Hybrid elastomer-plastic microfluidic device as a convenient model for mimicking the blood-brain barrier in vitro

Abstract

In this study, we fabricated a hybrid elastomer-plastic microdevice using the silicone elastomer poly(dimethylsiloxane) (PDMS) and the plastic polycarbonate (PC), to mimic the human blood-brain barrier (BBB) in vitro. Specifically, the microchannel-imprinted elastomer was first coated with 3-aminopropyltriethoxysilane to produce amine-terminated PDMS. Then, simply by conformal contact at room temperature, the amine-functionalized PDMS was bonded to pristine PC through the formation of urethane linkages. Aside from realizing device bonding, the amine functionalization also assisted in subsequent dopamine coating to form polydopamine and provide a stable surface for culturing human endothelial cells and central nervous system-related cells (e.g., astrocytes) inside the microchannels. Successful mimicking of the BBB-like microenvironment was assessed by 3D co-culturing of human endothelial cells and astrocytes, where the microdevice was verified as an acceptable in vitro BBB model according to the following four criteria: the formation of tight junctions at the cell-cell boundaries of the endothelial cells, evaluated by the expression of the tight junction marker ZO-1; the formation of actin filaments, evaluated using rhodamine phalloidin dye; low permeability, tested using the fluorescent tracer 40-kDa FITC-dextran; and good transendothelial electrical resistance (a measure of the tight junction integrity formed between the endothelial cells). The fabricated PDMS-PC microfluidic device ensured simple yet stable device sealing, and simultaneously enhanced BBB-mimicking cell attachment, thus fulfilling all major criteria for its application as a convenient in vitro BBB model.