Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays

Non-invasive electrical stimulation can be used to study and control neural activity in the brain or to alleviate somatosensory dysfunctions. One intriguing prospect is to precisely stimulate individual targeted neurons. Here, we investigated single-neuron current and voltage stimulation in vitro us...

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Main Authors: Silvia Ronchi, Michele Fiscella, Camilla Marchetti, Vijay Viswam, Jan Müller, Urs Frey, Andreas Hierlemann
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-03-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnins.2019.00208/full
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author Silvia Ronchi
Michele Fiscella
Michele Fiscella
Camilla Marchetti
Vijay Viswam
Vijay Viswam
Jan Müller
Jan Müller
Urs Frey
Urs Frey
Andreas Hierlemann
author_facet Silvia Ronchi
Michele Fiscella
Michele Fiscella
Camilla Marchetti
Vijay Viswam
Vijay Viswam
Jan Müller
Jan Müller
Urs Frey
Urs Frey
Andreas Hierlemann
author_sort Silvia Ronchi
collection DOAJ
description Non-invasive electrical stimulation can be used to study and control neural activity in the brain or to alleviate somatosensory dysfunctions. One intriguing prospect is to precisely stimulate individual targeted neurons. Here, we investigated single-neuron current and voltage stimulation in vitro using high-density microelectrode arrays featuring 26,400 bidirectional electrodes at a pitch of 17.5 μm and an electrode area of 5 × 9 μm2. We determined optimal waveforms, amplitudes and durations for both stimulation modes. Owing to the high spatial resolution of our arrays and the close proximity of the electrodes to the respective neurons, we were able to stimulate the axon initial segments (AIS) with charges of less than 2 pC. This resulted in minimal artifact production and reliable readout of stimulation efficiency directly at the soma of the stimulated cell. Stimulation signals as low as 70 mV or 100 nA, with pulse durations as short as 18 μs, yielded measurable action potential initiation and propagation. We found that the required stimulation signal amplitudes decreased with cell growth and development and that stimulation efficiency did not improve at higher electric fields generated by simultaneous multi-electrode stimulation.
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spelling doaj.art-b9c0721e1d48408c8592d7a4720752132022-12-22T01:22:56ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-03-011310.3389/fnins.2019.00208442971Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode ArraysSilvia Ronchi0Michele Fiscella1Michele Fiscella2Camilla Marchetti3Vijay Viswam4Vijay Viswam5Jan Müller6Jan Müller7Urs Frey8Urs Frey9Andreas Hierlemann10Department of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandMaxWell Biosystems AG, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandMaxWell Biosystems AG, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandMaxWell Biosystems AG, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandMaxWell Biosystems AG, Basel, SwitzerlandDepartment of Biosystems Science and Engineering, ETH Zürich, Basel, SwitzerlandNon-invasive electrical stimulation can be used to study and control neural activity in the brain or to alleviate somatosensory dysfunctions. One intriguing prospect is to precisely stimulate individual targeted neurons. Here, we investigated single-neuron current and voltage stimulation in vitro using high-density microelectrode arrays featuring 26,400 bidirectional electrodes at a pitch of 17.5 μm and an electrode area of 5 × 9 μm2. We determined optimal waveforms, amplitudes and durations for both stimulation modes. Owing to the high spatial resolution of our arrays and the close proximity of the electrodes to the respective neurons, we were able to stimulate the axon initial segments (AIS) with charges of less than 2 pC. This resulted in minimal artifact production and reliable readout of stimulation efficiency directly at the soma of the stimulated cell. Stimulation signals as low as 70 mV or 100 nA, with pulse durations as short as 18 μs, yielded measurable action potential initiation and propagation. We found that the required stimulation signal amplitudes decreased with cell growth and development and that stimulation efficiency did not improve at higher electric fields generated by simultaneous multi-electrode stimulation.https://www.frontiersin.org/article/10.3389/fnins.2019.00208/fullHD-MEAvoltage stimulationcurrent stimulationsingle-cell stimulationaxon initial segment
spellingShingle Silvia Ronchi
Michele Fiscella
Michele Fiscella
Camilla Marchetti
Vijay Viswam
Vijay Viswam
Jan Müller
Jan Müller
Urs Frey
Urs Frey
Andreas Hierlemann
Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays
Frontiers in Neuroscience
HD-MEA
voltage stimulation
current stimulation
single-cell stimulation
axon initial segment
title Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays
title_full Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays
title_fullStr Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays
title_full_unstemmed Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays
title_short Single-Cell Electrical Stimulation Using CMOS-Based High-Density Microelectrode Arrays
title_sort single cell electrical stimulation using cmos based high density microelectrode arrays
topic HD-MEA
voltage stimulation
current stimulation
single-cell stimulation
axon initial segment
url https://www.frontiersin.org/article/10.3389/fnins.2019.00208/full
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