There is a significant need for technological advancement in blood processing. New technologies in rapid processing of frozen blood products could significantly improve management of the blood supply chain in the United States by enabling on-demand use of frozen blood products that can be stored for 10 years instead of the current 6 weeks of refrigerated shelf life. In addition, advancements in blood processing for the extracorporeal treatment of sepsis could potentially save over 100,000 lives every year in the United States alone. Here we describe a new mathematical modeling approach for the design of procedures to rapidly remove the cryoprotectant glycerol from frozen-thawed red blood cells. We employ a concentration dependent permeability parameter to account for the varied glycerol transport rates of red blood cells over the wide range of glycerol concentrations encountered during deglycerolization. Additionally, variability of glycerol permeability is addressed by optimizing procedures to account for faster and slower responding cells within the population. These mathematically optimized procedures resulted in a significant reduction in hemolysis when compared to previous procedures that used a fixed value for permeability and did not account for cell variability. Our findings here indicate higher variability than anticipated within the cell population and between donors. Although ultra-rapid (< 1 min) removal of glycerol was not achieved, we achieved a significant reduction in processing times compared to the current standard. In addition to advancements in cryopreservation of blood products, new technologies were developed for applications in the extracorporeal treatment of sepsis. We presented a new hot embossing rapid prototyping approach for creation of high aspect ratio microfluidic devices in polycarbonate. We used a model system to test the effects of bifurcated microchannels on the removal of endotoxin from blood. We saw no significant effect of bifurcations on endotoxin removal, but reduction of channel width resulted in a significant increase in removal efficiency with up to 80% single pass clearance in the smallest width channel. This work forwards understanding on design of absorption-based blood perfusion devices to harness the unique flow properties of blood in microchannels.
Blood Processing Technologies for Cryopreserved Transfusion Products and Extracorporeal Treatment Applications
Type
Thesis
Year of Publication
2018
Volume
Ph.D.
Date Published
Jan. 1, 2018
Publisher
Oregon State University
Abstract