Reagentless Sensor Technologies For Continuous Monitoring of Heart Failure Biomarkers

项目总结： 心力衰竭影响着全球约2600万人，是一种重大的经济和 社会负担。这包括仅在美国就有600多万成年人，这是一个预计的数字 在接下来的15年里增长46%。心力衰竭是一种进行性疾病，其特征是反复发作 病情加重。先前的工作表明，生物标记物监测可以帮助评估风险并提供 对疾病管理有意义的数据。但为了让这一点能够持续进行，自我 作为可穿戴系统的再生传感器，可以动态和连续地检测生物分子物种 仍然是一个未得到满足的需求。完全实现这些系统的一个主要挑战是开发 允许无需试剂即可分析复杂生物分子，如蛋白质、核酸和代谢物 时间到了。 我们最近开发了第一个可以适应任何蛋白质的无试剂传感器，并展示了 能够使用植入式传感器阵列在体内进行连续监测。在这个项目中，我们将适应 我们的心力衰竭标志物技术为远程监测高危心脏提供了一种新的方法 失败的病人。实现这一点的技术是最近开发的一种无酶和无试剂 具有适合生物样品分析的灵敏度水平的电化学报告系统 而不需要进行前处理。电化学传感器是环境或环境研究的强大平台 基于廉价仪器和直接式电气测量的生物监测 洋流。 在拟议的项目中，我们将把这些电化学传感器集成到生物兼容的探针中，用于原位 生化监测。我们将对传感器进行敏感和稳健的检测，以确定面板标记 作为心脏健康的临床指标。随后，我们将把这些探测器设计成可穿戴平台 能够持续监测间质液体中存在的生物标记物。必备硬件和软件 为了控制可穿戴式监控设备，将在项目中进行开发和测试，并进行自动化分析 将在心力衰竭的动物模型中得到验证。项目交付成果将包括一流的生物标志物 监测系统可能会对美国人口产生巨大影响，因为它提供了持续的 慢性疾病医疗保健中的生物标记物监测。

Project Summary: Heart failure affects approximately twenty-six million people globally and represents a major economic and societal burden. This includes more than six million adults in the United States alone, a number that is predicted to rise by 46% over the next 15 years. Heart failure is a progressive condition characterized by recurrent exacerbations. Prior work indicates that biomarker monitoring can aid in the assessment of risk and provide meaningful data in management of the disease. But in order to allow this to be done on a continuous basis, self- regenerating sensors that can dynamically and continuously detect biomolecular species as a wearable system remain an unmet need. One major challenge to fully realize these systems is the development of platforms that allow for reagent-free analysis of complex biomolecules such as proteins, nucleic acids, and metabolites in real time. We recently developed the first reagentless sensor that can be adapted to any protein and demonstrated the ability to perform continuous monitoring in vivo using an implantable sensor array. In this project, we will adapt our technology for markers of heart failure to provide a new approach for remote monitoring of at-risk heart failure patients. The technology that enables this is a recently developed an enzyme-free and regent-free electrochemical reporter system that exhibits levels of sensitivity suitable for analysis of biological samples without the need for pre-processing. Electrochemical sensors are a powerful platform for environmental or biological monitoring based on inexpensive instrumentation and straightforward measurements of electrical currents. In the proposed project we will integrate these electrochemical sensors into biocompatible probes for in situ biochemical monitoring. We will test the sensors for sensitive and robust detection of a panel markers identified to be clinical indicators of cardiac health. Subsequently we will engineer these probes into a wearable platform capable of continuous monitoring of biomarkers present in the interstitial fluid. Requisite hardware and software for controlling the wearable monitoring device will be developed and tested in the project and automated analysis will be validated in an animal model of heart failure. The project deliverables will include first-in class biomarker monitoring systems with the potential to have a large impact on the American population by providing continual biomarker monitoring in healthcare for chronic conditions.