Acquisition of a Highly Sensitive Time of Flight (ToF) Mass Spectrometry System with Novel Fragmentation Capabilities for Qualitative and Quantitative Analysis - PROJECT SUMMARY/ABSTRACT Cutting-edge research at the University of Wisconsin-Madison has led to pioneering efforts in quantitative and investigational proteomics, functional glycomic interrogation, structural characterization of bioactive molecules, pharmacokinetic and pharmacodynamic analyses, and natural product discovery and metabolomic profiling with significant focus on human health and disease. Upon evaluating the current needs of 23 investigators and dutiful comparison of commercial high-resolution mass spectrometer offerings, this proposal seeks funding for the purchase of instrumentation capable of alleviating the limitations in analytical sensitivity, quantitative accuracy, precursor dissociation, and duty cycle presented by currently-accessible spectrometers and that directly benefits each research focus. Given the complexity of human and disease-relevant samples, electrospray (ESI) and matrix-assisted laser desorption ionization (MALDI)-based mass spectrometry (MS) instrumentation demonstrate limitations in sensitivity due to limited precursor selection, interference from singly-charged ions, and low duty cycles that eliminate up to 90% of ions prior to analysis. Of the species that do survive initial selection, identification of biomolecules through tandem MS scans can be severely hindered by precursor co- isolation and signal suppression of low abundance analytes. With these limitations in mind, emerging literature and personal evaluations demonstrate the Sciex ZenoTOF 7600+ is uniquely capable of expanding analytical sensitivity in proteomic, glycoproteomic, and small molecule analyses, while also presenting the most effective commercial offering for accurate absolute biomolecular quantitation. The innovative instrument design of the Sciex ZenoTOF 7600+ MS system incorporates several novel design improvements to the source area, Zeno trap, and quadrupole to dramatically enhance instrument performance. Our initial testing of the ZenoTOF 7600+ and comparison to other current high-resolution triple quadrupole instruments indicate the acquisition of the ZenoTOF 7600+ provides the greatest benefit to our research partners, as it is the most sensitive and efficient regime in proteomic, glycoproteomic, and metabolomic analyses. This new instrument will provide advanced MS capabilities to support the research of 23 highly productive investigators, 20 of which have 66 ongoing projects. Progress on this broad array of projects will be catalyzed by the effective usage of the new instrument through close cooperation among the user groups, Dr. Li, a highly productive faculty member with more than 30 years of experience in biological mass spectrometry, and Dr. Scarlett, the UW-Madison Pharmacy-MS Facility Director. Alternative instruments or allocation of funds would certainly be considered, should this application be funded.
