February 9, 2023

A Microelectronics-based in-Vitro Platform for Testing Major Arrhythmic Events in the Rare Cardiac Disease ARVC/D

2nd Call, iDoc

Short Summary

This project is about developing an in vitro model of the arrhythmogenic right-ventricular cardiomyopathy/dysplasia (ARVC/D) disease by using patient-derived tissue. We will characterize the electrophysiological activity of various ARVC mutation types using high-density microelectrode arrays (HD-MEAs) to extract characteristic cardiac signatures and disease biomarkers. The use of HD-MEAs is pivotal as cell-to-cell communication and electrical-signal propagation need to be assessed. Moreover, we will develop an analytics pipeline to extract those cardiac signatures from large-volume electrical recordings.

Goals

The core objective of this grant is to develop an in vitro model of the arrhythmogenic right-ventricular cardiomyopathy/dysplasia (ARVC/D) disease. This model will be electrophysiologically characterized by high-density microelectrode arrays and validated by comparion with clinical results.

Significance

Political efforts and regulatory aspects in the EU and US indicate that improved in vitro human microtissue-based systems are needed. Due to their increased predictive capacities, in-vitro systems as proposed here will be applicable to research and development in pharmaceutical industry.

Background

Arrhythmogenic right-ventricular cardiomyopathy/dysplasia (ARVC/D) is a rare disease, affecting 1:5000 patients in the general population. As ARVC/D causes sudden death, diagnosis is often only post-mortem. Currently, ARVC/D treatment is limited to a symptomatic approach with a combination of beta-blockers to stabilize the heart rhythm and an implanted pacemaker or defibrillator to prevent sudden cardiac death.

Publications

Lee, J., Gänswein, T., Ulusan, H., Emmenegger, V., Saguner, A.M., Duru, F. and Hierlemann, A., 2022. Repeated and On-Demand Intracellular Recordings of Cardiomyocytes Derived from Human-Induced Pluripotent Stem Cells. ACS sensors, 7(10), pp.3181-3191.