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Combinatoric theory states that the number of compounds of length N, composed of Y different subunits, is equal to Y^N, and one can synthesize each of Y^N compounds in Y times N steps. Applying this theory to the genome, 25mer probes are created by using four nucleotides, A, C, T & G, enabling the synthesis of roughly 10^15 probes in 4 times 25, or 100 steps. In this way, it’s possible to make an array of virtually any size–including arrays that can examine the entire 3.1 billion bases in the human genome–in 100 steps or less. In-process quality control (to assure that each step occurs correctly) is possible because of the relatively few synthesis steps required.
By reducing array feature size, more probes can be packaged onto the same size surface, increasing the genetic processing power of each individual array. For instance, the first commercial GeneChip products shipped in 1994 had a feature size of 100 microns. By 2005 feature size was reduced to 5 microns, allowing over 400 times more content on each array. Yet, microarray technology has tremendous room for continued growth–submicron lithographic methods are routinely used in semiconductor fabrication–allowing for higher densities and more content on the same size arrays, with the same flexibility for different “power” chips as is evident in the microprocessor industry. |