Triple Quadrupole - Ion Trap Hybrid LC/MS/MS System

描述（由申请人提供）：该提案是关于新的Q-TRAP 4000 LC-MS/MS系统，既可以增强我们的质谱资源的现有能力，又可以最终取代目前正在使用的老化的QuattroLC。目前的质谱资源位于中央仪器设施（CIF）， Karmanos癌症研究所（KCI）的药理学核心和韦恩州立大学的蛋白质组学核心。其中，只有CIF和Pharmacology Core提供LC-MS/MS功能。参与教师研究的主要领域之一涉及小分子的鉴定和/或定量，如炎症的脂质介质，饮食成分中的抗癌天然产物等。另一个主要的研究领域是与癌症相关的信号转导。这些研究项目目前利用分布在校园三个核心设施中的现有质谱资源。CIF和Proteomics Core提供的飞行时间（TOF）仪器用于蛋白质鉴定工作，CIF和Pharmacology Core的三重四极杆仪器用于结构鉴定和LC-MS定量。其中，Pharmacology Core的LC-MS主要被KCI研究人员用于药物代谢、药代动力学和临床试验。CIF的QuattroLC是参与本提案的研究人员进行小分子分析的主要资源。虽然该仪器仍然有效，并被这些研究人员大量用于小分子定量和肽测序工作，但其在纳摩尔范围内的灵敏度不足以分析和鉴定生物标志物。此外，这台仪器已经使用了七年多，经常需要维修。Q-TRAP LC- MS/MS系统将服务于许多项目，要求检测限在fmol范围内，以及快速MRM扫描能力，以识别和定量炎症和癌症的生物标志物。此外，新系统的蛋白质组学能力以及Nanospray离子源，将对肽测序的研究项目非常有价值，以确定相互作用蛋白质的化学交联结构域。参与本提案的教师的研究项目由NIH持续资助，有些已经超过二十年，Q-TRAP 4000 LC-MS/MS系统将是他们持续成功的不可或缺的资源。此外，该仪器将催化韦恩州立大学急需的脂质组学核心设施的建立。

DESCRIPTION (provided by applicant): This proposal is for a new Q-TRAP 4000 LC-MS/MS system, both to enhance the existing capabilities of our mass spectrometry resources and eventually to replace the aging QuattroLC that is currently in use. The current mass spectrometry resources are located at the Central Instrument Facility (CIF), the Pharmacology Core of the Karmanos Cancer Institute (KCI), and the Proteomics Core of Wayne State University. Of these, only the CIF and Pharmacology Core offer LC-MS/MS capability. One of the major areas of the participating faculty's research involves identification and/or quantitation of small molecules such as, lipid mediators of inflammation, anticancer natural products from dietary ingredients, etc. The other major area of interest is the signal transduction pertaining to cancer. The research projects currently utilize the existing mass spectrometry resources distributed among three core facilities on campus. While the Time of Flight (TOF) instruments available at CIF and Proteomics Core are used for the protein identification work, the triple quadrupole instruments at CIF and Pharmacology Core are used for structure identification and LC-MS quantitation. Of these, the LC-MS of Pharmacology Core is primarily used by KCI researchers for drug metabolism, pharmacokinetics, and clinical trials. The QuattroLC at the CIF is the primary resource for small molecule analysis by the investigators participating in this proposal. While this instrument is still functional and heavily used by these investigators for small molecule quantitation and peptide sequencing work, its sensitivity in the nanomolar range is inadequate for the analysis and identification of biomarkers. Moreover, this instrument is more than seven years old and is frequently in need of service. Many of the projects that will be served by the proposed Q-TRAP LC- MS/MS system require detection limits in the fmol range as well as fast MRM scan capability for the identification and quantification of biomarkers of inflammation and cancer. Additionally, the proteomics capability of the new system along with the Nanospray ion source, would be immensely valuable for the research projects in peptide sequencing to identify chemically cross linked domains of interacting proteins. Research projects of the faculty participating in this proposal are continuously funded by NIH, some for more than two decades, and the Q-TRAP 4000 LC-MS/MS system would be an indispensable resource for their continued success. Additionally, this instrument will catalyze the setup of a much needed Lipidomics core facility at Wayne State University. PUBLIC HEALTH RELEVANCE: The type of LC-MS/MS system requested is used for the measurement of small molecule analytes present at extremely low concentrations in biological samples. These include biomarkers of inflammation, cancer, and related diseases. Identification of novel biomarkers and validation of known biomarkers of diseases that facilitate early detection, diagnosis, and treatment is the primary purpose of this instrument.