Shell microelectrode arrays (MEAs) for brain organoids

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 µm 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. ### Competing Interest Statement T. H. is named inventor on a patent by Johns Hopkins University on the production of brain organoids, which is licensed to AxoSim, New Orleans, LA, USA, and receives royalty shares. T. H. and L.S. consult AxoSim. D. H. G. has several patents filed by Johns Hopkins University related to self-folding devices. Some are licensed by Kley Dom Biomimetics, LLC. for which he is entitled to royalty payments.