Abstract

We developed a novel high-throughput screening platform based on small-molecule microarrays (SMMs) and oblique-incidence reflectivity difference (OI-RD) microscope. OI-RD microscope is able to monitor tens of thousands of biomolecular interaction in a single experiment without the need to label any biomolecule. We also developed surface chemistry to prepare SMMs which is able to immobilize compounds with any nucleophilic residues on phenyl-isocyanate functionalized glass slides with high efficiencies. By using OI-RD microscope and SMMs with 3,375 bioactive compounds, we screened target proteins in high-throughput and label-free mode and we found hits for respective target protein. The novel high-throughput screening platform enables target proteins with unknown structure and/or unknown function to be effectively screened.

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