Synthesis and screening of immobilized oligonucleotide arrays

A method of synthesizing and screening oligonucleotides comprising the sequential steps of:

• a) generating a pattern of light and dark areas by selectively irradiating at least a first area of a surface of a substrate, said surface comprising immobilized nucleotides on said surface, said nucleotides capped with a photoremovable protective group, without irradiating at least a second area of said surface, to remove said protective group from said nucleotides in said first area;
• b) simultaneously contacting said first area and said second area of said surface with a first nucleotide to couple said first nucleotide to said immobilized nucleotides in said first area, and not in said second area, said first nucleotide capped with said photoremovable protective group;
• c) generating another pattern of light and dark areas by selectively irradiating with light at least a part of said first area of said surface and at least a part of said second area to remove said protective group in said at least a part of said first area and said at least a part of said second area;
• d) simultaneously contacting said first area and said second area of said surface with a second nucleotide to couple said second nucleotide to said immobilized nucleotides in at least a part of said first area and at least a part of said second area;
• e) performing additional irradiating and nucleotide contacting and coupling steps so that a matrix array of at least 100 oligonucleotides having different sequences is formed on said surface, said at least 100 oligonucleotides in at least 100 respective areas of less than 0.1 cm.sup.2, whereby said at least 100 oligonucleotides have sequences and locations on said surface defined by the patterns of light and dark areas formed during the irradiating steps and the nucleotides coupled in said contacting steps;
• and
• f) contacting said at least 100 oligonucleotides with a receptor to identify an oligonucleotide showing complementarity to said receptor.