Point of care diagnosis of gastrointestinal disease using laser spectroscopy

使用激光光谱对胃肠道疾病进行即时诊断

基本信息

批准号：
EP/P015603/1
负责人：
Ralph Tatam
金额：
$ 118.56万
依托单位：
CRANFIELD UNIVERSITY
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FP015603%2F1
关键词：
Point care diagnosis gastrointestinal disease

项目摘要

Medical diagnostics is moving from laboratory to bedside. There is a strong trend for complex laboratory analyses to be supplemented, or even replaced, by tests that can be performed at the point-of-care (PoC) by personnel with little or no specialist training. An important feature of PoC tests is their short time-to-result. Provision of diagnostic information at or near real-time supports clinical decisionmaking by enabling rapid and targeted intervention, which improves patient outcome and promotes efficient use of limited healthcare resources. To this end, development of novel instrumentation capable of rapid and accurate measurement of chemical indicators of disease (biomarkers) is a strategic priority.Clostridium difficile infection (CDI) is an example of an unmet clinical need for PoC diagnostics and is the main focus of this study. CDI is a hospital-acquired infection which produces catastrophic diarrhoea, prolongs hospital stays and can prove fatal in vulnerable individuals. It is highly contagious - current UK NHS intervention policy requires that patients with unexplained diarrhoea must be isolated and treated for the disease before a positive diagnosis is available. Current tests for CDI use traditional laboratory "wet chemistry" enzymatic and nucleic acid assays, with limited diagnostic performance and a lead time measured in hours. Misdiagnosis can lead to patients being unnecessarily isolated from wards or treated unnecessarily with antibiotics, which contributes to the development of antimicrobial resistance.Variation in the levels of volatile organic compounds (VOCs) emitted from a range of human samples (e.g. breath, blood, urine) are known to be associated with metabolic status and have been linked to particular diseases. The gastrointestinal tract offers a particularly rich source of information, since many disease states are associated with changes in the bacterial population of the gut (the microbiome) resulting in changes to the VOCs produced, which can be measured using optical spectroscopy. Our vision is to develop a novel approach based on optical measurement of these volatile biomarkers in the gas phase. By measuring the level of specific biomarker chemicals produced by samples of patients' faeces, we aim to provide early warning of the development of gastric disease. Important benefits of this approach are:- Samples of faeces are taken using standard clinical procedures, as is normal practice today when symptoms develop.- Volatile markers may be measured using laser spectroscopy, with a short time-to-result (1-2 minutes). The measurement is highly selective to individual VOCs, which importantly will allow identification of biomarkers against a complex background matrix of over 300 species.- The method requires minimal sample preparation, avoiding the use of reagents and making it suitable for point-of-care diagnosis.- Because the measurement system is not in physical contact with the sample, there is no interference or fouling of the sensor.- It is clinically non-invasive, so is suitable for repeated use in disease monitoring, unlike techniques such as colonoscopy and sigmoidoscopy which are widely used in chronic disease diagnosis but cannot be used on a daily basis.- The method will allow active disease to be distinguished from mere carriage of Clostridium difficile (the latter being present in a significant percentage of the UK population without ill effect).We will develop a flexible diagnostic platform targeted at diagnosis of CDI. Disturbances in the gut microbiome are also associated with a range of other gastrointestinal conditions including inflammatory bowel disease and colorectal cancer, and with other diseases such as diabetes. This technique therefore has wide potential application for medical diagnosis and monitoring of a range of diseases at point of care.

医疗诊断正在从实验室转移到临床。复杂的实验室分析有一个强烈的趋势，即由很少或没有经过专业培训的人员在现场护理 (PoC) 进行的测试来补充甚至取代。 PoC 测试的一个重要特点是得出结果的时间短。实时或接近实时地提供诊断信息，通过实现快速和有针对性的干预来支持临床决策，从而改善患者的治疗结果并促进有限医疗资源的有效利用。为此，开发能够快速准确测量疾病化学指标（生物标志物）的新型仪器是一项战略重点。艰难梭菌感染（CDI）是 PoC 诊断未满足的临床需求的一个例子，也是该领域的主要关注点。这项研究。 CDI 是一种医院获得性感染，会导致灾难性腹泻、延长住院时间，并且对弱势个体可能致命。它具有高度传染性——当前英国 NHS 干预政策要求，在获得阳性诊断之前，必须隔离不明原因腹泻患者并对其进行治疗。目前的 CDI 测试使用传统的实验室“湿化学”酶和核酸检测，诊断性能有限，交付时间以小时为单位。误诊可能导致患者被不必要地隔离出病房或接受不必要的抗生素治疗，从而导致抗菌素耐药性的产生。一系列人体样本（例如呼吸、血液、尿液）中挥发性有机化合物 (VOC) 排放水平的变化）已知与代谢状态有关，并与特定疾病有关。胃肠道提供了特别丰富的信息来源，因为许多疾病状态都与肠道细菌群（微生物组）的变化有关，从而导致产生的挥发性有机化合物发生变化，这些变化可以使用光谱法进行测量。我们的愿景是开发一种基于气相中这些挥发性生物标志物的光学测量的新方法。通过测量患者粪便样本产生的特定生物标记化学物质的水平，我们的目标是对胃病的发展提供早期预警。这种方法的重要优点是： - 使用标准临床程序采集粪便样本，这是当今症状出现时的正常做法。 - 可以使用激光光谱法测量挥发性标记物，出结果时间短（1-2 分钟））。该测量对单个 VOC 具有高度选择性，重要的是可以根据 300 多种物种的复杂背景基质识别生物标志物。-该方法需要最少的样品制备，避免使用试剂，使其适合即时诊断.- 由于测量系统不与样本进行物理接触，因此传感器不会受到干扰或污染。- 与结肠镜检查和乙状结肠镜检查等技术不同，它在临床上是非侵入性的，因此适合在疾病监测中重复使用哪个广泛用于慢性病诊断，但不能每天使用。 - 该方法将能够将活动性疾病与仅携带艰难梭菌（后者存在于英国人口中很大一部分而没有不良影响）区分开来。我们将开发一个针对 CDI 诊断的灵活诊断平台。肠道微生物组的紊乱还与一系列其他胃肠道疾病有关，包括炎症性肠病和结直肠癌，以及糖尿病等其他疾病。因此，该技术在医疗诊断和护理点监测一系列疾病方面具有广泛的潜在应用。