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GeneChip microarrays are a classic Silicon Valley innovation, combining several disciplines to create a new technology and more useful research tool. The integration of semiconductor fabrication techniques, solid phase chemistry, combinatorial chemistry, molecular biology, and sophisticated robotics results in a unique photolithographic manufacturing process that produces GeneChip arrays with millions of probes on a small glass chip.
The photolithographic process begins by coating a 5″ x 5″ quartz wafer with a light-sensitive chemical compound that prevents coupling between the wafer and the first nucleotide of the DNA probe being created. Lithographic masks are used to either block or transmit light onto specific locations of the wafer surface. The surface is then flooded with a solution containing either adenine, thymine, cytosine, or guanine, and coupling occurs only in those regions on the glass that have been deprotected through illumination.
The coupled nucleotide also bears a light-sensitive protecting group, so the cycle can be repeated. In this way, the microarray is built as the probes are synthesized through repeated cycles of deprotection and coupling. The process is repeated until the probes reach their full length, usually 25 nucleotides. Commercially available arrays are typically manufactured at a density of over 1.3 million unique features per array. Depending on the demands of the experiment and the number of probes required per array, each quartz wafer can be diced into tens or hundreds of individual arrays.
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