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

Area of Science:

• Neuroscience
• Bioelectronics
• Biomedical Engineering

Background:

• Traditional electrical stimulation of brain slices faces challenges with direct current electric field (dcEF) dosage and electrochemical by-products.
• These limitations in conventional methods may hinder the translation of findings from ex vivo studies to in vivo applications like transcranial direct current stimulation (tDCS).
• A need exists for improved experimental platforms offering greater control and reduced artifacts in brain tissue stimulation research.

Purpose of the Study:

• To develop an innovative on-chip bioelectronic platform for controlled electrical stimulation of ex vivo brain tissue slices.
• To overcome the limitations of conventional stimulation methods by integrating fluidic, electrochemical, and magnetic control.
• To enable detailed mechanistic investigations of direct current electric field (dcEF) effects on neural tissue.

Main Methods:

• An on-chip platform was engineered featuring a microfluidic chamber for precise dcEF delivery and tissue recovery.
• Conducting hydrogel electrodes were utilized to minimize electrochemical by-products and faradaic reactions during stimulation.
• Magnetic substrates and an external magnet allowed for in situ rotational control of the tissue relative to the dcEF, coupled with live-cell calcium imaging and electrophysiological recordings.

Main Results:

• The platform successfully demonstrated precise dcEF delivery and environmental control for ex vivo brain slice stimulation.
• The use of hydrogel electrodes mitigated undesirable electrochemical reactions.
• The system facilitated the study of acute and lasting effects of dcEFs, including potential for multi-session stimulation.

Conclusions:

• The developed on-chip bioelectronic platform offers a modernized and controlled solution for electrical stimulation of explanted brain tissue.
• This platform addresses key limitations of traditional methods, paving the way for more accurate and translational brain stimulation research.
• It unlocks new avenues for in-depth mechanistic investigations of dcEFs and their impact on neural function.