Dual flow bioreactor with ultrathin microporous TEER sensing membrane for evaluation of nanoparticle toxicity

Abstract

Permeability studies across biological barriers are of primary importance in drug delivery as well as in toxicology when investigating the absorption and translocation of a substance. The study of nanomaterial interaction with epithelial barriers is of particular interest given their growing use in nanomedicine as well as concerns about their potential hazard. Here we describe the design and fabrication of a new bioreactor with an ultrathin microporous sensing support for the study of nanoparticle toxicity in intestinal epithelial cells in conditions which better recapitulate the physiological environment. Thanks to the integration of 4 electrodes in the microporous membrane, the system allows real-time and continuous sensing of TEER (trans epithelial electrical resistance) during flow without interruption or perturbation of experiments. The TEER bioreactor was tested using Caco-2 cells as an in vitro model of intestinal epithelia. When exposed to silver nanoparticles, which are known to be toxic, the embedded electrodes enabled non-invasive evaluation of barrier impairment over time. This device can be used to study barrier integrity and the kinetics of nanomaterial induced damage to epithelial barriers in physiologically relevant conditions.