Dr. Yiyan Fei Profile

Dr. Yiyan Fei

at Fudan Univ

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Proceedings Article | 23 February 2017 Paper

High-throughput screening based on label-free detection of small molecule microarrays

Chenggang Zhu, Yiyan Fei, Xiangdong Zhu

Proceedings Volume 10081, 100810S (2017) https://doi.org/10.1117/12.2246462

KEYWORDS: Microscopes, Proteins, Chemistry, Glasses, Reflectivity, Ellipsometry, Printing, Annealing, Molecules, Scanners, Drug discovery, Molecular interactions, Polarizers, Distortion

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Based on small-molecule microarrays (SMMs) and oblique-incidence reflectivity difference (OI-RD) scanner, we have developed a novel high-throughput drug preliminary screening platform based on label-free monitoring of direct interactions between target proteins and immobilized small molecules. The screening platform is especially attractive for screening compounds against targets of unknown function and/or structure that are not compatible with functional assay development. In this screening platform, OI-RD scanner serves as a label-free detection instrument which is able to monitor about 15,000 biomolecular interactions in a single experiment without the need to label any biomolecule. Besides, SMMs serves as a novel format for high-throughput screening by immobilization of tens of thousands of different compounds on a single phenyl-isocyanate functionalized glass slide. Based on the high-throughput screening platform, we sequentially screened five target proteins (purified target proteins or cell lysate containing target protein) in high-throughput and label-free mode. We found hits for respective target protein and the inhibition effects for some hits were confirmed by following functional assays. Compared to traditional high-throughput screening assay, the novel high-throughput screening platform has many advantages, including minimal sample consumption, minimal distortion of interactions through label-free detection, multi-target screening analysis, which has a great potential to be a complementary screening platform in the field of drug discovery.

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