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

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.