Optomechanical biosensor for cardiomyocyte contractility measurement: from single-cell to network activity

Accurate, high-throughput assessment of cardiomyocytes contractility is essential for cardiac drug screening and toxicity testing. Herein, we present a label-free, optomechanical biosensor for non-invasive monitoring of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The device features a silicon nitride membrane patterned with polydimethylsiloxane (PDMS) micromembranes (~30 µm) each functioning as a mechanical sensor that transduces the cell beating in an optical signal. The latter is measured by collecting the local variation of fluorescence dye densities located in a chamber below the micromembranes and then completely separated by the cell culture. This platform enables real-time measurement of beating frequency, contraction duration, synchronicity and wave propagation velocity. Functional validation with isoprenaline and blebbistatin confirmed sensitivity to pharmacological modulation, while immunostaining verified structural integrity of the cardiomyocyte layer. Compared to conventional techniques, this approach offers improved spatial resolution, parallel single-cell and network measurement as well as the ability to estimate contractile force. Its scalable design and multiplexing capability make it a promising tool for cardiac drug screening, disease modeling, and electrophysiological studies.