Solid-State\nNanopores for Spatially Resolved Chemical\nNeuromodulation

Most neural prosthetic devices are based on electrical\nstimulation,\nalthough the modulation of neuronal activity by a localized chemical\ndelivery would better mimic physiological synaptic machinery. In\nthe past decade, various drug delivery approaches attempted to emulate\nsynaptic transmission, although they were hampered by poor retention\nof their cargo while reaching the target destination, low spatial\nresolution, and poor biocompatibility and stability of the materials\ninvolved. Here, we propose a planar solid-state device for multisite\nneurotransmitter translocation at the nanoscale consisting of a nanopatterned\nceramic membrane connected to a reservoir designed to store neurotransmitters.\nWe achieved diffusion-mediated glutamate stimulation of primary neurons,\nwhile we showed the feasibility to translocate other molecules through\nthe pores by either pressure or diffusion, proving the versatility\nof the proposed technology. Finally, the system proved to be a promising\nneuronal stimulation interface in mice and nonhuman primates <i>ex vivo</i>, paving the way toward a biomimetic chemical stimulation\nin neural prosthetics and brain machine interfaces.