A multi-scale electrode array (MSEA) to study excitation–contraction coupling of cardiomyocytes for high-throughput bioassays

Excitation–contraction coupling, a process of linking electrical activity to contraction, is the basis of cardiac function at cellular level. Here we developed a multi-scale electrode array (MSEA) as an in vitro platform to synchronously monitor excitation and contraction of cultured cardiomyocytes. The electrodes of MSEA were with sizes ranging from several tens of micrometers to about 1 mm and were classified into type_1, type_2 and type_3 by their electrode area. The former two types of electrodes were electroplated with platinum black to reduce baseline noise and no extra treatment was done on type_3 electrodes. In experiment, the micrometer-scale electrodes recorded extracellular field potentials like generally used multielectrode arrays and especially, the millimeter-scale electrodes recorded a “hump” followed after extracellular field potential. By analyzing temporal behavior of hump and observing its change under treatment of microtubule inhibitor vinblastine, it was verified that the hump expressed mechanical contraction of cardiomyocytes. In addition, we analyzed that the pathway of contraction recording was through cell–electrode contractile coupling, in which charges at electrode–electrolyte interface were reestablished due to contractile behavior of cellular layer and then the hump was formed. Finally, the dependence of amplitude and time duration of hump on electrode area, electrode property and contractile strength was also explored.