PARALLEL TIME OF FLIGHT MASS SPECTROMETER

并行飞行时间质谱仪

• 批准号: 2794315
• 负责人: JAMES G BOYLE
• 金额: $ 10.08万
• 依托单位: ANALYTICA OF BRANFORD, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2794315
• 关键词: analytical method; biomedical automation; combinatorial chemistry; electrospray ionization mass spectrometry; liquid chromatography; method development

Large compound libraries are being generated in pharmaceutical discovery applications, placing a growing burden on the analytical scientist to rapidly characterize these samples both at the gross scale for synthesis confirmation and in focused studies for more promising compounds. Exacerbating this throughput challenge, the purity of compounds generated fran multi-step synthetic organic reactions on polymeric beads is often compromised. In the absence of chromatographic separation, these impurities may lead to both false positives and false negatives in flow injection mass spectrometry (MS), depending upon the physio-chemical properties of the analyte, competing inter-mediate products and resin contributed impurities. Analytical groups with Ms responsibilities must therefore choose between (a) faster but less informative flow injection methods and (b) more reliable, but slower LC-MS methods. A method is proposed to deliver significantly increased Ms sample throughput, while at the same time addressing the need for high chemical selectivity which only LC-MS can deliver. Exploiting the characteristics of a specialized API time-of-flight mass spectrometer, multiple time-varying liquid streams will be simultaneously mass analyzed without resorting to flow switching or any other time-slice scheme. This new approach will allow multiple LC systems to be coupled to a single API-TOF-MS while maintaining research grade figures of merit. PROPOSED COMMERCIAL APPLICATION: This apparatus will allow significantly greater numbers of these samples to be characterized via LC-MS, without deploying additional MS analyzers. Such an instrument would find immediate utility in those high throughput screening applications which are presently bottle-necked by serial sample introduction to analytical instruments. Less a research tool than an automation tool, such an instruments would be ideally suited for automated, high speed, LC-MS in quality control and manufacturing operations.

在药物发现应用中，大量的化合物文库正在产生，这给分析科学家带来了越来越大的负担，他们需要在合成确认的总体规模上快速表征这些样品，并在更有前途的化合物的重点研究中快速表征这些样品。加剧这种吞吐量挑战的是，在聚合物珠上进行多步合成有机反应所产生的化合物的纯度经常受到损害。在没有色谱分离的情况下，这些杂质可能导致流动注射质谱（MS）中的假阳性和假阴性，这取决于被分析物的理化性质、竞争的中间产物和树脂贡献的杂质。因此，负责质谱分析的分析小组必须在(a)更快但信息量更少的流动注射方法和(b)更可靠但速度更慢的LC-MS方法之间做出选择。提出了一种方法来提供显着增加Ms样品通量，同时解决了只有LC-MS才能提供的高化学选择性的需求。利用专门的API飞行时间质谱仪的特性，多个时变液体流将同时进行质量分析，而无需采用流量切换或任何其他时间片方案。这种新方法将允许多个LC系统耦合到单个API-TOF-MS，同时保持研究等级数字的优点。建议的商业应用：该设备将允许更多数量的这些样品通过LC-MS进行表征，而无需部署额外的MS分析仪。这种仪器将在那些高通量筛选应用中发现直接效用，这些应用目前是由连续样品引入分析仪器的瓶颈。与其说是一种研究工具，不如说是一种自动化工具，这种仪器非常适合于质量控制和制造操作中的自动化、高速、LC-MS。