A Multimodal CMOS MEA for High-Throughput Intracellular Action Potential Measurements and Impedance Spectroscopy in Drug-Screening Applications

• Published in: IEEE journal of solid-state circuits 2018-11, Vol.53 (11), p.3076-3086
• Main Authors: Lopez, Carolina Mora, Chun, Ho Sung, Wang, Shiwei, Berti, Laurent, Putzeys, Jan, Van Den Bulcke, Carl, Weijers, Jan-Willem, Firrincieli, Andrea, Reumers, Veerle, Braeken, Dries, Van Helleputte, Nick
• Format: Article
• Language: English
• Subjects: Active electrode; Biocompatibility; cardiotoxicity; Channels; CMOS; Computer architecture; drug screening; Drugs; electrical recording; electrical stimulation; Electrodes; Extracellular; high throughput; Impedance; Impedance spectroscopy; impedance spectroscopy (IS); intracellular recording; Microprocessors; Monitoring; multi-electrode array (MEA); multi-modality; Power consumption; Recording; Screening; Silicon substrates; Spectrum analysis; Stimulation
• ISSN: 0018-9200; 1558-173X
• DOI: 10.1109/JSSC.2018.2863952

Multi-electrode arrays (MEAs) are a candidate technology to screen cardiotoxicity in vitro because they enable noninvasive recording of cardiac beating rate, electrical field potential duration, and other parameters. In this paper, we present an active MEA chip featuring 16 384 electrodes, 1024 simultaneous readout channels, and 64 stimulation units (SUs) to enable six different cell-interfacing modalities: extracellular and intracellular recording, current and voltage stimulation, fast impedance motoring, and impedance spectroscopy (IS). The chip was designed and fabricated in a 0.13- \mu \text{m} Al CMOS technology, and the electrodes were fabricated on top of the silicon substrate using biocompatible TiN. Measurement results show a total input-referred noise of 7.5 \pm 0.6~\mu \text{V}_{\mathrm{rms}} and 12.0 \pm 2.4~\mu \text{V}_{\mathrm {rms}} for the action potential and full bands, respectively, with a total power consumption of 95 mW for 1024 readout channels. We have experimentally validated the CMOS MEA in in vitro experiments, demonstrating all the different modalities. This novel platform will potentially enable high-throughput electrical activity monitoring and drug screening of cardiomyocytes.