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[Preprint]. 2024 Jun 2:2024.05.29.596533. [Version 1] doi: 10.1101/2024.05.29.596533

Brain implantation of tissue-level-soft bioelectronics via embryonic development

Hao Sheng, Ren Liu, Qiang Li, Zuwan Lin, Yichun He, Thomas S Blum, Hao Zhao, Xin Tang, Wenbo Wang, Lishuai Jin, Zheliang Wang, Emma Hsiao, Paul Le Floch, Hao Shen, Ariel J Lee, Rachael Alice Jonas-Closs, James Briggs, Siyi Liu, Daniel Solomon, Xiao Wang, Nanshu Lu, Jia Liu
PMCID: PMC11160708  PMID: 38853924

Abstract

The design of bioelectronics capable of stably tracking brain-wide, single-cell, and millisecond-resolved neural activities in the developing brain is critical to the study of neuroscience and neurodevelopmental disorders. During development, the three-dimensional (3D) structure of the vertebrate brain arises from a 2D neural plate 1,2 . These large morphological changes previously posed a challenge for implantable bioelectronics to track neural activity throughout brain development 3–9 . Here, we present a tissue-level-soft, sub-micrometer-thick, stretchable mesh microelectrode array capable of integrating into the embryonic neural plate of vertebrates by leveraging the 2D-to-3D reconfiguration process of the tissue itself. Driven by the expansion and folding processes of organogenesis, the stretchable mesh electrode array deforms, stretches, and distributes throughout the entire brain, fully integrating into the 3D tissue structure. Immunostaining, gene expression analysis, and behavioral testing show no discernible impact on brain development or function. The embedded electrode array enables long-term, stable, brain-wide, single-unit-single-spike-resolved electrical mapping throughout brain development, illustrating how neural electrical activities and population dynamics emerge and evolve during brain development.

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