Project Summary We request the next generation Orbitrap Tribrid Orbitrap Eclipse instrument to place in the Oregon Health & Science University Proteomics Shared Resource (PSR). The new instrument will better serve the needs of researchers at the university due to its greater sensitivity, more accurate quantitation using tandem mass tagging technology, improved electron dissociation source, and FAIMS devise to increase the depth of proteomic analysis in complex mixtures. The instrument will support new experiments at OHSU pushing the boundaries of proteomics by: allowing the analysis of single cell proteomes, localizing post-translational modifications and drug binding sites in membrane protein receptors, more accurately and sensitively measuring differential protein abundance in complex tissue and cellular lysates, measuring newly synthesized proteins in tissues isolated by laser-capture micro-dissection, performing hydrogen/deuterium exchange measurements, and refining cryo-EM derived protein structures using chemical cross-linking experiments. The instrument will support the study of a wide range of diseases, including cancer, cataracts, glaucoma, drug addiction, and hearing loss. The instrument will allow the PSR to expand its services to a growing group of proteomics researchers at the university who need access to the most advanced mass spectrometry instrumentation to support their research needs.