Integrating Inhalation/Exhalation Aerodynamics Into Lung on a Chip Platforms

K. Haffey, J-H Huang, A. Arefin, O. Ishak, E. Higgins, J.F. Harris, R. Iyer, P. Nath
Los Alamos National Laboratory,
United States

Keywords: microfluidics, lung-on-a-chip, aerodynamics

Summary:

Current lung on a chip models include co-culture of cells, cyclic stretching, and air liquid interface showing significant progress to emulate the lung micro-physiological environment1,2. However, as the first line of defense, the architecture of the lung implements specific aerodynamic features to control exposure of aerosolized materials in the air that we breathe. To recapitulate these features, in the next generations of lung on chip models will require the integration of 1) the branched the generations of bronchiole, 2) 3D circular alveolar sac shape and 3) breathing like motions of inhalation and exhalation3. There are significant challenges associated with capturing 3D alveolar sacs and breathing like inhalation/exhalation dynamics using conventional fabrication methods. In this work, a laser based micro-patterning and lamination method was used to circumvent these challenges by integrating (1) a multiplayer approach to build complex 3D geometries; (2) install difficult-to-handle, thin, stretchable, porous membranes, enabling the creation of circular alveolar features; and (3) a microfluidic stretching method that can facilitate inhalation and exhalation dynamics. In addition, the fabrication method allows to seamlessly integrate branched microchannels with the alveolar chamber to appropriately capture the aerodynamics of inhalation and exhalation. Fig 1 shows a fully fabricated device that integrates both the small airways and alveoli of the lung. The alveoli is composed of ~10 micons thin polymeric membranes. Similar to lung physiology, the alveoli can be inflated by the fluid-structure interaction created by an integrated microfluidic aspirator (Fig 2). The actuation of the membrane results in (1) cyclic stretching of the cells cultured on the membranes; (2) balloon shapes; and (3) a negative pressure inside the alveoli. Consequently, our platform is able not only to capture the aerodynamics of exposure that mimics the human lung, but also to simulate different breathing conditions based on age, physical activities, and medical conditions (e.g. Fig. 3).