F (2006) A robotic DNA purification protocol and real-time PCR for the detection of Enterobacter sakazakii in powdered infant formulae. Bmc Microbiology 6Google Scholar
  32. Don RH, Cox PT, Wainwright BJ, Baker K, Mattick JS (1991) ‘Touchdown’ PCR to circumvent spurious priming during gene amplification. Nucleic Acids Res 19:4008CrossRefGoogle Scholar
  33. DuPont Qualicon (2007) BAX (R) System Q7 - The power to do more. DuPontQualicon brochureGoogle Scholar
  34. Feustel A, Muller J, Relling V (1994) A Microsystem Mass Spectrometer. International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) 299–304Google Scholar
  35. Forsdyle DR (1995) Sense in anti-sense? Journal of Molecular Evolution 41:582–586Google Scholar
  36. Friedman NA, Meldrum DR (1998) Capillary tube resistive thermal cycling. Anal Chem 70:2997–3002CrossRefGoogle Scholar
  37. Fuhr G, Wagner B (1994) Electric Field Mediated Cell Manipulation, Characterisation and Cultivation in Highly Conductive Media. International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS) 209–214Google Scholar
  38. Gilbert TR, Clay AM (1973) Determination of Ammonia in Aquaria and Sea Water using the ammonia electrode. Anal Chem 45:1757–1759CrossRefGoogle Scholar
  39. Han J, Craighead G (2000) Separation of long DNA molecules in a microfabricated entropic trap array. Science 288:1026–1029CrossRefGoogle Scholar
  40. Hardt S, Dadic D, Doffing F, Drese KS, Münchov G, Sörensen O (2004) Development of a slug-flow PCR chip with minimum heating cycle times. The nanotechnology conference and trade show. Boston, MA, USA, p. 55.Google Scholar
  41. Harrison DJ, Glavina PG, Manz A (1993) Towards Miniaturized Electrophoresis and Chemical-Analysis Systems on Silicon - an Alternative to Chemical Sensors. Sens Actuators B 10:107–116CrossRefGoogle Scholar
  42. Harrison DJ, Manz A, Fan ZH, Ludi H, Widmer HM (1992) Capillary Electrophoresis and Sample Injection Systems Integrated on a Planar Glass Chip. Anal Chem 64:1926–1932CrossRefGoogle Scholar
  43. Harrison DJ, Manz A, Glavina PG (1991) Transducers ’91 792–795Google Scholar
  44. Higuchi R, Dollinger G, Walsh PS, Griffith R (1992) Simultaneous Amplification and Detection of Specific DNA- Sequences. Bio-Technology 10:413–417Google Scholar
  45. Higuchi R, Fockler C, Dollinger G, Watson R (1993) Kinetic PCR Analysis - Real-Time Monitoring of DNA Amplification Reactions. Bio-Technology 11:1026–1030Google Scholar
  46. Huang FC, Liao CS, Lee GB (2006) An integrated microfluidic chip for DNA/RNA amplification, electrophoresis separation and on-line optical detection. Electrophoresis 27:3297–3305CrossRefGoogle Scholar
  47. Jacobson DR, Xu JJ, Smith IC (1996) Lung cancer screening and diagnosis via k-ras mutation detection. International symposium on the impact of cancer biotechnology on diagnostics and prognostics indicators. Nice, FranceGoogle Scholar
  48. Jacobson SC, Hergenröder R, Koutny LB, Ramsey JM (1994) High-Speed Separations on a Microchip. Anal Chem 66:1114–1118CrossRefGoogle Scholar
  49. Jareo PW, Preheim LC, Snitily MU, Gentry MJ (1997) Use of magnetic cell sorting to isolate blood neutrophils from rats. Lab Anim Sci 47:414–418Google Scholar
  50. Kamei T, Toriello NM, Lagally ET, Blazej RG, Scherer JR, Street RA, Mathies RA (2005) Microfluidic genetic analysis with an integrated a-Si : H detector. Biomedical Microdevices 7:147–152CrossRefGoogle Scholar
  51. Khandurina J, McKnight TE, Jacobson SC, Waters LC, Foote RS, Ramsey JM (2000) Integrated system for rapid PCR-based DNA analysis in microfluidic devices. Anal Chem 72:2995–3000CrossRefGoogle Scholar
  52. Kopp MU, de Mello AJ, Manz A (1998) Chemical amplification: Continuous-flow PCR on a chip. Science 280: 1046–1048CrossRefGoogle Scholar
  53. Kourkine IV, Hestekin CN, Magnusdottir SO, Barron AE (2002) Optimized sample preparation methods for tandem capillary electrophoresis single -strand conformation polymorphism/heteroduplex analysis (CE-SSCP/HA), Biotechniques, 33:318–325.Google Scholar
  54. Krishnan M, Ugaz VM, Burns MA (2003) PCR in a Rayleigh-Benard convection cell. Science 298:793CrossRefGoogle Scholar
  55. Krizova J, Spanova A, Rittich B, Horak D (2005) Magnetic hydrophilic methacrylate-based polymer microspheres for genomic DNA isolation. Journal of Chromatography A 1064:247–253CrossRefGoogle Scholar
  56. Lagally ET, Medintz I, Mathies RA (2001) Single-molecule DNA amplification and analysis in an integrated microfluidic device. Anal Chem 73:565–570CrossRefGoogle Scholar
  57. Lee JG, Cheong KH, Huh N, Kim S, Choi JW, Ko C (2006) Microchip-based one step DNA extraction and real-time PCR in one chamber for rapid pathogen identification. Lab on a Chip 6:886–895CrossRefGoogle Scholar
  58. Lee LG, Connell CR, Bloch W (1993) Allelic Discrimination by Nick-Translation PCR with Fluorogenic Probes. Nucleic Acids Res 21:3761–3766CrossRefGoogle Scholar
  59. Li HH, Gyllensten UB, Cui XF, Saiki RK, Erlich HA, Arnheim N (1988) Amplification and Analysis of Dna-Sequences in Single Human-Sperm and Diploid-Cells. Nature 335:414–417CrossRefGoogle Scholar
  60. Liakopoulos TM, Choi JW, Ahn CH (1997) A bio-magnetic bead separator on glass chips using semi-encapulated spiral electromagnets. Transducers ’97 1:485–488Google Scholar
  61. Liu J, Enzelberger M, Quake S (2002) A nanoliter device for polymerase chain reaction. Electrophoresis 23:1531–1536CrossRefGoogle Scholar
  62. Liu L (2003) Bioinformatics III: Primer Design. ICBR Molecular Biology International – Bioinformatic Workshop in Nicaragual.Google Scholar
  63. Liu RH, Yang J, Lenigk R, Bonanno J, Grodzinski P (2004) Self-contained, fully integrated biochip for sample preparation, polymerase chain reaction amplification, and DNA microarray detection. Anal Chem 76:1824–1831CrossRefGoogle Scholar
  64. Llop P, Bonaterra A, Penalver J, Lopez MM (2000) Development of a highly sensitive nested-PCR procedure using a single closed tube for detection of Erwinia amylovora in asymptomatic plant material. Applied and Environmental Microbiology 66:2071–2078CrossRefGoogle Scholar
  65. Lundberg KS, Short JM, Sorge JA, Mathur EJ (1991) A New Thermostable Polymerase with High Fidelity. Faseb J 5:A1549Google Scholar
  66. Manz A, Graber N, Widmer HM (1990b) Miniaturized Total Chemical-Analysis Systems - a Novel Concept for Chemical Sensing. Sens Actuators B 1:244–248CrossRefGoogle Scholar
  67. Manz A, Harrison DJ, Fettinger JC, Verpoorte E, Ludi H, Widmer HM (1991) Transducers ’91 939–941Google Scholar
  68. Manz A, Harrison DJ, Verpoorte EMJ, Fettinger JC, Paulus A, Ludi H, Widmer HM (1992) Planar Chips Technology for Miniaturization and Integration of Separation Techniques into Monitoring Systems - Capillary Electrophoresis on a Chip. J Chromatogr 593:253–258CrossRefGoogle Scholar
  69. Manz A, Miyahara Y, Miura J, Watanabe Y, Miyagi H, Sato K (1990a) Design of an Open-tubular Column Liquid Chromatograph Using Silicon Chip Technology. Sensors and Actuators B1:249–255CrossRefGoogle Scholar
  70. Marras SAE, Kramer FR, Tyagi S (2002) Efficiencies of fluorescence resonance energy transfer and contact-mediated quenching in oligonucleotide probes. Nucleic Acids Res 30:e122CrossRefGoogle Scholar
  71. Mattila P, Korpela J, Tenkanen T, Pitkanen K (1991) Fidelity of DNA-Synthesis by the Thermococcus-Litoralis DNA- Polymerase - an Extremely Heat-Stable Enzyme with Proofreading Activity. Nucleic Acids Res 19:4967–4973CrossRefGoogle Scholar
  72. Mavrou A, Colialexi A, Tsangaris GT, Antsaklis A, Panagiotopoulou P, Tsenghi C, Metaxotoy C (1998) Fetal cells in maternal blood isolation by magnetic cell sorting and confirmation by immunophenotyping and FISH. In Vivo 12:195–200Google Scholar
  73. Miyashita N, Saito A, Kohno S, Yamaguchi K, Watanabe A, Oda H, Kazuyama Y, Matsushima T (2004) Multiplex PCR for the simultaneous detection of Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila in community-acquired pneumonia. Respiratory Medicine 98:542–550CrossRefGoogle Scholar
  74. Molday RS, MacKenzie D (1982) Immunospecific ferromagnetic iron dextran reagents for the labeling and magnetic separation of cells. J Immunol Methods 52:353–367CrossRefGoogle Scholar
  75. Nagakura T, Maruo S, Ikuta K (2003) The study of micro blood sugar control device without energy supply for diabetes therapy. Transducers ’03 2:1209–1212Google Scholar
  76. Nakano H, Matsuda K, Yohda M, Nagamune T, Endo I, Yamane T (1994) High-Speed Polymerase Chain-Reaction in Constant Flow. Biosci Biotechnol Biochem 58:349–352Google Scholar
  77. Northrup MA, Ching MT, White RM, Watson RT (1993) DNA amplification with a microfabricated reaction chamber. Transducers ’03 924–926Google Scholar
  78. Northrup MA, Gonzelez C, Hadley D, Hills RF, Landre P, Lehew S, Saiki R, Sinski JJ, Watson R, Whatson J (1995) A MEMS-based miniature DNA analysis system. Transducers 95 1:746–767Google Scholar
  79. Obeid PJ, Christopoulos TK, Crabtree HJ, Backhouse CJ (2003) Microfabricated device for DNA and RNA amplification by continuous-flow polymerase chain reaction and reverse transcription-polymerase chain reaction with cycle number selection. Anal Chem 75:288–295CrossRefGoogle Scholar
  80. Oda RP, Strausbauch MA, Huhmer AFR, Borson N, Jurrens SR, Craighead J, Wettstein PJ, Eckloff B, Kline B, Landers JP (1998) Infrared-Mediated Thermocycling for Ultrafast Polymerase Chain Reaction Amplification of DNA. Anal Chem 70:4361CrossRefGoogle Scholar
  81. Olsvik O, Popovic T, Skjerve E, Cudjoe KS, Hornes E, Ugelstad J, Uhlen M (1994) Magnetic separation techniques in diagnostic microbiology. Clinical microbiology reviews 7:43–54Google Scholar
  82. Opekun AR, Abdalla N, Sutton FM, Hammond F, Kuo GM, Torres E, Steinbauer J, Graham DY (2002) Urea breath testing and analysis in the primary care office. J Fam Pract 51:1030–1032Google Scholar
  83. Pal D, Venkataraman V (2002) A portable battery-operated chip thermocycler based on induction heating. Sensors and Actuators A 102:151–156CrossRefGoogle Scholar
  84. Pollack MG, Fair RB, Shenderov AD (2000) Electro-wetting based actuation of liquid droplets for microfluidic applications. Appl Phys Lett 77:1725–1726CrossRefGoogle Scholar
  85. Poser S, Schulz T, Dillner U, Baier V, Kohler JM, Schimkat D, Mayer G, Siebert A (1997) Chip elements for fast thermocycling. Sens Actuator A-Phys 62:672–675CrossRefGoogle Scholar
  86. Powledge TM (2004) The polymerase chain reaction. Advances in Physiology Education, 28:44–50CrossRefGoogle Scholar
  87. Prodelalova J, Rittich B, Spanova A, Petrova K, Benes MJ (2004) Isolation of genomic DNA using magnetic cobalt ferrite and silica particles. Journal of Chromatoghraphy A 1056:43–48Google Scholar
  88. Rodriguez-Lazaro D, Pla M, Scortti M, Monzo HJ, Vazquez-Boland JA (2005) A novel real-time PCR for Listeria monocytogenes that monitors analytical performance via an internal amplification control. Applied and Environmental Microbiology 71:9008–9012CrossRefGoogle Scholar
  89. Safarikova M, Safarik I (1995) Magnetic Separations in Biosciences and Biotechnologies. Chem Listy 89:280–287Google Scholar
  90. Schneegaß I, Bräutigam R, Köhler JM (2001) Miniaturized flow-through PCR with different templates types in a silicon chip thermocycler. Lab Chip 1:42–49CrossRefGoogle Scholar
  91. Stratis-Cullum DN, Giffrin GD, Mobley J, Vass AA, Vo-Dinh T (2003) A miniature biochip for detection of aerosolized Bacillus globigii spores. Anal Chem 75:275–280CrossRefGoogle Scholar
  92. SuperArray–Bioscience Corporation (2004) The advantages of Hot-Start PCR technology, Newsletter – Pathway, 1(4):3.Google Scholar
  93. Taylor TB, Winn-Deen ES, Picozza E, Woudenberg TM, Albin M (1997) Optimization of the performance of the polymerase chain reaction in silicon-based microstructures. Nucleic Acids Res 25:3164–3168CrossRefGoogle Scholar
  94. Terry SC, Jerman JH, Angell JB (1979) A gas chromatographic air analyzer fabricated on a silicon wafer, I.E.E.E.Transactions on Electron Devices, ED->26:1880–86.CrossRefGoogle Scholar
  95. Thiel A, Scheffold A, Radbruch A (1998) Immunomagnetic cell sorting - pushing the limits. Immunotechnology 4:89–96CrossRefGoogle Scholar
  96. Thompson C, Loeffelholz M (1995) Detection of HIV-1 infection by polymerase chain reaction (PCR). Hotlines - University of Iowa 34:1–2Google Scholar
  97. Toma C, Lu Y, Higa N, Nakasone N, Chinen I, Baschkier A, Rivas M, Iwanaga M (2003) Multiplex PCR assay for identification of Human Diarrheagenic Escherichia coli. J Clin Microbiol 41:2669–2671CrossRefGoogle Scholar
  98. Tsai NC, Sue CY (2006) SU-8 based continuous-flow RT-PCR bio-chips under high-precision temperature control. Biosensors & Bioelectronics 22:313–317CrossRefGoogle Scholar
  99. Tyagi S, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotechnol 14:303–308CrossRefGoogle Scholar
  100. Vilkner T, Janasek D, Manz A (2004) Micro total analysis systems. Recent developments. Anal Chem 76:3373–3386CrossRefGoogle Scholar
  101. Wahr JA, Lau W, Tremper KK, Hallock L, Smith K (1996) Accuracy and precision of a new, portable, handheld blood gas analyzer, the IRMA(R). J Clin Monit 12:317–324CrossRefGoogle Scholar
  102. Walcott RR (2003) Detection of seedborne pathogens. Horttechnology 13:40–47Google Scholar
  103. Wallenborg SR, Bailey CG (2000) Separation and detection of explosives on a microchip using micellar electrokinetic chromatography and indirect laser- induced fluorescence. Anal Chem 72:1872–1878CrossRefGoogle Scholar
  104. Waters LC, Jacobson SC, Kroutchinina N, Khandurina J, Foote RS, Ramsey JM (1998) Microchip device for cell lysis, multiplex PCR amplification, and electrophoretic sizing. Anal Chem 70:158–162CrossRefGoogle Scholar
  105. Watson JD, Crick FHC (1953) A structure for deoxyribose nucleic acid. Nature 171:737–738CrossRefGoogle Scholar
  106. Whitcombe D, Theaker J, Guy SP, Brown T, Little S (1999) Detection of PCR products using self-probing amplicons and fluorescence. Nat Biotechnol 17:804–807CrossRefGoogle Scholar
  107. Wittwer CT, Garling DJ (1991) Rapid cycle DNA amplification: time and temperature optimization. BioTechniques 10:76–83Google Scholar
  108. Woolley AT, Hadley D, Landre P, de Mello AJ, Mathies RA, Northrup MA (1996) Functional Integration of PCR Amplicfication and Capillary Electrophoresis in Microfabricated DNA Analysis device. Anal Chem 68:4081CrossRefGoogle Scholar
  109. Wootton RCR, Fortt R, de Mello AJ (2001) On-chip generation and reaction of unstable intermediates - monolithic nanoreactors for diazonium chemistry: Azo dyes. Lab on a Chip 2:5–7CrossRefGoogle Scholar
  110. Xu F, Jabasini M, Baba Y (2002) DNA separation by microchip electrophoresis using low-viscosity hydroxypropylmethylcellulose-50 solutions enhanced by polyhydroxy compounds. Electrophoresis 23:3608–3614CrossRefGoogle Scholar
  111. Yang JN, Liu YJ, Rauch CB, Stevens RL, Liu RH, Lenigk R, Grodzinski P (2002) High sensitivity PCR assay in plastic micro reactors. Lab on a Chip 2:179–187CrossRefGoogle Scholar
  112. Yeung SW, Lee TMH, Cai H, Hsing IM (2006) A DNA biochip for on-the-spot multiplexed pathogen identification. Nucleic Acids Research 34Google Scholar
  113. Yoon DS, Lee YS, Lee YK, Cho HJ, Sung SW, Oh KW, Cha J, Lim G (2002) Precise temperature control and rapid thermal cycling in a micromachined DNA polymerase chain reaction. Journal of Micromechanics & Microengineering 12:813–823CrossRefGoogle Scholar
  114. Zaletaev DV, Nemtsova MV, Strelnikov VV, Babenko OV, Vasil’ev EV, Zemlyakova VV, Zhevlova AI, Drozd OV (2004) Diagnostics of epigenetics alterations in hereditary and oncological disorders. Molecular Biology 38:174–182CrossRefGoogle Scholar
  115. Zou Q, Miao Y, Chen Y, Sridhar U, Chong CS, Chai T, Tie Y, Teh CHL, Lim JS, Heng CK (2002) Micro-assembled multi-chamber thermal cycler for low-cost reaction chip thermal multiplexing. Sensors and Actuators A 102: 114–121CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Pierre-Alain Auroux
    • 1
  1. 1.National Institute for Standards and TechnologyEEEL, Semiconductor Electronics DivisionGaithersburgUSA

Personalised recommendations