Integrated DNA Biochips: Past, Present and Future

  • Piotr Grodzinski
  • Robin Hui Liu
  • Abraham P. Lee
Part of the Biotechnology Intelligence Unit book series (BIOIU)


DNA biochip is becoming a widespread tool used in life science, drug screening and diagnostic applications due to its many benefits of miniaturization and integration. The term “DNA biochip” is used broadly and includes various technologies: DNA microarrays, microfluidics/Lab-on-a-Chip and other biochips (such as integrated real-time PCR, mass spectrometry and nanotechnology-based biochips). With the abundance of gene targets and combinatorial chemistry/biology libraries now available, researchers need the ability to study the effects of diseases, environmental factors, drugs and other treatments on thousands of genes at once. Biochips can provide this information in a number of ways, depending on the type of chips and chosen design of the experiment. They can be used for pharmacogenomics that includes gene expression profiling, the measurement and analysis of regulated genes under various conditions and genotyping, the detection of polymorphisms or mutations in a gene sequence. Another major application for DNA biochips is molecular diagnostics, which includes genetic screening (e.g., detection of mutations or inherited disorders), identification of pathogens and resistance in infections and molecular oncology (e.g., cancer diagnosis). Biochips can also be use for high-throughput drug screening, chemical synthesis and many other applications.


Surface Enhance Raman Spectroscopy Surface Enhance Raman Spectroscopy Nucleic Acid Hybridization Surface Enhance Raman Spectroscopy Rotary Drive 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fodor SPA, Read JL, Pirrung MC et al. Light-Directed, Spatially Addressable Parallel Chemical Synthesis. Science 1991; 251(4995):767–773.PubMedCrossRefGoogle Scholar
  2. 2.
    Schena M. Microarray BiochipTechnology. Natick, MA: Eaton Publishing; 2000.Google Scholar
  3. 3.
    Harrison DJ, Fluri K, Seiler K et al. Micromachining a Miniaturized Capillary Electrophoresis-based Chemical Analysis System on a Chip. Science 1993; 261:895–897.PubMedCrossRefGoogle Scholar
  4. 4.
    Manz A, Harrison DJ, Verpoorte E et al. Planar Chips Technology for Miniaturization and Integration of Separation Techniques into Monitoring Systems: Capillary Electrophoresis on a Chip. J of Chromatogr 1992; 593:253–258.CrossRefGoogle Scholar
  5. 5.
    Woolley AT, Mathies RA. Ultra-High-Speed DNA Fragment Separations Using Microfabricated Capillary Array Electrophoresis. Proc Natl Acad Sci USA 1994; 91:11348.PubMedCrossRefGoogle Scholar
  6. 6.
    Kovacs GTA. Micromachined Transducers Sourcebook. Boston: WCB McGraw-Hill, 1998.Google Scholar
  7. 7.
    Shi YN, Simpson PC, Scherer JR et al. Radial capillary array electrophoresis microplate and scanner for high-performance nucleic acid analysis. Anal Chem 1999; 71(23):5354–5361.PubMedCrossRefGoogle Scholar
  8. 8.
    Nuwaysir EF, Huang W, Albert TJ. Gene Expression Analysis Using Oligonucleotide Arrays Produced by Maskless Photolithography. Genome Res 2002: 1749–1755.Google Scholar
  9. 9.
    Gao X, Yu P, LeProust E et al. Oligonucleotide Synthesis Using Solution Photogenerated Acids. J Am Chem Soc 1998; 120:12698–12699.CrossRefGoogle Scholar
  10. 10.
    Oleinikov AV, Gray MD, Zhao J et al. Self-Assembling Protein Arrays Using Electronic Semiconductor Microchips and in vitro Translation. J Proteome Res 2003; 2:313.PubMedCrossRefGoogle Scholar
  11. 11.
    Dill K, Montgomery DD, Ghindilis AL et al. Immunoassays and sequence-specific DNA detection on a microchip using enzyme amplified electrochemical detection. J Biochem Biophys Methods 2004; 59:181–187.PubMedCrossRefGoogle Scholar
  12. 12.
    Gunderson KL, Kruglyak S, Graige MS. Decoding randomly ordered DNA arrays. Genome Res 2004; 14:870–877.PubMedCrossRefGoogle Scholar
  13. 13.
    Fortina P, Delgrosso K, Sakazume T et al. Simple two-color array-based approach for mutation detection. EJHG 2000; 8:884–894.PubMedCrossRefGoogle Scholar
  14. 14.
    Wang J. Electroanalysis and Biosensors. Anal Chem 1999; 71:328R–332R.PubMedCrossRefGoogle Scholar
  15. 15.
    Wang J. From DNA biosensors to gene chips. Nucleic Acids Res 2000; 28(16):3011–3016.PubMedCrossRefGoogle Scholar
  16. 16.
    Farkas DH. Bioelectronic detection of DNA and the automation of molecular diagnostics. J Assoc Laboratory Automation 1999; 4(20–24).Google Scholar
  17. 17.
    Umek RM, Vielmetter J, Terbrueggen RH et al. Electronic detection of nucleic acids: a versatile platform for molecular diagnostics. J Mol Diagn 2001; 3:74–84.PubMedGoogle Scholar
  18. 18.
    Drummond TG, Hill MG, J.K.B. Electrochemical DNA Sensors. Nat Biotechnol 2003; 10:1192–1199.CrossRefGoogle Scholar
  19. 19.
    Edelstein RL, Tamanaha CR, Shechan PE et al. The BARC biosensor applied to the detection of biological warfare agents. Biosens Bioclectron 2000; 14:805–813.CrossRefGoogle Scholar
  20. 20.
    Miller MM, Sheehan PE, Edelstein RL et al. A DNA array sensor utilizing magnetic microbeads and magnetoelectronic detection. MAGMA 2001; 225(138–144).Google Scholar
  21. 21.
    Edman C, Raymond D, Wu D et al. Electric Field Directed Nucleic Acid Hybridization on Microchips. Nucl Acids Res 1998; 25:4907–4914.CrossRefGoogle Scholar
  22. 22.
    Radtkey R, Feng L, Muralhidar M et al. Rapid, high fidelity analysis of simple sequence repeats on an electronically active DNA microchip. Nucleic Acids Res 2000; 28:E17.PubMedCrossRefGoogle Scholar
  23. 23.
    Fan ZH, Mangru S, Granzow R et al. Dynamic DNA hybridization on a chip using paramagnetic beads. Anal Chem 1999; 71:4851–4859.PubMedCrossRefGoogle Scholar
  24. 24.
    Chee M, Yang R, Hubbell E et al. Accessing genetic information with high-density DNA arrays. Science 1996; 274:610–614.PubMedCrossRefGoogle Scholar
  25. 25.
    Cheek BJ, Steel AB, Torres MP et al. Chemiluminescence Detection for Hybridization Assays on the Flow-Thru Chip, a Three-Dimensional Microchannel Biochip. Anal Chem 2001; 73:5777–5783.PubMedCrossRefGoogle Scholar
  26. 26.
    Lenigk R, Liu RH, Athavale M et al. Plastic biochannel hybridization devices: a new concept for microfluidic DNA arrays. Anal Biochem 2002; 311(1):40–49.PubMedCrossRefGoogle Scholar
  27. 27.
    Liu RH, Lenigk R, Yang J et al. Hybridization Enhancement Using Cavitation Microstreaming. Anal Chem 2003; 75:1911–1917.PubMedCrossRefGoogle Scholar
  28. 28.
    Wilding P, Kricka LJ, Cheng J et al. Integrated cell isolation and polymerase chain reaction analysis using silicon microfilter chambers. Anal Biochem 1998; 257(2):95–100.PubMedCrossRefGoogle Scholar
  29. 29.
    Anderson RC, Su X, Bogdan GJ et al. A miniature integrated device for automated multistep genetic assays. Nucleic Acids Res 2000; 28(12):E60.PubMedCrossRefGoogle Scholar
  30. 30.
    Liu Y, Rauch C, Stevens R et al. DNA Amplification and Hybridization Assays in Integrated Plastic Monolithic Devices. Anal Chem 2002; 74(13):3063–3070.PubMedCrossRefGoogle Scholar
  31. 31.
    Liu RH, Yang J, Lenigk R et al. Self-Contained, Fully Integrated Biochip for Sample Preparation, Polymerase Chain Reaction Amplification and DNA Microarray Detection. Anal Chem 2004; 76:1824.PubMedCrossRefGoogle Scholar
  32. 32.
    Yuen P, Kricka L, Fortina P et al. Microchip Module for Blood Sample Preparation and Nucleic Acid Amplication Reactions. Genome Res 2001; 11:405–412.PubMedCrossRefGoogle Scholar
  33. 33.
    Woolley AT, Sensabaugh GF, Mathies RA. High-speed DNA genotyping using microfabricated capillary array electrophoresis chips. Anal Chem 1997; 69:2181–2186.PubMedCrossRefGoogle Scholar
  34. 34.
    Paegel BM, Emrich CA, Weyemayer GJ et al. High throughput DNA sequencing with a microfabricated 96-lane capillary array electrophoresis bioprocessor. Proc Natl Acad Sci USA 2002; 99(2):574–579.PubMedCrossRefGoogle Scholar
  35. 35.
    Emrich CA, Tian HJ, Medintz IL et al. Microfabricated 384-lane capillary array electrophoresis bioanalyzer for ultrahigh-throughput genetic analysis. Anal Chem 2002; 74(19):5076–5083.PubMedCrossRefGoogle Scholar
  36. 36.
    Lagally ET, Medintz I, Mathies RA. Single-Molecule DNA Amplification and Analysis in an Integrated Microfluidic Device. Anal Chem 2001; 73:565–570.PubMedCrossRefGoogle Scholar
  37. 37.
    Breadmore MC, Wolfe KA, Arcibal IG et al. Microchip-based purification of DNA from biological samples. Anal Chem 2003; 75:1880–1886.PubMedCrossRefGoogle Scholar
  38. 38.
    Burns MA, Johnson BN, Brahmasandra SN et al. An integrated nanoliter DNA analysis device. Science 1998; 282(5388):484–487.PubMedCrossRefGoogle Scholar
  39. 39.
    Gao X et al. Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding. J Biomed Optics 2003; 7:532–537.CrossRefGoogle Scholar
  40. 40.
    Nicewarner-Pena SR, al e. Submicrometer metallic barcodes. Science 2001; 294:137–141.PubMedCrossRefGoogle Scholar
  41. 41.
    Bruchez MJ, al. e. Semiconductor nanocrystals as fluorescent biological labels. Science 1998; 281:2013–2016.PubMedCrossRefGoogle Scholar
  42. 42.
    Chan WC, al. e. Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotechnol 2002; 13:40–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Wang J, al e. Electrochemical coding technology for simultaneous detection of multiple DNA targets. J Am Chem Soc 2003; 125:3214–3215.PubMedCrossRefGoogle Scholar
  44. 44.
    Wang J. From DNA biosensors to gene chips. Nucleic Acids Res 2000; 28(16): 3011–3016.PubMedCrossRefGoogle Scholar
  45. 45.
    Yi M, Jeong K, Lee LP. Theoretical and Experimental Study towards a Nanogap Dielectric Biosensor. Biosens Bioelectron 2005; 20:1320–1326.PubMedCrossRefGoogle Scholar
  46. 46.
    Ionescu-Zanetti C, Nevill JT, Carlo DD et al. Nanogap Capacitors: Sensitivity to Sample Permittivity Changes. J Appl Phys 2006; 99:024305.CrossRefGoogle Scholar
  47. 47.
    Fritz J et al. Translating biomolecular recognition into nanomechanics. Science 2000; 288:316–318.PubMedCrossRefGoogle Scholar
  48. 48.
    Wu G, al e. Bioassay of prostate-specific antigen (PSA) using microcantilevers. Nat Biotechnol 2001b; 19:856–860.PubMedCrossRefGoogle Scholar
  49. 49.
    Li J, al e. Solid state nanopore as a single DNA molecule detector. Biophys J 2003; 84:134A–135A.CrossRefGoogle Scholar
  50. 50.
    Meller A, al. e. Rapid nanopore discrimination between single polynucleotide molecules. Proc Nat Acad Sci USA 2000; 97:1079–1084.PubMedCrossRefGoogle Scholar
  51. 51.
    Bensch K, Gordon G, Miller L. Electron microscopic and cytochemical studies on DNA-containing particles phagocytized by mammalian cells. Trans NY Acad Sci 1966; 28(6):715–725.Google Scholar
  52. 52.
    Cao Y, Jin R, Mirkin CA. DNA-modified core-shell Ag/Au nanoparticles. J Am Chem Soc 2001; 123(32):7961–7962.PubMedCrossRefGoogle Scholar
  53. 53.
    Elghanian R, Storhoff JJ, Mucic RC et al. Selective Colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold-nanoparticles. Sciences 1997; 277:1078–1081.Google Scholar
  54. 54.
    Baltog I, Mihut L, Timucin V. Laboratory optics and spectroscopy. Natl Inst Mater Phys Ann Rep 2000; 58-60.Google Scholar
  55. 55.
    Nam JM, Stoeva SI, Mirkin CA. Bio-bar-code-based DNA detection with PCR-like sensitivity. J Am Chem Soc 2004; 126(19):5932–5933.PubMedCrossRefGoogle Scholar
  56. 56.
    Lagally ET, Scherer JR, Blazej RG et al. Integrated portable genetic analysis microsystem for pathogen/infectious disease detection. Anal Chem 2004; 76:3162–3170.PubMedCrossRefGoogle Scholar
  57. 57.
    Taylor MT, Belgrader P, Joshi R et al. Fully Automated Sample Preparation for Pathogen Detection Performed in a Microfluidic Cassette. In: Van den Berg A, ed. Micro Total Analysis Systems 2001. Monterey, CA: Kluwer Academic Publishers 2001:670–672.Google Scholar
  58. 58.
    Belgrader P, Okuzumi M, Pourahmadi F et al. A microfluidic cartridge to prepare spores for PCR analysis. Biosens Bioelectron 2000; 14:849–852.PubMedCrossRefGoogle Scholar
  59. 59.
    Cui Y, Wei Q, Park H et al. Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species. Science 2001; 293; 1289–1292.PubMedCrossRefGoogle Scholar
  60. 60.
    Chen RJ, Bangsaruntip S, Drouvalakis KA et al. Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc Natl Acad Sci USA 2003; 100(9):4984–4989.PubMedCrossRefGoogle Scholar
  61. 61.
    Jin S, Whang D, McAlpine MC et al. Scalable interconnection and integration of nanowire devices without registration. Nano Lett 2004; 4:915–919.CrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Piotr Grodzinski
    • 3
  • Robin Hui Liu
    • 1
  • Abraham P. Lee
    • 2
  1. 1.Osmetech Molecular DiagnosticsPasadenaUSA
  2. 2.University of California at IrvineIrvineUSA
  3. 3.National Cancer InstituteBethesdaUSA

Personalised recommendations