Transwell-Based Microfluidic Platform for High-Resolution Imaging of Airway Tissues

Abstract

Transwell-based airway models have become increasingly important in studying the effects of respiratory diseases and drug treatment at the air–liquid interface of the lung epithelial barrier. However, the underlying mechanisms at the tissue and cell level often remain unclear, as transwell inserts feature limited live-cell imaging compatibility. Here, a novel microfluidic platform is reported for the cultivation of transwell-based lung tissues providing the possibility to alternate between air–liquid and liquid–liquid interfaces. While the air–liquid interface recapitulates physiological conditions for the lung model, the liquid–liquid interface enables live imaging of the tissue at high spatiotemporal resolution. The plastics-based microfluidic platform enables the insertion and recuperation of the transwell inserts, which allows for tissue cultivation and analysis under standardized well plate conditions. The device is used to monitor infections of Pseudomonas aeruginosa in human stem-cell-derived bronchial epithelial tissue. The progression of a P. aeruginosa infection in real-time at high resolution is continuously imaged, which provides insights into bacterial spreading and invasion on the apical tissue surface, as well as insights into tissue breaching and destruction over time. The airway tissue culture system is a powerful tool to visualize and elucidate key processes of developing respiratory diseases and to facilitate drug testing and development.