A 16384 Electrode 1024 Channel Multimodal Cmos MEA for High throughput Drug Screening

Abstract

Drug attrition is a major concern for the pharmaceutical industry. Besides the loss of the large investment needed to develop novel drugs, many lives have been lost due to lethal side effects. Cardiotoxicity accounts for more than one third of the drug withdrawals from the market. Although the Food and Drug Administration has set guidelines to tackle this issue, there is still room for improvement on the methodology of safety screening. Multi-electrode arrays (MEAs) are a candidate technology to screen in vitro cardiac parameters because of its non-invasive recording of cardiac beating rate and electrical field potential duration. Here we present a novel active MEA chip featuring 16,384 electrodes, 1024 simultaneous readout channels and 4 different electrode sizes to perform extracellular and intracellular recording from cardiomyocytes. Biocompatible TiN (height of 300nm) electrodes were processed on top of the in-house designed circuits. The circuit noise for the recording mode was 7.5±0.6 µVrms and 12±2.4 µVrms for extracellular and intracellular recording, respectively. Electrode impedance at 1kHz was determined using the built-in impedance circuitry and was 4.2, 2.2, 1.1 and 0.5 MΩ for electrode areas of 8.75, 10.5, 45.5 and 121µm2, respectively. Further, we recorded extracellular signals of 1.4 mV and intracellular signals of 12.7mV on average (peak to peak) from primary rat cardiomyocytes cultured for 3 days in vitro on the chip. Finally, applying 1µM nifedipine, a drug to treat hypertension and angina, on the cells changed the shape and duration of intracellular action potential significantly. The novel platform thus allows for high throughput electrical activity monitoring and drug screening of cardiomyocytes, and can be used for toxicity screening or drug development.