Rate and Rhythm Analysis of Cardiac Organoid Electrophysiological Recordings Using the PhysioMEA Platform

Introduction: Cardiac organoids provide a valuable platform for studying physiological and pathophysiological processes affecting heart rate and rhythm. Multi-electrode arrays (MEA) are widely used for high-throughput electrophysiological assessments. Despite the widespread use of MEA technology in cardiac research, current analysis tools are limited, focusing primarily on 1D electrophysiological biomarkers and on average inter beat intervals calculation. Thus, we aim to develop innovative algorithms for standardized biomarker calculation, spatiotemporal biomarker dynamics assessment, and comprehensive beat rate variability (BRV) analysis of cardiac organoids.

Material and method: We recorded electrograms from spontaneously beating cardiac organoids (n=14), generated from human-induced pluripotent stem cell derived cardiomyocytes, using 8x8 electrode MEA plates. We developed novel algorithms for R-, S-, and T-peak detection as well as advanced 2D electrical signal processing tools of these biomarkers. These algorithms were implemented on the open-source PhysioMEA platform.

Results and discussion: Cardiac organoids exhibited a high degree of similarity among biomarker distributions under basal conditions, indicated by their coefficients of variation (p-value > 0.2). Additionally, comprehensive analysis of BRV in cardiac organoids is presented for the first time, revealing high very low frequency content (78.21%) in cardiac organoid inter-beat intervals spectra compared to low- and high-frequency components (11.11% and 10.68%, respectively).

Conclusion: We present a comprehensive method for 1D and 2D electrophysiological analysis and BRV assessment of cardiac organoids using the PhysioMEA platform, aiming to advance the cardiac electrophysiology field using unique standardized analytical tools.