Feature tracking microfluidic analysis reveals differential roles of viscosity and friction in sickle cell blood

Characterization of blood flow rheology in hematological disorders is critical for understanding disease pathophysiology. Existing methods to measure blood rheological parameters are limited in their physiological relevance, and there is a need for new tools that focus on the microcirculation and extract properties at finer resolution than overall flow resistance. Herein, we present a method that combines microfluidic systems and powerful object-tracking computational technologies with mathematical modeling to separate the red blood cell flow profile into a bulk component and a wall component. We use this framework to evaluate differential contributions of effective viscosity and wall friction to the overall resistance in blood from patients with Sickle Cell Disease (SCD) under a range of oxygen tensions. Our results demonstrate that blood from patients with SCD exhibits elevated frictional and viscous resistances at all physiologic oxygen tensions. Additionally, the viscous resistance increases more rapidly than the frictional resistance as oxygen tension decreases, which may confound analyses that extract only flow velocities or overall flow resistances. Furthermore, we evaluate the impact of transfusion treatments on the components of the resistance, revealing patient variability in blood properties that may improve our understanding of the heterogeneity of clinical responses to such treatments. Overall, our system provides a new method to analyze patient-specific blood properties and can be applied to a wide range of hematological and vascular disorders

Ionophore-mediated swelling of erythrocytes as a therapeutic mechanism in sickle cell disease

Sickle cell disease (SCD) is characterized by sickle hemoglobin (HbS) which polymerizes under deoxygenated conditions to form a stiff, sickled erythrocyte. The dehydration of sickle erythrocytes increases intracellular HbS concentration and the propensity of erythrocyte sickling. Prevention of this mechanism may provide a target for potential SCD therapy investigation. Ionophores such as monensin can increase erythrocyte sodium permeability by facilitating its transmembrane transport, leading to osmotic swelling of the erythrocyte and decreased hemoglobin concentration. In this study, we treated 13 blood samples from patients with SCD with 10 nM of monensin ex vivo. We measured changes in cell volume and hemoglobin concentration in response to monensin treatment, and we perfused treated blood samples through a microfluidic device that permits quantification of blood flow under controlled hypoxia. Monensin treatment led to increases in cell volume and reductions in hemoglobin concentration in most blood samples, though the degree of response varied across samples. Monensin-treated samples also demonstrated reduced blood flow impairment under hypoxic conditions relative to untreated controls. Moreover, there was a significant correlation between the improvement in blood flow and the decrease in hemoglobin concentration. Thus, our results demonstrate that a reduction in intracellular HbS concentration by osmotic swelling improves blood flow under hypoxic conditions. Although the toxicity of monensin will likely prevent it from being a viable clinical treatment, these results suggest that osmotic swelling should be investigated further as a potential mechanism for SCD therapy

Hydrodynamic interactions between rough surfaces

In the study of particle suspensions, away from the jamming threshold, it is common to interpret the effective viscosity in terms of the volume fraction, neglecting roughness effects. Here we show that particle roughness can significantly modify viscous dissipation in configurations that represent fixed volume-fraction conditions. We derive a hydrodynamic model for the forced interaction of a two-dimensional particle, where roughness is represented by a periodic corrugation, with an adjacent wall. In particular, we address the limit of small nominal particle-wall separation, with the corrugation amplitude comparable with said separation. A lubrication analysis provides the rectilinear and angular velocities of the particle as functions of the instantaneous angular configuration. The particle may either translate while rotating or become “locked” in a specific phase and translate without rotation. The time-averaged rectilinear velocity, which is the object of interest, is a purely geometric quantity, obtained without the need to address any time dynamics