MICA: Development of Boron Doped Diamond Based Transcutaneous Blood Gas Sensors for Improved Patient Ventilation Status Monitoring and Control

体内的溶解氧和二氧化碳血气水平是呼吸健康状况的关键指标，因此是疾病严重程度的重要诊断测试。这些信息对于正确诊断和治疗患者的需求至关重要。然而，如果只可能不频繁地监测呼吸气体，那么威胁生命的变化就不会被注意到，这可能会导致患者遭受严重的并发症，如器官损伤和脑损伤。因此，持续监测的能力为患者在治疗效果和康复的长期预后方面提供了相当大的临床优势。对于每年接受重症监护的30万名患者的健康结果来说，持续监测更为重要，其中包括7万名重症监护婴儿。导致病人严重呼吸窘迫的新冠肺炎疫情，亦进一步凸显持续监测呼吸系统气体的需要。目前医院病房的标准做法是使用血气分析仪。这是一种独立的仪器，需要从患者体内取出血液，并将血液放置在仪器中。每家医院的血气分析仪数量有限(由于成本原因)，使用需要训练有素的工作人员，而且由于突破皮肤屏障，在采集血样时可能会发生患者感染。可用的数量及其操作模式排除了实时测量患者呼吸机状态的可能性。这种方法虽然不理想，但在重症监护或新生儿环境中尤其有问题，在这些环境中，患者快速变化的生理特征、难以接触到血管、可接触的血容量小以及疼痛和失血引起的高度痛苦使测量变得复杂。这项工作的目的是从定期采样转向皮肤上的经皮传感器，提供实时和连续的呼吸气体监测，而不需要从患者体内抽血。这些传感器旨在提供对患者通风状态的响应和持续测量，重要的是，临床工作人员只需最少的输入即可进行长期非侵入性操作。尽管存在二氧化碳和氧气的经皮传感器，但由于传感器的性能低于预期，它们进入医院的吸收一直受到限制。电流传感器使用两种不同的电极材料，通过不同的测量方法对两种不同的呼吸气体进行传感。实际上，传感器的响应随时间漂移，这需要频繁地将传感器从体内取出，拆解和重建传感器，通过在传感器上流动气体来重新校准，然后在患者身上更换。这会导致许多时间没有测量，这对临床工作人员来说是耗时的，并且需要工作人员经过适当的培训。我们的目标是通过使用传感器材料和测量方案来解决这些问题，使我们能够解决目前阻碍当前经皮传感器的问题。该项目建立在研究团队在电化学传感和相关测量方法领域取得的世界领先成就的基础上。电极材料对传感器的稳定性、重复性和稳健性至关重要。出于这个原因，我们将使用功能化的掺硼钻石，这种钻石可以以具有竞争力的成本生产，并且可以一次测量两种呼吸气体。所采用的测量方法也为传感器漂移问题提供了解决方案。只使用一个测量电极，我们的目标也是减少传感器的空间足迹。除了医院护理，传感器还在例如体育和睡眠科学，以及社区的条件管理和诊断方面提供好处。

Dissolved oxygen and carbon dioxide blood gas levels in the body are key indicators of respiratory health status and thus represent an important diagnostic test for illness severity. This information is essential to enabling correct diagnosis and treatment of the patients' needs. However, if only infrequent monitoring of the respiratory gases is possible then life threatening changes go unnoticed which can lead to the patient suffering severe complications such as organ impairment and brain damage. The ability to continuously monitor thus provides considerable clinical advantages to the patient in both the efficacy of their treatment and long term prognosis for recovery. Continuous monitoring is even more important for the health-outcomes of the 300,000 patients treated each year in critical care, including the 70,000 critical care babies. The Covid-19 pandemic, which resulted in patients with severe respiratory distress has also further highlighted the need for continuous respiratory gas monitoring.The current standard approach on hospital wards is to use the blood gas analyser. This is an stand-alone instrument which requires blood removal from the patient and placement of the blood in the instrument. The number of blood gas analysers per hospital is limited (due to cost), use requires trained staff and patient infection is possible when removing blood samples as a result of breaking the skin barrier. The number available and its mode of operation precludes real time measurement of patient ventilation status. This method whilst being non-ideal is particularly problematic in critical care or neonatal settings where the rapidly changing physiology of the patient, difficult to access blood vessels, small accessible blood volumes, and heightened distress caused by pain and blood loss complicate measurements. The infrequent nature of the measurement also precludes fast reactive treatment.The aim of this work is to move away from periodic sampling and move towards on-skin transcutaneous sensors, to provide real time and continuous blood gas monitoring of the respiratory gases, without the need to withdraw blood from the patient. The sensors aim to offer responsive and continuous measurement of patient ventilation status, importantly with minimal input required from clinical staff for long term operation, non-invasively. Whilst transcutaneous sensors for carbon dioxide and oxygen exist their uptake into hospitals has been limited due to the below-expectation performance properties of the sensors. Current sensors use two different electrode materials which sense the two different respiratory gases by different measurements methods. The sensor responses, in practise, drift with time, this necessitates frequent removal of the sensors from the body, taking apart and reconstructing the sensor, recalibrating by flowing gas over the sensor, and then replacing on the patient. This results in many periods of no measurement, it is time consuming for clinical staff and requires the staff to have undergone the appropriate training.We aim to address these issues by using a sensor material and measurement protocols which allow us to tackle the problems which currently hamper current transcutaneous sensors. The project builds upon the world leading achievements of the research team in the field of electrochemical sensing and associated measurement methodologies. The electrode material is essential to sensor stability, reproducibility and robustness. For this reason we will use functionalised boron doped diamond, which can be produced at a competitive cost and can detect both respiratory gases in one measurement. The measurement method adopted, also provides a solution to the sensor drift problem. Using only one measurement electrode we also aim to reduce the spatial footprint of the sensor. Beyond hospital care, the sensors offer benefits in, for example, sport and sleep science, and condition management and diagnostics in the community.