Waters Xevo TQ-XS system

项目摘要/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 校园内的实验室使用质谱仪，致力于满足日益增长和复杂的 美国国立卫生研究院资助的研究人员的需求。这些需求远远超出了当前的能力，主要限制包括 缺乏在暴露组学、代谢组学和脂类组学领域进行超灵敏目标分析的能力。 这些应用程序是主要和次要用户的核心，包括NIH资助的5个中心和22个 专注于环境毒理学、心血管、肝脏和代谢的个人研究项目 疾病、运动科学和免疫学。我们建议增加一款超灵敏、坚固的Waters Xevo TQ-XS 采用Acquity I-Class Premier超性能液相色谱仪的三重四极杆质谱仪， 它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率和灵敏度，目前用现有的LC-MS仪器达不到 在大学校园内提供。建议的系统将补充现有的生物分析仪器， 目前处于满负荷状态，并提供所需的硬件来开发和传输高吞吐量、超灵敏 有针对性的方法来迎合我们用户的需求。具体地说，我们将建立：i)一个量化超低- 用硫代尿酸和肌肽水平的异种加合物来辅助人类暴露组学研究；ii)有针对性的 尿液中生物挥发性有机化合物代谢物的测定方法； 四)特定靶向脂肪组学分析(主要脂类、短链脂肪酸和异前列腺素 包括皮质醇和皮质醇在内的皮质类固醇的定量，作为慢性疾病的标志物 血浆儿茶酚胺及其代谢物的靶向性测定；vii)一种定量反应性羰基的方法 烟草产品气雾剂；viii)肠道微生物胺类代谢物的定量；ix)高通量分析 用于测定各种生物基质中的氨基酸和二肽。建议使用该仪器进行的工作 包括在质谱学和方法开发方面的详细培训和教育，这将进一步 推进该中心的研究，最大限度地发挥拟议系统的效用。DOC拥有基础设施 在大学的支持下，维护和支持新设备。

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.