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

A multimodal CMOS MEA for high-throughput intracellular action potential measurements and impedance spectroscopy in drug-screening applications
A multimodal CMOS MEA for high-throughput intracellular action potential measurements and impedance spectroscopy in drug-screening applications
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-μm 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 ± 0.6 μV rms and 12.0 ± 2.4 μV 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.
Active electrode, cardiotoxicity, drug screening, electrical recording, electrical stimulation, high throughput, impedance spectroscopy (IS), intracellular recording, multi-electrode array (MEA), multi-modality
0018-9200
3076-3086
Lopez, Carolina Mora
b7db9e25-fd8b-4d0e-8e91-2e201640a1eb
Chun, Ho Sung
6ad26c90-a735-46ac-89f1-05ab383a05b9
Wang, Shiwei
97433cb6-7752-4c68-89f8-933f233d8642
Berti, Laurent
475e1e9c-5225-4904-91ec-661e2a3aebc0
Putzeys, Jan
91ca8966-67bd-4b72-82f6-023b78437154
Van den Bulcke, Carl
3a6023d6-2b7c-4aa4-89c3-739e96459b02
Weijers, Jan-Willem
e5d19ec4-eb95-4507-850a-f5bed37b209f
Firrincieli, Andrea
01334896-43a3-463e-9aa5-1cf4d952000b
Reumers, Veerle
0aefdd19-5766-4012-9de8-800d12d60730
Braeken, Dries
9f0912a6-07eb-4f1c-908b-3e8a74ef468e
Van Helleputte, Nick
bad8e4b6-6d24-440f-97c3-e1ddeda371f1
Lopez, Carolina Mora
b7db9e25-fd8b-4d0e-8e91-2e201640a1eb
Chun, Ho Sung
6ad26c90-a735-46ac-89f1-05ab383a05b9
Wang, Shiwei
97433cb6-7752-4c68-89f8-933f233d8642
Berti, Laurent
475e1e9c-5225-4904-91ec-661e2a3aebc0
Putzeys, Jan
91ca8966-67bd-4b72-82f6-023b78437154
Van den Bulcke, Carl
3a6023d6-2b7c-4aa4-89c3-739e96459b02
Weijers, Jan-Willem
e5d19ec4-eb95-4507-850a-f5bed37b209f
Firrincieli, Andrea
01334896-43a3-463e-9aa5-1cf4d952000b
Reumers, Veerle
0aefdd19-5766-4012-9de8-800d12d60730
Braeken, Dries
9f0912a6-07eb-4f1c-908b-3e8a74ef468e
Van Helleputte, Nick
bad8e4b6-6d24-440f-97c3-e1ddeda371f1

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 and Van Helleputte, Nick (2018) A multimodal CMOS MEA for high-throughput intracellular action potential measurements and impedance spectroscopy in drug-screening applications. IEEE Journal of Solid-State Circuits, 53 (11), 3076-3086. (doi:10.1109/JSSC.2018.2863952).

Record type: Article

Abstract

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-μm 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 ± 0.6 μV rms and 12.0 ± 2.4 μV 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.

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More information

e-pub ahead of print date: 3 September 2018
Published date: November 2018
Keywords: Active electrode, cardiotoxicity, drug screening, electrical recording, electrical stimulation, high throughput, impedance spectroscopy (IS), intracellular recording, multi-electrode array (MEA), multi-modality

Identifiers

Local EPrints ID: 450926
URI: http://eprints.soton.ac.uk/id/eprint/450926
ISSN: 0018-9200
PURE UUID: 0d788c63-83f1-4f83-b0b0-99806d0c0b22
ORCID for Shiwei Wang: ORCID iD orcid.org/0000-0002-5450-2108

Catalogue record

Date deposited: 24 Aug 2021 16:52
Last modified: 26 Nov 2021 03:23

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Contributors

Author: Carolina Mora Lopez
Author: Ho Sung Chun
Author: Shiwei Wang ORCID iD
Author: Laurent Berti
Author: Jan Putzeys
Author: Carl Van den Bulcke
Author: Jan-Willem Weijers
Author: Andrea Firrincieli
Author: Veerle Reumers
Author: Dries Braeken
Author: Nick Van Helleputte

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