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Moving Chips to the Clinic - What Sits on a Chip

They are tiny and quick, but beyond that, most chips used in genomics have little in common with their silicon counterparts.

DNA microarrays were the first biological chips (also referred to as arrays) and offered scientists their first high-throughput tool for studying gene function. The first microarrays to come into widespread use were the spotted arrays developed by Patrick Brown in the mid-1990s at Stanford University. Affymetrix's GeneChips, the first commercial arrays, were released in 1996.

Both types of arrays measure gene expression. The array contains a set of probes, either full-length genes or short oligonucleotides, that interrogate the genes in the test sample. If a gene is present on both the array and the sample, a signal results. The intensity of the bound signal reflects the level at which a gene is being expressed. Arrays are usually made from glass or plastic and are typically about 1.5 centimeters square. The densest arrays can contain probes for tens of thousands of genes.

Affymetrix uses a process akin to microscopic photolithography (used in semiconductor manufacturing) to synthesize its probes. Nucleotides are added to each probe one by one through a precise series of stencil-like masks. For spotted arrays, whether manufactured or homemade, the genes are applied by direct printing, and now also through an inkjet-like spraying process.

Affymetrix's semiconductor-like process, the rapid popularity of its arrays, and its GeneChip brand led to a growing use of the term "chip" to refer to arrays.

Other types of arrays can also be used to measure single nucleotide polymorphisms, which are single base-pair variations, and which reflect the measure of genetic difference between individuals. Protein arrays are also coming into use, as well as new "high content" arrays that provide gene function details beyond the level of gene expression.

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