Towards optimizing particle deposition in bifurcating structures
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Particle deposition patterns formed in the lung upon inhalation are of interest to a wide spectrum of biomedical sciences, particularly for their influence on non-invasive therapies which deliver drugs to the respiratory track. Before reaching the alveoli, particles, or a collection of liquid droplets called aerosols, must transverse this bifurcating network. This dissertation proposes a multi-faceted strategy for optimizing current methods of drug delivery by analyzing particle deposition in a single bifurcation and a complex 3-dimensional tree as a model of the airways. In this thesis, previous probabilistic formulations of particle deposition in a single bifurcation were first examined, combined and verified by computational fluid dynamic modeling. The traditional single bifurcation model was then extended to a multigenerational network as a Markov chain. The probabilistic approach combined with detailed fluid mechanics in bifurcating structures, permits a more realistic treatment of particle deposition. The formulation enables a rapid comparative analysis among different flow policies, i.e. how varying modes of inhalation affect local particle deposition and total particle escape rates. For example, this approach showed that body position has a minimal effect on deposition pattern, while a specific flow profile maximize deposition into the periphery of the lung. Also included are novel experimental results of particle deposition. Most experimental deposition studies are restricted to total deposition. Regional deposition can only be estimated but not directly measured without the destruction of the lung like models. As a result, the measurement requires multiple models which adds to the variance. To this end a standard physical model for investigating effects of various ventilation strategies on regional particle deposition was developed. Results suggest that a brief pause in flow can increase deposition into regions of blocked airways where drugs would not otherwise enter. Experiments were also conducted to investigate the effects of inertia dominated flow in symmetric and asymmetric structures revealing novel features in 3D compared to 2D. This dissertation combines experimental and computation results to propose a strategy to efficiently move particles through a symmetric and asymmetric bifurcating structure. It also introduces possible strategies for maximizing deposition to a desired region of a lung structure.