Editing Biochip (section)

==History==
The development started with early work on the underlying [[sensor]] technology. One of the first portable, chemistry-based sensors was the [[glass of electrode|glass pH electrode]], invented in 1922 by Hughes.<ref>W. S. Hughes, "The potential difference between glass and electrolytes in contact with water," ''J. Am. Chem. Soc.'' 44, pp.&nbsp;2860–2866, 1922</ref>  The basic concept of using exchange sites to create permselective membranes was used to develop other ion sensors in subsequent years. For example, a K<sup>+</sup> sensor was produced by incorporating [[valinomycin]] into a thin membrane.<ref>J. S. Schultz and R. F. Taylor in ''Handbook of Chemical and Biological Sensors'', J. S. Schultz and R. F. Taylor, eds., ch. Introduction to Chemical and Biological Sensors, pp.&nbsp;1–10, Institute of Physics Publishing, Philadelphia, 1996</ref>

In 1953, [[James D. Watson|Watson]] and [[Francis Crick|Crick]] announced their discovery of the now familiar [[double helix]] structure of [[DNA]] molecules and set the stage for [[genetics]] research that continues to the present day.<ref name=Nelson>D. L. Nelson and M. M. Cox, ''Lehninger Principles of Biochemistry'', Worth Publishers, New York, 2000</ref> The development of [[sequencing]] techniques in 1977 by [[Walter Gilbert|Gilbert]]<ref>A. M. Maxam and W. Gilbert, "A new method for sequencing DNA," ''Proc. Natl. Acad. Sci.'' 74, pp.&nbsp;560–564, 1977</ref> and [[Frederick Sanger|Sanger]]<ref>F. Sanger, S. Nicklen, and A. R. Coulson, "DNA sequencing with chainterminating inhibitors," ''Proc. Natl. Acad. Sci.'' 74, pp.&nbsp;5463–5467, 1977</ref> (working separately) enabled researchers to directly read the genetic codes that provide instructions for [[protein biosynthesis|protein synthesis]]. This research showed how [[hybridisation (molecular biology)|hybridization]] of complementary single [[oligonucleotide]] strands could be used as a basis for DNA sensing. Two additional developments enabled the technology used in modern DNA-based. First, in 1983 [[Kary Mullis]] invented the [[polymerase chain reaction]] (PCR) technique,<ref name=Nelson/> a method for amplifying DNA concentrations. This discovery made possible the detection of extremely small quantities of DNA in samples. Secondly in 1986 Hood and co-workers devised a method to label DNA molecules with [[fluorescent tag]]s instead of radiolabels,<ref>L. M. Smith, J. Z. Sanders, R. J. Kaiser, P. Hughes, C. Dodd, C. R. Connell, C. Heiner, S. B. H. Kent, and L. E. Hood, "Fluorescence detection in automated DNA sequence analysis," ''Nature'' 321, pp.&nbsp;61–67, 1986</ref> thus enabling hybridization experiments to be observed optically.

[[image:Biochip platform.jpg|thumb|right|300px|Figure 1. Biochips are a platform that require, in addition to microarray technology, transduction and signal processing
technologies to output the results of sensing experiments.]]
Figure 1 shows the make up of a typical biochip platform. The actual sensing component (or "chip") is just one piece of a complete analysis system. [[Transducer|Transduction]] must be done to translate the actual sensing event (DNA binding, [[redox|oxidation/reduction]], ''etc.'') into a format understandable by a computer ([[voltage]], light intensity, mass, ''etc.''), which then enables additional analysis and processing to produce a final, [[human-readable]] output. The multiple technologies needed to make a successful biochip&mdash;from sensing chemistry, to [[microarray]]ing, to signal processing&mdash;require a true multidisciplinary approach, making the barrier to entry steep. One of the first commercial biochips was introduced by [[Affymetrix]]. Their "GeneChip" products contain thousands of individual DNA sensors for use in sensing defects, or single nucleotide polymorphisms (SNPs), in genes such as [[p53]] (a tumor suppressor) and [[BRCA1]] and [[BRCA2]] (related to breast cancer).<ref>P. Fortina, D. Graves, C. Stoeckert, Jr., S. McKenzie, and S. Surrey in ''Biochip Technology'', J. Cheng and L. J. Kricka, eds., ch. Technology Options and Applications of DNA Microarrays, pp.&nbsp;185–216, Harwood Academic Publishers, Philadelphia, 2001</ref> The chips are produced by using [[microlithography]] techniques traditionally used to fabricate [[integrated circuit]]s (see below).