Microfluidic Platform for Real-Time Impedance Profiling of Transwell-Based Barrier Models

Abstract

We propose a microfluidic platform with integrated microfabricated electrodes for real-time impedance profiling of transwell-based barrier models, which can be subjected to dynamic microfluidic flow. This platform overcomes the limitations of conventional methods that are based on invasive permeability assays and single time-point impedance measurements: It enables continuous, non-invasive monitoring of tissue barrier integrity at high spatial and temporal resolution. We demonstrate the capabilities of our system by continuously monitoring the gradual loss of barrier integrity in upper-airway-tissue models exposed to non-physiological liquid-liquid interface conditions.

Keywords: barrier model; impedance spectroscopy; transepithelial electrical resistance (TEER); transwell inserts.

Fig. 1

(a) Microfluidic platform for real-time impedance measurement. (b) Schematics of the impedance measurement setup using an upper airway barrier model in transwell inserts in a 4-electrode setup. 1: 3D-printed lid with Au-plated Cu electrode pair, 2: Transwell, 3: Silicone gasket, 4: Microfluidic chip, 5: Glass coverslip with ITO electrodes, 6: Microscope objective, 7: Upper airway epithelium.

Fig. 2

(a) Instrumentation setup, (b) Core measurement unit comprising PCB and microfluidic chip.

Fig. 3

(a) TEER recordings of tissue-coated transwell inserts measured by the developed microfluidic setup and the commercial EVOM setup during LLI exposure, (b) representative live microscopy images evidencing the gradual barrier disruption.