Abstract

Red blood cells (RBCs) are the most abundant cells in human blood. Remarkably RBCs deform and bridge together to form aggregates under very low shear rates. The theory and mechanics behind aggregation are, however, not yet completely understood. The main objective of this work is to quantify and characterize RBC aggregates in order to enhance the current understanding of the non-Newtonian behaviour of blood in microcirculation. Suspensions of human blood were flowed and observed in vitro in poly-di-methyl-siloxane (PDMS) microchannels to characterize RBC aggregates. These microchannels were fabricated using standard photolithography methods. Experiments were performed using a micro particle image velocimetry (μPIV) system for shear rate measurements, coupled with a high-speed camera for flow visualization. RBC aggregate sizes were quantified in controlled and measurable shear rate environments for 5, 10 and 15% hematocrit. Aggregate sizes were determined using image processing techniques, while apparent viscosity was measured using optical viscometry. For the samples suspended at 5% H, aggregate size was not strongly correlated with shear rate. For the 10% H suspensions, in contrast, lowering the shear rate below 10 s-1 resulted in a significant increase of RBC aggregate sizes. The viscosity was found to increase with decreasing shear rate and increasing hematocrit, exemplifying the established non-Newtonian shear-thinning behaviour of blood. Increase in aggregation size did not translate into a linear increase of the blood viscosity. Temperature was shown to affect blood viscosity as expected, however, no correlation for aggregate size with temperature was observed. Non-Newtonian parameters associated with power law and Carreau models were determined by fitting the experimental data and can be used towards the simple modeling of blood’s non-Newtonian behaviour in microcirculation. This work establishes a relationship between RBC aggregate sizes and corresponding shear rates and one between RBC aggregate sizes and apparent blood viscosity at body and room temperatures, in a microfluidic environment for low hematocrit. Effects of hematocrit, shear rate, viscosity and temperature on RBC aggregate sizes have been quantified.

Highlights

  • Red blood cells (RBCs) play a key role in dictating the rheological behaviour of blood in microcirculation. They are responsible for the non-Newtonian behaviour of blood, due to their unique properties; solid but pliable RBCs aggregate and form three-dimensional cell clusters and one-dimensional “rouleaux” stacks that account for the variation of blood viscosity in microcirculation, as they flow, tumble, form, disband and squeeze through small blood vessels

  • Healthy and fresh human blood samples obtained from six volunteers were used for the experiments conducted at 23 ̊C

  • It is important to note that, for the different hematocrits, RBCs were suspended in their native plasma where protein concentration varied from one sample to another, causing some natural variation in aggregation

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Summary

Introduction

Red blood cells (RBCs) play a key role in dictating the rheological behaviour of blood in microcirculation. They are responsible for the non-Newtonian behaviour of blood, due to their unique properties; solid but pliable RBCs aggregate and form three-dimensional cell clusters and one-dimensional “rouleaux” stacks that account for the variation of blood viscosity in microcirculation, as they flow, tumble, form, disband and squeeze through small blood vessels. A further consequence of this effect is that blood in microcirculation exhibits a decrease of local hematocrit with decreasing vessel diameter [2]. This is due to plasma skimming effects in microcirculation caused by the formation of the cell free layer, which greatly influences the Fåhraeus-Lindqvist effect [3]. It has been shown that the local hematocrit, defined as the percentage by volume of RBCs (denoted H), in microcirculation does not exceed 20% H, compared to 45% H typical of macrocirculation [4]

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