Orbitrap Elite/H-ESI Bundle

描述(由申请人提供)：此资金申请用于Orbitrap Elite/H-ESI质谱计捆绑，以支持NIH赞助的项目，涉及临床生物标记物开发、疾病预测和分类以及个性化药物的治疗开发。由PI与埃默里大学医学、化学、生物统计和生物信息学与环境健康系的研究人员合作开发的新分析工作流程，提供了常规和可重复地测量人类血浆和其他生物材料提取物中的20,000个高分辨率m/z特征的能力。其中许多m/z特征与特定疾病显著相关，但大多数都是低丰度的，超过一半与人类新陈代谢数据库中的化学物质不匹配。对不明化学品的身份和特征进行核实是具有挑战性的，但对于获得NIH赠款的主要用户在基础、翻译和临床研究方面的目标来说，这是至关重要的。所要求的仪器将用于应用专门的反卷积MS/MS方法，以确认这些项目中重要的低丰度化学品的身份，并用预测的MS/MS光谱表征适合于输入和搜索化学品数据库的未知化学品。医学部(DOM)临床生物标记物实验室与埃默里质谱学中心一起制定了一些策略，使用去卷积MS/MS来创建预测的MS/MS谱，并使用MSN来帮助识别这些存在于复杂混合物中的显著、低丰度的化学物质，如人类血浆。所要求的仪器的特别理由是能够积累和分解低丰度离子，并以足够的质量、精度和分辨率测量产物离子，以便深入了解元素组成和结构。该仪器将由DOM临床生物标记物实验室的熟练人员进行维护和操作，并接受过高分辨率质谱学和计算生物学、生物统计学和生物信息学方面的专门培训。主要用户和次要用户将为DOM临床生物标记物实验室内熟练技术人员的服务提供标准费用。购买仪器的费用将由DOM临床生物标记物实验室分担，并在该实验室内运行，优先考虑指定的主要用户和一组也得到NIH赠款支持的次要用户。根据高分辨率代谢组学咨询委员会制定的政策，过剩产能将优先用于NIH赞助的其他研究、NIH赠款提交的试点和可行性项目以及其他赞助项目。该仪器将由DOM临床生物标记物实验室维护，并签订服务合同和成本回收系统，以确保长期运营和维护。

DESCRIPTION (provided by applicant): This funding request is for an Orbitrap Elite/H-ESI Mass Spectrometer Bundle to support NIH-sponsored projects involving clinical biomarker development, disease prediction and classification and therapeutic development for personalized medicine. New analytic workflow developed by the PI in collaboration with investigators in the Departments of Medicine, Chemistry, Biostatistics and Bioinformatics and Environmental Health at Emory University has provided capability to routinely and reproducibly measure >20,000 high- resolution m/z features in extracts of human plasma and other biological materials. Many of these m/z features are significantly associated with specific diseases, but most are of low abundance, and over half do not match chemicals in human metabolic databases. Verification of identities and characterization of unidentified chemicals are challenging yet critical to the goals of major users with NIH grants in basic, translational and clinical research. The requested instrument will be used to apply specialized deconvolution MS/MS methods to confirm identities of significant, low abundance chemicals in these projects, and to characterize unidentified chemicals with predicted MS/MS spectra suitable for chemical database entry and searches. Strategies have been developed within the Department of Medicine (DOM) Clinical Biomarkers Laboratory, in conjunction with the Emory Mass Spectrometry Center, to use deconvolution MS/MS to create predicted MS/MS spectra, and MSn, to aid in identification of these significant, low-abundance chemicals present in complex mixtures such as human plasma. The requested instrument is specifically justified by the capability to accumulate and dissociate low-abundance ions and measure product ions with sufficient mass accuracy and resolution to gain insight into elemental composition and structure. The instrument will be maintained and operated by skilled personnel in the DOM Clinical Biomarkers Laboratory with specific training in high-resolution mass spectrometry and computational biology, biostatistics and bioinformatics. Major and minor users will provide a standard fee for service by skilled technicians within the DOM Clinical Biomarkers Laboratory. The instrument purchase will be cost-shared by the DOM Clinical Biomarkers Laboratory and operated within this laboratory with priority given to the named major users and a group of minor users also supported by NIH grants. Excess capacity will be used with priority given to other NIH-sponsored research, pilot and feasibility projects for NIH grant submissions, and other sponsored projects according to policies established by a High-Resolution Metabolomics Advisory Committee. The instrument will be maintained by the DOM Clinical Biomarkers Laboratory with a service contract and a cost recovery system to assure long-term operation and maintenance.