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

IDBR：用于超高通量生物分子筛选的编码组合微盘阵列

• 批准号: 1256193
• 负责人: Tingrui Pan
• 金额: $ 39.01万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1256193&HistoricalAwards=false
• 关键词: IDBR; Encoded; Combinatorial; Microdisc; Array

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.

授予加州大学戴维斯分校一个奖项，以开发用于超高通量生物分子合成和筛选的创新仪器平台。 通过采用新兴的微加工，微流体，自组装和编码技术，该计划旨在解决集成功能，化学鉴定，合成通量和组合化学的效率，通过引入在固体支持物上制造的编码microdisc阵列和改进的分裂混合合成方法与条形码扫描和解码步骤。 在高效数字组合合成之后，每个显示独特分子序列和独特二进制条形码的微盘载体可以自组装成紧密堆积的阵列，用于并行定量表征大量细胞-配体相互作用。 为了展示这一变革性生物分子平台的广泛用途和适用性，将针对多种癌细胞系合成、筛选和优化随机和环状肽库，从中有望高效发现具有高特异性和高亲和力的癌症靶向配体。组合化学在癌症生物学和药物发现的许多领域实现了分子发现和生物标志物鉴定。 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很好的机会，让年轻的科学家和工程师参与和培训尖端的跨学科研究领域，更重要的是，通过各种教育和宣传活动，招募和促进妇女和代表性不足的少数民族。 有关分子发现仪器开发的详细信息将通过会议介绍（例如，年度microTAS会议），开放获取期刊（例如，Journal of Visualized Experiments）和在线视频资源（例如，该奖项由BIO理事会的IDBR计划（生物研究仪器开发）和工程理事会的生物技术，生物化学和生物质工程（BBBE）计划共同资助。