Development of a Mega-Dalton Mass Spectrometer for Biological Research

用于生物研究的兆道尔顿质谱仪的开发

• 批准号: 0454980
• 负责人: Mark Bier
• 金额: $ 54.31万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0454980&HistoricalAwards=false
• 关键词: Development; Mega; Dalton; Mass; Spectrometer

This award supports the development of a mass spectrometer capable of mass analyzing mega-Dalton biomolecules with unprecedented sensitivity at Carnegie Mellon University. State-of-the-art mass spectrometers currently lack the combined sensitivity, resolution and mass accuracy necessary for routine analysis of singly-charged high molecular weight ions. This next-generation matrix-assisted laser desorption ionization (MALDI) ion trap mass spectrometer will be designed to overcome the high m/z (mass/charge) barrier. The project incorporates a cross-disciplinary collaborative effort by chemists, physicists and biologists both in academia and industry and should greatly impact the mass analysis of mega-Dalton biomolecules. The proposed heavy-ion mass spectrometer will have ultra-high sensitivity by interfacing three innovative MS components: i.) a unique MALDI source, ii.) a mega-Dalton mass range ion trap and iii.) a detector with 100% detection efficiency at high mass. The goal is to analyze large molecules or complexes with m/z ranging from 10,000 to 15,000,000 at the attomole level. The development of this new instrument should provide breakthrough performance for the direct mass analysis of mega-Dalton biomolecules, bio-structures, non-covalent and covalent multi-protein complexes, protein/adducts, DNA and viruses. This project is directed at a long-term research goal of single cell proteomics. The development and dissemination of a next-generation mass spectrometer for analysis of macromolecules will impact many fields. For the biological sciences, the proposed instrument should significantly advance research in proteomics, where the challenge is to identify all proteins and characterize all protein-protein interactions in a biological system. In addition, the instrument's capabilities should benefit the field of nanotechnology, which currently lacks a good method to characterize large molecules. To educate students and scientists about the heavy-ion mass spectrometer, presentations about this development will target both small colleges and major universities. The mega-Dalton mass spectrometer will be used to teach undergraduates, graduate students and post doctorial students about MS instrumentation development both in these presentations and in courses taught at Carnegie Mellon (Chem 09-543: Mass Spectrometry and Chem 09-445: Undergraduate Research). Undergraduate research positions will be offered to students from under-represented groups. To widen the impact to the greatest number of students, the development of the new spectrometer will be incorporated into a NSF Internet educational tool called the Virtual Mass Spectrometry Laboratory (http://svmsl.chem.cmu.edu).

该奖项支持卡内基梅隆大学开发一种质谱仪，该质谱仪能够以前所未有的灵敏度对百万道尔顿生物分子进行质量分析。目前，最先进的质谱仪缺乏常规分析单电荷高分子量离子所需的灵敏度、分辨率和质量精度。这种下一代基质辅助激光解吸电离（MALDI）离子阱质谱仪将被设计用于克服高m/z（质量/电荷）势垒。该项目结合了学术界和工业界化学家、物理学家和生物学家的跨学科合作努力，将极大地影响巨道尔顿生物分子的质量分析。提出的重离子质谱仪将通过连接三个创新的质谱组件具有超高灵敏度：i.)一个独特的MALDI源，ii.)一个百万道尔顿质量范围的离子阱，iii.)一个在高质量下具有100%检测效率的检测器。目标是在原子水平上分析m/z范围从10,000到15,000,000的大分子或复合物。该仪器的开发将为巨道尔顿生物分子、生物结构、非共价和共价多蛋白复合物、蛋白质/加合物、DNA和病毒的直接质量分析提供突破性的性能。本项目以单细胞蛋白质组学为长期研究目标。用于分析大分子的下一代质谱仪的发展和推广将影响许多领域。对于生物科学，该仪器将显著推进蛋白质组学的研究，其中的挑战是识别生物系统中所有蛋白质和表征所有蛋白质-蛋白质相互作用。此外，该仪器的能力应该有利于纳米技术领域，该领域目前缺乏表征大分子的好方法。为了教育学生和科学家关于重离子质谱仪的知识，有关这一发展的演讲将以小型学院和主要大学为目标。超级道尔顿质谱仪将用于教授本科生、研究生和博士后关于质谱仪器发展的内容，包括在这些演讲和卡内基梅隆大学的课程中（Chem 09-543：质谱学和Chem 09-445：本科生研究）。本科研究职位将提供给来自代表性不足群体的学生。为了扩大对尽可能多的学生的影响，新光谱仪的开发将被纳入国家科学基金会的互联网教育工具，称为虚拟质谱实验室（http://svmsl.chem.cmu.edu）。