Second-Order IMEX Time-Stepping Methods for Efficient Bidomain Multi-Electrode Array Simulations of Cardiac Stem Cell Monolayers

Abstract

Multi-electrode Arrays (MEAs) enable tissue-level electrophysiological studies of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by recording extracellular field potentials. Recent computational models have improved MEA simulations by coupling detailed electrode descriptions with the Bidomain framework, a parabolic-elliptic system of nonlinear PDEs coupled with a stiff ionic model. The standard numerical strategy relies on operator splitting techniques that decouple the PDE and ODE components. In most implementations, the ionic subsystem is treated explicitly while the diffusive operator is handled implicitly, resulting in a first-order implicit-explicit (IMEX) time discretization. Although computationally convenient, this approach limits temporal accuracy and may reduce efficiency in large-scale simulations. In this work, we investigate higher-order IMEX Runge-Kutta schemes within a Strang-based operator splitting, specifically tailored for the MEA model of hiPSC-CMs monolayers. First- and second-order schemes are compared in terms of computational cost and global error against a high-fidelity reference solution obtained with a very small time step. For a fixed computational cost, the second-order schemes achieve errors that are 2-3 orders of magnitude smaller than those of the first-order method. These results demonstrate that higher-order IMEX integration significantly improves the accuracy-to-cost ratio of MEA simulations, providing a practical and reliable approach for large-scale electrophysiological studies.