Waters Xevo TQ-XS system

项目总结/摘要 路易斯维尔大学糖尿病和肥胖中心（DOC）的生物分析核心实验室和其他 校园内的实验室操作质谱仪，致力于满足日益增长和复杂的 需要NIH资助的研究人员。这些需求远远超出了目前的能力，主要的限制包括 缺乏在代谢组学、代谢组学和脂质组学领域进行超灵敏靶向分析的能力。 这些应用程序是主要和次要用户的核心，包括五个NIH资助的中心和二十二个 侧重于环境毒理学、心血管、肝脏和代谢的个别研究项目 运动科学和免疫学。我们建议添加一个超灵敏、耐用的沃茨Xevo TQ-XS 配备Acquity I-Class Premier超高效液相色谱的三重四极杆质谱仪， 这将通过显著提高分析物的广度来满足主要和次要用户的分析需求。 目标生物分析的覆盖范围和灵敏度，目前可用的LC-MS仪器无法达到 可在大学校园。所提出的系统将补充目前的生物分析仪器， 目前处于满负荷状态，并提供所需的硬件，以开发和转移高通量，超灵敏的 有针对性的方法来满足我们用户的需求。具体而言，我们将建立：i）一个量化超低- 与巯基尿酸和肌肽的水平异生物质加合物，以帮助人类肿瘤学研究; ii）靶向 用于尿生物源挥发性有机化合物代谢物的方法; iii）用于测量胆汁酸的工作流程; iv）特异性靶向脂质组学测定（主要脂质类别、短链脂肪酸和异前列烷 v）皮质类固醇的定量，包括皮质醇和可的松，作为慢性炎症的标志物 血浆中儿茶酚胺及其代谢物的靶向测定; vii）定量反应性羰基的方法 在烟草产品气溶胶中; viii）肠道微生物胺代谢物的定量; ix）高通量测定 用于测量各种生物基质中的氨基酸和二肽。拟议的文书工作 包括质谱和方法开发方面的详细培训和教育， 推进中心的研究，并最大限度地提高拟议系统的效用。DOC拥有基础设施 维护和支持由大学支持的新设备。

Project Summary/Abstract The Bioanalytics Core laboratory at the University of Louisville Diabetes and Obesity Center (DOC) and other laboratories on campus operate mass spectrometers dedicated to meeting the ever-increasing and complex needs of NIH-funded investigators. These needs far exceed current capabilities, with major limitations comprising a lack of ability for ultrasensitive targeted analyses in the areas of exposomics, metabolomics, and lipidomics. These applications are central to Major and Minor Users, including five NIH-funded centers and twenty-two individual research projects focusing on environmental toxicology, cardiovascular, hepatic and metabolic disease, exercise science, and immunology. We propose to add an ultrasensitive, robust Waters Xevo TQ-XS triple-quadrupole mass spectrometer with the Acquity I-Class Premier ultraperformance liquid chromatography, which will address the analytical needs of major and minor users by significantly enhancing breadth of analyte coverage and sensitivity of targeted bioanalyses, currently out of reach with available LC-MS instruments available at the University Campus. The proposed system will complement current bioanalytical instrumentation, currently at full capacity, and provide needed hardware to develop and transfer high-throughput, ultrasensitive targeted methods to cater to the needs of our users. Specifically, we will set up: i) A platform to quantify ultralow- level xenobiotic adducts with mercapturic acid and carnosine to aid human exposomics studies; ii) A targeted method for urinary biogenic volatile organic compound metabolites; iii) A workflow for measurement of bile acids; iv) specific targeted lipidomics assays (major lipid classes, short-chain fatty acids, and isoprostanes respectively); v) Quantification of corticosteroids, including cortisol and cortisone, as markers of chronic vi) A targeted assay for catecholamines and their metabolites in plasma; vii) A method to quantify reactive carbonyls in tobacco product aerosols; viii) quantification of gut microbial amine metabolites; ix) A high-throughput assay for measuring amino acids and dipeptides in various biological matrices. Proposed work with the instrument includes detailed training and education in mass spectrometry and method development, which will further advance research in the Center and maximize the utility of the proposed system. The DOC has the infrastructure to maintain and support the new equipment backed by the support of the University.