ing by ligation, exploits the tendency of DNA strands to bind, or hybridize, with their complementary sequences and not with mismatched sequences. This system, employed by Affymetrix, Perlegen Sciences and Illumina, is already in widespread commercial use, primarily to look for variations in known gene sequences. It requires synthesizing short single strands of DNA in every possible combination of base sequences and then arranging them on a large slide. When copies of the template strand whose sequence is unknown are washed across this array, they will bind to their complementary sequences. The best match produces the brightest fluorescent signal. Illumina also adds a base-extension step to this test of hybridization specificity. One final technique with great long-term promise takes an entirely different approach to identifying the individual bases