Project Summary/Abstract The goal of this proposal is to bring a Thermo Fisher Scientific Orbitrap Eclipse mass spectrometer with Electron Transfer Dissociation (ETD) capability and a High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS-Pro) devise plus a nano-LC to the Proteomics Core at Wayne State University. The Proteomics Core supports an extensive user base including 9 Major Users and 16 Minor Users who have contributed to the proposal and who have NIH-funded projects that will be advanced by having access to the Orbitrap Eclipse. The Proteomics Core at Wayne State also supports the Karmanos Cancer Institute and P30 funded Cancer Center as well as the NIEHS funded CURES P30 Center. This Orbitrap Eclipse has unique capabilities for deep profiling of complex proteomes and isobaric tag based multiplexing due to the 40 Hz scan speed and the unique feature of Real Time Search that is enabled on the on- board computer. The computational advances incorporated into the Orbitrap Eclipse make it an exceptional instrument for proteomic isotopic based quantitation and for newer approaches such as Data Independent Analysis. Combined with the experienced mass spectrometrists in the Core, the Orbitrap Eclipse will be a major asset to research programs of NIH-funded investigators at WSU and in the SE Michigan region. As investigator needs have evolved they have developed an increased need for higher resolution, greater sensitivity and higher mass accuracy proteomic mass spectrometry. The Orbitrap Eclipse is designed to address todays needs in proteomic analysis. The instrument excels at deep sequencing and quantitative proteomics as well as accurate characterization of post translational modifications. The current mass spectrometers in the Core lack fast duty cycles and the advanced ion optics that make detection of low abundance species routine on the Eclipse. The ability to unambiguously localize post translational modifications (PTM) in peptides is a critical feature in any proteomic MS system and the Eclipse is outstanding in this due to the availability of multiple fragmentation modes. Wayne State University and the Henry Ford Health System are both strongly committed to this proposal as evidenced by a combined $680,000 in new support for the instruments management, operation, maintenance, informatics and usage. The technical expertise of Proteomics Core personnel as well as the physical and administrative infrastructures are all in place and ready to immediately put this new mass spectrometer to work on NIH-funded biomedical research projects. This instrument will provide transformative technologies for advancing dozens of NIH-funded, ongoing projects, as well as catalyzing new research directions for investigators at Wayne State University.