Use of computational fluid dynamics for optimization of cell-based in vitro methods in inhalation research

To understand effects of inhalable substances in the lung, it is reasonable to investigate these substances using biological models. Until recently, tests for this purpose had to be performed mainly in vivo. Due to ethical, political and scientific reasons, alternative in vitro test methods are of increasing importance. At the Fraunhofer Institute ITEM, a testing procedure based on air-liquid interface (ALI) culture technology was developed for this purpose (P.R.I.T.® ExpoCube®). In cooperation with the Fraunhofer Institute SCAI this in vitro testing procedure was revised by applying Computational Fluid Dynamics (CFD) for the layout of the aerosol conduction and sampling. The aim of the study was to characterize and improve the deposited amount of test aerosols on cultured human cells and to increase the amount of aerosols extracted from a sampling box. The calculations focused the construction layout of the aerosol box, the shape of inlets for cell exposure and the thermophoresis effect as a measure for improvement of particle deposition on exposed cells. For this purpose commercial CFD software was applied in which the airborne aerosols were regarded as solid particles in a Lagrangian frame of reference. Due to the partially submicronic size of the particles, Brownian motion and Cunningham correction for the drag and thermophoretic forces were considered. Results demonstrated improvements of the particle extraction from the aerosol sampling by optimization of the construction, only minor effects of the inlet shape on the particle deposition on cells and a clear improvement of the particle deposition by applying thermophoretic effects.