Microfluidic methods to advance mechanistic understanding and translational research in sickle cell disease

Sickle cell disease (SCD) is caused by a single point mutation in the ??-globin gene of hemoglobin, which produces an altered sickle hemoglobin (HbS). The ability of HbS to polymerize under deoxygenated conditions gives rise to chronic hemolysis, oxidative stress, inflammation, and vaso-occlusion. Herein, we review recent find-ings using microfluidic technologies that have elucidated mechanisms of oxygen -dependent and-independent induction of HbS polymerization and how these mechanisms elicit the biophysical and inflammatory consequences in SCD patho-physiology. We also discuss how validation and use of microfluidics in SCD provides the opportunity to advance development of numerous therapeutic strategies, including curative gene therapies. (Translational Research 2022; 246:1-14)