A Multiplexed Microfluidic Device to Measure Blood-Brain Barrier Disruption by Pulsed Electric Fields

Local disruption of the blood-brain barrier (BBB) by pulsed electric fields shows significant potential for treating neurological conditions. Microfluidic BBB models can provide low-cost, controlled experiments with human cells and test a range of parameters for preclinical studies. We developed a multiplexed BBB device that can test a three-fold range of electric field magnitudes. A tapered channel creates a linear gradient of the electric field within the device, and an asymmetric branching channel enables an on-chip control. We monitored BBB permeability in real-time using the diffusion of a fluorescent marker across an endothelial monolayer to determine BBB disruption after high-frequency bipolar electrical pulses (HFIRE). We show that HFIRE pulses can transiently open the BBB. Unexpectedly, electrofusion of cells resulted in decreased permeability for some conditions. Our multiplexed device can efficiently probe treatment variables for efficient preclinical testing of optimal parameters for reversible BBB disruption.Clinical Relevance-This in vitro model of the BBB can inform preclinical studies by investigating a range of electroporation parameters for BBB disruption.