A microfluidic platform for simultaneous quantification of oxygen-dependent viscosity and shear thinning in sickle cell blood.

Yvonne H Datta,José M Valdez,David K Wood,John M Higgins

doi:10.1063/1.5118212

Abstract

The pathology of sickle cell disease begins with the polymerization of intracellular hemoglobin under low oxygen tension, which leads to increased blood effective viscosity and vaso-occlusion. However, it has remained unclear how single-cell changes propagate up to the scale of bulk blood effective viscosity. Here, we use a custom microfluidic system to investigate how the increase in the stiffness of individual cells leads to an increase in the shear stress required for the same fluid strain in a suspension of softer cells. We characterize both the shear-rate dependence and the oxygen-tension dependence of the effective viscosity of sickle cell blood, and we assess the effect of the addition of increasing fractions of normal cells whose material properties are independent of oxygen tension, a scenario relevant to the treatment of sickle patients with blood transfusion. For untransfused sickle cell blood, we find an overall increase in effective viscosity at all oxygen tensions and shear rates along with an attenuation in the degree of shear-thinning achieved at the lowest oxygen tensions. We also find that in some cases, even a small fraction of transfused blood cells restores the shape of the shear-thinning relationship, though not the overall baseline effective viscosity. These results suggest that untransfused sickle cell blood will show the most extreme relative rheologic impairment in regions of high shear and that introducing even small fractions of normal blood cells may help retain some shear-thinning capability though without addressing a baseline relative increase in effective viscosity independent of shear.

Highlights

Sickle cell disease (SCD) is a hematological disorder that affects millions worldwide with an expected 300 000 infants born with the disease per year.1,2 The major cause of morbidity and mortality in SCD is impaired blood flow culminating in vaso-occlusions, which includes contributions from hypoxia-induced changes in sickle blood cell mechanics, increased adhesion to endothelial cells, intravascular hemolysis, and increased inflammation.3–5 disease course often includes high rates of hospitalization and complications, there is a large range of clinical phenotypes including patient groups who experience completely benign disease
We previously developed a microfluidic system to quantify sickle blood flow in a range of oxygen tensions and shear rates and in microchannels that mimic the size of vessels seen in the microvasculature
Experimental and bypass gas reservoirs were modeled as gas supplies of nitrogen or air to verify each blood channel oxygen tension could be independently controlled, respectively

Summary

Introduction

Sickle cell disease (SCD) is a hematological disorder that affects millions worldwide with an expected 300 000 infants born with the disease per year. The major cause of morbidity and mortality in SCD is impaired blood flow culminating in vaso-occlusions, which includes contributions from hypoxia-induced changes in sickle blood cell mechanics, increased adhesion to endothelial cells, intravascular hemolysis, and increased inflammation. disease course often includes high rates of hospitalization and complications, there is a large range of clinical phenotypes including patient groups who experience completely benign disease. Most previous studies that have quantified sickle blood rheology have relied on cone-and-plate or Couette viscometers, which typically use surface driven flows, do not recapitulate the velocity profiles observed in the microvasculature, and can have artifacts in suspensions like blood.. Most previous studies that have quantified sickle blood rheology have relied on cone-and-plate or Couette viscometers, which typically use surface driven flows, do not recapitulate the velocity profiles observed in the microvasculature, and can have artifacts in suspensions like blood.11,12 To address these challenges, we previously developed a microfluidic system to quantify sickle blood flow in a range of oxygen tensions and shear rates and in microchannels that mimic the size of vessels seen in the microvasculature.. One limitation of these studies, was that they did not explore a range of shear rates

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