Microfluidic technologies are commonly used for the manipulation of red blood cell (RBC) suspensions and analyses of flow-mediated biomechanics. To enhance the performance of microfluidic devices, understanding the dynamics of the suspensions processed within is crucial. We report novel aspects of the spatio-temporal dynamics of RBC suspensions flowing through a typical microchannel at low Reynolds number. Through experiments with dilute RBC suspensions, we find an off-centre two-peak (OCTP) profile of cells contrary to the centralised distribution commonly reported for low-inertia flows. This is reminiscent of the well-known "tubular pinch effect" which arises from inertial effects. However, given the conditions of negligible inertia in our experiments, an alternative explanation is needed for this OCTP profile. Our massively-parallel simulations of RBC flow in real-size microfluidic dimensions using the immersed-boundary-lattice-Boltzmann method (IB-LBM) confirm the experimental findings and elucidate the underlying mechanism for the counterintuitive RBC pattern. By analysing the RBC migration and cell-free layer (CFL) development within a high-aspect-ratio channel, we show that such a distribution is co-determined by the spatial decay of hydrodynamic lift and the global deficiency of cell dispersion in dilute suspensions. We find a CFL development length greater than 46 and 28 hydraulic diameters in the experiment and simulation, respectively, exceeding typical lengths of microfluidic designs. Our work highlights the key role of transient cell distribution in dilute suspensions, which may negatively affect the reliability of experimental results if not taken into account.
We report on a microfluidic method that allows measurement of a small concentration of large contaminants in suspensions of solid micrometer-scale particles. To perform the measurement, we flow the colloidal suspension through a series of constrictions, i.e. a microchannel of varying cross-section. We show and quantify the role of large contaminants in the formation of clogs at a constriction and the growth of the resulting filter cake. By measuring the time interval between two clogging events in an array of parallel microchannels, we are able to estimate the concentration of contaminants who…
We investigate the stability of the pressure-driven, low-Reynolds flow of Brownian suspensions with spherical particles in microchannels. We find two general families of stable/unstable modes: (i) degenerate modes with symmetric and anti-symmetric patterns; (ii) single modes that are either symmetric or anti-symmetric. The concentration profiles of degenerate modes have strong peaks near the channel walls, while single modes diminish there. Once excited, both families would be detectable through high-speed imaging. We find that unstable modes occur in concentrated suspensions whose velocity pr…
During the transport of colloidal suspensions in microchannels, the deposition of particles can lead to the formation of clogs, typically at constrictions. Once a clog is formed in a microchannel, advected particles form an aggregate upstream from the site of the blockage. This aggregate grows over time, which leads to a dramatic reduction of the flow rate. In this paper, we present a model that predicts the growth of the aggregate formed upon clogging of a microchannel. We develop an analytical description that captures the time evolution of the volume of the aggregate, as confirmed by experi…
Flowing blood displays a phenomenon called margination, in which leukocytes and platelets are preferentially found near blood vessel walls, while erythrocytes are depleted from these regions. Here margination is investigated using direct hydrodynamic simulations of a binary suspension of stiff (s) and floppy (f) capsules, as well as a stochastic model that incorporates the key particle transport mechanisms in suspensions -- wall-induced hydrodynamic migration and shear-induced pair collisions. The stochastic model allows the relative importance of these two mechanisms to be directly evaluated …
Red blood cells flowing through capillaries assume a wide variety of different shapes owing to their high deformability. Predicting the realized shapes is a complex field as they are determined by the intricate interplay between the flow conditions and the membrane mechanics. In this work we construct the shape phase diagram of a single red blood cell with a physiological viscosity ratio flowing in a microchannel. We use both experimental in-vitro measurements as well as 3D numerical simulations to complement the respective other one. Numerically, we have easy control over the initial starting…
Motivated by the complex rheological behaviors observed in small/micro scale blood vessels, such as the Fahraeus effect, plasma-skimming, shear-thinning, etc., we develop a non-linear suspension model for blood. The viscosity is assumed to depend on the volume fraction (hematocrit) and the shear rate. The migration of the red blood cells (RBCs) is studied using a concentration flux equation. A parametric study with two representative problems, namely simple shear flow and a pressure driven flow demonstrate the ability of this reduced-order model to reproduce several key features of the two-flu…
Adhesive interactions between white blood cells and the interior surface of the blood vessels they contact is important in inflammation and in the progression of heart disease. Parallel-plate microchannels have been useful in characterizing the strength of these interactions, in conditions that are much simplified over the complex environment these cells experience in the body. Recent computational and experimental work by several laboratories have attempted to bridge this gap between behavior observed in flow chamber experiments, and cell-surface interactions observed in the microvessels of a…
We investigate the shear thinning of red blood cell - dextran suspensions. Microscopic images show that at low polymer concentration, aggregation increases with increasing concentration until it reaches a maximum and then decreases again to non-aggregation. This bell shape dependency is also deduced from the rheological measurements, if the data are correctly normalized by the viscosity of the suspending phase since a significant amount of polymers adsorb to the cell surfaces. We find that the position of the maximum of this shear rate dependent bell shape increases with increasing viscosity o…
The distribution of Red Blood Cells in a confined channel flow is inhomogeneous and shows a marked depletion near the walls due to a competition between migration away from the walls and shear-induced diffusion resulting from interactions between particles. We investigated the lift of RBCs in a shear flow near a wall and measured a significant lift velocity despite the tumbling motion of cells. We also provide values for the collective and anisotropic shear-induced diffusion of a cloud of RBCs, both in the direction of shear and in the direction of vorticity. A generic down-gradient subdiffusi…
It is often necessary to extract a small amount of a suspension, such as blood, from a larger sample of the same material for the purposes of diagnostics, testing or imaging. A practical challenge is that blood sediments noticeably on the time scale of a few minutes, making a representative subsampling of the original sample challenging. Guided by experimental data, we develop a Kynch sedimentation model to discuss design considerations that ensure a representative subsampling of blood for the entire range of physiologically relevant hematocrit over a specified time of interest. Additionally, …
Computational modeling and simulation are presented on the motion of red blood cells behind a moving interface in a capillary. The methodology is based on an immersed boundary method and the skeleton structure of the red blood cell (RBC) membrane is modeled as a spring network. The computational domain is moving with either a designated RBC or an interface in an infinitely long two-dimensional channel with an undisturbed flow field in front of the domain. The tanking-treading and the inclination angle of a cell in a simple shear flow are briefly discussed for the validation purpose. We then pr…
The transient electroosmotic flow of Maxwell fluid in a rotating microchannel is investigated both analytically and numerically. We bring out the complex dynamics of the flow during the transience due to the combination of rotation and rheological effects. We show the regimes of operation under which our analysis holds the most significance. We also shed some light on the volumetric flow rate characteristics as dictated by the underlying flow physics. Analytical solution compares well with the numerical solution. We believe that the results from the present study could potentially have far rea…
Formation of recirculating wakes is a prominent feature of inertial flow around bluff bodies. Below the onset of vortex shedding in uniform unbounded flows, the fluid in the recirculating wake region moves on closed planar orbits. The steady wake is thus an isolated zone in the flow and does not exchange fluid with the free stream. In this work, we utilize lattice-Boltzmann simulations and microfluidic experiments to demonstrate that in microchannel inertial flow of Newtonian fluids, the recirculating wake is replaced by a three-dimensional vortical flow. Spiraling streamlines generate a conti…
We present a numerical analysis of the rheology of a suspension of red blood cells (RBCs) in a wall-bounded shear flow. The flow is assumed as almost inertialess. The suspension of RBCs, modeled as biconcave capsules whose membrane follows the Skalak constitutive law, is simulated for a wide range of viscosity ratios between the cytoplasm and plasma: $λ$ = 0.1-10, for volume fractions up to $ϕ$ = 0.41 and for different capillary numbers ($Ca$). Our numerical results show that an RBC at low $Ca$ tends to orient to the shear plane and exhibits the so-called rolling motion, a stable mode with hig…
We investigate the effect of particle volume fraction on the efficiency of deterministic lateral displacement (DLD) devices. DLD is a popular passive sorting technique for microfluidic applications. Yet, it has been designed for treating dilute suspensions, and its efficiency for denser samples is not well known. We perform 3D simulations based on the immersed-boundary, lattice-Boltzmann and finite-element methods to model the flow of red blood cells (RBCs) in different DLD devices. We quantify the DLD efficiency in terms of appropriate "failure" probabilities and RBC counts in designated devi…
A mechanistic theory is developed to describe segregation in confined multicomponent suspensions such as blood. It incorporates the two key phenomena arising in these systems at low Reynolds number: hydrodynamic pair collisions and wall-induced migration. In simple shear flow, several regimes of segregation arise, depending on the value of a "margination parameter" M. Most importantly, there is a critical value of M below which a sharp "drainage transition" occurs: one component is completely depleted from the bulk flow to the vicinity of the walls. Direct simulations also exhibit this transit…
Blood is a complex suspension that demonstrates several non-Newtonian rheological characteristics such as deformation-rate dependency, viscoelasticity and yield stress. In this paper we outline some issues related to the non-Newtonian effects in blood circulation system and present modeling approaches based mostly on the past work in this field.
Numerical analyses of transient electro-osmosis of a typical non-Newtonian liquid induced by DC and AC electric fields in a rectangular microchannel are conducted in the framework of continuum fluid mechanics. The famous power-law constitutive model is used to express the fluid dynamic viscosity in terms of the velocity gradient. Transient start-up characteristics of electro-osmotic power-law liquid flow in rectangular microchannels are simulated by using finite element method. Under a DC electric field, it is found out and the fluid is more inert to the external electric field and the steady-…
The fluid dynamics video presented here outlines recent advances in the simulation of multiphase cellular blood flow through the direct numerical simulations of deformable red blood cells (RBCs) demonstrated through several numerical experiments. Videos show RBC deformations in variety of numerical simulations, relative viscosity of a suspension of RBCs in shear, and the cell-depleted wall layer for blood Hagen--Poiseuille flow.
Due to evergrowing importance of understanding flow of bio-fluids in Lab-on-CD based systems, we investigate the flow behaviour of power-law fluids in the rotating electroosmotic flow through a polyelectrolyte grafted (soft) narrow channel. We use a in-house numerical code to solve the governing transport equations for the velocities and flow rates in a rotating channel subjected to an applied external electric field. We show the strong effect of polyelectrolyte layer on the flow behaviour and find an increase in flow rate as we increase the size of the polyelectrolyte layer. We also show that…
Laboratory experiments were conducted to study particle migration and flow properties of non- Brownian, non-colloidal suspensions ranging from 10% to 40% particle volume fraction in a pressure-driven flow over and through a porous structure at low Reynolds number. Particle concentration maps, velocity maps and corresponding profiles were acquired using a magnetic resonance imaging (MRI) technique. The model porous medium consists of square arrays of circular rods oriented across the flow in a rectangular microchannel. It was observed that the square arrays of the circular rods modify the veloc…
Instability mechanism based on Coriolis force, on a rapidly rotating portable device handling shear thinning fluids such as blood, is of utmost importance for eventual detection of diseases by mixing with the suitable reagents. Motivated by this proposition, the present study renders a modal stability analysis of shear thinning fluids in a rotating microchannel modelled by the Carreau rheological law. When a microchannel is engraved a rotating compact disc (CD) based device, the centrifugal force acts as the driving force that actuates the flow and the Coriolis force enhances the mixing proces…
Flux of rigid or soft particles (such as drops, vesicles, red blood cells, etc.) in a channel is a complex function of particle concentration, which depends on the details of induced dissipation and suspension structure due to hydrodynamic interactions with walls or between neighboring particles. Through two-dimensional and three-dimensional simulations and a simple model that reveals the contribution of the main characteristics of the flowing suspension, we discuss the existence of an optimal volume fraction for cell transport and its dependence on the cell mechanical properties. The example …
Knowledge about the flow field of the plasma around the red blood cells in capillary flow is important for a physical understanding of blood flow and the transport of micro- and nanoparticles and molecules in the flowing plasma. We conduct an experimental study on the flow field around red blood cells in capillary flow that are complemented by simulations of vortical flow between red blood cells. Red blood cells were injected in a 10x12 micrometer rectangular microchannel at a low hematocrit and the flow field around a single or two cells have been characterized thanks to a highspeed camera an…
Driven or active suspensions can display fascinating collective behavior, where coherent motions or structures arise on a scale much larger than that of the constituent particles. Here, we report experiments and numerical simulations revealing that red blood cells (RBCs) assemble into regular patterns in a confined shear flow. The order is of pure hydrodynamic and inertialess origin, and emerges from a subtle interplay between (i) hydrodynamic repulsion by the bounding walls which drives deformable cells towards the channel mid-plane and (ii) intercellular hydrodynamic interactions which can b…
We analyze the dynamics of a microswimmer in pressure-driven Poiseuille flow, where fluid inertia is small but non-negligible. Using perturbation theory and the reciprocal theorem, we show that in addition to the classical inertial lift of passive particles, the active nature generates a `swimming lift', which we evaluate for neutral and pusher/puller-type swimmers. Accounting for fluid inertia engenders a rich spectrum of novel complex dynamics including bistable states, where tumbling coexists with stable centerline swimming or swinging. The dynamics is sensitive to the swimmer's hydrodynami…
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 compu…
We study the shearing rheology of dense suspensions of elastic capsules, taking aggregation-free red blood cells as a physiologically relevant example. Particles are non-Brownian and interact only via hydrodynamics and short-range repulsive forces. An analysis of the different stress mechanisms in the suspension shows that the viscosity is governed by the shear elasticity of the capsules, whereas the repulsive forces are subdominant. Evidence for a dynamic yield stress above a critical volume fraction is provided and related to the elastic properties of the capsules. The shear stress is found …
The effect of tube diameter $D$ and capillary number $Ca$ on platelet margination in blood flow at $\approx 37\%$ tube haematocrit is investigated. The system is modelled as three-dimensional suspension of deformable red blood cells and nearly rigid platelets using a combination of the lattice-Boltzmann, immersed boundary and finite element methods. Results show that margination is facilitated by a non-diffusive radial platelet transport. This effect is important near the edge of the cell-free layer, but it is only observed for $Ca > 0.2$, when red blood cells are tank-treading rather than tum…
A mixed suspension of red blood cells (RBCs) and microparticles flows through a cylindrical channel with a constriction mimicking a stenosed blood vessel. Our three-dimensional Lattice-Boltzmann simulations show that the RBCs are depleted right ahead and after the constriction. Although the RBC mean concentration (hematocrit) is 16.5% or 23.7%, their axial concentration profile is very similar to that of isolated tracer particles flowing along the central axis. Most importantly, however, we find that the stiff microparticles exhibit the opposite behavior. Arriving on a marginated position near…
We consider suspensions of deformable particles in a Newtonian fluid by means of fully Eulerian numerical simulations with a one-continuum formulation. We study the rheology of the visco-elastic suspension in plane Couette flow in the limit of vanishing inertia and examine the dependency of the effective viscosity $μ$ on the solid volume-fraction $Φ$, the capillary number $\mbox{Ca}$, and the solid to fluid viscosity ratio $\mbox{K}$. The suspension viscosity decreases with deformation and applied shear (shear-thinning) while still increasing with volume fraction. We show that $μ$ collapses to…
A hybrid computational method coupling the lattice-Boltzmann (LB) method and a Langevin-dynamics (LD) method is developed to simulate nanoscale particle and polymer (NPP) suspensions in the presence of both thermal fluctuation and long-range many-body hydrodynamic interactions (HI). Brownian motion of the NPP is explicitly captured by a stochastic forcing term in the LD method. The LD method is two-way coupled to the non-fluctuating LB fluid through a discrete LB forcing source distribution to capture the long-range HI. To ensure intrinsically linear scalability with respect to the number of p…
Using a multiscale blood flow solver, the complete diffusion tensor of nanoparticle (NP) in sheared cellular blood flow is calculated over a wide range of shear rate and haematocrit. In the short-time regime, NPs exhibit anomalous dispersive behaviors under high shear and high haematocrit due to the transient elongation and alignment of the red blood cells (RBCs). In the long-time regime, the NP diffusion tensor features high anisotropy. Particularly, there exists a critical shear rate ($\sim$100 $s^{-1}$) around which the shear-rate dependence of the diffusivity tensor changes from linear to …
The study of viscous fluid flow coupled with rigid or deformable solids has many applications in biological and engineering problems, e.g., blood cell transport, drug delivery, and particulate flow. We developed a partitioned approach to solve this coupled Multiphysics problem. The fluid motion was solved by Palabos (Parallel Lattice Boltzmann Solver), while the solid displacement and deformation was simulated by LAMMPS (Large-scale Atomic/Molecular Massively Parallel Simulator). The coupling was achieved through the immersed boundary method (IBM). The code modeled both rigid and deformable so…
Quantifying the Biophysical Properties of Red Blood Cells in Gaucher Disease
Brown University（布朗大学）；Université Paris Saclay（巴黎萨克雷大学）；CNRS UMR 8000（法国国家科学研究中心第8000联合研究单位）；Institut de Chimie Physique（物理化学研究所）；Université Paris Cité（巴黎西岱大学）；INSERM（法国国家健康与医学研究院）；EFS（法国血液服务机构）；BIGR U1134（BIGR第1134联合研究单位）；Team BioTiGR（BioTiGR团队）；Initiatives IdEx Globule Rouge d’Excellence (InIdex GR-Ex)（卓越红细胞倡议（InIdex GR-Ex））；Team PAMS（PAMS团队）
Red blood cells (RBCs) -- erythrocytes -- suspended in plasma tend to aggregate and form rouleaux. During aggregation the first stage consists in the formation of RBC doublets [Blood cells, molecules, and diseases 25, 339 (1999)]. While aggregates are normally dissociated by moderate flow stresses, under some pathological conditions the aggregation becomes irreversible, which leads to high blood viscosity and vessel occlusion. We perform here two-dimensional simulations to study the doublet dynamics under shear flow in different conditions and its impact on rheology. We sum up our results on t…
The steady motion and deformation of a lipid-bilayer vesicle translating through a circular tube in low Reynolds number pressure-driven flow are investigated numerically using an axisymmetric boundary element method. This fluid-structure interaction problem is determined by three dimensionless parameters: reduced volume (a measure of the vesicle asphericity), geometric confinement (the ratio of the vesicle effective radius to the tube radius), and capillary number (the ratio of viscous to bending forces). The physical constraints of a vesicle -- fixed surface area and enclosed volume when it i…
