Graduate Thesis Or Dissertation


Improving the post-thaw processing of cryopreserved red blood cells using a combined approach of mathematical modeling and microfluidics Public Deposited

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  • This study lays the groundwork on potential techniques that could be employed to improve the post-thaw wash processing of cryopreserved human red blood cells. Transfusion of red blood cells is one of the most commonly practiced procedures in clinical medicine. Millions of red blood cell units are transfused to patients every year. The current method of preservation of red blood cells only allows a short refrigerated shelf life of 6 weeks, which causes logistical issues and frequent shortages during the time when donor availability is decreased. Cryopreserving red blood cells in the presence of 40% w/v glycerol extends the stable shelf life of red blood cells to 10 years. The long stable shelf life allows stockpiling of transfusable RBC units. Although this preservation method is clinically approved and routinely performed, the use of cryopreservation in blood banking is limited to only autologous and rare units. One of the main reasons for this limitation is the time consuming post-thaw wash process required to remove the glycerol before the unit can be used for transfusion. The need to plan the amount of washed units makes the use of cryopreserved red blood cells for unscheduled transfusion particularly challenging. In this work, we have attempted to improve the efficiency of the post-thaw removal process by using modern scientific approaches. Using the mathematical model for cell membrane transport, we have demonstrated that glycerol can be rapidly extracted from red blood cells without excessively damaging the cell membrane in a batch process. This rapid glycerol removal approach was then applied into a membrane based microfluidic platform for adaptation into an efficient continuous process. A mathematical model of the membrane based microfluidic device capable of predicting the transport of water and solutes was developed to assist in the design of an efficient deglycerolization process. Glycerol removal experiments using a prototype of the device validated model predictions and demonstrated successful partial continuous deglycerolization of cryopreserved red blood cells. Simulations generated using the mathematical model shows that it is possible to rapidly deglycerolize cryopreserved red blood cells in a continuous process to levels acceptable for transfusion. With the potential for efficient continuous post-thaw wash processing, it is hoped that cryopreserved red blood cells may become a more attractive option for use in clinical therapy
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