Contactless Particle Image Velocimetry (PIV) Method of Screening Drugs Using Human iPSC-derived Cardiomyocytes

Introduction: The development of cardiac arrhythmias as a pharmacological side effect has become the single most common cause of the withdrawal or restriction of previously marketed drugs. Currently available drug screening models are not efficient in detecting cardiac toxicity. Here we demonstrate in vitro Particle Image Velocimetry (PIV) assays followed by fourier spectrum and heatmap analyses for measuring the impact of different cardiac drugs on the rate and frequency of beating cardiomyocytes (CMCs). Hypothesis: Our PIV method of measuring CMCs contractility could be beneficial for drug testing, preclinical screening to detect cardio toxicity without jeopardizing the biology of cells. Methods and Results: The novelty of our system is that we can record the spatiotemporal maturation of human iPSC-derived CMCs at specific positions. We have evaluated the contractility of CMCs with the response to various chemical compounds such as Verapamil (Ca2+ channel blocker), Isoproterenol (Ca2+ channel activator), E-4031 (K+ channel inhibitor) and NS-1643 (K+ channel activator). Our data shows that the chronotropic effect of verapamil and E-4031 at the concentration of 1 μM and 500 nM respectively, has significantly reduced the beating frequency. Similarly, the chronotropic effect of Isoproterenol and NS-1643 at the concentration of 1 μM and 60 nM respectively, has meaningfully increased the beating frequency. Moreover, our fourier spectrum and heatmap analyses further confirmed the spatiotemporal changes occur due to the addition of chronotropic drugs. Conclusions: We report for the first time the applications of PIV assays for prospective cardiac drug efficacy screening by measuring the contractility of CMCs from the video image without jeopardizing the biology of cells.