Brain stimulation-on-a-chip: a neuromodulation platform for brain slices

Abstract

Electrical stimulation of ex vivo brain tissue slices has been a method used to understand mechanisms imparted by transcranial direct current stimulation (tDCS), but there are significant direct current electric field (dcEF) dosage and electrochemical by-product concerns in conventional experimental setups that may impact translational findings. Therefore, we developed an on-chip platform with fluidic, electrochemical, and magnetically-induced spatial control. Fluidically, the chamber geometrically confines precise dcEF delivery to the enclosed brain slice and allows for tissue recovery in order to monitor post-stimulation effects. Electrochemically, conducting hydrogel electrodes mitigate stimulation-induced faradaic reactions typical of commonly-used metal electrodes. Magnetically, we applied ferromagnetic substrates beneath the tissue and used an external permanent magnet to enable in situ rotational control in relation to the dcEF. By combining the microfluidic chamber with live-cell calcium imaging and electrophysiological recordings, we showcased the potential to study the acute and lasting effects of dcEFs with the potential of providing multi-session stimulation. This on-chip bioelectronic platform presents a modernized yet simple solution to electrically stimulate explanted tissue by offering more environmental control to users, which unlocks new opportunities to conduct thorough brain stimulation mechanistic investigations.