Bronchiolar Airways-on-a-Chip: Respiratory Droplet Formation

Respiratory droplet formation in bronchiolar airways and their subsequent release into the air are believed to play a critical role in the transmission of airborne infectious diseases such as influenza and COVID-19. However, the underlying physics and key parameters governing this process remain poorly understood. Direct in vivo investigation is technically challenging, motivating the development of in vitro models. Here, we present a novel airway-on-a-chip device uniquely designed to mimic breathing dynamics in bronchiolar airways through the integration of airflow and flexible airway walls, enabling controlled investigation of mucus fragmentation and droplet generation mechanisms. We demonstrate that during simulated exhalation, the airway walls become partially blocked with respiratory fluid, and during subsequent inhalation, the expansion of the airway walls stretches the fluid into isolated mucus filaments. Depending on the rheological properties of the mucus, these filaments exhibit a "beads-on-a-string" structure and eventually break at their thinnest points. At low airflow rates, the resulting filament segments adhere to the channel walls, limiting droplet formation. However, at sufficiently high airflow rates, similar to those encountered during deep exhalation or loud speech, the segments undergo further elongation, leading to capillary pinch-off and droplet generation. Our findings provide the first experimental evidence that respiratory droplets can form in bronchiolar airways under physiologically relevant conditions, highlighting their potential importance in airborne disease transmission. This work advances our understanding of respiratory droplet formation dynamics and introduces a versatile airway-on-a-chip platform that can be used not only to study droplet generation but also particle deposition dynamics in the lungs, with important applications in both disease transmission and pulmonary drug delivery.