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

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.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biomedical Engineering

Grantor

University of Houston

Year dc:date.issued

2020

Author dc:creator

• Lu, Madeleine

Advisor dc:contributor.advisor

• Shevkoplyas, Sergey S.

Committee members dc:contributor.committeemember

• Sheehan, Vivien A.
• Majd, Sheereen
• Mohan, Chandra
• Wu, Tianfu

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

Statement dc:rights

• The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/10657/7962

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/7962