Traditional molecular biology and biotechnology dealt with the phenomenon of one gene for one experiment basis. However, this traditional view did not give the overview of the whole genetic activity played in a cell. GeneChips were developed in order to obtain a more complete picture of the genetic activity of the cell. The GeneChip is nothing but a specialized microarray (See also DNA Arrays) which has DNA sequences built on top of it such that, if sample DNA is incubated within it, it will bind to it and produce visual signal which can be detected. The method developed by Stephen Fodor has been described in detail in the animation below.
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In the early 1990s, Stephen Fodor and his team developed a technique to produce miniature arrays of biological molecules. Their work led to the first DNA chip, and became the basis of techniques for large-scale genomic studies. The company Affymetrix was spun off in the early 1990s to focus on DNA GeneChips®.
Stephen Fodor developed a technique called GeneChip® probe arrays where he built the sequences he wanted to screen. These GeneChip® arrays are printed on special glass.
DNA sequences are built up using light-directed chemical synthesis. First, a substrate with a nucleotide is fixed onto the chip at specific positions.
The nucleotide has a protecting group (X) that blocks polymerization. This protector group is photolabile and is released on exposure to UV light. Without the protector, polymerization and chain build-up occur.
A filter is added to the chip so tha only some of the nucleotides are exposed to light. These deprotected groups are then free to add the next nucleotide to the chain.
By alternating the position of the filter, Fodor can build a GeneChip® with an array of different sequences about 20 nucleotides long.
Fodor added a cDNA probe to the GeneChip®. He can simultaneously assay tens of thousands of different sequences at the same time.
When a cDNA probe is added to the GeneChip®, tens of thousands of different sequences can be assayed at the same time.
Since this entire process is done with a computer, the matching sequences can be quickly pinpointed, and then be matched to available DNA sequences in gene databases.