Improvements of an air-liquid interface in-vitro testing method for inhalable compounds using CFD-methods

Within the last decade the air liquid interphase (ALI) cell culture technology became the state-of-the-art method for in-vitro testing of airborne substances. Cells are cultured on microporous membranes and thereby get efficiently into contact with the test atmosphere while being supplied with nutrients and being humidified from the basal side of the membrane. Biological models like cell lines from the human lung or complex ex vivo models like precision cut lung slices (PCLS) can be applied. However, especially for the application of this basic technology on the testing of a broader range of airborne materials like droplet and particle aerosols, there is still no general scientific consensus on the question of the most suitable exposure design. Concepts including complex physical phenomena like electrostatic deposition of particles or thermophoresis have been introduced to address specific scientific questions. To develop a concept for a more general application of the ALI culture technology for all kinds of airborne materials in the long run, this study aimed at the characterization of the influence of the aerosol conduction system on the particle deposition and the behaviour of the liquid supply by the use of computational fluid dynamics (CFD). In the CFD simulation models for the aerosol applied within the scope of this project the fluid air is treated as an incompressible continuum in an Euler frame of reference and as a laminar flow. The particles are regarded as solid spheres of different size in a Lagrangian frame of reference. As the particles are dispersed and the portion of volume is rather small in the continuous phase the influence of the dispersed phase on the continuous phase is neglected. The particles exhibit inertia and are exposed to drag, pressure, and gravity forces. Due to the partially submicronic size of the particles it was accounted for brownian motion, a Cunningham correction for the drag and thermophoresis when applying temperature gradients in the system. The behaviour of particles which hit or touch a wall was defined as ""stuck"", so that these particles were removed from the flow field and were accumulated on the wall for visual and numerical evaluation. The system was modified due to the CFD-results in two areas, both the branch-off and the direction change over the membranes were altered to improve the deposition rate. Concerning the liquid supply the existing system was analysed and improved with respect to an equal distribution, a tolerable pressure of the cells and a convenient behaviour of trapped air bubbles in the system. For the simulations the CFD software STAR-CCM+ (CD-adapco) and FLUENT (ANSYS, Inc.) were applied.