Engineering a multiplexed Blood-Brain Barrier-on-a-chip

The blood-brain barrier (BBB) poses a major challenge for drug delivery to the brain due to its restrictive nature, and is therefore of particular interest in pharmacology. The lack of physiologically relevant test models hinders the development of new effective drugs for brain diseases. Organ-on-chip (OOC) devices aim to closely mimic key aspects of human physiology and pathology and have been developed as a promising alternative to in vitro and animal models for drug screening. One of the significant disadvantages of existing OOC models is their low throughput, thus, it is not possible to test different experimental stimuli in parallel, limiting readout. To address this challenge, we propose a BBB-on-chip model with increased throughput, which contains eight microfluidic channels that can be addressed simultaneously or independently. To recreate the barrier model, a novel membrane is developed which acts as a cell scaffold and separates the channels on the basal and luminal compartments. We study the applicability of the developed membrane for the cell cultures and compare the results with the commercially available membrane. Furthermore, we discuss two different ways to integrate online readouts for the monitoring of barrier formation inside the chip. One of them requires clean-room expertise, while another is a clean-room-free method and can be implemented in an ordinary laboratory environment. Finally, we study the reversible way to open the BBB using ultrasound and monodisperse microbubbles. The end goal of this research is to develop a parallelized and automated model suitable for multiplexing OOC systems. This increased-throughput screening platform may enhance the drug screening process and help to minimize animal experiments in the future.