Advanced tandem quadrupole mass spectrometer with an automated sample extractor for a multiuser interdisciplinary translational research facility

带有自动样品提取器的先进串联四极杆质谱仪，适用于多用户跨学科转化研究设施

• 批准号: MR/X012565/1
• 负责人: Donald Jones
• 金额: $ 41.03万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX012565%2F1
• 关键词: Advanced; tandem; quadrupole; mass; spectrometer

There have been billions of pounds spend in research on new tests for diseases (biomarkers) but only a handful have made it to clinical use. The reasons are that there is often a lack of direct clinical question asked by research labs studying biomarkers and often a lack of robust method development and validation such that it can be used clinically. The van Geest Multi-OMIC facility is a world leader in the discovery and translation of biomarkers. We, in joint partnership with the University Hospitals of Leicester have developed the National Centre of Adherence Testing (NCAT), for assessing whether patients are adhering to their prescribed medications. This work has had impact not just on patient outcomes and international guidelines but to the design of clinical trials. The van Geest Multi-OMIC facility participated in the DHSC Moonshot Project. This national programme established a framework for rapid development, validation and implementation of a triple quadrupole mass spectrometer (LC-MS) method for the SARS-CoV-2 virus in swabs. The programme took about 5 months to develop a valid method for use clinically. The LC-MS instrument is state of the art and was provided with minimal fee for a year by the manufacturer Waters and is on site in our laboratory.LC-MS have exquisite levels of sensitivity and incredible levels of ability to identify only the protein of interest (specificity). An example of this is the use of LC-MS in identification of doping by elite athletes. Before samples can be loaded on the LC-MS they need to be prepared. These manual steps of purifying and isolating are slow and can lead to errors. Therefore, in this proposal we are requesting also an Agilent Bravo liquid handling unit to enable us to do a wide range of sample preparation approaches in a swift, reproducible and robust manner. We request the purchase of the above LC-MS to develop four main clinical projects that can be translated into clinically relevant assays using lessons learnt from the Moonshot programme and NCAT. The equipment offers very good value for money as it is being offered at a 53.5% discount by Waters. The first project is to develop a method that can detect multiple viruses seen in the winter such as influenza and Covid-19- in a rapid and scalable manner. We can also use MS to identify variants of viruses and look to see whether this can be used in determining viral persistence in Long COVID.The second project will deliver vastly improved methods for NCAT. It will reduce analysis time from 80 minutes to between 45 seconds to 3.5 minutes. Currently, due to the time taken, the method is available mainly for hypertension clinics. The new methods will enable the use to be expanded to other conditions including heart failure and rheumatoid arthritis, in hospitalised patients and those seeing their GP. We will also develop capabilities to study large research populations and the tailoring of medications according to an individual's medication blood level.The third project will lead a pioneering effort to develop ten methods to study a key pathway in blood pressure regulation- the renin-angiotensin aldosterone system (RAAS). These methods will help understand subgroups of hypertension and response to medications.The fourth project will allow remote patient monitoring of patients with long term conditions such as diabetes, thyroid disease and heart disease. Patients will self-collect their blood by finger prick, and we will develop methods for measurements of routine tests such their liver and kidney function. Successful completion will help provide robustness in patient management remotely- especially during future pandemics and free resources both in patient time and of the NHS.These projects are exemplars of the type of project that will enable us to swiftly validate and gain accreditation for assays that can then be taken straight into NHS laboratories.

关于疾病的新测试（生物标志物），已经花费了数十亿英镑的支出，但只有少数才能临床使用。原因是研究实验室研究生物标志物的研究实验室通常缺乏直接的临床问题，并且通常缺乏可靠的方法开发和验证，因此可以在临床上使用。 Van Geest多摩尼克设施是生物标志物发现和翻译的世界领导者。我们与莱斯特大学医院联合合作开发了国家依从性测试中心（NCAT），用于评估患者是否遵守处方药。这项工作不仅影响了患者的结果和国际准则，还影响了临床试验的设计。 Van Geest多OMIC设施参加了DHSC Moonshot项目。该国家计划为签名的SARS-COV-2病毒的三倍四极杆质谱仪（LC-MS）方法建立了一个框架，用于快速开发，验证和实施。该计划花了大约5个月的时间来开发一种有效的临床使用方法。 LC-MS仪器是最先进的，制造商水的收费最低，并且在我们的实验室中现场。LC-MS具有精致的敏感性和令人难以置信的能力水平，仅识别感兴趣的蛋白质（特异性）。一个例子是使用LC-MS来识别精英运动员的兴奋剂。在将样品加载到LC-MS上之前，需要准备就绪。这些纯化和隔离的手动步骤很慢，可能导致错误。因此，在此提案中，我们还要求一个安捷伦的Bravo液体处理单元，以使我们能够以迅速，可重复和健壮的方式进行广泛的样品制备方法。我们要求购买上述LC-MS，以开发四个主要的临床项目，可以使用从Moonshot计划和NCAT中学到的经验教训将其转化为临床相关测定。该设备物有所值，因为水域以53.5％的折扣提供了资金。第一个项目是开发一种可以以快速且可扩展的方式检测冬季观察到的多种病毒，例如流感和covid-19-。我们还可以使用MS来识别病毒的变体，并查看是否可以用于确定长时间的病毒持久性。第二个项目将为NCAT提供大大改进的方法。它将将分析时间从80分钟减少到45秒至3.5分钟。目前，由于花费的时间，该方法主要用于高血压诊所。新方法将使住院患者和看到GP的患者在包括心力衰竭和类风湿关节炎（包括心力衰竭和类风湿关节炎）中扩展到其他疾病。我们还将发展能够研究大量研究人群和根据个人药物血液水平的药物量身定制的能力。第三个项目将领导开创性的努力，以开发十种方法来研究血压调节的关键途径 - 肾素 - 血管紧张素醛固酮系统（RAAS）。这些方法将有助于了解高血压和对药物反应的亚组。第四个项目将允许对患有糖尿病，甲状腺病和心脏病等长期病情的患者进行远程监测。患者将通过手指刺来自我收集血液，我们将开发用于测量常规检查（例如其肝脏和肾功能）的方法。成功的完成将有助于远程患者管理的鲁棒性 - 尤其是在未来的大流行期间和在患者时间和NH的自由资源中。这些项目都是项目类型的典范，这些项目将使我们能够迅速验证并获得可以直接将其直接带入NHS实验室的测定的认证。