Droplet fluidics for time-dependent analysis of barrier permeability in an epithelial barrier on chip system

Abstract

A droplet generator has been developed that interfaces with a barrier-on-chip platform for temporal analyte compartmentalisation and analysis. Droplets are generated every 20 minutes in 8 separate parallel microchannels, with an average droplet volume of 9.47 ± 0.6 μL, allowing simultaneous analysis of 8 different experiments. The device was tested using an epithelial barrier model by monitoring the diffusion of a fluorescent high molecular weight dextran molecule. The epithelial barrier was perturbed using detergent leading to a peak at 3–4 hours, correlating with simulations. For the untreated (control) a constant, very low level of dextran diffusion was observed. The epithelial cell barrier properties were also continuously measured using electrical impedance spectroscopy to extract an equivalent trans epithelial resistance.