LC-MS/MS FOR HIGHLY SENSITIVE BIOMARKER DETECTION

用于高灵敏度生物标志物检测的 LC-MS/MS

• 批准号: 6877300
• 负责人: JAMES A SWENBERG
• 金额: $ 41.84万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2007-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877300
• 关键词: DNA damage; biomarker; biomedical equipment purchase; high performance liquid chromatography; liquid chromatography mass spectrometry; protein quantitation /detection

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.

描述（由申请人提供）：生物标记质谱设施通过提供暴露生物标记的质谱鉴定、表征和定量来支持北卡罗来纳大学教堂山校区的研究。生物标记质谱设施寻求资金来购买超高性能台式三重四极杆 LC-MS/MS 系统。我们对所需工具的需求有两个方面。目前，Biomarker MS 设施运行的仪器全天候运行（仪器停机和维护除外），分析需要提前四个星期或更长时间安排。目前对该设施分析服务的需求量超出了我们的能力，导致分析计划的延迟，并且没有给正在启动的新项目留下余地，因为我们开发的 DNA 损伤检测方法正在转移给校园内的其他用户。我们的另一个迫切需求是比当前仪器提供更高灵敏度的分析。由于我们测量的是人体组织等样品中含量较低的分析物，而人体组织的数量非常有限，因此我们需要的检测灵敏度远远超出了设施中当前运行的仪器所能达到的灵敏度。因此，我们寻求一种具有 LC-MS/MS、高通量能力和高灵敏度的仪器。我们还需要该仪器接受纳流和毛细管 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 加合物的分子剂量测定，以及胆碱代谢、癌症因果关系和易感性、DNA 损伤和修复、分子流行病学、暴露研究评估和其他健康相关主题。选择的仪器是 Applied Biosystems/MDS Sciex API 4000 与 LC Packings (Dionex) 毛细管/纳流高压液相色谱系统的接口。该仪器将安装在一个由经验丰富的人员组成的成熟且高效的共享设施中，该设施将支持 11 名当前或待定的 R01 和 U01 NIH 拨款的 10 名持有者的研究。