IDBR: Encoded Combinatorial Microdisc Array for Ultrahigh-Throughput Biomolecule Screening

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An award is made to the University of California, Davis to develop an innovative instrumental platform for ultrahigh-throughput biomolecular synthesis and screening. By employing emerging microfabrication, microfluidics, self-assembly, and encoding techniques, the program is aimed at addressing integrated functionality, chemical identification, synthetic throughput and efficiency of combinatorial chemistry, by introducing encoded microdisc array fabricated on solid support and a modified split-mix synthetic approach with barcode scanning and decoding steps. Following the high-efficiency digital combinatorial synthesis, microdisc carriers, each displaying a unique molecular sequence and a distinct binary barcode, can be self-assembled into a closely packed array for quantitative characterization of massive cell-ligand interactions in parallel. To demonstrate the broad utility and applicability of the transformative biomolecular platform, both random and cyclic peptide libraries will be synthesized, screened and optimized against multiple cancer cell lines, from which cancer-targeting ligands with high specificity and high affinity are expected to be efficiently discovered.Combinatorial chemistry has enabled molecular discovery and biomarker identification in many areas of cancer biology and drug discovery. The encoded microdisc array will significantly reduce the complexity of operations, facilitate chemical synthesis, and allow direct sequence identification of the combinatorial chemistry. This versatile platform can be adapted in the future to an even broader range of combinatorial biochemical and biomedical discoveries. The proposed collaborative research program will provide an excellent opportunity to engage and train young scientists and engineers in the cutting-edge interdisciplinary research field, and more importantly, to recruit and promote women and underrepresented minorities via various educational and outreach activities. Detailed information about the development of the molecular discovery instrument will reach the broader biology and biochemistry communities through conference presentations (e.g., annual microTAS conferences), open-access journals (e.g., Journal of Visualized Experiments), and online video resources (e.g., YouTube).This award is co-funded by the IDBR program (Instrument Development for Biological Research) in the BIO Directorate, and Biotechnology, Biochemical, and Biomass Engineering (BBBE)program in the Engineering Directorate.