A 16384-electrode 1024-channel multimodal CMOS MEA for high-throughput intracellular action potential measurements and impedance spectroscopy in drug-screening applications

Patch clamp is currently the gold standard for studying cell electrophysiology in preclinical drug discovery. Since it is a time-consuming technique, passive and active multielectrode arrays (MEAs) have been introduced for increased throughput in extracellular (ExC) in vitro measurements [1-3]. However, most of these tools cannot capture the essential features of intracellular (InC) action potentials (APs) used for studying drug toxicity. It has been shown that InC access can be achieved by highly localized electroporation [4], which allows low-impedance electrical recording of the InC voltage. While this technique was explored in recent designs [4-5], a tool that enables high-throughput InC measurements is not yet available. Impedance measurement is also used to study cell morphology, adhesion, differentiation and contractility [6]. Recent designs [1-3] already include impedance spectroscopy (IS), but their methods are not fast enough to capture in detail the contractile activity of cardiomyocytes. Since some drugs can inhibit cell beating without affecting the APs [6], ExC/InC recording and impedance measurement are complementary.