LC-MS/MS FOR HIGHLY SENSITIVE BIOMARKER DETECTION

描述（由申请人提供）：生物标志物质谱设施通过提供暴露生物标志物的质谱鉴定、表征和定量来支持北卡罗来纳大学教堂山校区的研究。生物标志物质谱设施寻求资金以获得超高性能台式三重四极杆LC-MS/MS系统。我们对所要求的文书的需要是双重的。目前，生物标志物MS设施运行的仪器全天候运行（仪器停机和维护除外），分析需要提前四周或更长时间安排。目前对该设施分析服务的需求量超过了我们的能力，导致分析时间表的延误，并使我们开发的DNA损伤分析方法被转移给园区内其他用户时，没有为正在启动的新项目留下任何余地。我们的另一个迫切需要是比现有仪器更高灵敏度的分析。由于我们测量的是样品中低水平的分析物，如人体组织，其数量非常有限，我们需要的检测灵敏度远远超过目前在设施中运行的仪器所能达到的灵敏度。因此，我们寻求具有LC-MS/MS、高通量能力和高灵敏度的仪器。我们还需要这个仪器接受纳米和毛细管LC输入。该仪器将支持对顺铂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加合物的分子剂量测定的研究，以及对胆碱代谢、癌症因果关系和易感性、DNA损伤和修复、分子流行病学、接触评估和其他与健康有关的主题的研究。选择的仪器是Applied Biosystems/MDS Sciex API 4000接口，其具有LC Packings（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已建立的生产性共享使用设施中，在那里它将支持11个当前或待定的R 01和U 01 NIH赠款的10个持有者的研究。

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.