Abstract

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

Janick Stucki, Chief Technology Officer, AlveoliX

Organs-on-chips (OOC) are widely seen as the next generation of in-vitro models. In comparison 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 important to improve experimental throughput and robustness of these systems. The AlveoliX breathing lung-on-chip array is based on a two-part design and equipped with a passive medium exchange mechanism. This allows a user-friendly handling of the system and a precise control of the ultra-thin, elastic and porous PDMS membrane. The standard well-plate footprint of the chip includes an array of 12 independent wells. This standard format increases experimental throughput and allows high compatibility with laboratory equipment. By modelling a healthy alveolus-on-chip, we were able to show that primary alveolar epithelial cells from patients, cultured at the air-liquid-interface and exposed to a physiological cyclic mechanical stress, preserve their typical alveolar epithelial phenotype. Long-term co-culturing of lung epithelial and endothelial cells leads to an increased barrier functionality and improved tissue integrity. Together with our cooperation partners, we are working on different alveolar disease models using inflammatory modulators such as endotoxins, cytokines and immune cells. Additionally, we are constantly adjusting our system for new applications and analyzing tools. With our partner VITROCELL we are aiming to develop the first commercialized aerosol exposure system on chip. Furthermore, we are testing the lung-on-chip on its applicability and performance in the fields of live cell imaging, genome sequencing and cell culture automation.