Strain Sensor-Integrated Tri-Layer Cantilever with Enhanced Sensitivity and Stability for Quantitative Cardiotoxicity Screening.

Cantilever-based biosensors provide a powerful approach for monitoring cardiomyocyte contractility, but conventional designs often exhibit baseline bending that compromises sensitivity and limits predictive accuracy in drug screening. Here, we present a tri-layer polymer cantilever biosensing platform integrated with a full-bridge piezoresistive strain sensor for the quantitative measurement of cardiomyocyte contractility. The hybrid KMSF-SU-8-KMSF structure minimizes residual stress and reduces baseline deformation by more than 85% compared to SU-8-only cantilevers. This architecture improves strain transfer to the embedded sensors and achieves a limit of detection of approximately 1.2 kPa, which is lower than that of previously reported cantilever systems. The top KMSF layer functions as both an encapsulation barrier and a tissue-guiding interface, promoting alignment, enhancing sarcomere organization, and increasing connexin-43 expression to support cardiomyocyte maturation. Drug screening further confirms the platform's predictive accuracy, as the device successfully detects the expected pharmacological effects: verapamil decreases contractile force, isoproterenol increases both force and beat rate, blebbistatin suppresses myofilament activity, and astemizole induces arrhythmic beating consistent with hERG channel blockade. By providing stable, label-free, and high-sensitivity electronic readouts of cardiomyocyte contractility, this platform establishes a robust and scalable solution for preclinical cardiotoxicity testing, disease modeling, and personalized medicine.