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.

在疾病的新测试(生物标记物)的研究上已经花费了数十亿英镑，但只有少数投入到临床使用。原因是，研究生物标记物的研究实验室往往缺乏直接的临床问题，而且往往缺乏强有力的方法开发和验证，从而使其能够用于临床。Van Geest多组学设施是发现和翻译生物标记物的世界领先者。我们与莱斯特大学医院联合开发了国家依从性测试中心(NCAT)，用于评估患者是否坚持他们的处方药。这项工作不仅对患者的结果和国际指南产生了影响，而且对临床试验的设计也产生了影响。Van Geest多组学设施参与了DHSc登月项目。这一国家方案为快速开发、验证和实施拭子中SARS-CoV-2病毒的三重四极质谱计(LC-MS)方法建立了一个框架。该计划花了大约5个月的时间才开发出一种有效的临床使用方法。LC-MS仪器是最先进的，由制造商Waters以最低的费用提供了一年，并在我们的实验室现场。LC-MS具有精致的灵敏度和令人难以置信的能力，仅识别感兴趣的蛋白质(特异性)。这方面的一个例子是使用LC-MS来鉴定精英运动员的兴奋剂。在将样品装载到LC-MS上之前，需要对其进行准备。这些手工提纯和分离的步骤很慢，可能会导致错误。因此，在这份提案中，我们还要求安捷伦布拉沃液体处理装置，使我们能够以快速、可重复和坚固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，这些项目可以利用从Moonshot计划和NCAT中吸取的经验教训转化为临床相关的分析方法。这种设备物有所值，因为Waters正在以53.5%的折扣出售。第一个项目是开发一种方法，可以快速且可扩展地检测到冬季出现的多种病毒，如流感和新冠肺炎。我们还可以使用MS来识别病毒的变种，并看看这是否可以用于确定病毒在长期COVID中的持久性。第二个项目将为NCAT提供极大改进的方法。它将把分析时间从80分钟减少到45秒到3.5分钟之间。目前，由于耗时较长，该方法主要适用于高血压诊所。新方法将使其能够扩展到其他疾病，包括心力衰竭和类风湿性关节炎，用于住院患者和那些看医生的人。我们还将发展研究大规模研究人群的能力，并根据个人的药物血液水平定制药物。第三个项目将领导一项开创性的努力，开发10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的亚型和对药物的反应。第四个项目将允许对患有糖尿病、甲状腺疾病和心脏病等长期疾病的患者进行远程患者监测。患者将通过手指刺伤自行采集血液，我们将制定肝肾功能等常规检查的测量方法。成功完成将有助于提供远程患者管理的健壮性-特别是在未来大流行期间，以及患者时间和NHS的免费资源。这些项目是项目类型的典范，将使我们能够快速验证和获得检测的认证，然后可以直接带到NHS实验室。