Functional assessment of cardiac beat dynamics under dynamic flow: insights from the Mera microphysiological system

Cardiac rhythm is a critical clinical indicator for cardiac arrhythmias and adverse events during drug toxicity studies. In vivo, cardiomyocyte responses to pharmacological agents occur within minutes and are strongly influenced by dynamic drug delivery through blood flow. However, conventional 2D and 3D static culture systems fail to replicate these fluid flow kinetics, limiting their physiological relevance for assessing beat rate responses. Here, we present Mera, a microphysiological system (MPS) developed by Hooke Bio, designed to support long-term culture and functional analysis of 3D cardiac spheroids composed of human induced pluripotent stem cell-derived cardiomyocytes and cardiac fibroblasts. Mera enables dynamic perfusion, allowing investigation of cardiomyocyte beat rates under physiologically relevant flow conditions. The platform is designed to support up to 640 spheroids per run across its modular architecture, and integrates automated imaging, fluid handling, and user-friendly software, operating under controlled physiological conditions (37 °C, 5% CO₂); flow rates are tunable between 0 and 12.5 mL/min to mimic in vivo environments. In the present study, we demonstrate its use at a smaller experimental scale (up to n = 18 per condition), with full-scale throughput and parallelisation remaining to be validated in future work. Pharmacological testing with verapamil, isoproterenol, calcium chloride, and propranolol demonstrated real-time, reversible modulation of beat rate under flow, including recovery following drug-induced suppression. System variability was comparable to a temperature-controlled reference platform, supporting robust statistical analysis. Dose-response studies yielded IC₅₀ values consistent with literature, confirming physiological relevance. Collectively, these results demonstrate that Mera provides a reproducible, human-relevant platform for modelling cardiomyocyte beat-rate responses to pharmacological modulation under dynamic flow. By enabling dynamic drug exposure and automated analysis, Mera represents a promising approach methodology (NAM) for cardiac drug response testing; incorporation of contractility and electrophysiological readouts will be an important next step toward supporting its use in predictive cardiac safety assessment.