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

Abstract

Despite the development of microfluidics, experimental challenges are considerable for achieving a quantitative study of phase separation, i.e., the non-proportional distribution of Red Blood Cells (RBCs) and suspending fluid, in microfluidic bifurcations with channels smaller than 20 lm. Yet, a basic understanding of phase separation in such small vessels is needed for understanding the coupling between microvascular network architecture and dynamics at larger scale. Here, we present the experimental methodologies and measurement techniques developed for that purpose for RBC concentrations (tube hematocrits) ranging between 2% and 20%. The maximal RBC velocity profile is directly measured by a temporal cross-correlation technique which enables to capture the RBC slip velocity at walls with high resolution, highlighting two different regimes (flat and more blunted ones) as a function of RBC confinement. The tube hematocrit is independently measured by a photometric technique. The RBC and suspending fluid flow rates are then deduced assuming the velocity profile of a Newtonian fluid with no slip at walls for the latter. The accuracy of this combination of techniques is demonstrated by comparison with reference measurements and verification of RBC and suspending fluid mass conservation at individual bifurcations. The present methodologies are much more accurate, with less than 15% relative errors, than the ones used in previous in vivo experiments. Their potential for studying steady state phase separation is demonstrated, highlighting an unexpected decrease of phase separation with increasing hematocrit in symmetrical, but not asymmetrical, bifurcations and providing new reference data in regimes where in vitro results were previously lacking. Published by AIP Publishing. [http://dx

Red blood cell phase separation in symmetric and asymmetric microchannel networks: effect of capillary dilation and inflow velocity

“…2B. We observed a drastic reduction of the hematocrit when the suspension passed from the reservoir into the microdevice which is in line with other observations11. This could be explained by the Fåhræus effect4243 and by residual particle sedimentation in the reservoir (despite the use of Optiprep).…”

“…This results in a reduction of the flow rate difference between the two daughter branches. The basic mechanisms have been extensively investigated in single bifurcations6891011. In networks of bifurcating (diverging and converging) vessels, RBC dynamics becomes more complex and often counter-intuitive5121314151617.…”

Modeling the hematocrit distribution in microcirculatory networks: A quantitative evaluation of a phase separation model

“…Indeed, a recent in vitro study of phase separation in microchannels beyond 20 μm concluded that “These data clearly show that the ‘ad hoc’ law proposed by Gould and Linninger is inappropriate for parametrizing the phase separation effect. By contrast, they are consistent with the empirical description of Pries et al.”…”

“…22 Indeed, a recent in vitro study of phase separation in microchannels beyond 20 μm concluded that "These data clearly show that the 'ad hoc' law proposed by Gould and Linninger is inappropriate for parametrizing the phase separation effect. By contrast, they are consistent with the empirical description of Pries et al" 23 Of note, Gould and Linninger based part of their analysis on a network representation that they derived from a photomontage of a mesentery network, originating for a database of 7 networks. 5 The PS model has previously been shown to provide plausible hematocrit predictions on these networks.…”

Neutrophil adhesion in brain capillaries contributes to cortical blood flow decreases and impaired memory function in a mouse model of Alzheimer’s disease

“…The model was used to calculate the flow and hematocrit in each vessel and the pressure at each intersection of vessels. For the human dataset, the parameters for the empirical descriptions of the Fåhraeus, Fåhraeus -Lindqvist and phase separation effects were re-scaled in order to account for the difference in characteristic size between human and rat RBCs, as proposed by Lorthois et al 23 and Roman et al 60 . This simulation approach has no free parameters.…”