Ultra-high-throughput mass spectrometry for quantitative metabolomics

代谢组学是指在生物系统中发现的小分子（代谢物）补体的定量测量。鉴别这类分子的一种方法依赖于测定它们的质量，即质谱法。质谱法（MS）结合液相或气相色谱法的预先分离，在代谢组学领域占据主导地位，用于分析这些结构多样的代谢物。然而，这带来了巨大的成本，因为色谱步骤虽然对化合物的分离很有价值，但却增加了大量的分析时间：每个样品通常需要30分钟。三年前，我们在利物浦大学建立了代谢组学研究中心（CMR）。在CMR中，我们正在开发和应用代谢组学在许多不同的领域，包括（除其他外）人类生理学和健康衰老，抗菌素耐药性，合成生物学，工业生物技术，以及加强对哺乳动物系统和作物发育和恢复力的理解。我们也在培养下一代跨学科代谢组学科学家，我们为我们在这里的能力感到自豪。我们在CMR的重点是开发基于ms的代谢组学，使用预先的“慢”色谱-这限制了高样品通量分析，因为一天中没有足够的时间来进行这些测量。因此，我们仍然从根本上缺乏的是对特定代谢物进行超高通量分析的方法。所要求的仪器是SCIEX公司的回声质谱系统。这对于我们能够增强我们的代谢组学能力至关重要，并将加速我们的代谢组学工作在生物科学研究的许多领域的应用。我们可以确认，这种仪器在CMR，利物浦大学，西北部一般是不可用的，事实上制造商已经确认，这将是英国任何学术机构中嵌入的第一个这样的仪器。因此，该提案的目的是为利物浦和其他地方具有超高吞吐量能力的广泛用户社区确保这种基于ms的Echo仪器。在利物浦大学共享研究设施的支持下，该平台将提供给其他研究所和工业合作伙伴，从而增强更广泛的英国科学基础。

Metabolomics refers to the quantitative measurement of the complement of small molecules (metabolites) found within a biological system. One way to identify such molecules relies on the determination of their masses, known as mass spectrometry. Mass spectrometry (MS), coupled to prior separation with either liquid or gas chromatography, dominates the metabolomics field for the analysis of these structurally diverse metabolites. However, this comes with a significant cost because the chromatography step, while valuable for separation of compounds, adds significant time to the analysis: 30 minutes per sample is typical.Three years ago we established the Centre for Metabolomics Research (CMR) within the University of Liverpool. In the CMR we are developing and applying metabolomics in many different fields including (amongst others) human physiology and healthy ageing, antimicrobial resistance, synthetic biology, industrial biotechnology and for the enhanced understanding of mammalian systems and crop development and resilience. We are also training the next generation of interdisciplinary metabolomics scientists and we are proud of our capabilities here.Our focus within the CMR has been to develop MS-based metabolomics, with up front 'slow' chromatography - this limits high sample throughput analysis as there is simply not enough time in the day to make these measurements. Therefore, what we still fundamentally lack are ultra-high-throughput methods for the analysis of specific metabolites. The instrument requested is the Echo Mass Spectrometry System from SCIEX. This is vital for us to be able to enhance our metabolomics capabilities and will turbo charge the speed of our metabolomics work with applications in many areas of bioscience research.We can confirm that this instrumentation is not available in CMR, the University of Liverpool, the North West in general, and indeed the manufacturers have confirmed that this will be the first such instrument embedded in any academic institution in the UK. The aim of this proposal is thus to secure this Echo MS-based instrument for an extensive User Community in Liverpool and elsewhere with ultra-high-throughput capability. With support from the University of Liverpool Shared Research Facilities this platform would be made available to other institutes as well as industrial partners thus enhancing the wider UK science base.