Cardiomyocyte electrical-mechanical synchronized model for high-content,dose-quantitative and time-dependent drug assessment

摘要

Cardiovascular diseases have emerged as a significant threat to human health.However,drug development is a time-consuming and costly process,and few drugs pass the preclinical assessment of safety and efficacy.The existing patch-clamp,Ca2+imaging,and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput,limited long-term assessment,or inability to synchronously and correlatively analyze electrical and mechanical signals.Here,we develop a high-content,dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized(EMS)biosensing system.This microfabricated EMS can record both firing potential(FP)and mechanical beating(MB)signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals(FP-MB)for further analysis.This system was applied to test typical ion channel drugs(lidocaine and isradipine),and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed.The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples.Furthermore,a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs.The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.