Acquisition of a Dual-Source, High-Performance, Ion Mobility, Quadrupole Time-of-Flight Mass Spectrometry System for Biomedical Research at UW-Madison

威斯康辛大学麦迪逊分校采购双源、高性能、离子淌度、四极杆飞行时间质谱系统用于生物医学研究

• 批准号: 10177384
• 负责人: LINGJUN LI
• 金额: $ 127.57万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177384
• 关键词: Area; Biological; Biomedical Research; Cells; Charge; Disease; Evaluation; Faculty; Funding; Gases; Health; Human; Investigation; Ions; Literature; Mass Spectrum Analysis; Mind; Molecular Conformation; Natural Products; Performance; Pharmacy facility; Phase; Proteomics; Research; Research Personnel; Research Support; Resolution; Sampling; Scanning; Signal Transduction; Source; Spectrometry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; System; Testing; United States National Institutes of Health; Universities; Wisconsin; base; design; experience; glycoproteomics; human disease; innovation; instrument; instrumentation; ion mobility; mass spectrometer; member; metabolomics; novel; small molecule; tandem mass spectrometry; time of flight mass spectrometry

PROJECT SUMMARY/ABSTRACT Cutting-edge research at the University of Wisconsin-Madison has led to pioneering efforts in quantitative and investigational proteomics, functional glycomic interrogation, structural characterization of bioactive molecules, natural product discovery and metabolomic profiling with significant focus on human health and disease. Upon evaluating the current needs of 26 NIH-supported investigators and dutiful comparison of commercial high- resolution mass spectrometer offerings, this proposal seeks funding for the purchase of instrumentation capable of alleviating the limitations in analytical sensitivity, mass resolution, ion separation, and duty cycle presented by currently-accessible spectrometers and that directly benefits each research focus. Given the complexity of human and disease-relevant samples, electrospray (ESI) and matrix-assisted laser desorption ionization (MALDI)-based mass spectrometry (MS) instrumentation demonstrate limitations in sensitivity due to limited precursor selection, interference from singly-charged ions, and low duty cycles that eliminate up to 90% of ions prior to analysis. Of the species that do survive initial selection, identification of biomolecules through tandem MS scans can be severely hindered by precursor co-isolation and signal suppression of low abundance analytes. With these limitations in mind, emerging literature and personal evaluations demonstrate that trapped ion mobility spectrometry (TIMS) is the paradigm uniquely capable of expanding analytical sensitivity in proteomic, glycoproteomic, and small molecule analyses, while also presenting the highest gas-phase resolution regime for structural and conformational investigation. The innovative instrument design of the Bruker timsTOF fleX MS system incorporates several novel design improvements to the source area, TIMS cell, and quadrupole to dramatically enhance instrument performance. Our initial testing of the timsTOF fleX and comparison to other current high-resolution orbitrap and ion mobility instruments indicate the acquisition of the timsTOF fleX provides the greatest benefit to our research partners, as it is the most effective regime in proteomic, glycoproteomic, metabolomic and ion mobility analysis. This new instrument will provide advanced MS capabilities to support the research of 26 highly productive NIH-funded investigators with 73 ongoing projects. Progress on this broad array of projects will be catalyzed by the effective usage of the new instrument through close cooperation among the user groups, Dr. Li, a highly productive faculty member with more than 27 years of experience in biological mass spectrometry, and Dr. Scarlett, the UW-Madison Pharmacy-MS Facility Director. Alternative instruments or allocation of funds would certainly be considered, should this application be funded.

项目摘要/摘要 威斯康星大学麦迪逊分校的尖端研究导致了定量和 研究蛋白质组学，功能性糖质询问，生物活性分子的结构表征， 自然产品发现和代谢组分析，重点关注人类健康和疾病。之上 评估26名NIH支持的研究人员的当前需求，并尽职尽责地比较商业高级 分辨率质谱仪产品，该提案寻求资金以购买能够仪器 减轻分析灵敏度，质量分辨率，离子分离和占空比的局限性 当前可访问的光谱仪，直接受益于每个研究重点。考虑到复杂的 人和疾病相关的样品，电喷雾（ESI）和基质辅助激光解吸电离电离 （MALDI）的质谱（MS）仪器表明，由于有限 前体的选择，单荷离子的干扰以及消除多达90％离子的低占空比周期 在分析之前。在最初选择的物种中，通过串联鉴定生物分子 MS扫描可能会严重阻碍低丰度分析物的前体共隔离和信号抑制。 考虑到这些局限 光谱法（TIMS）是能够扩大蛋白质组学的分析灵敏度的独特范式 糖蛋白质组学和小分子分析，同时也呈现最高的气相分辨率。 结构和构象研究。 Bruker Timstof Flex MS的创新仪器设计 系统将源区域，TIMS单元和四极的一些新颖的设计改进到 急剧增强仪器性能。我们对Timstof Flex的初步测试以及与其他的比较 当前的高分辨率Orbitrap和离子移动仪器表示flex的获取 对我们的研究伙伴来说是最大的好处 代谢组和离子迁移率分析。这种新工具将提供高级MS功能来支持 对26名高产NIH资助的研究人员的研究，共有73个正在进行的项目。在这个广泛的阵列上进展 通过在新工具之间有效使用新工具，可以通过密切合作来催化项目 用户群体Li博士是一位高产的教职员工，在生物群众方面拥有超过27年的经验 光谱法和UW-Madison Pharmacy-MS设施总监Scarlett博士。替代仪器或 如果资助此申请，则肯定会考虑资金的分配。