A. PROJECT SUMMARY This shared instrument grant requests funding to acquire an inductively coupled plasma time-of-flight mass spectrometer (icpTOF-MS) for ultrafast laser ablation (LA)-assisted multi-elemental mapping of high-value clinical and preclinical biospecimens. The proposed icpTOF-MS (R-series, TOFWerk) will be sited at the Boston University School of Medicine Center for Biometallomics (CBM), the only hospital/medical school- based analytical core facility of its kind in the region. The icpTOF-MS enables >3000 mass resolution power for multiplexed detection of all possible elements every 30 µs. Hyphenation to the CBM’s state-of-the-art LA platform (300 Hz laser firing rate, <4 ns pulse width, spot size to 1 µm) will accelerate NIH-funded research requiring ultrafast multi-elemental imaging mass spectrometry (MIMS) mapping at single-cell spatial resolution in high-value organ, tissue, cell, and fluid biospecimens from humans, non-human primates, and small lab animals (mice, rats) as well as experimental preparations, environmental samples, and other biomedically- relevant specimens. The hyphenated LA-ICP-TOF-MS system will accelerate a core group of 11 major and 5 minor users who are funded by the NIH (NIA, NINDS, NHLBI, NIDDK) and other sponsors to conduct innovative clinical and preclinical research on Alzheimer’s disease (AD), AD-related dementias (ADRDs, including tau protein neurodegenerative diseases, such as chronic traumatic encephalopathy, CTE), vascular dementia, stroke, traumatic brain injury, cardiovascular disease, chronic renal disease, cataracts, retinopathy, and heavy metal toxicology linked to environmental and consumer product exposures (exposome research). The proposed icpTOF-MS will also facilitate novel techniques (developed by CBM investigators) to detect, localize, and quantitate microvascular dysfunction. The major user group includes NIH-funded investigators at Boston University School of Medicine, affiliated national human tissue repositories (BU Alzheimer’s Disease Research Center, BU-Concussion Legacy Foundation-VA Boston Brain Bank, Boston Chronic Kidney Disease Research Center, and the Framingham Heart Study,) as well as major biomedical research institutions in the region (Mass General Hospital, Harvard Medical School, The Jackson Laboratory), across the nation (Indiana University, UCLA, Navy Medical Research, Lawrence Livermore National Laboratory), and around the globe (Queen’s University Belfast). The proposed icpTOF-MS will greatly decrease MIMS scan time while increasing spatial resolution, simultaneous acquisition of multi-element spectra, and analytical mapping throughput. These enhanced analytical capabilities will not only accelerate cutting-edge NIH-funded research but also enable novel 3D mapping reconstructions, multi-elemental colocalization analyses, and other data-intensive applications enabled by this powerful analytical technology.