Hybrid Integrated Cardiomyocyte Biosensors for Bitter Detection and Cardiotoxicity Assessment

Abstract

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, bitterinduced 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.

Emerging Bioelectronic Strategies for Cardiovascular Tissue Engineering and Implantation

“…[39] Wei et al developed a multifunctional hybrid integrated cardiomyocyte biosensor, which can detect bitter receptor-induced cardiotoxicity by synchronously recording extracellular field potentials and mechanical beating signals from the cultured cardiomyocytes (Figure 4A). [40] This microchip is a promising solution to explore cardiotoxicity in the laboratory. A similar system was developed by Liu et al [41] who established a heart-on-a-chip composed of PDMS microfluidic channels, gold, and cardiac cells, which proved to be a suitable platform for exploring in real-time the electrophysiological properties of cells under disease conditions, such as hypoxia (Figure 4B).…”

“…Despite the limited number of cells employed in microfluidic models (ranging from a few thousands to single cells), integrated bioelectronics have successfully recorded high-amplitude low-noise extracellular signals (electrical and mechanical) [40][41][42][43] and intracellular action potentials (via Pt nanopillars) [41] (Figure 4A,B). Nanopillar microelectrodes are a recent important development in electrophysiology sensing as, unlike [40] Copyright 2021, American Chemical Society. B) Heart-on-a-chip allowing both extracellular and intracellular recordings to explore cell status under hypoxic conditions.…”

“…Reproduced with permission. [ 40 ] Copyright 2021, American Chemical Society. B) Heart‐on‐a‐chip allowing both extracellular and intracellular recordings to explore cell status under hypoxic conditions.…”

“…Wei et al developed a multifunctional hybrid integrated cardiomyocyte biosensor, which can detect bitter receptor‐induced cardiotoxicity by synchronously recording extracellular field potentials and mechanical beating signals from the cultured cardiomyocytes ( Figure A). [ 40 ] This microchip is a promising solution to explore cardiotoxicity in the laboratory. A similar system was developed by Liu et al.…”

“…(Bottom) Schematics of synchronised recordings of extracellular field potentials and mechanical beating signals from cultured cardiomyocytes using a hybrid integrated cardiomyocyte biosensor. Reproduced with permission [40]. Copyright 2021, American Chemical Society.…”