National User Resource for Biological Accelerator Mass Spectrometry

项目摘要 生物加速器质谱的国家用户资源（用户资源）将提供超 通过加速器质谱（AMS）进行灵敏的同位素分析（主要是放射性碳或碳-14）， 美国国立卫生研究院资助和其他研究人员。这将是美国唯一的用户资源。用户 资源将利用20年的专业知识，在开发和应用AMS的广泛基础 生物医学研究通过生物医学技术研究资源的发展 生物医学加速器质谱（BTRRAMS）：NIGMS生物医学技术中心 （P41 GM 103483 09/01/2000 - 05/31/2020），这是在其最后一年的运作。自2014年6月以来， BTRRAMS每年为其用户社区测量20，000多个样本（每年4，000个）。用户 资源将继续满足当前用户的需求，并为新用户提供能力， 将AMS作为一种测量工具纳入其研究计划中会受益匪浅。用户 资源的强项将是放射性碳和选定的其他放射性同位素的超高灵敏度定量， 需要同位素的研究。放射性同位素标记研究仍然是一个重要的工具 解决生物医学科学中许多复杂的问题。AMS是一种专门的、独特的 提供放射性碳和相关的其他同位素的绝对定量的质谱法 在真实的样品中的检测的数量级为几个attograms/mg样品。作为国家资源， AMS的重要工作可能是量化人类健康状态下的代谢途径 以及与离体和体内动物模型的比较。所提供的技术将使更深层次的 通过以下方式了解人类健康问题的病因：（1）能够量化 直接在人体内的药代动力学和其他分子终点;（2）提供进行 使用蛋白质或脂质等生物制剂进行定量研究;以及（3）使更多相关研究 代谢途径在健康和疾病通过使用低得多，更生物相关， 细胞和完整生物体中代谢底物的浓度。这些研究支持NIGMS的基本 生物医学研究领域，有助于了解基本的细胞和生理 原则用户资源有三个目标：（1）提供高通量，超灵敏的14 C分析， NIH用户社区;（2）通过安装新的 AMS系统的接口、离子源效率的提高和数据分析的升级 代码;和（3）增加超灵敏14 C测量的可及性和可见性，用于生物医学 通过培训新的研究人员和扩大研究人员的国家用户群， 需要超灵敏的碳14分析

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.