Spatiotemporal Dynamics of Dilute Red Blood Cell Suspensions in Low-Inertia Microchannel Flow

Abstract

Microfluidic technologies are commonly used for the manipulation of red blood cell (RBC) suspensions and analyses of flow-mediated biomechanics. To maximise the usability of microfluidic devices, understanding the dynamics of the suspensions processed within is crucial. We report novel aspects of the spatio-temporal dynamics of an RBC suspension 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 resembling the well-known "tubular pinch effect" which would arise from inertial effects. However, given the negligible inertia under our experimental condition, an alternative explanation is needed for this OCTP profile contrary to the centralised distribution commonly reported for low-inertia flows. 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. and immune cells. Pioneered by Chien and Skalak in the 1960s-1980s [1, 2, 3], there has been extensive research carried out theoretically, experimentally and numerically to elucidate the behaviour of single RBC and characterise the dynamics of RBC suspensions (see recent reviews [4,5,6,7,8]). However, despite major progress, a rigorous and quantitative connection between microscale RBC dynamics and macroscale haemorheology is still lacking [9]. Up to date, various factors affecting blood microrheology have been determined by theoretical/numerical models of RBCs or biomimetic vesicles, including (but not limited to): (i) viscosity contrast (between inner and outer fluids) [10], deformability [11], orientation [12] and initial position [13] of the cell; (ii) shear component (distinct in linear/quadratic flows) [14], suspending viscosity [15], flowline curvature [16] and wall confinement [17] of the flow; (iii) two-body or multi-body hydrodynamic interactions between cells [18]. Most studies focus on the individual dynamics/pairwise interaction of cells or the characteristic signatures of the overall suspension system, e.g., effective viscosity and normal stress differences.Much less attention has been paid to the collective behaviour of cells, e.g., their spatiotemporal organisation or local microstructures, at a realistic length scale in three-dimens...

Emergent cell-free layer asymmetry and biased haematocrit partition in a biomimetic vascular network of successive bifurcations

“…This may have caused a certain degree of quantitative discrepancy between the simulation and experiments. However, the influence on results of the suspension behaviour should be limited to quantitative instead of qualitative differences (see evidence from our previous paper [49]). (2) Quantitative agreement of the CFL thickness as well as the critical outflow ratio for complete RBC depletion in low-flow fraction of the network between experiments and simulations remains challenging due to our numerical treatment of the flow entry region (required for tractable computational cost), where geometric contraction in the width direction is deliberately removed to enable the generation of an artificial CFL immediately after the inlet (see Sec.…”

“…Under the circumstances of locally reduced flow or diluted RBC concentration in individual branches, the CFL recovery process may be further prolonged due to weakened hydrodynamic lift or lack of shear-induced diffusion. In our previous study of dilute RBC suspensions in low-inertia channel flow (D h ≈ 46 µm, Ht ∈ [1%, 5%]), a stationary CFL was not established even after 46D h [49]. The length required for the haematocrit profile to achieve equilibrium is in general more demanding, which can go beyond 78D h (D h ≈ 29 µm) according to [78].…”

“…The blood samples consist of RBC suspensions in Dextran40, prepared using horse blood in anticoagulant EDTA (1.5 mg/mL) (TCS Biosciences). The sample-processing procedures have been detailed in our previous work [49] and are therefore not repeated here for brevity. The steady shear rheology of Dextran 40 was determined by a rotational rheometer (DHR2, TA Instruments, with minimum resolvable torque 0.1 nNm) using a…”

“…The computational domain for numerical simulations is reconstructed using design dimensions of the microfluidic device (see Figure 1b and Table 1). The flow inlets/outlets are modelled as cylindrical regions with the same geometry as the CTRACT-S configuration ("smaller inflow contraction") of the microchannel simulated in our previous work [49]. This geometric feature enables an RBC distribution with considerate initial CFLs upon entry into the main channel, therefore a much shorter length of the parent branch PB (≈ 10D h,0 ) than its experimental counterpart (= 30D h,0 ) is needed for the CFL to fully develop before reaching the first bifurcation.…”

“…The numerical model for simulating blood flow as a suspension of deformable RBCs as in our recent work [49] employs the immersed-boundary-lattice-Boltzmann method (IB-LBM [50]). The model is implemented in the parallel flow simulator HemeLB [51,52] (open source at https://github.com/hemelb-codes/hemelb) by incorporating a new module for discrete deformable cells.…”