Abstract
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.
Highlights
With changes in human diets and lifestyles in modern society, various diseases have emerged as significant threats to human health
In order to maintain human-specific characteristics, hiPSC-CMs were selected as the cells with which to establish the electrical-mechanical synchronized model
In order to establish the cardiomyocyte electrical-mechanical synchronized (EMS) model for drug assessment, the performance of the model was first characterized based on the common solvent dimethyl sulfoxide (DMSO)
Summary
With changes in human diets and lifestyles in modern society, various diseases have emerged as significant threats to human health. It is necessary to carry out comprehensive preclinical research on the efficacy and safety of drugs to avoid potential threats to human health as well as immense economic losses[6,7,8]. Cultured cardiomyocytes are a conventional in vitro model for preclinical analysis of drugs, typically by cellbased biosensing detection technologies, which include invasive/label-based detection technologies and noninvasive/label-free detection technologies[9,10,11,12,13]. Patch-clamp recording[14,15] and Ca2+ imaging[16,17] are typical invasive detection techniques for a cardiomyocyte model. The invasive technology of patch-clamp recording[18,19] can monitor the activity of ion channels in the cell membrane, providing a high-quality signal that serves as
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