SCH: INT: Disposable High Sensitivity Point of Care Immunosensors for Multiple Disease and Pathogen Detection

这项研究计划提出调查有时在汗液中发现的物质，如蛋白质，可以检测健康和疾病（生物标志物）。汗液是一种生物液体，可以为一个人的健康状况提供一个窗口。目前，还没有一种快速的方法来测量汗液中蛋白质的变化，这种变化是疾病的信号。目标是测量运动前、运动中和运动后汗液中这些蛋白质的变化，包括使用低成本的一次性即时生物传感器测量压力激素和免疫标记物的水平。从本质上讲，这个提议的目的是开发一种廉价的、一次性的贴片传感器，可以戴在皮肤上，最终成为像大多数家庭药柜里的绷带盒或口腔温度计一样广泛使用。这种设备的关键工程障碍之一是低成本制造技术的可用性，该技术可以与最先进的生物标志物蛋白质组学检测技术相结合，以医学实验室级别的灵敏度诊断和监测多种疾病。本提案提出了一种将低成本商业显示技术（可以在电视、电脑显示器或手机中找到）与蛋白质微阵列打印技术相结合的新方法，以制造一种低成本的一次性皮肤贴片，用于在家庭或其他非临床环境中更有效地自我管理患者的医疗保健。这些测量结果将通过智能手机技术实时提供给患者和他们的护理人员。为了实现这一研究目标，提出了一种类似织物的柔性皮肤贴片，可以对人体汗液中的多种生物标志物进行无创监测。这种新方法旨在利用现有的商业制造技术，这种技术可以很容易地用于每年生产数亿个设备，每个设备的成本仅为几美元。该研究计划建议利用多种蛋白质组学研究平台（质谱，蛋白质和抗体微阵列）来建立汗液蛋白质组的轮廓，这将对进一步了解汗液和皮肤的生物学知识产生根本影响，并将高成本的基于荧光的分析平台转变为低成本，一次性，高灵敏度的基于护理点的荧光分析，这是最低到无创的。提出的开发工作的亮点包括：利用质谱法进行详细的蛋白质组学分析，以及用于发现汗液中存在的蛋白质和抗体的定制蛋白质和抗体微阵列；低成本荧光识别横向流动试验生物传感器光学和电子元件的开发与优化利用鉴定的血清和汗液生物标志物开发荧光识别侧流分析，并将该分析与我们的光学生物传感器集成。这项研究计划加速了技术的发展，将医疗保健从被动和以医院为中心转变为预防、主动、循证和以人为中心。下一代医疗保健解决方案将为家庭监控提供突破性的传感器技术。医疗保健的这种转变对免疫功能低下的个体尤其重要，例如器官移植受者、癌症患者、手术后患者和老年人。

This research program proposes to investigate substances sometimes found in sweat, such as protein, which can detect health and disease (biomarkers). The sweat is a biofluid that can provide a window to a person's health. At this time, there is no rapid method to measure the changes in proteins in the sweat that signal disease. The goal is to measure changes in these proteins in the sweat before, during, and after physical activity, including measuring levels of stress hormones and immune markers using a low cost and disposable point-of-care biosensor. In essence, the aim of this proposal is to develop a cheap and disposable patch sensor that can be worn on the skin, and eventually become as widely used as the box of bandages or oral thermometer found in most home medicine cabinets. One of the key engineering roadblocks to such a device is the availability of a low-cost manufacturing technology that can be combined with state-of-the-art biomarker proteomic detection technology to diagnose and monitor multiple diseases with medical laboratory level sensitivity. This proposal presents a new approach combining low-cost commercial display technology (found in your TV, computer monitor, or cell phone) with protein microarray printing technology to fabricate a low-cost, disposable skin patch for more effective self-management of patient health care in the home or in other non-clinical settings. The measurements will be available in real time for both patients and their caregivers using smart-phone technology. To meet this research objective, a fabric-like flexible skin patch is proposed that would provide non-invasive monitoring of multiple biomarkers in human sweat. This new approach is designed to use existing commercial manufacturing technology that can be readily adapted to produce hundreds of millions of devices per year at a cost of only a few dollars each.The research program proposes to utilize multiple proteomic research platforms (mass spectrometry, protein, and antibody microarrays) to establish a profile of the sweat proteome that will have a fundamental impact on furthering the biological understanding of sweat and skin, and transition high-cost fluorescent-based assay platforms into a low-cost, disposable, highly sensitive fluorescent point-of-care based assay that is minimally to non-invasive. Highlights of the proposed development effort include: a detailed proteomic analysis utilizing mass spectrometry as well as custom protein and antibody microarrays for the discovery of proteins and antibodies present in sweat; development and optimization of the biosensor's optical and electronic components for the utilization of low-cost fluorescent recognition lateral flow assay; development of fluorescent recognition lateral flow assays utilizing identified serum and sweat biomarkers and the integration of the assay with our optical biosensor. This research program accelerates the development of technology that will transform healthcare from reactive and hospital-centered to preventative, proactive, evidence-based, and person-centered. This next generation health care solution will provide breakthrough sensor technology for in-home monitoring. This transformation in healthcare is especially critical for immune-compromised individuals, such as organ transplant recipients, cancer patients, post-operative patients, and the elderly.