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

加州大学戴维斯分校因开发用于超高通量生物分子合成和筛选的创新仪器平台而获奖。通过采用新兴的微制造、微流控、自组装和编码技术，该计划旨在通过引入在固体载体上制造的编码微盘阵列和带有条形码扫描和解码步骤的改进的分裂混合合成方法，来解决集成功能、化学鉴定、合成产量和组合化学的效率。在高效的数字组合合成之后，每个都显示唯一的分子序列和不同的二进制条形码的微盘载体可以自组装成紧密排列的阵列，用于并行地定量表征大量的细胞-配体相互作用。为了展示转化生物分子平台的广泛实用性和适用性，将针对多个肿瘤细胞系合成、筛选和优化随机和环肽文库，从中有望有效地发现高特异性和高亲和力的肿瘤靶向配体。组合化学已使分子发现和生物标记物识别在癌症生物学和药物开发的许多领域成为可能。编码的微盘阵列将显著降低操作的复杂性，促进化学合成，并允许组合化学的直接序列鉴定。这个多功能的平台未来可以适应更广泛的组合生化和生物医学发现。拟议的合作研究计划将提供一个极好的机会，吸引和培训尖端跨学科研究领域的年轻科学家和工程师，更重要的是，通过各种教育和外联活动招募和提拔女性和代表性不足的少数群体。关于分子发现仪器开发的详细信息将通过会议报告(例如，年度MicroTAS会议)、开放获取期刊(例如，可视化实验杂志)和在线视频资源(例如，YouTube)到达更广泛的生物和生化社区。该奖项由生物理事会的IDBR计划(生物研究仪器开发)和工程局的生物技术、生化和生物质工程(BBBE)计划共同资助。

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.