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.