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      Transparent Microelectrode Arrays Fabricated by Ion Beam Assisted Deposition for Neuronal Cell In Vitro Recordings

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          Abstract

          Microelectrode array (MEA) is a tool used for recording bioelectric signals from electrically active cells in vitro. In this paper, ion beam assisted electron beam deposition (IBAD) has been used for depositing indium tin oxide (ITO) and titanium nitride (TiN) thin films which are applied as transparent track and electrode materials in MEAs. In the first version, both tracks and electrodes were made of ITO to guarantee full transparency and thus optimal imaging capability. In the second version, very thin (20 nm) ITO electrodes were coated with a thin (40 nm) TiN layer to decrease the impedance of Ø30 µm electrodes to one third (1200 kΩ → 320 kΩ) while maintaining (partial) transparency. The third version was also composed of transparent ITO tracks, but the measurement properties were optimized by using thick (200 nm) opaque TiN electrodes. In addition to the impedance, the optical transmission and electric noise levels of all three versions were characterized and the functionality of the MEAs was successfully demonstrated using human pluripotent stem cell-derived neuronal cells. To understand more thoroughly the factors contributing to the impedance, MEAs with higher IBAD ITO thickness as well as commercial sputter-deposited and highly conductive ITO were fabricated for comparison. Even if the sheet-resistance of our IBAD ITO thin films is very high compared to the sputtered one, the impedances of the MEAs of each ITO grade were found to be practically equal (e.g., 300–370 kΩ for Ø30 µm electrodes with 40 nm TiN coating). This implies that the increased resistance of the tracks, either caused by lower thickness or lower conductivity, has hardly any contribution to the impedance of the MEA electrodes. The impedance is almost completely defined by the double-layer interface between the electrode top layer and the medium including cells.

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          Atomic layer deposition: an overview.

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            Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture

            SUMMARY Long QT syndrome (LQTS) is caused by functional alterations in cardiac ion channels and is associated with prolonged cardiac repolarization time and increased risk of ventricular arrhythmias. Inherited type 2 LQTS (LQT2) and drug-induced LQTS both result from altered function of the hERG channel. We investigated whether the electrophysiological characteristics of LQT2 can be recapitulated in vitro using induced pluripotent stem cell (iPSC) technology. Spontaneously beating cardiomyocytes were differentiated from two iPSC lines derived from an individual with LQT2 carrying the R176W mutation in the KCNH2 (HERG) gene. The individual had been asymptomatic except for occasional palpitations, but his sister and father had died suddenly at an early age. Electrophysiological properties of LQT2-specific cardiomyocytes were studied using microelectrode array and patch-clamp, and were compared with those of cardiomyocytes derived from control cells. The action potential duration of LQT2-specific cardiomyocytes was significantly longer than that of control cardiomyocytes, and the rapid delayed potassium channel (IKr) density of the LQT2 cardiomyocytes was significantly reduced. Additionally, LQT2-derived cardiac cells were more sensitive than controls to potentially arrhythmogenic drugs, including sotalol, and demonstrated arrhythmogenic electrical activity. Consistent with clinical observations, the LQT2 cardiomyocytes demonstrated a more pronounced inverse correlation between the beating rate and repolarization time compared with control cells. Prolonged action potential is present in LQT2-specific cardiomyocytes derived from a mutation carrier and arrhythmias can be triggered by a commonly used drug. Thus, the iPSC-derived, disease-specific cardiomyocytes could serve as an important platform to study pathophysiological mechanisms and drug sensitivity in LQT2.
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              A new planar multielectrode array for extracellular recording: application to hippocampal acute slice.

              The present paper describes a new planar multielectrode array (the MED probe) and its electronics (the MED system) which perform electrophysiological studies on acute hippocampal slices. The MED probe has 64 planar microelectrodes, is covered with a non-toxic, uniform insulation layer, and is further coated with polyethylenimine and serum. The MED probe is shown to be appropriate for both stimulation and recording. In particular, multi-channel recordings of field EPSPs obtained by stimulating with a pair of planar microelectrodes were established for rat hippocampal acute slices. The recordings were stable for 6 h. Finally a spatial distribution of long-term potentiation was studied using the MED system.
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                Author and article information

                Journal
                Micromachines (Basel)
                Micromachines (Basel)
                micromachines
                Micromachines
                MDPI
                2072-666X
                14 May 2020
                May 2020
                : 11
                : 5
                : 497
                Affiliations
                [1 ]Micro and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, 33720 Tampere, Finland; ella.merilainen@ 123456tuni.fi (E.M.); jukka.lekkala@ 123456tuni.fi (J.L.); pasi.kallio@ 123456tuni.fi (P.K.)
                [2 ]Neuro Group, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland; ropafadzo.mzezewa@ 123456tuni.fi (R.M.); tanja.k.hyvarinen@ 123456helsinki.fi (T.H.); susanna.narkilahti@ 123456tuni.fi (S.N.)
                Author notes
                [* ]Correspondence: tomi.ryynanen@ 123456tuni.fi ; Tel.: +358-294-5211
                Author information
                https://orcid.org/0000-0001-7424-1841
                https://orcid.org/0000-0001-9293-2240
                https://orcid.org/0000-0002-7602-4418
                Article
                micromachines-11-00497
                10.3390/mi11050497
                7281740
                32423145
                a78a7298-ee57-42ab-80b9-f5f2dc60428d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 March 2020
                : 12 May 2020
                Categories
                Article

                microelectrode array (mea),ion beam assisted electron beam deposition (ibad),indium tin oxide (ito),titanium nitride (tin),neurons,transparent

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