Laser Ablation System for Ultrafast Elemental Mapping of Clinical and Preclinical Biospecimens

A. PROJECT SUMMARY We request funding for an Iridia 1kHz excimer laser ablation system (Teledyne Instruments Inc) to enable ultrafast laser ablation (LA)-assisted multi-elemental mapping of high-value clinical and preclinical tissue specimens at the Boston University Center for Biometallomics (CBM), the only hospital/medical school-based core facility of its kind in the region. The requested instrument will replace the CBM’s existing LA system, which, after years of heavy usage, requires extensive refurbishment. The requested Iridia LA system is much faster and has far shorter washout time that leverage the full analytical potential of hyphenation with the CBM’s new icpTOF mass spectrometer (icpTOF-MS). The Iridia LA platform is the only system proven to generate high-quality data at all repetition rates up to 1kHz required for ultrafast tissue mapping with icpTOF-MS. Thus, the benefits of acquiring a new state-of-the-art ultrafast LA system far outweigh renovating the CBM’s outdated instrument. The state-of-the-art Iridia LA instrument will accelerate NIH-funded research requiring ultrafast multi-elemental imaging mass spectrometry mapping (single-cell spatial resolution) of high-value organ, tissue, cell, and fluid biospecimens from humans, non-human primates, and small animals (mice, rats) as well as environmental samples, and other biomedically-relevant specimens. The hyphenated LA-ICP-TOF-MS system will accelerate a core group of 11 major and 4 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 chronic traumatic encephalopathy, CTE), cerebrovascular disease, 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 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-VA-Concussion Legacy Foundation Brain Bank, Boston Chronic Kidney Disease Center, Framingham Heart Study) as well as major biomedical research institutions in the region (Massachusetts 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 LA platform will greatly increase the sensitivity of the CBM’s hyphenated LA-ICP-TOF-MS system while decreasing scan time and increasing spatial resolution and analytical throughput. These enhanced analytical capabilities will accelerate cutting-edge NIH-funded research by enabling 3D mapping reconstruction, multi-elemental colocalization analysis, and other data-intensive applications.