HT Label-Free Screening and Kinetic Analysis of Small Molecules and Biologics

小分子和生物制剂的 HT 无标记筛选和动力学分析

• 批准号: 8832297
• 负责人: Benjamin Delbert Brooks
• 金额: $ 51.04万
• 依托单位: CARTERRA, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8832297
• 关键词: Affinity; Antibodies; Antigens; Automation; Binding; Biosensing Techniques; Biosensor; Chemistry; Computer software; Coupling; Data; Data Analyses; Data Collection; Data Quality; Detection; Devices; Grant; Healthcare; Hour; Image; Imaging technology; Interferometry; Investments; Kinetics; Label; Legal patent; Libraries; Light; Location; Marketing; Measurement; Membrane; Microfluidics; Molecular Weight; Monitor; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phosphotransferases; Preparation; Probability; Process; Protocols documentation; Race; Research; Research Personnel; Resolution; Risk; Role; Sampling; Sampling Studies; Scientist; Secondary to; Small Business Technology Transfer Research; Specificity; Spottings; Staging; Surface; Surface Plasmon Resonance; System; Technology; Testing; Time; Work; computerized data processing; cost; detector; drug discovery; high throughput screening; improved; industry partner; instrument; instrumentation; novel; pressure; protein protein interaction; public health relevance; research and development; screening; sensor; small molecule; small molecule libraries; stoichiometry; success; tool

DESCRIPTION (provided by applicant): Real-time label-free technologies such as surface plasmon resonance biosensors provide high-resolution information about the kinetics, affinity, stoichiometry, activity, and specificity, of two (or more) binding partners. While the application f biosensors is well established, current instrumentation has limited sampling throughput. Screens of even a fairly small chemical library (e.g., 3000-5000 compounds) require days to weeks to complete using traditional label-free instruments. Because of the quality of the data generated by SPR, drug discovery scientists are clamoring to use enhanced biosensors as a screening tool for small molecule applications; however, lack of throughput hinders their ability to move in this direction. We propose to develop a biosensor platform that has increased throughput yet maintains the data quality and ease of use to which researchers are accustomed. We will couple our novel Continuous Flow Microspotter (CFM) with an enhanced-sensitivity SPR biosensor from BiOptix to enable label-free screening and kinetic analsyis of small molecules and biologics. In high-throughput screening mode our 96 channel integrated CFM/E-biosensor platform will be capable of collecting data for >30,000 samples in less than 24 hours - a sampling rate 24x faster than fastest small-molecule capable label-free biosensor, the Biacore 4000.

描述（由申请人提供）：实时无标签技术，如表面等离子体共振生物传感器，提供关于两个（或更多）结合伙伴的动力学、亲和力、化学计量、活性和特异性的高分辨率信息。虽然生物传感器的应用已经很成熟，但目前的仪器取样吞吐量有限。使用传统的无标签仪器，即使是相当小的化学文库（例如3000-5000种化合物）的筛选也需要几天到几周的时间才能完成。由于SPR产生的数据质量高，药物发现科学家们强烈要求使用增强型生物传感器作为小分子应用的筛选工具；然而，缺乏吞吐量阻碍了他们向这个方向发展的能力。我们建议开发一种生物传感器平台，该平台增加了吞吐量，同时保持了研究人员习惯的数据质量和易用性。我们将把我们的新型连续流微点仪（CFM）与BiOptix的高灵敏度SPR生物传感器结合起来，实现小分子和生物制剂的无标签筛选和动力学分析。在高通量筛选模式下，我们的96通道集成CFM/ e生物传感器平台将能够在不到24小时内收集100万份样品的数据-采样速率比最快的小分子无标签生物传感器Biacore 4000快24倍。