skip to main content

Title: Red blood cell hitchhiking enhances the accumulation of nano- and micro-particles in the constriction of a stenosed microvessel
We investigate the circulation of nano- and micro-particles, including spherical particles and filamentous nanoworms, with red blood cells (RBCs) suspension in a constricted channel that mimics a stenosed microvessel. Through three-dimensional simulations using the immersed boundary-based Lattice Boltzmann method, the influence of channel geometries, such as the length and ratio of the constriction, on the accumulation of particles is systematically studied. Firstly, we find that the accumulation of spherical particles with 1 μm diameter in the constriction increases with the increases of both the length and ratio of the constriction. This is attributed to the interaction between spheres and RBCs. The RBCs “carry” the spheres and they accumulate inside the constriction together, due to the altered local hydrodynamics induced by the existence of the constriction. Secondly, nanoworms demonstrate higher accumulation than that of spheres inside the constriction, which is associated with the escape of nanoworms from RBC clusters and their accumulation near the wall of main channel. The accumulated near-wall nanoworms will eventually enter the constriction, thus enhancing their concentration inside the constriction. However, an exceptional case occurs in the case of constrictions with large ratio and long length. In such circumstances, the RBCs aggregate together tightly and concentrate at more » the center of the channel, which makes the nanoworms hardly able to escape from RBC clusters, leading to a similar accumulation of nanoworms and spheres inside the constriction. This study may provide theoretical guidance for the design of nano- and micro-particles for biomedical engineering applications, such as drug delivery systems for patients with stenosed microvessels. « less
; ; ;
Award ID(s):
Publication Date:
Journal Name:
Soft Matter
Page Range or eLocation-ID:
40 to 56
Sponsoring Org:
National Science Foundation
More Like this
  1. This study investigates the shear rate dependent margination of micro-particles (MPs) with different shapes in blood flow through numerical simulations. We develop a multiscale computational model to handle the fluid–structure interactions involved in the blood flow simulations. The lattice Boltzmann method (LBM) is used to solve the plasma dynamics and a coarse-grained model is employed to capture the dynamics of red blood cells (RBCs) and MPs. These two solvers are coupled together by the immersed boundary method (IBM). The shear rate dependent margination of sphere MPs is firstly investigated. We find that margination of sphere MPs dramatically increases with the increment of wall shear rate  ω under 800 s −1 , induced by the breaking of rouleaux in blood flow. However, the margination probability only slowly grows when  ω > 800 s −1 . Furthermore, the shape effect of MPs is examined by comparing the margination behaviors of sphere-like, oblate-like and prolate-like MPs under different wall shear rates. We find that the margination of MPs is governed by the interplay of two factors: hydrodynamic collisions with RBCs including the collision frequency and collision displacement of MPs, and near wall dynamics. MPs that demonstrate poor performance in one processmore »such as collision frequency may stand out in the other process like near wall dynamics. Specifically, the ellipsoidal MPs (oblate and prolate) with small aspect ratio (AR) outperform those with large AR regardless of the wall shear rate, due to their better performance in both the collision with RBCs and near wall dynamics. Additionally, we find there exists a transition shear rate region 700 s −1 <  ω < 900 s −1 for all of these MPs: the margination probability dramatically increases with the shear rate below this region and slowly grows above this region, similar to sphere MPs. We further use the surface area to volume ratio (SVR) to distinguish different shaped MPs and illustrate their shear rate dependent margination in a contour in the shear rate–SVR plane. It is of significance that we can approximately predict the margination of MPs with a specific SVR. All these simulation results can be potentially applied to guide the design of micro-drug carriers for biomedical applications.« less
  2. The margination and adhesion of micro-particles (MPs) have been extensively investigated separately, due to their important applications in the biomedical field. However, the cascade process from margination to adhesion should play an important role in the transport of MPs in blood flow. To the best of our knowledge, this has not been explored in the past. Here we numerically study the margination behaviour of elastic MPs to blood vessel walls under the interplay of their deformability and adhesion to the vessel wall. We use the lattice Boltzmann method and molecular dynamics to solve the fluid dynamics and particle dynamics (including red blood cells (RBCs) and elastic MPs) in blood flow, respectively. Additionally, a stochastic ligand–receptor binding model is employed to capture the adhesion behaviours of elastic MPs on the vessel wall. Margination probability is used to quantify the localization of elastic MPs at the wall. Two dimensionless numbers are considered to govern the whole process: the capillary number $Ca$ , denoting the ratio of viscous force of fluid flow to elastic interfacial force of MP, and the adhesion number $Ad$ , representing the ratio of adhesion strength to viscous force of fluid flow. We systematically vary them numerically and amore »margination probability contour is obtained. We find that there exist two optimal regimes favouring high margination probability on the plane $Ca{-}Ad$ . The first regime, namely region I, is that with high adhesion strength and moderate particle stiffness; the other one, region II, has moderate adhesion strength and large particle stiffness. We conclude that the existence of optimal regimes is governed by the interplay of particle deformability and adhesion strength. The corresponding underlying mechanism is also discussed in detail. There are three major factors that contribute to the localization of MPs: (i) near-wall hydrodynamic collision between RBCs and MPs; (ii) deformation-induced migration due to the presence of the wall; and (iii) adhesive interaction between MPs and the wall. Mechanisms (i) and (iii) promote margination, while (ii) hampers margination. These three factors perform different roles and compete against each other when MPs are located in different regions of the flow channel, i.e. near-wall region. In optimal region I, adhesion outperforms deformation-induced migration; and in region II, the deformation-induced migration is small compared to the coupling of near-wall hydrodynamic collision and adhesion. The finding of optimal regimes can help the understanding of localization of elastic MPs at the wall under the adhesion effect in blood flow. More importantly, our results suggest that softer MP or stronger adhesion is not always the best choice for the localization of MPs.« less
  3. Hydrodynamic interactions generate a diffusive motion in particulates in a shear flow, which plays seminal roles in overall particulate rheology and its microstructure. Here we investigate the shear induced diffusion in a red-blood cell (RBC) suspension using a numerical simulation resolving individual motion and deformation of RBCs. The non-spherical resting shape of RBCs gives rise to qualitatively different regimes of cell dynamics in a shear flow such as tank-treading, breathing, tumbling and swinging, depending on the cell flexibility determined by the elastic capillary number. We show that the transition from tumbling to tank-treading causes a reduction in the gradient diffusivity. The diffusivity is computed using a continuum approach from the evolution of a randomly packed cell-layer width with time as well as by the dynamic structure factor of the suspension. Both approaches, although operationally different, match and show that for intermediate capillary numbers RBCs cease tumbling accompanied by a drop in the coefficient of gradient diffusivity. A further increase of capillary number increases the diffusivity due to increased deformation. The effects of bending modulus and viscosity ratio variations are also briefly investigated. The computed shear induced diffusivity was compared with values in the literature. Apart from its effects in marginationmore »of cells in blood flow and use in medical diagnostics, the phenomenon broadly offers important insights into suspensions of deformable particles with non-spherical equilibrium shapes, which also could play a critical role in using particle flexibility for applications such as label free separation or material processing.« less
  4. We propose a new pore-scale/channel model, or hybrid model, for the fluid flow and particulate transport in gasoline particulate filters (GPFs). GPFs are emission control devices aimed at removing particulate out of the exhaust system of a gasoline direct injection engine. In this study, we consider a wall-flow uncoated GPF, which is made of a bundle of inlet and outlet channels separated by porous walls. The particulate-filled exhaust gas flows into the inlet channels, and passes through the porous walls before exiting out of the outlet channels. We model the flow inside the inlet and outlet channels using the incompressible Navier–Stokes equation coupled with the spatially averaged Navier–Stokes equation for the flow inside the porous walls. For the particulate transport, the coupled advection and spatially averaged advection–reaction equations are used, where the reaction term models the particulate accumulation. Using OpenFOAM, we numerically solve the flow and the transport equations and show that the concentration of deposited particles is nonuniformly distributed along the filter length, with an increase of concentration at the back end of the filter as Reynolds number increases. Images from X-ray computed tomography (XCT)-scanning experiments of the soot-loaded filter show that such a nonuniform distribution is consistent withmore »the prediction obtained from the model. Finally, we show how the proposed model can be employed to optimize the filter design to improve filtration efficiency.« less
  5. The motion of cells orthogonal to the direction of main flow is of importance in natural and engineered systems. The lateral movement of red blood cells (RBCs) distal to sudden expansion is considered to influence the formation and progression of thrombosis in venous valves, aortic aneurysms, and blood-circulating devices and is also a determining parameter for cell separation applications in flow-focusing microfluidic devices. Although it is known that the unique geometry of venous valves alters the blood flow patterns and cell distribution in venous valve sinuses, the interactions between fluid flow and RBCs have not been elucidated. Here, using a dilute cell suspension in an in vitro microfluidic model of a venous valve, we quantified the spatial distribution of RBCs by microscopy and image analysis, and using micro-particle image velocimetry and 3D computational fluid dynamics simulations, we analyzed the complex flow patterns. The results show that the local hematocrit in the valve pockets is spatially heterogeneous and is significantly different from the feed hematocrit. Above a threshold shear rate, the inertial separation of streamlines and lift forces contribute to an uneven distribution of RBCs in the vortices, the entrapment of RBCs in the vortices, and non-monotonic wall shear stresses inmore »the valve pockets. Our experimental and computational characterization provides insights into the complex interactions between fluid flow, RBC distribution, and wall shear rates in venous valve mimics, which is of relevance to understanding the pathophysiology of thrombosis and improving cell separation efficiency.

    « less