Volatile organic compound sensing in healthcare using optical interrogation of metal-organic frameworks

对人体排泄的某些化合物（称为生物标志物）进行真实的检测，这些化合物与人体样本（例如呼吸、血液、尿液、汗液和唾液）中的药物代谢过程和化学组成相关，可以提供有关患者生理状况的有价值的信息。人体中的挥发性有机化合物（VOCs）具有识别和监测各种疾病的潜力，如肺癌，糖尿病和体内药物的存在。精确传感的关键是能够检测低浓度的生物标志物（高灵敏度），但不受其他化合物的影响（高特异性）。金属有机框架（MOF）是目前用于气体储存等应用的材料，但尚未在传感中广泛开发。该提案旨在开发一种基于测量MOF中光学变化的颠覆性传感平台，并将其应用于医疗保健领域的挑战。为了实现最佳性能并提供扩大规模和广泛使用的潜力，必须拥有稳健的制造工艺。在该应用中，我们将开发一种新的传感器制造工艺，其基于（i）筛选、设计和合成MOF结构以提供对目标的最高灵敏度和选择性;（ii）使用微波处理涂覆光纤以确保最佳表面覆盖和最大灵敏度;（iii）在被配置为以高灵敏度提供容易使用的光纤上实现。我们将实现具有高灵敏度和选择性的传感平台，以快速监测呼吸中存在的麻醉剂丙泊酚的临床相关浓度。这是提高重症监护患者生存率的重要关键，是监测重要的生理参数，如患者的血液动力学、体温、呼吸频率、通气、营养和代谢，以及准确和连续监测血液中药物和生物标志物的浓度。至关重要的是，所提出的方法可以扩展到其他VOC，如酮，醛类和醇类可用作不同疾病的生物标志物，如肺癌和糖尿病，或药物代谢的指标。

Real time detection of certain chemical compounds, referred to as biomarkers, excreted from human body which are related to metabolic processes and chemical composition of drugs in human samples such as breath, blood, urine, sweat and saliva can provide a valuable information about patients' physiological conditions. Volatile organic compounds (VOCs) in the human body have the potential to identify and monitor various diseases such as lung cancer, diabetes and the presence of drugs in the body. The key to precise sensing is to be able to detect a biomarker at low concentrations (high sensitivity) but not be affected by other compounds (high specificity). A metal-organic framework (MOF) is a material current used in applications such as gas storage but has not been extensively exploited in sensing. This proposal aims to develop a disruptive sensing platform based on measuring optical changes in MOFs and to apply this to challenges in healthcare. To achieve the optimum performance and provide the potential for scale-up and widespread use, it is essential to have a robust manufacturing process. In this application we will develop a new sensor fabrication process based on (i) screening, designing and synthesising the MOF structures to provide the highest sensitivity and selectivity towards the target; (ii) coating an optical fibre using microwave processing to ensure optimum surface coverage and maximum sensitivity; (iii) implementing on a optical fibre configured to provide easy use with high sensitivity.As an end to end process exemplar, we will implement a sensing platform with high sensitivity and selectivity to rapidly monitor clinically relevant concentrations of the anaesthetic propofol present in the breath. This is important key to improving survival in intensive care is monitoring of the vital physiological parameters such as patient's hemodynamics, temperature, respiratory rate, ventilation, nutrition, and metabolism, as well as the accurate and continuous monitoring of concentration of drugs and biomarkers in blood.Crucially, the proposed methodology can be extended to other VOCs such as ketones, aldehydes and alcohols that can be used as biomarkers for different diseases, such as lung cancer and diabetes, or indicators of the metabolism of drugs.