Heterogeneous partition of cellular blood-borne nanoparticles through microvascular bifurcations.

Blood flowing through microvascular bifurcations has been an active research topic for many decades, while the partitioning pattern of nanoscale solutes in the blood remains relatively unexplored. Here we demonstrate a multiscale computational framework for direct numerical simulation of the nanoparticle (NP) partitioning through physiologically relevant vascular bifurcations in the presence of red blood cells (RBCs). The computational framework is established by embedding a particulate suspension inflow-outflow boundary condition into a multiscale blood flow solver. The computational framework is verified by recovering a tubular blood flow without a bifurcation and validated against the experimental measurement of an intravital bifurcation flow. The classic Zweifach-Fung (ZF) effect is shown to be well captured by the method. Moreover, we observe that NPs exhibit a ZF-like heterogeneous partition in response to the heterogeneous partition of the RBC phase. The NP partitioning prioritizes the high-flow-rate daughter branch except for extreme (large or small) suspension flow partition ratios under which the complete phase separation tends to occur. By analyzing the flow field and the particle trajectories, we show that the ZF-like heterogeneity in the NP partition can be explained by the RBC-entrainment effect caused by the deviation of the flow separatrix preceded by the tank treading of RBCs near the bifurcation junction. The recovery of homogeneity in the NP partition under extreme flow partition ratios is due to the plasma skimming of NPs in the cell-free layer. These findings, based on the multiscale computational framework, provide biophysical insights to the heterogeneous distribution of NPs in microvascular beds that are observed pathophysiologically.