SBIR Phase II: High Speed Chemical Analysis of Combinatorial Libraries

SBIR 第二阶段：组合文库的高速化学分析

• 批准号: 9983700
• 负责人: Jack Syage
• 金额: $ 39.92万
• 依托单位: SYAGEN TECHNOLOGY INC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2003-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9983700&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Speed; Chemical

This Small Business Innovation Research Phase II project will develop a high through-put drug screening technology based on the successful Phase I feasibility demonstration. High throughput methods in parallel and combinatorial organic synthesis are revolutionizing the field of drug discovery and biological screening. However, progress is seriously impeded by lack of reliable methods for conducting high throughput chemical analysis (HTCA) for composition and purity assessment. Current approaches rely on liquid chromatography/mass spectrometry (LC/MS). With a cycle time of about 5 min, an LC/MS instrument can analyze about 300 samples in a 24 hr period. We propose an innovative MS concept that reduces cycle time to about 10 sec, raising the potential analysis rate to 5,000 samples/day. The innovation is based on a novel ionization source that achieves (1) near-universal and efficient ionization of drug compounds, (2) minimal fragmentation molecular ion spectra for accurate analysis, (3) minimal interference from air constituents and commonly used solvents, and (4) suppression of competition-for-charge and ion suppression effects experienced by conventional methods. The proposed technology advances analytical and research capabilities to improve fundamental understanding of drug molecules and to build a knowledge base for implementing more rational approaches to lead drug optimization.Market research indicates the potential for exponential growth on the basis of quick penetration of the chemical analysis niche of the rapidly growing field of combinatorial and parallel synthesis methods for drug discovery. The proposed high throughput chemical analysis system has the potential to dominate the market for combinatorial library analysis, which is a rapidly growing field of drug discovery. Our real-time, complex mixture analyzers will also be marketed for applications in drug testing, environmental monitoring, and on-line process monitoring.

这个小企业创新研究第二阶段项目将在成功的第一阶段可行性论证的基础上开发高通量药物筛选技术。 并行和组合有机合成中的高通量方法正在彻底改变药物发现和生物筛选领域。然而，由于缺乏可靠的方法进行高通量化学分析（HTCA）的组成和纯度评估的进展严重受阻。目前的方法依赖于液相色谱/质谱（LC/MS）。循环时间约为5分钟，LC/MS仪器可在24小时内分析约300个样品。 我们提出了一个创新的MS概念，将周期时间缩短到约10秒，将潜在的分析速率提高到5,000个样品/天。 该创新基于一种新型电离源，该电离源实现了（1）药物化合物的近乎通用和有效的电离，（2）用于准确分析的最小碎片分子离子光谱，（3）来自空气成分和常用溶剂的最小干扰，以及（4）抑制传统方法所经历的电荷竞争和离子抑制效应。 所提出的技术推进分析和研究能力，以提高对药物分子的基本理解，并建立一个知识库，以实施更合理的方法来领导药物优化。市场研究表明，在快速增长的组合和并行合成方法用于药物发现的化学分析利基领域的快速渗透的基础上，有指数增长的潜力。 所提出的高通量化学分析系统有可能主导组合库分析市场，这是一个快速增长的药物发现领域。 我们的实时复杂混合物分析仪也将用于药物测试、环境监测和在线过程监测。