Development of a Mega-Dalton Mass Spectrometer for Biological Research

该奖项支持卡内基梅隆大学开发能够以前所未有的灵敏度大量分析巨型道尔顿生物分子的质谱仪。目前最先进的质谱仪缺乏常规分析单电荷高分子离子所需的综合灵敏度、分辨率和质量精度。这种新一代基质辅助激光解吸电离(MALDI)离子陷阱质谱仪将被设计用于克服高m/z(质量/电荷)势垒。该项目融合了学术界和工业界的化学家、物理学家和生物学家的跨学科合作努力，应该会对巨型道尔顿生物分子的质量分析产生重大影响。拟议的重离子质谱仪将通过连接三个创新的MS组件而具有超高灵敏度：i.)一个独一无二的MALDI来源，II。)一个兆道尔顿质量范围的离子陷阱和III。)一种在高质量时具有100%检测效率的探测器。目标是在全摩尔水平上分析m/z从10,000到15,000,000的大分子或络合物。这一新仪器的开发将为大道尔顿生物大分子、生物结构、非共价和共价多蛋白质络合物、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。该项目是针对单细胞蛋白质组学的长期研究目标。用于大分子分析的新一代质谱计的发展和推广将对许多领域产生影响。对于生物科学，拟议的仪器应该大大促进蛋白质组学的研究，这方面的挑战是识别所有蛋白质并描述生物系统中所有蛋白质-蛋白质相互作用的特征。此外，该仪器的能力应该会使纳米技术领域受益，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计的知识，关于这一发展的演讲将针对小型学院和主要大学。Mega-Dalton质谱仪将在这些演讲和卡内基梅隆大学教授的课程(化学09-543：质谱学和化学09-445：本科生研究)中用于教授本科生、研究生和博士后关于MS仪器开发的知识。将向代表性不足群体的学生提供本科生研究职位。为了扩大对最多学生的影响，新光谱仪的开发将被纳入美国国家科学基金会名为虚拟质谱学实验室(http://svmsl.chem.cmu.edu).)的互联网教育工具中

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).