# Air Quality Effects on Human Health and Approaches for Its Assessment through Microfluidic Chips
## 5 OoC for Assessing Health Effects
### OoC Technology for Modeling Healthy and Pathological Lung Function
To recreate physiological strain patterns, [PERSON] and colleagues introduced a microfluidic system that recreates the widening of alveoli in lung induced by stretching of the diaphragm [156]. In their model, primary cells are seeded on a thin Polydimethylsiloxane (PDMS) membrane that is stretched in all three dimensions by a micro-diaphrag that is electro-pneumatically actuated, therefore recreating the physiological strains that cells experience in the alveoli more closely (Figure 2D). [PERSON] and colleagues presented a similar approach, with the addition that the artificial alveoli were partially flooded with media, to additionally simulate the surface tension stress experienced by cells through the cyclic propagation of the air-liquid interface [157]. Systems that recapitulate other anatomical structures of the lung were also published. For example, [PERSON] and colleagues developed a human airway musculature on a chip that allows modeling the constriction and dilation of bronchi [158]. This system mimics human bronchial smooth muscle (BSM) lamellae, the simplest structural and functional unit of the airways. For this, bronchial smooth muscular thin films were engineered by seeding primary BSM cells on elastic PDMS cantilevers. Once the BSM cells contract, the thin film bends, leading to a reduction of the tissues' curvature radius, thus modeling bronchoconstriction (Figure 2E). Other approaches focus on modeling physiological parameters, rather than anatomical structures found in the lung, such as differences in oxygenation. In their microfluidic model, [PERSON] and colleagues recapitulate the anaerobic, micro-aerobic, and highly aerobic environment found in sinuses, trachea/bronchi, and alveoli, respectively [159]. These differences in oxygenation play an important role during infections of the airways, since oxygen is needed for proper immune cell function, and also, limits bacterial growth according to the pathogens respiration mode (aerobic, facultative anaerobic or anaerobic). Therefore, antibiotic treatment of infections in different airway compartments can be modeled with this system. In various diseases of the lung, a deficiency of pulmonary surfactant can give rise to a disturbed liquid lining of the small airways, and to the formation of occluding liquid plugs. The propagation of liquid plugs devoid of surfactant can lead to large mechanical forces experienced by cells of the airways. In their model, [PERSON] and colleagues present a microfluidic model that recapitulates airway architecture, simulates physiologic levels of pulmonary pressures, and allows for the cultivation of airway cells (Figure 2F). The latter enables the study of A549 cells exposed to repeated liquid plug propagation, and therefore, to mechanical shear forces that can rise to harmful levels [160]. Figure 2: Different lung-on-a-chip design principles. (**A**) The cross-sectional view though the microfluidic device shows an early attempt to recreate lung physiology by introducing an air–liquid interface to the cells. Reprinted from [150], with permission from Elsevier; (**B**) 3D cross-sectional view illustrates the use of an epithelial and endothelial cell line separated by a porous membrane that divides air and a media channel. Reprinted by permission from Macmillan Publishers Ltd: Nature Methods [151], copyright (2015); (**C**) Building on similar design considerations, the stretchability of the separating membrane is introduced by using vacuum chambers at both sides of the actual compartments for cell growth. From [154], reprinted with permission from AAA; (**D**) Since breathing introduces 3D multidirectional mechanical stress to the alveoli in human lung, a system was introduced that simulates this stretching more close than unidirectional stretching does. [156]—Published by The Royal Society of Chemistry under creative commons Attribution 3.0 Unported License; (**E**) Schematic depicting engineered bronchial smooth muscular thin films adopting (i) basal tone, (ii) preconstriction, and (iii) bronchodilator-induced relaxation.