Abstract

A Breathing Human Lung-on-Chip Array For Drug Transport and Safety Studies

Janick Stucki, Chief Technology Officer, AlveoliX

Organs-on-chip (OOC) are widely seen as the next generation of in-vitro models. In contrast to standard cell culture systems, based on static 2D and 3D tissue systems, they additionally allow to better model the dynamic biomechanical microenvironment of specific organs. However, for the successful implementation of OOC in drug safety assessment and preclinical decision making, it is also important to develop easy to handle OOC systems. The breathing lung-on-chip array is based on a two-part design and equipped with a passive medium exchange mechanism. This allows ease of use and the precise control of the ultra-thin, elastic and porous PDMS membrane. The 96-well plate footprint of the chip and the array of 12 independent lung-on-chips increases experimental throughput and allows compatibility with standard laboratory equipment that highly facilitates its adoption in commercial use. By modelling a healthy alveolus-on-chip, we could show that primary alveolar epithelial cells from patients cultured at the air-liquid-interface and exposed to a physiological cyclic mechanical stress preserves their typical alveolar epithelial phenotype and their barrier function. Long-term co-culturing of epithelial and endothelial cells lead to an increased barrier functionality. Together with our cooperation partners we are working on different lung disease models such as acute lung injury, lung fibrosis and COPD. Additionally, we are constantly adapting our system for new applications such as exposure set-ups or automated stiffness and surfactant measurements.