Microfluidic cell engineering on high-density microelectrode arrays for assessing structure-function relationships in living neuronal networks

Abstract

Neuronal networks in dissociated culture combined with cell engineering technology offer a pivotal platform to constructively explore the relationship between structure and function in living neuronal networks. Here, we fabricated defined neuronal networks possessing a modular architecture on high-density microelectrode arrays (HD-MEAs), a state-of-the-art electrophysiological tool for recording neural activity with high spatial and temporal resolutions. We first established a surface coating protocol using a cell-permissive hydrogel to stably attach a polydimethylsiloxane microfluidic film on the HD-MEA. We then recorded the spontaneous neural activity of the engineered neuronal network, which revealed an important portrait of the engineered neuronal network–modular architecture enhances functional complexity by reducing the excessive neural correlation between spatially segregated modules. The results of this study highlight the impact of HD-MEA recordings combined with cell engineering technologies as a novel tool in neuroscience to constructively assess the structure-function relationships in neuronal networks.

Portrait of intense communications within microfluidic neural networks

“…Such hybrid electronic and microfluidic platforms have been widely used, for instance, to study spike propagation 40 – 47 and structure‒function relationships 8 , 48 – 50 . As an example, the widely used dual-compartment design enables the somas to be kept in large somatic chambers to isolate populations, while the axons and dendrites explore narrow fluidic channels aligned with the sensing devices (Fig.…”