RapidFire mass spectrometry system

 描述（由申请人提供）：代谢组学描述了对生物流体、细胞、组织和生物体中存在的小分子代谢物（<1000 Da）的系统和全面测量。鉴于生理学和代谢之间的密切耦合，代谢组学拥有深入分析人类表型的能力--整合DNA序列变异、mRNA物种水平、蛋白质水平、环境暴露、饮食和共生宿主微生物--所有这些都在一个单一的全球测量中。这种代谢组学测量允许理解人类疾病的基本发病机制，以及早期疾病的诊断，疾病亚状态的表征和预测药物反应性。鉴于人类循环代谢组的综合性和动态性，允许在群体水平规模（>100至1000个样品）上评估代谢组学的高通量方法至关重要。最近，机器人液体处理和固相萃取系统的发展，加上先进的质谱分析，现在能够在成千上万的人的代谢组的高通量询问。该提案是RapidFire质谱系统，用于健康和疾病状态下人体代谢组的高通量表征。该仪器将用于了解糖尿病、肾脏疾病和动脉粥样硬化等疾病的代谢决定因素;对他汀类药物等治疗药物的反应;以及探索肠道微生物的代谢调节。重要的是，这种RapidFire仪器将用于人类和人类样本的研究，这是使用目前可用的方法无法实现的。此外，这一工具将用于使科学界参与代谢组学，并用于对研究生和博士后研究员进行代谢组学新兴学科的培训。

 DESCRIPTION (provided by applicant): Metabolomics describes the systematic and comprehensive measure of small molecule metabolites (<1000 Da) present in biofluids, cells, tissues and organisms. Given the close coupling between physiology and metabolism, metabolomics holds the power to deeply phenotype humans - integrating DNA sequence variation, mRNA species levels, protein levels, environmental exposures, diet, and commensal host micro- organisms - all within a single global measurement. Such metabolomics measures allows for understanding the basic pathogenesis of human disease, as well as diagnosing of early disease, characterization of disease sub-states, and predicting drug responsiveness. Given the integrative and dynamic nature of the human circulating metabolome, high-throughput approaches that allow for assessment of metabolomics on population level scales (>100 to 1000 samples) are paramount. Recently, developments in robotic liquid handling and solid-phase extraction systems, coupled with advanced mass spectrometry now enable the high-throughput interrogation of the metabolome across tens of thousands of individuals. This proposal is for a RapidFire mass spectrometry system, to be used for the high-throughput characterization of the human metabolome in healthy and disease states. This instrument will be employed for understanding the metabolic determinants of diseases such as diabetes, renal disease and atherosclerosis; the response to therapeutic agents, such as statins; and probing the metabolic regulation of commensal micro-organisms. Importantly, this RapidFire instrument will be used for the study of humans and human samples, which are not possible using currently available approaches. In addition, this instrument will be used to engage the scientific community in metabolomics and for training of graduate students and postdoctoral fellows in the emerging discipline of metabolomics.