Engineered Metal Functionalized TiO2 Nanotube Sensing Platform for Assessment of Pneumonia Volatile Biomarkers

全球健康面临的一项重大挑战是开发便携式、低成本和非侵入性的疾病诊断技术，因为这种设备的可用性可以减少感染造成的死亡人数。例如，肺炎是一种每年夺去大约100万五岁以下儿童生命的疾病，原因是难以获得医疗保健或能够快速诊断该疾病的工具。这个研究项目的目标是开发创新的、非侵入性的生物传感方法来检测肺炎患者呼吸中释放的化合物。研究人员将用陶瓷材料二氧化钛制造直径约为几纳米的小管，然后在管的外部附着一层金属层。然后，他们将研究试管的电阻如何随其暴露于引起肺炎的微生物释放的化合物蒸气而变化。该研究项目将利用金属和挥发性有机生物标志物（vob）之间已知的特定分子相互作用。这些化合物是由引起疾病（如肺炎）的微生物释放出来的，并且在感染者的呼吸中发现。先前的研究表明，患者呼吸中的vob与糖尿病、结核病、结直肠癌和肺炎等病理状况之间存在明确的联系。该研究方法使用沉积在二氧化钛纳米管衬底上的金属作为感兴趣的vob的结合元素。结合事件引起传感器中电流的可测量变化，该变化将被表征。该项目将专注于通过以下方式创建肺炎传感器：(1)使用计算建模来了解与肺炎相关的已知vob的金属之间或金属组合之间的相互作用；(2)建立金属修饰的二氧化钛纳米管传感平台，能够检测与肺炎相关的vob；(3)研究传感器对肺炎相关vob的检出限；(4)开发一种传感器，用于检测培养物中的细菌负荷与使用肺炎链球菌、金黄色葡萄球菌和流感嗜血杆菌（已知VOB的肺炎中常见的微生物）产生的VOB量之间的生物学关系。这些研究工作将证明所提出方法的实用性，并为建立用于评估肺炎的基于呼吸的传感器奠定基础。

A major challenge for global health is the development of portable, low-cost, and non-invasive technologies for the diagnosis of diseases, because the availability of such devices could reduce the number of mortalities caused by infection. For example, pneumonia is a disease that annually takes the lives of approximately one million children under the age of five due to poor access to health care or tools that can rapidly diagnose the disease. The goal of this research project is to develop innovative, non-invasive biosensing methods to detect compounds emitted in the breath of individuals suffering from pneumonia. The researchers will create small tubes of a ceramic material, titanium dioxide, that have diameters on the order of several nanometers and then attach a metal layer to the exterior of the tubes. They will then study how the electrical resistance of the tube changes as a function of its exposure to vapors of compounds that are emitted by microorganisms that cause pneumonia. This research project will leverage known specific molecular interactions between metals and volatile organic biomarkers (VOBs). Such compounds are given off by microorganisms that cause diseases, such as pneumonia, and are found in the breath of infected individuals. Previous research has shown a clear link between VOBs from patient breath and pathological conditions such as diabetes, tuberculous, colorectal cancer, and pneumonia. The research approach uses metals deposited on a titanium dioxide nanotube substrate as a binding element for VOBs of interest. Binding events cause a measurable change in current in the sensor which will be characterized. The project will focus on creating a pneumonia sensor by (1) using computational modeling to understand the interactions between metals or combination of metals with known VOBs associated with pneumonia; (2) creating a metal-modified titanium dioxide nanotube sensing platform capable of detecting VOBs associated with pneumonia; (3) studying the limit of detection of the sensor for the VOBs associated with pneumonia; and (4) developing a sensor for examining the biological relationship between bacterial load in a culture and the amount of VOB generated using Streptococcus pneumonia, Staphylococcus aureus, and Haemophilus influenza (organisms commonly found in pneumonia with known VOBs). These research efforts will demonstrate the utility of the proposed approach and lay the foundation for building a breath-based sensor for assessing pneumonia.