Project Summary We request support for the purchase of a Jeol JMS-S3000 MALDI SpiralTOF spectrometer with TOF/TOF capability. The proposed instrument is an urgently needed replacement for an end-of-lifetime and inoperable Bruker Autoflex III MALDI-TOF instrument in the University of Rochester (UR) Department of Chemistry Instrumentation Facility (DCIF). Matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) is a high- throughput mass spectroscopy (MS) method that is used for the analysis of high molecular weight analytes includes peptides, proteins, oligonucleotides, lipids, and polymers. No other MS instruments at UR are appropriate for the routine analysis of these types of samples. The DCIF is an open access instrument center and is available to all UR researchers in 45 departments and over 800 laboratories in the College of Arts, Sciences, and Engineering and in the School of Medicine and Dentistry. The proposed MALDI-TOF/TOF instrument will be available for direct use by all researchers that are trained and certified to operate the instrument by DCIF technicians. The Jeol JMS-S3000 MALDI SpiralTOF is a robust bench-top instrument that is ideal for use as a multi-user instrument. Sample preparation, data acquisition, and data analysis are straightforward. DCIF technical staff are highly experienced with MS instrumentation and are available to assist users as needed after training and certification. Access to this user-based instrument will enable rapid analysis that will accelerate the pace of and reduce the cost of research projects for which mass analyses of high molecular weight materials. The expanded TOF/TOF capability of the proposed instrument will enable acquisition of both mass and sequence information for biopolymer substrates. The proposed instrument is urgently needed to support research in 18 NIH-funded projects at UR. These projects are described in the proposal by 7 major users. Additional projects that will utilize the instrument are described by 5 minor users with 2 additional NIH-funded projects. Two of the minor users are emerging investigators who will rely on the instrument to obtain data that will lead to future NIH grant applications. It is anticipated that the enhanced TOF/TOF capability of the instrument will also broaden the biomedical user base of the instrument. The proposed instrument will become an integral element of the research infrastructure at UR for projects that are focused on understanding human biology and improving human health.