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

Cardiac toxicity still represents a common adverse outcome causing drug attrition and post-marketing withdrawal. The development of relevant in vitro 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 in vitro the key aspects of the in vivo 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 in vitro 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.

Automated summary

Cardiac toxicity is a common adverse outcome in drug development that can lead to withdrawal of drugs from the market. Recent advancements in developing in vitro models resembling the human heart have allowed for more accurate detection of drug-induced cardiac toxicity early in the drug development process. Organs-on-chip are considered promising tools to replicate key aspects of in vivo cardiac physiology and provide a means for direct analysis of functional outputs.