Hypoxia-enhanced adhesion of red blood cells in microscale flow.

ObjectivesThe advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro-gas exchanger integrated with microfluidics to study RBC adhesion under hypoxic flow conditions mimicking postcapillary venules. MethodsWe simulated a range of physiological conditions and explored RBC adhesion to endothelial or subendothelial components (FN or LN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation of RBC adhesion was performed on 35 subjects with homozygous SCD. ResultsSignificant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a HEA population showed a significantly greater increase in adhesion compared to RBCs from a HNA population, for both FN and LN. ConclusionsThe approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification of RBC adhesion in a cost-efficient and patient-specific manner. We identified a unique patient population in which RBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup.