Sensors in heart-on-a-chip: A review on recent progress.

Drug-induced cardiotoxicity is a major problem in drug discovery. Many approaches to efficient drug screening have been developed, including animal testing in vivo and cell testing in vitro. However, due to intrinsic difference between species, animal-based toxicity testing cannot comprehensively determine the potential side effects in subsequent human clinical trials. Furthermore, conventional in vitro assays are costly and labour-intensive, and require numerous tests. Therefore, it would be necessary to develop heart-on-a-chips made with advanced materials and soft bioelectronic fabrication techniques that offer fast, efficient, and accurate sensing of cardiac cells' behaviors in vitro. In this review, we introduce two key sensing methods in heart-on-a-chip for physical and electrical measurements. First, optical (e.g., direct and calcium imaging, and fluorescent, laser-based, and colorimetric sensing) and electrical (e.g., impedance, strain, and crack sensing) sensors that record the contractility of cardiomyocytes are reviewed. Subsequently, various sensors composed of rigid planar/three-dimensional electrodes, soft/flexible electronics, and nanomaterial-based transistors to monitor extracellular and intracellular electrophysiological potentials are discussed. A brief overview of future technology and comments on the current challenges conclude the review.