Studying the blood-brain barrier on a microfluidic chip

A realistic model of the blood-brain barrier (BBB) is valuable to perform drug screening experiments and to improve the understanding of the barrier's physiology at normal and pathological conditions. Although the conventional in vitro systems (e.g. Transwell systems) have been used for this, they lack reproducibility and have a static environment. To overcome these disadvantages so called “organs-on-chips” have been developed, which use microfluidics and (human) cells to mimic organ function. An example of the BBB chip is shown in the work of Griep et al., where human cerebral endothelial cells (hCMEC/D3) were cultured in a microfluidic device made of polydimethyl siloxane (PDMS). Recently we improved this model. Two PDMS parts with microchannels are placed on top of each other, with a porous membrane in between at the intersection serving as scaffold for the cells. hCMEC/D3 cells (kindly provided by INSERM, Paris, France) were cultured in the chip for up to 15 days. With the four integrated electrodes, which did not block view on the intersection, reliable transendothelial electrical resistance measurements were carried out. Additionally, using immunohistochemistry it was shown that the endothelium expressed tight junction proteins, which is an essential characteristic of the BBB. To further improve the physiological relevance of this promising platform, the cells inside the channels will be cultured under fluid flow. As application, this platform will be used to study the transport of nanocarriers with Alzheimer medication through the BBB. In addition, the clearance of Alzheimer-associated proteins (amyloid β) by the BBB can be examined.