Miniaturized Electromechanical Biosensor for Preclinical Cardiac Drug Screening

Abstract Miniaturized bioelectronic systems offer new opportunities for drug screening by increasing sensitivity, reducing cell consumption, and enabling scalable integration. Here, we report for the first time a miniaturized drug screening platform that enables simultaneous assessment of cardiomyocyte contractility and electrophysiology. The compact design supports parallel integration of multiple sensing units on a single chip, lowering cell demand and facilitating high-throughput assays. The device detects cardiac forces as low as 6.9 nN with a stress resolution of 0.042 nN µm− 2, representing a substantial improvement in sensitivity over conventional strain-sensor-based devices. Using this platform, we evaluate key cardiac functional parameters, including contractile force, beating rate, and extracellular field potentials, in neonatal rat ventricular myocytes and human induced pluripotent stem cell–derived cardiomyocytes. Pharmacological testing with blebbistatin, verapamil, and astemizole reveals distinct, mechanism-specific drug responses, while long-term studies with doxorubicin establish an in vitro model of drug-induced arrhythmia, highlighting the platform’s potential for disease modeling and preclinical cardiotoxicity testing. By integrating high sensitivity, mechanical compliance, and stable dual-mode readout in a miniaturized format, this platform addresses key limitations of existing methods and provides a versatile tool for mechanistic studies, therapeutic evaluation, and next-generation cardiotoxicity screening.