PROJECT SUMMARY The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide ultra- sensitive isotopic analysis (primarily radiocarbon or Carbon-14) by accelerator mass spectrometry (AMS) for NIH-funded and other researchers. It will be the only User Resource of its type in the United States. The User Resource will leverage 20 years of expertise in the development and application of AMS in broad-based biomedical research through the Biomedical Technology Research Resource for the Development of Biomedical Accelerator Mass Spectrometry (BTRRAMS): a NIGMS Biomedical Technology Center (P41GM103483 09/01/2000 – 05/31/2020) that is in its final year of operation. Since June 2014, the BTRRAMS has measured over 20,000 samples (4,000 a year) a year for its user community. The User Resource will continue to meet the needs of current users as well as provide a capability for new users who would benefit from incorporating AMS as a measurement tool into their research programs. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies continue to be an important tool for addressing many complex problems in the biomedical sciences. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and relevant other isotopes with limits of detection in real samples on the order of a few attograms/mg sample. As a National Resource, the most significant work enabled by AMS is likely to be quantification of metabolic pathways in human health states and comparison to ex vivo and in vivo animal models. The technology made available will enable a deeper understanding of the etiology of human health concerns by (1) enabling the ability to quantify pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles. The User Resource has three goals: (1) provide high throughput, ultra-sensitive 14C analysis for the NIH user community ; (2) improve the efficiency of ultra-sensitive 14C analysis through installation of new interfaces to our AMS systems, improvements in ion source efficiency and upgrades to our data analysis codes; and (3) increase the accessibility and visibility of ultra-sensitive 14C measurements for the biomedical research community by training new investigators and expanding the National user base of researchers requiring ultra-sensitive 14C analysis.

PROJECT NARRATIVE The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide ultra-sensitive Carbon-14 isotopic analysis by accelerator mass spectrometry (AMS) for NIH-funded researchers. The User Resource will enable a deeper understanding of the etiology of human health concerns by enabling quantification of pharmacokinetics and other molecular endpoints directly in humans; offering the ability to conduct quantitative studies using biologics such as proteins or lipids; and enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. The User Resource will increase the accessibility and visibility of ultra-sensitive 14C measurements by training new investigators and expanding the National user base while concurrently improving the efficiency of AMS measurements through installation of new interfaces, technical modifications to ion sources and upgrades to data analysis software for improved ease of use and data reporting.