N3-MEA Probes: Scooping Neuronal Networks

Abstract

In the current work, we introduce a brand new line of versatile, flexible, and multifunctional MEA probes, the so-called Nano Neuro Net , or N 3 -MEAs. Material choice, dimensions, and room for further upgrade, were carefully considered when designing such probes in order to cover the widest application range possible. Proof of the operation principle of these novel probes is shown in the manuscript via the recording of extracellular signals, such as action potentials and local field potentials from cardiac cells and retinal ganglion cells of the heart tissue and eye respectively. Reasonably large signal to noise ratio (SNR) combined with effortless operation of the devices, mechanical and chemical stability, multifunctionality provide, in our opinion, an unprecedented blend. We show successful recordings of (1) action potentials from heart tissue with a SNR up to 13.2; (2) spontaneous activity of retinal ganglion cells with a SNR up to 12.8; and (3) local field potentials with an ERG-like waveform, as well as spiking responses of the retina to light stimulation. The results reveal not only the multi-functionality of these N 3 -MEAs, but high quality recordings of electrogenic tissues.

A flexible 3-dimensional microelectrode array for in vitro brain models

“…These visualizations, along with the potential for future spatial and temporal mapping of electrophysiology data across the 3D volume, are enabled by the integration of the 3DMEA within the culture substrate, as microfabrication of the probes facilitates identification of electrode locations in space via the quantified actuation angles. By comparison to the 3DMEA, non-integrated flexible "mesh" arrays like those described in Kireev, Tian and Zhou's papers are initially in the form of an extremely flexible sheet which requires additional support structures like electrospun nanofibers to allow handling, [33][34][35] and recording from multiple planes in the Z-direction requires meshes to be folded or rolled, further complicating handling and limiting precise electrode positioning.…”

“…31,32 An intriguing new style of MEA has also been introduced, intended to minimize mechanical impact of the array on the cell matrix by utilizing a thin, flexible polymer "mesh" containing either nanowire or thin-film electrodes. [33][34][35] This approach has been focused on in vivo or ex vivo tissue-based applications, and it is limited in its ability to be integrated with an in vitro system.…”

A mesh microelectrode array for non-invasive electrophysiology within neural organoids

“…22 Our microelectrodes are connected by unbroken thin film metal paths rather than complicated electrical packaging. 23,17,22 The microfabricated structures of our device are similar to the flexible devices reported by Soscia et al, although their device is intended for 3D cultures of cells suspended in hydrogel. 24 In comparison to the use of rigid devices for recording in 3D cell cultures, 11,12 devices such as ours or those of Soscia et al which integrate electrode on flexible filaments should allow for a better long-term cultivation of organoids.…”

Microengineered 2D and 3D modular neuronal networks represent structure-function relationship

“…Even though in our 3D modular model the readout efficiency was 10 times higher than in random 2D networks, planar electrodes allow recording only from the bottom side of the network [53]. This challenge could be resolved by recently developed 3D MEA systems that offer multisite recording from 3D neural culture microsystems and organoids [55,59,78,79]. Nevertheless, the feasibility of constructing functional 3D modular networks on currently available models of 3D MEAs needs to be tested.…”