Figure 8.

Overview of microfluidic device designs to mimic the lung-capillary interactions in the alveolus. (Left) (A) Diagram of the nanoparticle exposure to human lung. (B) Alveolar-capillary barrier in vitro. (C) Design and structure of the lung-on-a-chip. (D) Zoom-in showing the artificial alveolar-capillary barrier on the chip. Epithelial and endothelial cells are seeded on opposite sides of a Matrigel barrier. Media was flown through the endothelial channel⁸⁸. (Top right) (E) Schematic of alveolus Lung-on-a-chip model comprising compartmentalized PDMS microchannels to form an alveolar-capillary barrier. Alveolar epithelial and endothelial cells are co-cultured on porous PDMS membrane coated with ECM. (F) Physiological cyclic strain or ‘breathing’ is generated by applying vacuum to the side chambers⁹⁵. (G) Schematic diagram of device containing human lung epithelial cells and a low density of NSCLC tumor cells cultured on the upper surface of a porous ECM-coated membrane with an endothelial square cross-sectioned lumen. Physiological breathing motions were also mimicked in this device. (B) Confocal fluorescence micrograph of a cross-section of alveolus chip, showing lung cancer cells (green, anti-GFP), primary lung alveolar epithelial cells labeled with ZO-1 (white). A square cross-section endothelial cells lumen is created on the bottom microchannel and labeled with anti-VE-cadherin (red). (Scale bar, 200 μm)⁷⁷. Reproduced from ref. 88 with permission from Oxford University Press, copyright 2018. Reproduced from ref. 77 with permission from The American Association for the Advancement of Science, copyright 2012.