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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要威斯康星大学麦迪逊分校的尖端研究在定量和研究蛋白质组学、功能糖组学研究、生物活性分子的结构表征、天然产物发现和代谢组学分析，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，并尽职地比较商业高分辨率质谱仪产品，该提案寻求资金来购买具有能力的仪器减轻分析灵敏度、质量分辨率、离子分离和占空比方面的限制目前可用的光谱仪，这直接有利于每个研究重点。鉴于复杂性人类和疾病相关样品、电喷雾 (ESI) 和基质辅助激光解吸电离基于 (MALDI) 的质谱 (MS) 仪器显示出由于有限的灵敏度而导致的灵敏度限制前体选择、单电荷离子干扰以及可消除高达 90% 离子的低占空比在分析之前。在经过初步选择后存活下来的物种中，通过串联鉴定生物分子低丰度分析物的前体共分离和信号抑制可能会严重阻碍 MS 扫描。考虑到这些限制，新兴文献和个人评估表明，俘获离子淌度光谱分析 (TIMS) 是一种独特的范式，能够扩展蛋白质组学、糖蛋白质组和小分子分析，同时还提供了最高的气相分辨率方案结构和构象研究。布鲁克 timsTOF fleX MS 的创新仪器设计系统结合了对源区域、TIMS 单元和四极杆的多项新颖设计改进，显着提高仪器性能。我们对 timsTOF fleX 的初步测试以及与其他产品的比较当前的高分辨率轨道阱和离子淌度仪器表明收购了 timsTOF fleX 提供的对我们的研究合作伙伴来说最大的好处，因为它是蛋白质组学、糖蛋白质组学、代谢组学和离子淌度分析。这种新仪器将提供先进的 MS 功能来支持 26 位高产的 NIH 资助研究人员开展了 73 个正在进行的项目的研究。在这一广泛领域取得的进展的项目将通过各机构之间的密切合作有效利用新工具来促进用户群体，李博士是一位高产的教员，在生物量方面拥有超过 27 年的经验光谱测定法，以及威斯康辛大学麦迪逊分校药房-质谱设施主任 Scarlett 博士。替代工具或如果该申请得到资助，肯定会考虑分配资金。