A Microfluidic Platform to Study and Modulate the Blood-Brain Barrier

van der Helm, Marieke Willemijn ;   Frimat, Jean-Philippe ;   Odijk, Mathieu ;   van den Berg, Albert ;   Segerink, Loes Irene

A simple yet predictive model of the blood-brain barrier (BBB) is required to help drug development and improve the understanding of the barrier?s physiology. Previously, it was shown that this is possible with human cerebral endothelial cells (hCMEC/D3) in a PDMS device. However, that model has several drawbacks, such as limited reproducibility, difficulty of chip fabrication and electrodes blocking the view. In this paper we present an improved ?BBB on chip? in which these shortcomings are overcome. Long-term monitoring of medium-filled chips showed stable and reproducible impedance measurements. Chips loaded with hCMEC/D3 cells (cultured up to 15 days on chip) exhibited an increase in TEER up to 25 Ωcm^2 which is indicative of the formation of a tight endothelial barrier. Fluorescence ZO-1 staining also confirmed the presence of tight junction proteins, which is a prerequisite for the formation of a tight BBB. These results demonstrate an improvement from the previous BBB on chip model in terms of fabrication and reproducibility. We are currently evaluating the physiological relevance of this improved system by monitoring cellular responses to shear stress and inflammatory agents.