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In sickle cell disease (SCD), hemoglobin molecules polymerize intracellularly and lead to a cascade of events resulting in decreased deformability and increased adhesion of red blood cells (RBCs). Decreased deformability and increased adhesion of sickle RBCs lead to blood vessel occlusion (vaso-occlusion) in SCD patients. Here, we present a microfluidic approach integrated with a cell dimensioning algorithm to analyze dynamic deformability of adhered RBC at the single-cell level in controlled microphysiological flow. We measured and compared dynamic deformability and adhesion of healthy hemoglobin A (HbA) and homozygous sickle hemoglobin (HbS) containing RBCs in blood samples obtained from 24 subjects. We introduce a new parameter to assess deformability of RBCs: the dynamic deformability index (DDI), which is defined as the time-dependent change of the cell's aspect ratio in response to fluid flow shear stress. Our results show that DDI of HbS-containing RBCs were significantly lower compared to that of HbA-containing RBCs. Moreover, we observed subpopulations of HbS containing RBCs in terms of their dynamic deformability characteristics: deformable and non-deformable RBCs. Then, we tested blood samples from SCD patients and analyzed RBC adhesion and deformability at physiological and above physiological flow shear stresses. We observed significantly greater number of adhered non-deformable sickle RBCs than deformable sickle RBCs at flow shear stresses well above the physiological range, suggesting an interplay between dynamic deformability and increased adhesion of RBCs in vaso-occlusive events.
Bladder control problems affect both men and women and range from an overactive bladder, to urinary incontinence, to bladder obstruction and cancer. These disorders affect more than 200 million people worldwide. Loss of bladder function significantly affects the quality of life, both physically and psychologically, and also has a large impact on the healthcare system, i.e., the incurring costs related to diagnosis, treatment and medical/nursing care. Improvements in diagnostic capabilities and disease management are essential to improve patient care and quality of life and reduce the economic burden associated with bladder disorders. This paper summarizes some of the key contributions to understanding the mechanics of the bladder ranging from work conducted in the 1970s through the present time with a focus on material testing and theoretical modeling. Advancements have been made in these areas and a significant contribution to these changes was related to technological improvements.