Novel Technologies for Evaluating Red Blood Cell Rheology during Blood Processing and in Sickle Cell Disease



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Normal red blood cells (RBCs) are relatively simple in structure as they contain no major organelles and have no nucleus. Because of this, they typically assume a flat biconcave disk shape at low shear rates. This unique shape grants RBCs the flexibility to deform in response to the varying shear stresses it will experience in circulation as well as squeeze into narrow capillaries smaller than the RBC’s major diameter. Therefore the RBC’s ability to deform is crucial in ensuring the efficient delivery of oxygen throughout the entire body. However, under certain conditions or due to certain genetic disorders, the RBC changes in shape and becomes a non-deformable and rigid cell. Additionally, these RBCs have been shown to express surface markers that promote interactions and adherence to vasculature. The changes in RBC deformability and adhesiveness, two fundamental hemorheological properties, can impact RBC viability and are associated with a host of negative clinical implications. This dissertation first investigates how RBC morphology can be affected during the blood processing pathway and introduces novel methods for ameliorating such adverse effects. Next it explores the usage of hemorheological biomarkers a quantitative metric to assess the effectiveness of existing and novel therapeutic options for sickle cell disease (SCD). Current modalities for studying RBC rheology involve the use of large and costly machinery, making it difficult to employ these studies in a wider variety of clinical and academic settings. To address these needs, this dissertation also proposes the use of novel microfluidic technologies developed to (1) process stored RBCs to remove harmful residual plasma proteins, (2) investigate the effects of novel storage washing solutions on RBC morphology, and (3) aid in understanding the role both deformability and adhesion play in microvascular perfusion. The contributions of this work build upon our current knowledge on the importance of RBC deformability and adhesion on blood flow and provide low-cost techniques and approaches for processing, evaluating, and monitoring these hemorheological properties.



hematology, microfluidics, red blood cells, sickle cell disease, transfusion


Portions of this document appear in: Lu, Madeleine, Minke AE Rab, Sergey S. Shevkoplyas, and Vivien A. Sheehan. "Blood rheology biomarkers in sickle cell disease." Experimental Biology and Medicine 245, no. 2 (2020): 155-165. And in: Vörös, Eszter, Nathaniel Z. Piety, Briony C. Strachan, Madeleine Lu, and Sergey S. Shevkoplyas. "Centrifugation‐free washing: A novel approach for removing immunoglobulin A from stored red blood cells." American journal of hematology 93, no. 4 (2018): 518-526. And in: Vörös, Eszter, Madeleine Lu, Dalia Lezzar, and Sergey S. Shevkoplyas. "Centrifugation-free washing reduces buildup of potassium and free hemoglobin in washed red blood cells after the procedure." American journal of hematology 93, no. 12 (2018): E389. And in: Lu, Madeleine, and Sergey S. Shevkoplyas. "Dynamics of shape recovery by stored red blood cells during washing at the single cell level." Transfusion 60, no. 10 (2020): 2370-2378.