Shell Microelectrode Arrays (MEAs) for brain organoids

Abstract

Brain organoids are important models for mimicking some three-dimensional (3D) cytoarchitectural and functional aspects of the brain. Multielectrode arrays (MEAs) that enable recording and stimulation of activity from electrogenic cells are widely utilized in biomedical engineering. However, conventional MEAs, initially designed for monolayer cultures, offer limited recording contact area restricted to the bottom of the 3D organoids. Inspired by the shape of electroencephalography (EEG) caps, we developed miniaturized chip-integrated MEA caps for organoids. The optically transparent shells are composed of self-folding polymer leaflets with conductive polymer-coated metal electrodes. Tunable folding of the minicaps polymer leaflets guided by mechanics simulations enables versatile recording from organoids of different sizes and we validate the feasibility of electrophysiology recording from 400-600 micrometer sized organoids for up to four weeks and in response to glutamate stimulation. Our studies suggest that 3D shell MEAs offer significant potential for high signal-to-noise and 3D spatiotemporal brain organoid recording.

Self‐Folding Graphene‐Based Interface for Brain‐Like Modular 3D Tissue

“…In previous electrophysiological measurements of 3D cell spheroids, the 3D cell spheroids had to be manually positioned on electrodes. [21][22][23][24] On the other hand, the cell encapsulation approach provides an electrical interface with a 3D cellular tissue without the need to align cells with the electrode. Since the cell-electrode coupling can be achieved in multiple electrodes with a batch release of the sacrificial layer, the individually addressable electrodes allow the simultaneous measurement of multiple 3D cellular tissues.…”

“…Although other designs of deformable MEAs have demonstrated electrical measurements with high spatiotemporal resolution in 3D, they were applied to a few 3D spheroids or 2D cell culture. [20][21][22][23][24] This work shows an extended application of deformable MEAs for investigation of network dynamics among multiple 3D aggregates. Our in vitro neuronal model mimics two important architectures of the human brain.…”

“…Therefore, deformable MEA substrates that utilize stress-based self-folding to wrap 3D tissues have recently attracted great attention and have achieved reliable spatiotemporal recordings from a 3D spheroid and assembloid. [20][21][22][23][24][25][26] To extend the application of 3D electrophysiology for investigation of modular neuronal networks, it is preferable to record firing dynamics among multiple interconnected 3D tissues. However, it is still challenging to individually interface multiple 3D tissues using self-folding devices due to the difficulty in aligning the tissues with electrodes.…”

Bioelectric Interface Technologies in Cells and Organoids

“…[21] A variety of nanostructured architectures with strategically designed layout of integrated electrodes or FETs have been developed to offer conformal and stable interfaces with diversely shaped cells/organoids, and to provide long-term, continuous recording of biophysiological signals with high sensitivity and high fidelity. [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56] For example, many different forms of needle type architectures were developed for cell interfacing, ranging from nanoprobes, [57][58][59][60][61] nanopillars, [42,[62][63][64][65] nanotubes, [66] nanocrowns, [24] to nanovolcanos. [67] Aside from these 1D nanostructured configurations, 2D planar type, [68][69][70][71] as well as diverse 3D architectures have been devised to allow monitoring with higher spatial resolutions.…”

Hollow ring-like flexible electrode architecture enabling subcellular multi-directional neural interfacing

“…In this regard, the selection of electrode geometry and electrode coating material were found to have significant impact on enhancing the electrodes capabilities i.e., electrochemical impedance and charge transfer capacity. Several novel curved and folded electrode configurations were reported in the literature, such as nanowires 18 , star-shaped 19 , honeycomb-shaped 20 , spiral shaped [21][22] , spine-shaped 23 , shell-shaped 24 , cylindrical shaped electrode arrays 25 , to improve the neural surface interfacing capabilities. These unconventional electrode geometries offer higher perimeter-to-surface ratio, compared to the regular disk-type electrodes and exhibit minimal access resistance and increased ion flux to the electrode interface.…”