论文标题
通过微血管分叉的细胞血液传播纳米颗粒的异质分区
Heterogeneous partition of cellular blood-borne nanoparticles through microvascular bifurcations
论文作者
论文摘要
几十年来,流经微血管分叉的血液一直是一个活跃的研究主题,而血液中纳米级溶质的分配模式仍然相对尚未探索。在这里,我们演示了一个多尺度计算框架,用于在存在红细胞(RBC)的情况下通过与生理相关的血管分叉对纳米颗粒(NP)进行分区的直接数值模拟。计算框架是通过将新发达的颗粒悬架流入/流出边界条件嵌入多尺度血流求解器中来确定的。通过在没有分叉的情况下恢复管状血流,并根据静脉内分叉流的实验测量来验证计算框架。经典的Zweifach-fung(ZF)效果被该方法很好地捕获。此外,我们观察到NP表现出ZF样的异质分区,以应对RBC相的异质分区。 NP分区优先考虑高流量率的子分支,除了极端(大或小)悬浮流分区比例倾向于发生完整的相分离。通过分析流场和粒子轨迹,我们表明,NP分区中的ZF样异质性可以通过由RBC分离的偏差在分离交界处附近的RBC的储罐treade之前解释。在极端流分区比率下,NP分区中均匀性的恢复是由于NP在无细胞层中的血浆掠夺所致。这些发现基于多尺度计算框架,为在病理生理观察到的微血管床中NP的异质分布提供了生物物理见解。
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 newly-developed 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 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.