Select Series Cyclic IMS Mass Spectrometry System - PROJECT SUMMARY We request funds to purchase a high-resolution and high-sensitivity liquid chromatography-mass spectrometry system for the analysis of small molecules and biomolecules at the University of Colorado Boulder (CU-Boulder) as well as other research institutions in Colorado. The proposed instrument consists of a Waters SELECT SERIES Cyclic Ion Mobility QTOF (SS-cIMS) mass spectrometer, a Waters ACQUITY Premier UPLC, and a Waters ACQUITY HDX Manager UPLC. It will be housed in the Central Analytical Laboratory (CAL), which is the mass spectrometry service core facility at CU-Boulder. It will be used to support mass spectrometry needs for measuring small molecule high-resolution accurate mass, biomolecule mass including intact protein mass analysis, peptide LC-MS/MS and mapping of post-translational modifications, and hydrogen-deuterium exchange mass spectrometry (HDX-MS). This new instrument is needed to replace an existing Waters Synapt G2 system that is now 15 years old and in poor condition. Importantly, Waters Corp. will soon end service support for the Synapt G2 on December 31, 2024. Therefore, we have an urgent need to replace the Synapt G2 with a newer QTOF instrument that can fill the critical needs in synthetic chemistry and biomolecular analysis that is prevalent across our research community. In addition, the proposed instrument would enable the CAL facility to expand its research capabilities, by enabling new experiments using ion mobility mass spectrometry and native mass spectrometry to evaluate chemical and conformational heterogeneity of large macromolecular complexes. These will synergize and support emerging research among our large community of structural biology researchers at CU-Boulder, who are using single particle cryo-electron microscopy and cryo-electron tomography to determine structures of large complexes at atomic resolution.