Real-time Cellular Impedance Monitoring and Imaging of Biological Barriers in a dual flow membrane bioreactor

TL;DR

This paper introduces a real-time impedance monitoring system integrated into a dual flow membrane bioreactor to study biological barrier models, revealing that dynamic flow conditions enhance barrier formation and electrical properties.

Contribution

It presents an innovative bioreactor with integrated impedance measurement and imaging, enabling real-time analysis of cell barrier development under flow conditions.

Findings

Flow conditions increase impedance, indicating stronger barrier formation.

Impedance measurements differentiate between flow and static cultures.

Dynamic culture accelerates tight junction development.

Abstract

The generation of physiologically relevant in-vitro models of biological barriers can play a key role in understanding human diseases and in the development of more predictive methods for assessing toxicity and drug or nutrient absorption. Here, we present an advanced cell culture system able to mimic the dynamic environment of biological barriers while monitoring cell behaviour through real-time impedance measurements and imaging. It consists of a fluidic device with an apical and a basal flow compartment separated by a semi-permeable membrane. The main features of the device are the integration of a transepithelial electrical impedance (TEEI) meter and transparent windows for optical monitoring within a dual flow system. Caco-2 cells were cultured in the TEEI bioreactor under both flow and static conditions. Although no differences in the expression of peripheral actin and occludin were visible, the cells in dynamic conditions developed higher impedance values at low frequencies, indicative of a higher paracellular electrical impedance and thus suggesting accelerated barrier and tight junction formation with respect to the static cultures. TEEI measurements at high frequency also enabled monitoring the evolution of transcellular impedance during culture. The cells subject to flow showed a typical RC behaviour, while the controls showed minimal capacitive behaviour, again highlighting the differences between flow and static conditions.