TWO DIMENSIONAL MASS SPECTROMETER FOR PROTEOMIC RESEARCH

用于蛋白质组研究的二维质谱仪

• 批准号: 6994149
• 负责人: Houle Wang
• 金额: $ 40.29万
• 依托单位: MICHROM BIORESOURCES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6994149
• 关键词: bioengineering /biomedical engineering; bioinformatics; biomedical equipment development; computational biology; computer data analysis; computer program /software; computer system design /evaluation; high throughput technology; mass spectrometry; proteomics

DESCRIPTION (provided by applicant): The impact of mass spectrometry in life science has been increasingly draw attentions in the last two decades. As interests to mass spec applications getting broader and the techniques penetrate into each research area getting deeper, more challenges have been created. One of the challenges from proteomic researches is dealing with more complex samples with higher throughputs and wider dynamic range. Existing instruments and technologies are still far from meeting researchers demand. The goal of the proposed work is to develop a novel mass spectrometer and the associate methods which could provide much better peptide coverage at higher throughput for complex protein samples with lower detection limits, especially for low abundant proteins. This project will focus on tandem two-dimensional mass spectrometer and its applications. The new instrument will obtain complete MS/MS information, include fragmentation ions from all precursors with their parent-daughter linkage. The ions from the ion source will not be filtered out or under discriminatory selection, instead each of them will be fragmented to get MS/MS spectra, resulting much higher ion usage efficiency. Under phase I investigation, a prototype hybrid Qit-q-TOF instrument was built for 2D MS/MS experiments. Interfaces between each components have been studied, especially for ion trap ion ejection. Results from both computer simulation and experiments demonstrated the kinetic energy of ejected ions are low enough for interfacing TOF analyzer by using proposed reverse scan resonance ejection, which further approved Qit-q-TOF concept is technically feasible for 2D MS/MS. Under phase II funding, we will continue to improve the performance, eventually achieve the requirements of a commercial instrument. With the collaboration to cutting edge research groups, key applications and informatics tools will be developed.

描述（申请人提供）：近二十年来，质谱在生命科学中的作用日益受到关注。随着人们对质谱应用的兴趣越来越广泛，技术向各个研究领域的渗透越来越深入，也带来了更多的挑战。蛋白质组学研究的挑战之一是处理具有更高通量和更宽动态范围的更复杂样品。现有的仪器和技术还远远不能满足研究人员的需求。本论文的目标是开发一种新型的质谱仪及其相关方法，该质谱仪能够以更高的通量为复杂蛋白质样品提供更好的肽覆盖率，并且具有较低的检测限，特别是对于低丰度蛋白质。本计画主要研究串列二维质谱计及其应用。新仪器将获得完整的MS/MS信息，包括来自所有前体及其母-子连接的碎片离子。来自离子源的离子将不会被过滤掉或在歧视性选择下，而是它们中的每一个将被片段化以获得MS/MS谱，从而产生更高的离子使用效率。在第一阶段的研究中，建立了一个原型混合Qit-q-TOF仪器的二维MS/MS实验。已经研究了每个组件之间的接口，特别是对于离子阱离子喷射。计算机模拟和实验结果表明，通过使用所提出的反向扫描共振喷射，喷射离子的动能足够低以用于连接TOF分析器，这进一步证实了Qit-q-TOF概念在技术上用于2D MS/MS是可行的。在第二阶段的资助下，我们将继续改进性能，最终达到商业仪器的要求。通过与前沿研究小组的合作，将开发关键的应用程序和信息学工具。