HF-Sensor: A non-invasive biosensor system for heart failure diagnosis and monitoring at the point-of-care

Heart failure (HF) is a major public health challenge, contributing to high morbidity, mortality, and significant economic burden worldwide. Early diagnosis and accurate risk stratification are critical for improving patient outcomes and guiding clinical decisions. N-terminal pro–B-type natriuretic peptide (NT-proBNP) is a well-established blood biomarker of ventricular overload, widely used for diagnosing HF and assessing its severity. Beyond diagnosis, NT-proBNP provides valuable prognostic insights into treatment response and can predict adverse cardiovascular events, such as HF-related hospitalizations and mortality, thus playing a key role in personalized care and therapeutic management. Despite its clinical significance, current CE/FDA-certified methods for NT-proBNP measurement face critical limitations, particularly in point-of-care settings and for ongoing, minimally or non-invasive monitoring. These constraints hinder the ability to perform remote (e.g. community medical clinic) monitoring—a crucial capability for revolutionizing heart failure management. To address this challenge, we report the development and proof-of-concept validation of an ultrasensitive (compared to gold standard enzyme-linked immunosorbent assays), miniaturized electrochemical biosensor for fast and minute sample detection of NT-proBNP in tears from a well-characterized cohort of heart failure patients. Correlation analysis of NT-proBNP concentrations in tear fluid and blood plasma/serum, together with key clinical parameters, demonstrates that tear fluid is a promising non-invasive matrix for heart failure diagnosis and continuous monitoring in point-of-care settings. This approach provides a transformative pathway to advance heart failure management by enabling remote, point-of-care diagnostic monitoring outside of centralized hospitals and laboratories. • The HF-Sensor is a miniaturized electrochemical immunosensor developed for the non-invasive and quantitative detection of the heart failure biomarker N-terminal pro–B-type natriuretic peptide (NT-proBNP) in human tear fluid, requiring a minimal sample volume of just 1 μL. • HF-Sensor achieves a lower limit of detection and higher sensitivity than “gold-standard” commercial enzyme-linked immunosorbent assays (ELISA). • NT-proBNP levels in tear fluid, blood plasma, and serum, measured using the HF-Sensor, showed strong correlations across sample types and with standard clinical assessments of heart failure.