Abstract
Hemolysis usually happens instantly when red blood cells (RBCs) rupture under a high shear stress. However, it is also found to happen gradually in the extracorporeal membrane oxygenation (ECMO) under low but periodic squeezes. In particular, the gradual hemolysis is accompanied by a progressive change in morphology of RBCs. In this work, the gradual hemolysis is studied in a microfluidic device with arrays of narrow gaps the same as the constructions in ECMO. RBCs are seen to deform periodically when they flow through the narrow gaps, which causes the release of adenosine-triphosphate (ATP) from RBCs. The reduced ATP level in the cells leads to the fatigue of RBCs with the progressive changes in morphology and the gradual loss of deformability. An empirical model for the fatigue of RBCs is established under the periodic squeezes with controlled deformation, and it reveals a different way of the hemolysis that is dominated by the squeeze frequency. This finding brings a new insight into the mechanism of hemolysis, and it helps to improve the design of circulatory support devices.