Spatial Distributions of Red Blood Cells Significantly Alter Local Haemodynamics

Abstract

Although bulk changes in red blood cell concentration between vessels have been well characterised, local distributions are generally overlooked. Red blood cells aggregate, deform and migrate within vessels, forming heterogeneous distributions which have considerable effect on local haemodynamics. The present study reports data on the local distribution of human red blood cells in a sequentially bifurcating microchannel, representing the branching geometry of the microvasculature. Imaging methodologies with simple extrapolations are used to infer three dimensional, time-averaged velocity and haematocrit distributions under a range of flow conditions. Strong correlation between the bluntness of the velocity and haematocrit profiles in the parent branch of the geometry is observed and red blood cell aggregation has a notable effect on the observed trends. The two branches of the first bifurcation show similar characteristics in terms of the shapes of the profiles and the extent of plasma skimming, despite the difference in geometric configuration. In the second bifurcation, considerable asymmetry between the branches in the plasma skimming relationship is observed, and elucidated by considering individual haematocrit profiles. The results of the study highlight the importance of considering local haematocrit distributions in the analysis of blood flow and could lead to more accurate computational models of blood flow in microvascular networks. The experimental approaches developed in this work provide a foundation for further examining the characteristics of microhaemodynamics.

Going beyond 20 μm-sized channels for studying red blood cell phase separation in microfluidic bifurcations

“…In experiments, these simplifications concern shapes (straight square channels branching at right angles vs. curvilinear cylindrical vessels lined with endothelial cells and branching at larger angles 3,24 ), physico-chemical properties of the surface in contact with blood (non specific adsorption of bovine serum albumin vs. presence of the endothelial surface layer with glycocalyx 17 ), cell types (absence vs. presence of platelets and white blood cells), and suspending fluid (absence vs. presence of plasma proteins mediating RBC aggregation 46,47 ), while in simulations, the shapes are more realistic, with cylindrical channels possibly branching with realistic angles. 25 Note that the methodological developments presented here could be used to study the impact of some of these simplifications, e.g., by using autologous plasma for RBC resuspension, adding a controlled amount of platelets or white blood cells, or taking advantage of new micro-fabrication techniques (e.g., Ref.…”

“…Therefore, the optical density profile is not skewed any more, as seen by Sherwood et al in the close vicinity of bifurcations. 46,47 Note that for microchannels of section 10 lm  10 lm, the photometric method cannot be applied as important intensity oscillations due to light diffraction extend over the full width of the channel. Therefore, the hematocrit is determined by counting, which is possible when H t < 13% only.…”

“…2,8,10,15,37,[45][46][47] On one hand, despite the development of microfluidics in the last decade, in vitro experiments have not yet permitted to explore phase separation in bifurcations with branches of characteristic size smaller than 20 lm nor in asymmetric channels with at least one branch smaller (both in depth and width) than the other ones. In addition, "room-sized" experimental models, designed according to the principles of kinematic and dynamic similarity, cannot reproduce the complex rheological properties of RBCs.…”

“…This should ultimately allow a better understanding of the physics at play and a parametrical characterization of the phase-separation effect in steady state, potentially improving the phenomenological description of Pries et al 33,37 The aim of the present paper is to present the experimental methodologies and measurement techniques developed for that purpose, especially in the case of channels of capillary size or slightly larger (typically below 20 lm), including asymmetric bifurcations, in the full physiological hematocrit range. The main originalities of the experiment are the following: first, we design polydimethylsiloxane (PDMS) micro-bifurcations made of square channels with different sizes, while most of the recent previous studies used bifurcations made of rectangular channels with unique depth, 15,45,47 which are easier to fabricate; 48 second, we are interested in regimes which are seldom studied (moderately to highly concentrated RBC suspension flows in small micro-channels), while in most previous studies, channels with sizes superior or equal to 20 lm have been used; 2,8,10,15,[45][46][47] and third, we simultaneously aim at a rigorous control of the experimental conditions, including the possibility of varying independently the inlet hematocrit and the flow rate ratio between both daughter branches, and at an in situ quantitative measurement of the flow parameters. This is extremely challenging in the considered flow regimes and necessitates a combination of various metrologies, including the comparison with reference measurements, in order to validate the results.…”

“…It has to be performed along with blood and plasma flow rate measurements when one is interested in phase separation effect. 46 The remainder of the paper will be organized as follows: first, the Materials and Methods used will be described. The experimental techniques and assumptions required to obtain the hematocrit, the RBC and suspending fluid flow rates in the present microfluidic-based approach will be detailed.…”