Real-Time Continuous Troponin Monitoring: A Breakthrough in Personalized Cardiovascular Risk Assessment and Management - Cardiovascular diseases (CVDs) remain the leading cause of death globally, with acute coronary syndromes (ACS) and myocardial infarctions (MIs) representing major clinical and economic challenges. Current diagnostic methods, such as high-sensitivity cardiac troponin (hs-cTn) assays, rely on intermittent blood sampling and often fail to detect transient or silent ischemic events, leading to delayed diagnosis and suboptimal treatment. This diagnostic gap highlights the need for continuous, real-time biomarker monitoring to improve outcomes for patients at risk of ACS. Addressing this need, we propose the development of a wearable microneedle-based biosensor for continuous cardiac troponin I (cTnI) monitoring. The overall goal of this project is to demonstrate the feasibility of a transformative biosensor capable of real-time, reversible, and ultra-sensitive monitoring of cTnI in interstitial fluid (ISF). The proposed sensor integrates microneedle technology with aptamer-based electrochemical biosensing to achieve high sensitivity, specificity, and long-term stability in complex biofluid environments. This wearable device will provide clinicians with actionable insights into troponin kinetics, enabling earlier detection of ischemic events and personalized therapeutic interventions. The project is structured around three specific aims: In Aim 1, the electrochemical aptamer-based sensor for cTnI detection will be developed and optimized. This includes the selection and functionalization of aptamers, integration with microneedle arrays, and optimization of antifouling coatings to ensure robust signal stability in ISF. Aim 2 validates the sensor’s analytical performance in contrived ISF and human serum. This will include assessing sensitivity, specificity, and stability over multi-day operation in physiologically relevant conditions. Finally, Aim 3 evaluates the biocompatibility and sterility of the microneedle sensor to ensure safe, extended skin contact. The sensor will be tested for cytotoxicity and sterility using ISO-compliant protocols to prepare it for future human applications. This project also addresses the longstanding challenge of integrating biomarker diagnostics with wearable technologies, bridging the gap between laboratory-grade accuracy and real-world usability. The proposed research will establish the feasibility of a novel wearable cTnI monitoring platform, addressing critical gaps in cardiac diagnostics and advancing precision medicine. The device’s modular design allows integration with complementary biomarkers such as NT-proBNP, enabling comprehensive cardiac health profiling. Furthermore, its affordability and scalability will support widespread adoption, transforming cardiac care in both resource-limited and high-resource settings. Beyond individual benefits, this technology has the potential to reduce unnecessary hospitalizations, optimize resource utilization, and democratize access to advanced diagnostics in underserved settings. By focusing on continuous cardiac biomarker monitoring, this project aligns with the National Heart, Lung, and Blood Institute’s (NHLBI) mission to promote innovative technologies that improve health outcomes and reduce the burden of cardiovascular diseases.