Bruker RapifleX MALDI TOF/TOF Mass Spectrometer

项目摘要/摘要 该提案要求为Bruker RapifleX基质辅助激光解吸电离(MALDI)提供资金。 飞行/飞行时间(TOF/TOF)质谱仪将放置在 宾夕法尼亚大学化学系。RapifleX将取代2008款布鲁克 UltraFlex III MALDI TOF/TOF用于生物大分子的高分辨率和MS/MS分析。这是一个必不可少的 美国国立卫生研究院资助的宾夕法尼亚大学化学生物学研究人员的用户社区合成修饰的能力 多肽、蛋白质和寡核苷酸。RapifleX不仅仅是UltraFlex III的替代品，它的改进 分辨率和MS/MS功能将允许分析复杂的PTM或交叉链接，这些链接在 宾夕法尼亚大学目前的MALDI和电喷雾电离系统。此外，RapifleX还提供了新的功能 目前在宾夕法尼亚大学的任何MS系统中都没有发现，允许用户构思新的研究领域。超高 吞吐量筛选(UHTS)分析和MALDI MS成像(MSI)将在宾夕法尼亚大学进行生物医学研究 新方向。UHTS的能力将使实验能够表征酶和小分子 反应，包括监测正品多肽和蛋白质的翻译后修饰的动力学 探索试剂和添加剂组合效应的底物和机器学习增强实验 在反应中(与高吞吐量实验中心和默克公司的uHTS开发者合作 实验)。最重要的是，RapifleX将把MSI的激动人心的能力带给宾夕法尼亚大学。在这些人中 此应用程序中包含的项目使用最先进的成像方法和RapifleX 解决癌症、病毒和细菌感染、阿尔茨海默氏症和 帕金森病，或糖尿病和肥胖症。还包括一个超越最先进技术的项目 使用RapifleX开发新的MSI技术，将极大地增加目标用户的信息内容 成像。RapifleX的加入将对20多个高度活跃的人产生直接和持久的影响 研究人员和200多名受训人员在美国国立卫生研究院的九个研究所进行了研究。这包括 化学生物学、生物物理学、有机化学、神经科学和翻译研究计划，以及 NIH T32资助的实习生。RapifleX还将使NIH资助的学校研究项目受益匪浅 在整个宾夕法尼亚大学，包括佩雷尔曼医学院，工程和应用科学学院，以及 兽医学院，以及邻近的机构，如儿童医院 费城、德雷塞尔大学和托马斯·杰斐逊大学。RapifleX将成为一个广泛的 对宾夕法尼亚大学化学MS设施进行大修，使其成为该地区的卓越中心。

Project Summary/Abstract This proposal requests funding for a Bruker rapifleX matrix-assisted laser desorption ionization (MALDI) time-of- flight/time-of-flight (TOF/TOF) mass spectrometry (MS) instrument to be placed in the MS Facility in the Department of Chemistry at the University of Pennsylvania (UPenn). The rapifleX will replace a 2008 Bruker Ultraflex III MALDI TOF/TOF for high resolution and MS/MS analysis of biomacromolecules. This is an essential capability for the user community of NIH-funded chemical biology researchers at UPenn synthesizing modified peptides, proteins, and oligonucleotides. The rapifleX is not merely a replacement for the UltrafleX III, its improved resolution and MS/MS capabilities will permit analysis of complex PTMs or cross-links that are challenging on current MALDI and electrospray ionization systems at UPenn. Furthermore, the rapifleX provides new capabilities not currently found in any MS system at UPenn, allowing users to conceive of new areas of research. Ultra-high throughput screening (uHTS) analysis and MALDI MS imaging (MSI) will take biomedical research at UPenn in new directions. The uHTS capabilities will enable experiments to characterize enzyme and small molecule reactions, including monitoring the kinetics of post-translational modifications on authentic peptide and protein substrates and machine-learning enhanced experiments exploring combinatorial effects of reagents and additives in reactions (in collaboration with the High Throughput Experimentation Center and Merck developers of uHTS experiments). Most significantly, the rapifleX will bring the exciting capability of MSI to UPenn. Among the projects included in this application are those that use state-of-the-art imaging methods with the rapifleX to address important research questions in areas such as cancer, viral and bacterial infections, Alzheimer’s and Parkinson’s Disease, or diabetes and obesity. Also included is a project that pushes beyond the state-of-the-art to develop new MSI technologies using the rapifleX that will vastly increase the information content from targeted imaging. The addition of the rapifleX will have an immediate and lasting impact on more than 20 highly active investigators and more than 200 trainees carrying out research that spans nine institutes of the NIH. This includes chemical biology, biophysics, organic chemistry, neuroscience, and translational research programs, as well as NIH T32-funded trainees. The rapifleX will also significantly benefit NIH-funded research programs in schools across UPenn, including the Perelman School of Medicine, School of Engineering and Applied Science, and School of Veterinary Medicine, as well as at neighboring institutions such as the Children’s Hospital of Philadelphia, Drexel University, and Thomas Jefferson University. The rapifleX will be a key instrument in a broad overhaul of the UPenn Chemistry MS Facility, making it a center of excellence for the region.