The radial distribution of cells in blood flow inside vessels is highly non-homogeneous. This leads to numerous important properties of blood, yet the mechanisms shaping these distributions are not fully understood. The motion of cells is governed by a variety of hydrodynamic interactions and cell-deformation mechanics. Properties, such as the effective cell diffusivity, are therefore difficult to investigate in flows other than pure shear flows. In this work, several single-cell, cell-pair, and large-scale many-cell simulations are performed using a validated numerical model. Apart from the single-cell mechanical validations, the arising flow profile, cell free layer widths, and cell drift velocities are compared to previous experimental findings. The motion of the cells at various radial positions and under different flow conditions is extracted, and evaluated through a statistical approach. An extended diffusive flux-type model is introduced which describes the cell diffusivities under a wide range of flow conditions and incorporates the effects of cell deformability through a shear dependent description of the cell collision cross sections. This model is applicable for both red blood cells and platelets. Further evaluation of particle trajectories shows that the margination of platelets cannot be the net result of gradients in diffusivity. However, the margination mechanism is strongly linked to the gradient of the hematocrit level. Finally, it shows that platelets marginate only until the edge of the red blood cell distribution and they do not fill the cell free layer.

The influence of red blood cell (RBC) deformability in whole blood on platelet margination is investigated using confocal microscopy measurements of flowing human blood and cell resolved blood flow simulations. Fluorescent platelet concentrations at the wall of a glass chamber are measured using confocal microscopy with flowing human blood containing varying healthy-to-stiff RBC fractions. A decrease is observed in the fluorescent platelet signal at the wall due to the increase of stiffened RBCs in flow, suggesting a decrease of platelet margination due to an increased fraction of stiffened RBCs present in the flow. In order to resolve the influence of stiffened RBCs on platelet concentration at the channel wall, cellpair and bulk flow simulations are performed. For homogeneous collisions between RBC pairs, a decrease in final displacement after a collision with increasing membrane stiffness is observed. In heterogeneous collisions between healthy and stiff RBC pairs, it is found that the stiffened RBC is displaced most. The influence of RBC deformability on collisions between RBCs and platelets was found to be negligible due to their size and mass difference. For a straight vessel geometry with varying healthy-to-stiff RBC ratios, a decrease was observed in the red blood cell-free layer and platelet margination due to an increase in stiffened RBCs present in flow.

We study the effect of pulsatile flow on the transport of red blood cells (RBCs) and platelets into aneurysm geometries with varying dome-to-neck aspect ratios (AR). We use a validated two-dimensional lattice Boltzmann model for blood plasma with a discrete element method for both RBCs and platelets coupled by the immersed boundary method. Flow velocities and vessel diameters were matched with measurements of cerebral perforating arteries and flow was driven by a synthetic heartbeat curve typical for such vessel sizes. We observe a flow regime change as the aspect ratio increases from a momentum-driven regime in the small aspect ratio to a shear-driven regime in the larger aspect ratios. In the small aspect ratio case, we see the development of a re-circulation zone that exhibits a layering of high (greater than or equal to 7 s) and low (less than 7 s) residence cells. In the shear-driven regime, we see high and low residence cells well mixed, with an increasing population of cells that are trapped inside the aneurysm as the aspect ratio increases. In all cases, we observe aneurysms that are platelet-rich and red blood cell-poor when compared with their respective parental vessel populations. Pulsatility also plays a role in the small aspect ratio as we observe a smaller population of older trapped cells along the aneurysm wall in the pulsatile case when compared with a steady flow case. Pulsatility does not have a significant effect in shear-driven regime aspect ratios.

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In order to accurately describe the mechanics of red blood cells (RBCs) and resulting fluid dynamics, a cell-resolved blood flow fluid solver is required. The parameters of the material model for the RBC membranes are carefully tuned to reproduce the behavior of real cells under various experimental conditions. In this work, uncertainty in the parameters of the material model for RBCs used in a model for RBC suspensions was estimated with Inverse Uncertainty Quantification (IUQ) using Bayesian Annealed Sequential Importance Sampling (BASIS). Due to the relatively high computational cost of the model, a Gaussian Process regression metamodel was trained in order to feasibly draw the large number of samples required to obtain an accurate posterior distribution estimate. Additionally, the identifiability of the model parameters was estimated using Sobol sensitivity indices. The elongation index of simulated RBCs in a perfect sheared environment was the model prediction used to calibrate model parameters. The results show good identifiability of the parameter defining the tensile properties of the cell membrane and viscosity ratio, and poor identifiability of the parameter defining the response of the cell surface while undergoing bending. This suggests that the latter should be identified using a different quantity of interest. Overall, the model outputs with the optimal values of the parameters obtained using the Gaussian Process metamodel match better or close to the measurements than the results with the parameters' values obtained with the original model. Therefore, we can conclude that it is a valid method to decrease the computational cost of IUQ of the model.