A 3D Microfluidic Device with Vertical Channels toward In Vitro Reconstruction of Blood-Brain Barrier.

Abstract

This paper reports a three-dimensional microfluidic device with an array of vertical channels to enable regulated, continuous, vertical flows to emulate the environment for in vitro culturing of brain and blood vessel organoids. This is expected to ultimately lead to in vitro reconstruction of the blood-brain barrier that is of high interest to studies on mental illness mechanisms and drug delivery to the brain. Twelve vertical microfluidic channels, each with 300 µm diameter and 5 mm height, were formed in the high-permeability agar gel surrounding the organoid to realize the vertical circulation flows and to allow lateral diffusion flows. The combined vertical flow rate of all channels ranges from 2.1 to 6.8 mL/min under different control parameters. A 30-day-old human blood vessel organoid was planted into the device for initial culturing and flow function tests. The result indicates that the organoid was properly activated with effective flow generation in the culturing site of the device.