Orbitrap Fusion Lumos ETD with IRMPD for UM Chemistry MS Facility Expansion

 描述(由申请人提供)：本申请申请美国国立卫生研究院高端仪器项目，要求提供带电子转移解离(ETD)的Orbitrap Fusion Lumos；新一代Orbitrap Tribrid质谱仪将在提案截止日期后立即投放市场。通过一份保密协议(将于2015年5月31日到期)，我们获得了这款用于蛋白质组分析的改变游戏规则的仪器的报价，与当前最先进的Orbitrap Fusion Tribrid相比，其灵敏度提高了5倍，ETD效率提高了40%。在制造商(Thermo Fisher Science)的帮助下，我们寻求定制安装该仪器的红外多光子解离(IRMPD)。寻找的新一代Orbitrap Tribrid能够进一步将前体离子选择降低到0.4Amu，而不会造成分析物损失，从而大大提高了选择性。拟议的用户(7个主修，9个辅修)代表了密歇根大学(UM)的六个不同的系，所有这些系都位于密歇根大学中央校区，地理位置非常接近，完全缺乏共享蛋白质组分析的基础设施。UM在生物医学研究和质谱学(MS)技术方面都有良好的记录，这些技术使基础生物医学和疾病科学得以突破。建议的用户侧重于通过交联/MS分析与疾病相关的多蛋白复合体，量化蛋白质翻译后修饰中与疾病相关的变化，小量示踪分析肽、脂类和代谢物，以及发现天然产物生物合成途径和机制/结构询问。上述由美国国立卫生研究院资助的研究项目(17个R01、3个R37、1个DP2、2个U01和1个P50)将利用密歇根大学独特的世界级MS专家小组来开发/扩展Orbitrap Fusion Lumos的实用程序，包括定制的IRMPD功能，从而以新方法和技术的形式提供额外的好处。拟议的仪器将被安置在扩大的MS设施内，该设施正在发展成为UM化学系内的MS卓越中心。该设施被整个地区的研究人员高度使用，但仍然使用已有20至40年历史的过时仪器运行，因此迫切需要对本提案中描述的设备进行升级。仪器的操作和维护既将由化学系MS设施中现有的高素质工作人员执行，也将由文学、科学和艺术学院(LSA)资助的一名新的专职博士级工作人员执行，这意味着工作人员在五年内总共承诺约100万美元。此外，不同的UM单位已经为仪器提供了两年的服务成本分摊(除了一年的保修)，在此之后，我们预计主要用户/次要用户的仪器充值费用将支持化学MS设施内的仪器操作，包括对该设施的部分资金(~60%)的贡献 工作人员。其余40%的工作人员工资将继续由LSA支付。此外，UM LSA已同意翻新现有的MS设施空间，为所要求的Orbitrap Fusion Lumos做准备，以最大限度地提高其生产率和利用率。

 DESCRIPTION (provided by applicant): This application to the NIH high end instrumentation program requests an Orbitrap Fusion Lumos with electron transfer dissociation (ETD); a new generation Orbitrap Tribrid mass spectrometer to be released on the market immediately after the proposal deadline. Through a non-disclosure agreement (expiring May 31, 2015), we have obtained a quote for this game-changing instrument for proteomic analysis, including 5-fold sensitivity improvement and 40% higher ETD efficiency compared with the current state-of-the-art Orbitrap Fusion Tribrid. With the assistance of the manufacturer (Thermo Fisher Scientific) we seek to custom fit this instrument with infrared multiphoton dissociation (IRMPD). The sought new generation Orbitrap Tribrid is further capable of precursor ion selection down to 0.4 amu without analyte loss for greatly improved selectivity. The proposed users (7 major, 9 minor) represent six different University of Michigan (UM) Departments, all in close geographical proximity on the UM central campus, which is entirely void of infrastructure for shared proteomic analysis. UM has strong track records in both biomedical research and mass spectrometry (MS) technologies that enable breakthroughs in basic biomedical and disease science. The proposed users focus on analyzing disease- associated multiprotein complexes through crosslinking/MS, quantifying disease-associated changes in protein posttranslational modifications, small volume trace analysis of peptides, lipids, and metabolites, as well as discovery and mechanistic/structural interrogation of natural product biosynthetic pathways. The described, NIH- funded (17 R01, three R37, one DP2, two U01, and one P50 grant) research projects will leverage the unique group of world-class MS experts at UM to develop/extend the utility of the Orbitrap Fusion Lumos, including the custom IRMPD capability, thus providing additional benefits in the form of new methodologies and techniques. The proposed instrument will be housed within an expanded MS facility, being developed into an MS Center of Excellence, within the UM Department of Chemistry. This facility is highly used by researchers throughout the region, but still operates with out-of-date instruments that range between 20 to 40 years old, and is thus in desperate need of the upgrade described in this proposal. Operation and maintenance of the instrument will be performed both by existing highly qualified staff in the Chemistry Department MS facility, but also by a new dedicated PhD-level staff person funded by the College of Literature, Science and the Arts (LSA), representing a total five year staff commitment of ~$1,000,000. In addition, various UM units have provided cost sharing for two years of service for the instrument (in addition to the year one warranty), after which time we expect that instrument recharge costs from major/minor users will support instrument operations within the Chemistry MS Facility, including contributions to partial funding (~60%) of the Facility staff. The remaining 40% of staff salaries will continue to be covered by LSA. Furthermore, UM LSA has agreed to renovate the existing MS facility space in preparation for the requested Orbitrap Fusion Lumos to maximize its productivity and use.