[Microcirculation] Hypoxia enhanced adhesion of red blood cells in microscale flow
The 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 red blood cell (RBC) adhesion under hypoxic flow conditions mimicking post-capillary venules.
We simulated a range of physiological conditions and explored RBC adhesion to endothelial or sub-endothelial components (fibronectin, FN, or laminin, 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 sickle cell disease (SCD).
Significant heterogeneity in RBC adherence response to hypoxia was seen among SCD patients. RBCs from a hypoxia enhanced adhesion population showed a significantly greater increase in adhesion compared to RBCs from a hypoxia non-enhanced adhesion population, for both FN and LN.
The 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.
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Myeongseop Kim, Yunus Alapan, Anima Adhikari, Jane A. Little, Umut A. Gurkan Accepted manuscript online: 7 April 2017Full publication history DOI: 10.1111/micc.12374