Hybrid Integrated Cardiomyocyte Biosensors for Bitter Detection and Cardiotoxicity Assessment.

Among basic taste sensations, bitter taste is vital to the survival of mammals due to its indispensable role in toxin prediction or identification, so the identification of bitter compounds is of great value in the pharmaceutical and food industry. Recently, bitter taste receptor (T2Rs)-based biosensors have been developed for specific bitter detection. However, the taste biosensors based on taste cells/tissues suffer from simple function, low sensitivity, low content, and limited parameters. Here, to establish a high-content, highly sensitive, and multifunctional taste biosensor, we developed a multifunctional hybrid integrated cardiomyocyte biosensor (HICB) for bitter detection. Due to the expression of bitter taste receptors in cardiomyocytes, the HICB can recognize the specific bitter agonists by synchronously recording the extracellular field potential (EFP) and mechanical beating (MB) signals from the cultured cardiomyocytes in vitro. Multiple feature parameters were defined and extracted from the electromechanical signals of cardiomyocytes to analyze the specific responses to four typical bitter compounds. The radar map, heat map, and principal component analysis (PCA) were used to visualize and classify the specific responses. Moreover, bitter-induced cardiotoxicity also was chronically evaluated, and these bitter compounds presented an inhibition effect on the electrophysiological and contractile activities of cardiomyocytes. This high-content HICB offers an alternative platform for both bitter detection and cardiotoxicity assessment, showing promising applications in the fields of taste detection and toxicity screening.