IDBR: Type A:Development of a Digital Ion Trap Mass Spectrometer for Resolved Mass Analysis of Intact Singly-Charged Proteins, Complexes, RNA, DNA and Viruses

该奖项由生物基础设施部(生物科学局)的生物研究仪器开发机构授予华盛顿州立大学，由化学部(数学和物理科学局)的化学测量和成像计划联合资助。非技术描述20世纪80年代末，随着新的电离技术的出现，生物分子的质量分析从1,000个单位扩展到20,000个单位，使得生物分子的质量分析成为可能。不幸的是，这项技术受到限制，因为蛋白质、复合体、RNA、DNA和病毒的大小远远超过2万个单位，因此不容易分析。拟议中的新数字离子陷阱质谱仪的开发将把质量范围扩大到1000万个单位甚至更多，从而能够直接和定量地测量大量生物分子和复合体，并观察这些巨大物种与其他或小或大的物种的相互作用。这项技术的影响将在包括化学、生物化学、生物学、物理学、医学、兽医和植物科学在内的广泛学科中感受到。它将为学生提供合作的机会，并拓宽他们在特定学科之外的科学知识。这项工作的成果将通过出版物、合作、教学和包括本科生和高中生在内的外联活动来传播。出版和合作将产生对这种仪器的需求，仪器制造商最终将填补这一需求。这个为期三年的项目将开发一种数字离子陷阱(DIT)技术，将离子陷阱质谱仪的工作范围扩大五个数量级。在该项目的第一阶段，将开发一个原型，它将能够直接分析完整的单电荷蛋白质和蛋白质复合体及其与小分子的相互作用。该项目的第二阶段将安装一个质量无关的法拉第探测器，并将开发方法来分析完整的单电荷蛋白质、复合体、RNA和DNA及其弱的非共价相互作用。

This award to Washington State University by the Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate), is jointly funded by the Chemical Measurements and Imaging program, in the Division of Chemistry (Math and Physical Sciences Directorate).Non-Technical descriptionMass analysis of biological molecules was enabled in the late 1980s with the advent of new ionization techniques that extended the mass range from 1,000 units to 20,000 units. Unfortunately this technology is limited because the size of proteins, complexes, RNA, DNA and viruses greatly exceed 20,000 units, so they are not easily analyzed. The proposed development of a new digital ion trap mass spectrometer will extend the mass range out to 10,000,000,000 units and beyond, allowing direct and quantitative measurement of massive biological molecules and complexes, and to observe interaction of these massive species with others small or large. The effect of this technology will be felt across a wide range of disciplines including chemistry, biochemistry, biology, physics, medical, veterinary and plant science. It will provide opportunities for students to collaborate and broaden their scientific knowledge beyond their specific disciplines. The results of this work will be disseminated through publications, collaborations, teaching and outreach that include undergraduates and high school students. Publications and collaborations will create a demand for this instrumentation, which the instrument manufacturers will eventually fill. Technical descriptionThe three-year project will develop a digital ion trap (DIT) technology to extend the working range of ion trap mass spectrometers by five orders of magnitude. In the first phase of the project, a prototype that will enable direct analysis of intact singly-charged proteins and protein complexes and their interactions with small molecules will be developed. The second phase of this project will install a mass independent Faraday detector, and methods will be developed to analyze intact singly-charged proteins, complexes, RNA and DNA and their weak non-covalent interactions.