LC-MS/MS FOR HIGHLY SENSITIVE BIOMARKER DETECTION

描述(由申请人提供)：生物标记物质谱仪通过提供暴露生物标记物的质谱学鉴定、表征和量化，支持北卡罗来纳大学教堂山校区的研究。Biomarker质谱学设施寻求资金，以获得超高性能的台式三重四极LC-MS/MS系统。我们对所要求的仪器的需求是双重的。目前，由Biomarker MS设备操作的仪器全天候运行(仪器停机和维护除外)，分析需要提前4周或更长时间安排。目前对该设施的分析服务的需求量超出了我们的能力，导致延迟安排分析，并且没有为正在启动的新项目留出余地，因为我们开发的DNA损伤分析正在转移到校园内的其他用户。我们另一个迫切需要的是比目前仪器所能提供的更高灵敏度的分析。由于我们测量的是人体组织等样本中的低水平分析物，而这些样本的数量非常有限，因此我们需要的检测灵敏度远远超过目前在该设施中运行的仪器所能达到的水平。因此，我们寻求一种具有LC-MS/MS、高通量和高灵敏度的仪器。我们还需要这个仪器来接受纳米和毛细管LC输入。该仪器将支持顺铂DNA加合物、脂质成分、丁二烯、环氧乙烷、环氧丙烷和异戊二烯衍生的DNA加合物的分子剂量学研究，以及胆碱代谢、癌症病因和易感性、DNA损伤和修复、分子流行病学、暴露评估和其他健康相关课题的研究。选择的仪器是应用生物系统/MDS Sciex API 4000接口，带有LC填充(Dionex)毛细管/纳米流高压液相色谱系统。该仪器将安装在一个由经验丰富的人员组成的成熟和富有成效的共用设施中，在那里它将支持11个现有的或即将获得的R01和U01 NIH补助金的10名持有者的研究。

DESCRIPTION (provided by applicant): The Biomarker Mass Spectrometry Facility supports research on the UNC-Chapel Hill Campus by providing mass spectrometric identification, characterization and quantitation of biomarkers of exposure. The Biomarker Mass Spectrometry Facility seeks funding to acquire an ultra-high performance bench top triple quadrupole LC-MS/MS system. Our need for the requested instrument is two-fold. Currently the instruments operated by the Biomarker MS Facility are operating around the clock (except for instrument down-time and maintenance) and analyses require four or more weeks advance scheduling. The current volume of demand for the Facility's analytical services exceeds our capacity, resulting in delays in scheduling analyses and leaving no leeway for new projects that are being initiated as assays for DNA damage which we have developed are being transferred to other users on campus. Our other pressing need is for higher-sensitivity analysis than can be provided with the current instrumentation. Because we are measuring analytes which are present at low levels in samples such as human tissue which are available in very limited quantity only, we need sensitivity of detection well beyond what can be achieved with the instruments currently operating in the facility. We therefore seek an instrument with LC-MS/MS, high-throughput capability and high sensitivity. We also need this instrument to accept nano and capillary LC input. This instrument will support research into cisplatin DNA adducts, lipid composition, molecular dosimetry of DNA adducts derived from butadiene, ethylene oxide, propylene oxide and isoprene, and studies on choline metabolism, cancer causality and susceptibility, DNA damage and repair, molecular epidemiology, exposure assessment, and other healthrelated topics. The instrument of choice is an Applied Biosystems/MDS Sciex API 4000 interfaces with an LC Packings (Dionex) capillary/nanoflow high pressure liquid chromatography system. This instrument will be installed in an established and productive shared-use facility staffed by experienced personnel, where it will support the research of ten holders of eleven current or pending R01 and U01 NIH grants.