Point of care diagnosis of gastrointestinal disease using laser spectroscopy

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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.