Non-Invasive Label-Free Electrical and Optical Parrallel Recordings of Electrophysiological Action Potentials of hiPS Cardiomyocytes

Among the many molecules tested every years as potential drugs, 90% fail to reach the market despite sometimes more than 12 years of development and over two billion individual cost. As rejections are often related to cardiovascular issues, some cell-lines such as hiPSC cardiomyocytes have been extensively used to model drug toxicity <i>in vitro</i>, translating efficiently to clinical trials afterward. However, at the current state of art, parameters such as mechanical contractility, electrophysiological signals and calcium fluxes have to be measured separately, on different types of device and often on different <i>in vitro</i> cultures. This makes the interpretation of results difficult and therefore reduce their relevancy. In that context, we developed a novel device that: i) is able to optically record electrophysiological signals in a label-free and non-invasive manner. ii) has embedded electrodes for direct recordings of field potentials and for cell stimulation at the electrode location iii) is transparent enough to enable calcium imaging using fluorescence microscopy. Moving beyond the simple sum of these data , the device couples these modes that can be used independently and simultaneously. Thus, it provides a platform on which relevant and time-efficient studies of cardiotoxicity can be performed. One can use electrodes to pace the surrounding cells and detect discrepancies in cardiac frequency due to assayed drugs. The cardiotoxic effect can be detected at the whole culture level using the high density optical sensors. In this work, we could observe for example the respective increase and reduction in action potential duration using E-4031 and Nifedipine drugs. To conclude, this device exploits and combines microfluidics, fluorescent dyes, complex nanofabrication and pass-through electrodes to transduce the cardiac action potentials into optical signals. Using the same structure, it can also perform basic electrical recordings and stimulation, allowing deep studies of drugs cardiotoxicity, necessary to improve drug approval rates.