Abstract

AbstractElectrophysiology of 3D neuronal cultures is of rapidly growing importance for revealing cellular communications associated with neurodevelopment and neurological diseases in their brain‐like 3D environment. Despite that the brain also exhibits an inherent modular architecture that is essential for cortical processing, it remains challenging to interface a modular network consisting of multiple 3D neuronal tissues. Here, a self‐folding graphene‐based electrode array is proposed that enables to reconstruct modular 3D neuronal tissue and investigate firing dynamics among moduli. A graphene‐sandwiched parylene‐C film self‐folds into a cylindrical structure within which living cells can be encapsulated. Culture of encapsulated cells inside the folded graphene enables to spontaneously construct 3D cell aggregates and ensure firm contact between the graphene surface and encapsulated cells. As the inner graphene surface can be utilized as an electrode, the reliable cell–electrode contact allows for long‐term electrical recording from multiple 3D aggregates. Additionally, the modular network consisting of multiple 3D aggregates exhibits richer firing patterns than a conventional homogenous 2D network, which demonstrates that the approach enables measurements of firing dynamics in complex 3D neuronal networks. The deformable graphene electrode will be a powerful platform for investigating complex cellular communications in brain‐like 3D cultures.

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