A high sensitivity triple quadruple mass spectrometer coupled to an ultra-high pressure liquid chromatograph system for quantitative analysis

基于三重四极杆质谱仪的LC-MS/MS系统被广泛应用于工业和学术研究实验室中复杂生物样品中大小有机分子的最灵敏的定量方法。三重三重质谱系统还具有其他独特的功能，包括前体离子扫描和高灵敏度的中性损失扫描，这是疾病生物标志物和生物活性天然产物发现的重要工具。结构相似的化合物，无论是具有相同的主链还是官能团，都可以使用三联四联质谱仪提供的靶向扫描选项来识别。尽管华威化学拥有英国最大的质谱设备之一，包括多个ESI-Q-TOF， MALDI-TOF和esi -离子阱质谱仪，但我们缺乏一种适合超高灵敏度定量分析的仪器，这阻碍了我们从生物样品中获取重要信息。我们迫切需要一种三重四联质谱仪，用于多反应监测模式下基于LC-MS/MS的定量。新仪器将使我们能够大大扩展和加强我们目前在许多RCUK（主要是BBSRC）资助项目中的研究活动。这将包括对英国白蜡树的代谢组学研究（BB/N021452/1，由Murray Grant教授领导），其目的是发现白蜡树枯死病的可靠生物标志物，并建立英国白蜡树代谢组学数据库。反过来，这将为未来的疾病诊断和选择性培养抗病原体基因组型白蜡树铺平道路。另一个由BBSRC资助的主要项目（sLoLa BB/K002341/1，由Gregory Challis教授领导）旨在通过微生物基因组挖掘从细菌中发现生物活性农药。该仪器具有独特的前体离子扫描和中性损失扫描功能，能够以高灵敏度快速识别同族或具有相同官能团的化合物。许多其他项目，包括新型有机金属抗癌药物、抗炎药物和抗病毒药物的定量，以及它们的代谢研究，也将受益于使用拟议的仪器。新仪器还将使我们能够培训下一代科学家使用最先进的质谱仪，这将使他们获得实践经验，这对他们未来的职业发展非常有益。我们以研究为主导的教学意味着即使是本科生也可以从最先进的设施中受益。拟议的仪器将被纳入，并将补充和显著增强我们现有的质谱设备，通过增加新的功能。新的MS不仅将使华威的学生和员工受益，我们的学术和工业合作伙伴也将受益于接受培训，并获得最先进的MS技术。

The triple quadrupole mass spectrometer based LC-MS/MS system has been widely adopted as the most sensitive methodology for the quantitation of small and large organic molecules in complex biological samples for both industrial and academic research laboratories. The triple quadruple MS system has other unique capabilities, including precursor ion scan and neutral loss scan with high sensitivity, which are important tools for disease biomarker and bioactive natural products discoveries. Compounds that have a similar structure, either with identical backbone or functional groups, can be identified using the targeted scan option offered from a triple quadruple mass spectrometer. Despite the fact that Warwick Chemistry has one of the largest mass spectrometry facilities in the UK, consisting of multiple ESI-Q-TOF, MALDI-TOF and ESI-Ion trap mass spectrometers, we lack an instrument that is suitable for ultra-high sensitivity quantitative analysis, and this is hindering us from acquiring important information from biological samples. We urgently require a triple quadruple type of mass spectrometer for LC-MS/MS based quantitation in multiple reaction monitoring mode. The new instrument will enable us to significantly expand and enhance our current research activities in many RCUK (mainly BBSRC) funded projects. This will include metabolomics studies on British ash trees (BB/N021452/1, Led by Prof Murray Grant), where the aim is to discover reliable biomarkers for ash dieback disease, and establish a database for British ash tree metabolome. In turn this will pave the way for future disease diagnosis and the selective cultivation of a pathogen resistant genome type ash tree. Another major BBSRC funded project (sLoLa BB/K002341/1, led by Prof Gregory Challis) aims to discover bioactive agrichemicals from bacteria through microbial genome mining. The unique precursor ion scan and neutral loss scan capabilities on the proposed instrument will enable swift identification of compounds that belong to the same family, or which have the same functional groups, with high sensitivity. Many other projects including the quantitation of novel organometallic anticancer drugs, anti-inflammatory drugs and anti-viral drugs, as well as the investigation of their metabolism, will also benefit from accessing the proposed instrument. The new instrument will also enable us to train the next generation of scientists on the most advanced mass spectrometer, which will enable them to gain hands-on experience that will be extremely beneficial for their future career development. Our research led teaching means that even undergraduate students can also benefit from the access to a state of the art facility.The proposed instrument will be incorporated into, and will complement and significantly enhance our existing mass spectrometry facility though the addition of new capabilities. The new MS will not only benefit our students and staff in Warwick, our academic and industrial collaborators will also benefit from receiving training, and access to the most advanced MS technologies.