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）提供了超 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。它是美国唯一的用户资源。用户 资源利用了20年的专业知识，在开发和应用AMS在广泛的生物医学 研究通过生物医学技术研究资源的生物医学加速器的发展 质谱（BTRRAMS）：NIGMS生物医学技术中心（P41 GM 103483 09/01/2000 - 2020年5月31日）。自2014年6月以来，BTRRAMS和用户资源已经测量了大约4，000个样本， 一年来，用户社区。用户资源将继续满足当前用户的需求， 为新用户提供了一种能力，这些用户将受益于将AMS作为测量工具纳入其 研究项目。用户资源的强项是放射性碳的超高灵敏度定量， 其他放射性同位素，用于需要同位素的研究。放射性同位素标记研究继续 是解决生物医学科学中许多复杂问题的重要工具。AMS是一种专业的 和独特类型的质谱法，提供绝对定量的放射性碳和其他相关的 在真实的样品中具有几个阿托克/毫克样品数量级的检测极限的其它同位素。作为国家 资源，最重要的工作，使AMS可能是定量的代谢途径，在人类 健康状态以及与离体和体内动物模型的比较。现有的技术使 更深入地了解人类健康问题的病因学（1）能够量化 直接在人体中的药代动力学和其他分子终点;（2）提供进行定量分析的能力 使用蛋白质或脂质等生物制剂的研究;以及（3）能够对代谢途径进行更相关的研究 在健康和疾病通过使用低得多，更生物相关，代谢的浓度， 细胞和完整生物体中的底物。这些研究支持NIGMS的基础生物医学研究领域， 有助于理解基本的细胞和生理原理。用户资源有 三个目标：（1）为NIH用户社区提供高通量，超灵敏的14 C分析;（2）改善 通过在AMS系统上安装新的接口，提高超灵敏14 C分析的效率， 提高离子源效率并升级我们的数据分析代码;以及（3）增加可访问性和可见性 通过培训新的研究人员，为生物医学研究界提供超灵敏的14 C测量， 扩大需要超灵敏14 C分析的研究人员的全国用户群。该建议购买 的沃茨UHPLC系统将取代AMS中不再受支持的退役Agilent 1100/1200系统 样品制备实验室。

PROJECT SUMMARY The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) provides ultra sensitive isotopic analysis (primarily radiocarbon or Carbon-14) by accelerator mass spectrometry (AMS) for NIH-funded and other researchers. It is the only User Resource of its type in the United States. The User Resource leverages 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). Since June 2014, BTRRAMS and User Resource have measured approximately 4,000 samples 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 is 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 other 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 quantitation of metabolic pathways in human health states and comparison to ex vivo and in vivo animal models. The technology made available enables 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. The proposed purchase of the Waters UHPLC system will replace the no longer supported, retired Agilent 1100/1200 system in our AMS sample prep laboratory.