Micro-electrode channel guide (µECG) technology: an online method for continuous electrical recording in a human beating heart-on-chip.

Abstract

Cardiac toxicity still represents a common adverse outcome causing drug attrition and post-marketing withdrawal. The development of relevant<i>in vitro</i>models resembling the human heart recently opened the path towards a more accurate detection of drug-induced human cardiac toxicity early in the drug development process. Organs-on-chip have been proposed as promising tools to recapitulate<i>in vitro</i>the key aspects of the<i>in vivo</i>cardiac physiology and to provide a means to directly analyze functional readouts. In this scenario, a new device capable of continuous monitoring of electrophysiological signals from functional<i>in vitro</i>human hearts-on-chip is here presented. The development of cardiac microtissues was achieved through a recently published method to control the mechanical environment, while the introduction of a technology consisting in micro-electrode coaxial guides allowed to conduct direct and non-destructive electrophysiology studies. The generated human cardiac microtissues exhibited synchronous spontaneous beating, as demonstrated by multi-point and continuous acquisition of cardiac field potential, and expression of relevant genes encoding for cardiac ion-channels. A proof-of-concept pharmacological validation on three drugs proved the proposed model to potentially be a powerful tool to evaluate functional cardiac toxicity.