E-FLOAT: Extractable Floating Liquid Gel-Based Organ-on-a-Chip for Airway Tissue Modeling under Airflow

Microfluidic lung-on-a-chip systems are increasingly attractive tools for studying lung physiology and function because of their ability to accurately recapitulate spatiotemporal features of the airway tissue microenvironment including cellular organization, tissue architecture, and mechanical cues such as cyclic stretching and airflow. However, most lung-on-a-chip devices to date rely on integrated design elements like membranes for airway cell culture, and focus mainly on enabling on-chip monitoring and analysis while neglecting the need for off-chip analysis. Here, an extractable floating liquid-gel-based organ-on-a-chip for airway tissue modeling referred to as E-FLOAT is described that is arrayable, scalable, and uniquely amenable to withstand physiologic airflow by microanchors. It is shown that E-FLOAT can be combined with a custom airflow system that permits controlled injection of particulate matter for air pollution studies. Results show that airflow is critical to efficiently achieving physiologic mimicry of airway epithelium composition, tight junction expression, mucus production, and cilia formation on epithelial cells. It is also shown that E-FLOAT allows standard on-chip analysis while permitting complete sample extraction and off-chip analysis via immunocytochemistry, microscopy, and histological sectioning and staining, thereby expanding the number and types of biological assays that can be used and questions that can be tackled.

Automated summary

E-FLOAT is a novel extractable floating liquid-gel-based organ-on-a-chip that is arrayable, scalable, and can withstand physiologic airflow through microanchors. When combined with a custom airflow system, it efficiently mimics physiological features of airway epithelium. Additionally, E-FLOAT allows standard on-chip analysis as well as complete off-chip analysis, expanding the range of biological assays that can be conducted.