Bruker RapifleX MALDI TOF/TOF Mass Spectrometer

点击翻译按钮获取中文摘要

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.