A method for synthesizing and screening oligonucleotides on a solid substrate. The method provides for the irradiation of a first predefined region of a substrate comprising immobilized nucleotides on its surface, without irradiation of a second predefined region of the substrate. The irradiation step removes a protecting group from the immobilized nucleotides. The substrate is contacted with a first nucleotide to couple the nucleotide to the immobilized nucleotides in the first predefined region without coupling in the second predefined region. At least a part of the first predefined region and at least a part of the second predefined region are subjected to further irradiation. The substrate is contacted with a second nucleotide, which couples to the immobilized nucleotides in at least part of the first and at least part of the second predefined regions. By repeating these steps, an array of diverse oligonucleotides is formed on the substrate. The diverse oligonucleotides are then screened for specific binding to a receptor, e.g., a polynucleotide.