Polydimethylsiloxane microfluidic films for in vitro engineering of small-scale neuronal networks

Abstract

Polydimethylsiloxane microfluidic devices have become standard tools in cell engineering research. However, through-holes where cells access the microchannels are usually fabricated manually using biopsy punches, making it difficult to create a large array of sub-mm sized through-holes. Here, we present a fabrication process for a thin-film microfluidic device containing an array of through-holes, which are as small as 100 μm by 100 μm and span 10 mm by 10 mm. A proof-of-concept application of the device to neuronal patterning experiments shows that spatially complex network dynamics emerge when a non-random connectivity is imposed to cultured neuronal networks. We also demonstrate that the coupling strengths between neuronal modules, a major factor that defines the global network dynamics, can be effectively modulated by varying the microchannel widths. This work opens a new application of microfluidic devices to multicellular systems comprised of several tens to hundreds of neurons.