02389nas a2200301   4500000000100000000000100001008004100002260001500043653001800058653002300076100001800099700001400117700001800131700001900149700002600168700002300194700001600217700001800233700002700251700001800278700001900296245007400315856005500389300001000444490000600454520161300460022001402073       2018                            d  c2018-09-2510aLab-on-a-chip10aTissue engineering1 aJanick Stucki1 aNina Hobi1 aArtur Galimov1 aAndreas Stucki1 aNicole Schneider-Daum1 aClaus-Michael Lehr1 aHanno Huwer1 aManfred Frick1 aManuela Funke-Chambour1 aThomas Geiser1 aOlivier Guenat00aMedium throughput breathing human primary cell alveolus-on-chip model  uhttps://www.nature.com/articles/s41598-018-32523-x  a143590 v83 aOrgans-on-chips have the potential to improve drug development efficiency and decrease the need for animal testing. For the successful integration of these devices in research and industry, they must reproduce in vivo contexts as closely as possible and be easy to use. Here, we describe a ‘breathing’ lung-on-chip array equipped with a passive medium exchange mechanism that provide an in vivo-like environment to primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells. This configuration allows the preservation of the phenotype and the function of hAEpCs for several days, the conservation of the epithelial barrier functionality, while enabling simple sampling of the supernatant from the basal chamber. In addition, the chip design increases experimental throughput and enables trans-epithelial electrical resistance measurements using standard equipment. Biological validation revealed that human primary alveolar type I (ATI) and type II-like (ATII) epithelial cells could be successfully cultured on the chip over multiple days. Moreover, the effect of the physiological cyclic strain showed that the epithelial barrier permeability was significantly affected. Long-term co-culture of primary human lung epithelial and endothelial cells demonstrated the potential of the lung-on-chip array for reproducible cell culture under physiological conditions. Thus, this breathing lung-on-chip array, in combination with patients’ primary ATI, ATII, and lung endothelial cells, has the potential to become a valuable tool for lung research, drug discovery and precision medicine.  a2045-2322