Multisite Attenuated Intracellular Recordings by Extracellular Multielectrode Arrays, a Perspective

Abstract

Multielectrode arrays (MEA) are used extensively for basic and applied electrophysiological research of neuronal- and cardiomyocyte-networks. Whereas immense progress has been made in realizing sophisticated MEA platforms of thousands of addressable, high-density, small diameter, low impedance sensors, the quality of the interfaces formed between excitable cells and classical planar sensor has not improved. As a consequence in vitro and in vivo MEA are “blind” to the rich and important “landscape” of sub-threshold synaptic potentials generated by individual neurons. Disregarding this essential fraction of network signaling repertoire has become the standard and almost the “scientific ideology” of MEA users. To overcome the inherent limitations of substrate integrated planar MEA platforms that only record extracellular field potentials, a number of laboratories have developed in vitro MEA for intracellular recordings. Most of these novel devices use vertical nano-rods or nano-wires that penetrate the plasma membrane of cultured cells and record the electrophysiological signaling in a manner similar to sharp intracellular microelectrodes. In parallel, our laboratory began to develop a bioinspired approach in-which cell biological energy resources are harnessed to self-force a cell into intimate contact with extracellular gold mushroom-shaped microelectrodes to record attenuated synaptic- and action-potentials with characteristic features of intracellular recordings. Here we describe some of the experiments that helped evolve the approach and elaborate on the biophysical principles that make it possible to record intracellular potentials by an array of extracellular electrode. We illustrate the qualities and limitations of the method and discuss prospects for further improvement of this technology.

High‐Aspect‐Ratio Nanostructured Surfaces as Biological Metamaterials

“…B) SEM image of gold mushroom‐shaped electrode, plus C) engulfment of electrode by a neuroendocrine cell (PC12). B,C) Reproduced under terms of the CC BY Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/) . Copyright 2018, The Authors, published by Frontiers.…”

“…This problem is driven in part by the continuing development of equivalent circuit models that accurately describe the cell–electrode interface. A complete discussion of this ongoing debate is beyond our scope here, but we recommend the review of McGuire et al, and the works of Spira et al for a more complete discussion …”

Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording

“…Patch-clamp electrodes have been the "gold standard" for cell electrophysiology for decades, where it has been shown that accurate recording of the intracellular potential requires a high resistance seal against the cell membrane and low resistance between the recording element and the cell interior 5,6 . Recent studies have focused on several solid-state nanodevice architectures, including nanowire-based structures for optical neuronal stimulation 7,8 , scalable on-chip micro/nanostructured electrode arrays 9,10 for attenuated intracellular recording via electroporation 11,12 and/or optoporation 13,14 , and three-dimensional nanowire field effect transistor probes for intracellular recording of single cells 15,16 . Nanowire probes have recorded cardiac intracellular action potentials with amplitudes comparable to those recorded with patch-clamp micropipettes 15,16 , but have relied on 1-by-1 fabrication that has been difficult to scale-up.…”

Nanovolcano microelectrode arrays: toward long-term on-demand registration of transmembrane action potentials by controlled electroporation

“…By contrast, the use of electroporation in conjunction with arrays of nanoneedle-like electrodes recently enabled simultaneous recordings of intracellular action potentials (APs) from hundreds of electrotonically coupled rat cardiomyocytes over several days [15][16][17] as well as from thousands of neurons 18 . Recordings made with electrodes of various geometries such as micromushrooms [19][20][21][22] or nanotubes 23 demonstrated similar electrophysiological characteristics. Current limitations of these technologies include substantial signal attenuation, short intracellular recording durations, and low yield.…”