Effect of extracellular fluid tonicity on sickle red blood cell deformability and adhesion. (A) Exposure to excessively hypotonic admixtures increases occlusion risk for sRBCs resulting from excessive cellular hydration and swelling, although decreased microvascular adhesion is observed. (B) sRBCs exposed to moderately hypotonic admixtures exhibit increased deformability and decreased adhesion in our microfluidic models. (C) Exposure to mildly hypotonic admixtures increases sRBC adhesion to endothelium but decreases adhesion to laminin. Optimal deformability through microchannels, with decreased occlusion, is maintained. (D) Admixtures with increased sodium levels increase adhesion and occlusion risk in our microvascular models. Increased occlusion from exposure to these higher sodium levels was observed under both normoxic and hypoxic conditions.