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theses

A computational methodology for the direct numerical simulation of 3D cellular-scale blood flow in arbitrary and highly complex geometries is presented. The approach is based on immersed boundary methods, which provide an efficient means of modeling flows in such geometries while simultaneously resolving the large deformation and dynamics of every blood cell with high fidelity. The present methodology seamlessly integrates different modeling components, from stationary rigid boundaries of complex shape, to moving rigid bodies, to highly deformable interfaces governed by nonlinear elasticity. Thus it enables the simulation of `whole' blood suspensions flowing through, for example, physiologically realistic microvascular networks that are characterized by multiple bifurcating and merging vessels, as well as geometrically complex lab-on-chip devices.

The focus of this thesis is twofold: the development of such a versatile numerical tool, and the application of this tool to study blood flow in complex microvascular networks. Towards the first objective, after describing the methodology a series of validation studies are presented against analytical theory, experimental data, and previous numerical results. Then, the capability of the methodology is demonstrated by simulating flows of deformable blood cells and heterogeneous cell suspensions in a variety of highly complex and physiologically relevant geometries. In so doing it is shown that the methodology can predict several complex microhemodynamic phenomena. Towards the second objective, red blood cells (RBCs) are simulated flowing through realistic in vivo-like microvascular networks over a range of physiological conditions. Details are provided on the design of the networks, and an analysis of some general hemo- and hydro- dynamics is presented revealing several novel and unexpected phenomena. Next, an analysis of RBC partitioning at the network bifurcations is presented. At vascular bifurcations cells typically do not distribute to the daughter branches with the same proportion as the flow, which is important in physiology. Various aspects of such disproportionate partitioning are elucidated as it naturally arises in a complex network of multiple sequential bifurcations. Following this, an analysis of the cell free layer (CFL) in the simulated networks is presented. The CFL is a well known RBC-free plasma layer that forms near vessel walls in the microcirculation, and this provides the first simulation-based analysis of its 3D structure in complex in vivo-like networks, including hydrodynamic origins of the observed behavior. Lastly, a study is presented on the wall shear stress for the simulated vascular networks. The three-dimensional aspects of its highly varying nature are elucidated for the first time in a complex network. Additionally, the cellular influence on the wall shear stress as it arises in such geometries is isolated, quantitatively revealing the specific contribution of the cells. Overall, this work demonstrates that the present methodology is robust and versatile, and can be used to better understand the cellular-scale microphysics underlying important physiological phenomena. Going forward, it has the potential to scale up to very large microvascular networks at organ levels.

ETD_9224

doi:10.7282/T3H70KF1

Ph.D.

Includes bibliographical references

by Peter E. Balogh

ETD doctoral

The author owns the copyright to this work.