Integrated Cantilever-MEA Platform for High-Sensitivity and Scalable Recording of Cardiomyocyte Electromechanics.

Preclinical screening is critical for reducing drug attrition; however, current electromechanical platforms are often restricted by the trade-off between miniaturization and force sensitivity. Miniaturizing sensor dimensions to enable high-throughput assays inherently increases structural stiffness, rendering conventional devices incapable of resolving the weak contractile forces of cardiomyocytes. Here, we report a miniaturized cantilever-MEA platform that overcomes this limitation to enable simultaneous, highly sensitive assessment of cardiomyocyte contractility and electrophysiology. By integrating an ultrathin nanosilicon piezoresistive strain sensor with an intrinsically compliant polymer microcantilever array, the device effectively decouples geometric scaling from sensitivity degradation. It detects cardiac forces down to 6.9 nN with a stress resolution of 0.042 nN µm-2, supporting high-density integration without compromising signal fidelity. Using neonatal rat ventricular myocytes and human induced pluripotent stem cell-derived cardiomyocytes, we evaluated functional parameters including contractile force, beating rate, and extracellular field potentials. Pharmacological testing with blebbistatin, verapamil, and astemizole produced distinct electromechanical response patterns consistent with their known mechanisms. In addition, continuous monitoring under doxorubicin exposure over 48 h captured time-dependent deterioration of both mechanical and electrical activity. This miniaturized dual-mode platform addresses the limitations of macroscopic bulk-averaging sensors, providing a scalable, label-free approach for mechanistic studies and next-generation cardiotoxicity screening.