CMOS Device for Electrophysiological Investigations

Over a decade of research has led to the development of devices that are capable of intracellularly interfacing with neurons and cardiomyocytes at the network level using substrate integrated electrodes and complementary metal-oxide-semiconductor (CMOS) circuits. The researchers at Harvard have successfully demonstrated the ability to intracellularly record and stimulate up to ~1,700 disassociated rat neurons (~40% coupling rate using 4,096 electrodes) and over ~100 human induced pluripotent stem cell (hiPSC) derived neurons in parallel. As such, they have been able to investigate the inter-connections between the neurons and to measure pre- and post-synaptic potentials with high fidelity. For cardiomyocytes, they have demonstrated ~30% intracellular coupling rate using rat ventricular cardiomyocytes and demonstrated the ability to measure the subthreshold effects of drugs across the in vitro cardiac tissue. These developments far exceed previous network-level intracellular investigations, limited by ~10 parallel patch clamp electrodes, and greatly extend the fidelity of traditional microelectrode arrays which use low-fidelity extracellular measurement.

In this project, they are proposing to adapt our devices to a 96-well plate format to enable high throughput screening of ion-channel drugs for the treatment of neurological and cardiac disorders. Unlike automated planar-patch electrophysiology platforms which are limited to measurements from artificial cell lines designed to express the ion-channel of interest, our device would have the ability to measure the effects of potential drug candidates on the network activity of neurons and cardiomyocytes directly. In our initial experiments, they would combine the designed multiwell plate with traditional high-throughput technologies and use the system to identify novel drug treatments using iPSC-derived neurons from patients with neurological disorders. This screening assessment of the network-level effects of drugs using neurons and cardiomyocytes closely aligns with Servier’s interest in developing novel drugs for neuropsychiatric and cardiovascular diseases.

Intellectual Property Status: Patent(s) Pending