Utilizing Computational Fluid Dynamics Modeling to Create an Aerosol-Specific Cell Culture Exposure System to Evaluate the Toxicity of Aerosols at the Air-Liquid Interface
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Traditional in vitro studies utilize submerged exposures in which toxicants are solubilized in water or dimethyl sulfoxide (DMSO) and added to cell culture media. However, approximately 30% of compounds nominated for study in the U.S Environmental Protection Agency’s (EPA) Toxic Substances Control Act (TSCA) inventory are insoluble or volatile, and therefore cannot be adequately tested using traditional in vitro dosing methods. To address these challenges, the cell culture exposure system (CCES) was developed to expose human bronchial epithelial cells established at air-liquid interface (ALI) to volatile organic compounds (VOCs). The CCES successfully delivers six concentrations of VOCs to four technical replicates within a 24-well format which allows medium-throughput testing of volatile compounds.
However, insoluble and nonvolatile compounds must be generated and delivered as aerosols. We optimized an aerosol generation system that delivers a monodispersed aerosol population (d=1.4-1.6 μm) to the dilution manifold of the CCES. To quantify CCES performance in delivering aerosols, a fluorescent tracer was delivered through the system and its deposition was quantified. Results revealed that the VOC-optimized CCES was incompatible with particle delivery. In order to design a new aerosol-specific CCES, the original system was built as a computer-aided design (CAD) model for computational fluid dynamics (CFD) modeling. CFD results indicated that back-pressure influenced particle delivery and prevented the dilution manifold from delivering six serial dilutions. Visualization of velocity and pressure contours throughout the system highlighted the need to redesign air flow parameters and the geometry of the system. CAD and CFD modeling were then applied to test new prototypes until a serial half-log dilution scheme was established in a new dilution manifold. Overall, our study provides a robust framework to utilize CFD modeling to develop new technologies and optimize experimental conditions for aerosol exposures at ALI which will improve in vitro inhalation toxicology studies. This abstract does not reflect EPA policy.