Inflow/Outflow Boundary Conditions for Particle-Based Blood Flow Simulations: Application to Arterial Bifurcations and Trees

When blood flows through a bifurcation, red blood cells (RBCs) travel into side branches at different hematocrit levels, and it is even possible that all RBCs enter into one branch only, leading to a complete separation of plasma and RBCs. To quantify this phenomenon via particle-based mesoscopic simulations, we developed a general framework for open boundary conditions in multiphase flows that is effective even for high hematocrit levels. The inflow at the inlet is duplicated from a fully developed flow generated in a pilot simulation with periodic boundary conditions. The outflow is controlled by adaptive forces to maintain the flow rate and velocity gradient at fixed values, while the particles leaving the arteriole at the outlet are removed from the system. Upon validation of this approach, we performed systematic 3D simulations to study plasma skimming in arterioles of diameters 20 to 32 microns. For a flow rate ratio 6:1 at the branches, we observed the “all-or-nothing” phenomenon with plasma only entering the low flow rate branch. We then simulated blood-plasma separation in arteriolar bifurcations with different bifurcation angles and same diameter of the daughter branches. Our simulations predict a significant increase in RBC flux through the main daughter branch as the bifurcation angle is increased. Finally, we demonstrated the effectiveness of the new methodology in simulations of blood flow in vessels with multiple inlets and outlets, constructed using an angiogenesis model.Author Summary: Blood tests, which provide a wealth of information on the state of human health, are often performed on cell-free samples. Therefore, blood-plasma separation needs to be achieved. A simple but effective solution for isolating plasma from blood utilizes capillary bifurcations. In a particle-based simulation study of plasma skimming in capillary bifurcations, the blood flow properties such as velocity and pressure fields differ drastically at the inlet and outlet regions. Therefore, a new open (non-periodic) boundary is required. In this paper, we have developed and validated a general parallel framework for open boundary conditions. This is a non-trivial enabling technology that could be used in all open boundary systems and all particle-based Lagrangian simulations. We performed systematic 3D simulations of blood flow in arteriolar bifurcations and elucidated the biophysical mechanism of blood-plasma separation as well as quantified the effects of branch size and bifurcation angle on cell separation efficiency, which have not been addressed before. We also demonstrated the applicability of the methodology in arterial trees with multiple inlets and outlets.