Heterogeneous red blood cell adhesion and deformability in sickle cell disease

We present a microfluidic approach that allows simultaneous interrogation of RBC properties in physiological flow conditions at a single cell level. With this method, we studied healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs using whole blood samples from twelve subjects.We report that HbS-containing RBCs are heterogeneous in terms of adhesion and deformability in flow. R ed Blood Cell (RBC) deformability, adhesion, hemolysis, and alterations in flow are root pathophysiologic underpinnings of Sickle Cell Disease (SCD)1,2. Many facets of sickle RBCs have been investigated, including hemoglobin polymerization3–5, cellular deformability6–9, adhesion8,10–14, hemodynamic changes15,16, and clinical heterogeneity17,18. Specifically, sickle RBC adhesion (stickiness) and deformability have been identified as critical biophysical factors involved in vaso-occlusion14,19 and have been shown to correlate with disease severity20–22. These factors have been studied in isolation due to significant technological barriers faced in directly analyzing blood samples from diverse clinical phenotypes. Technical barriers included complicated custom designed systems, requirement for trained personnel, and extensive sample manipulation. These challenges have posed significant limitations to the cogent integration of complex biophysical phenomena into our understandin