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Microfluidic Models of the Microvasculature for Red Blood Cell Metrology in Sickle Cell Disease

The microvasculature plays an important role in the pathology of sickle cell disease. As erythrocytes deliver oxygen while traversing the arterial and capillary networks, deoxygenated sickle hemoglobin begins to polymerize into fibers, causing changes in erythrocyte mechanical and adhesive properties that contribute to the obstruction of capillaries and postcapillary venules. Micropipette aspiration, atomic force microscopy, optical tweezers, and other related experimental techniques have been used to measure mechanical and adhesive properties of erythrocytes, but these approaches require static conditions that ignore the effects of shear stress. More recently, microfluidic devices have been introduced that are capable of providing realistic shear rates, but employ channel diameters that are much larger than those of human capillaries. We used photolithography and soft lithography techniques to fabricate microfluidic devices from (poly)dimethylsiloxane that recapitulate the internal dimensions of human capillaries. The physical constraints imposed by these channels allow us to measure the dynamics of deformation and “reformation” ‐ how quickly a red cell recovers its biconcave disc shape upon exit from a capillary channel.