Abstract
BackgroundIn the cryopreservation of blood, removing cryoprotectants from the cryopreserved blood safely and effectively is always being focused on. In our previous work, a dilution-filtration system was proposed to achieve the efficient clearance of cryoprotectants from the cryopreserved blood.MethodIn this study, a theoretical method is presented to optimize the diluent flow rate in the system to further reduce the osmotic damage to red blood cells (RBCs) and shorten the washing time necessary to remove cryoprotective agents (CPAs), based on a discrete mass transfer concept. In the method, the diluent flow rate is automatically adjusted by a program code in each cycle to maximize the clearance of CPAs, whereas the volume of RBCs is always maintained below the upper volume tolerance limit.ResultsThe results show that the optimized diluent flow rate can significantly decrease the washing time of CPAs. The washing time under the optimized diluent flow rate can be reduced by over 50%, compared to the one under the fixed diluent flow rate. In addition, the advantage of our method becomes more significant when the blood flow rate is lower, the dilution region volume is larger, the initial CPA concentration is higher, or the cell-swelling limit set by the system is smaller.ConclusionThe proposed method for the dilution-filtration system is an ideal solution for not only guaranteeing the volume safety of RBCs but also shortening the washing time of CPAs. In practice, the optimization strategies provided here will be useful in the rapid preparation of cryopreserved blood for clinical use.
Highlights
Cryoprotective agents (CPAs) are widely used in the cryopreservation of blood to protect red blood cells (RBCs) from cryoinjury [1,2,3]
The results show that the optimized diluent flow rate can significantly decrease the washing time of CPAs
The washing time under the optimized diluent flow rate can be reduced by over 50%, compared to the one under the fixed diluent flow rate
Summary
Cryoprotective agents (CPAs) are widely used in the cryopreservation of blood to protect red blood cells (RBCs) from cryoinjury [1,2,3] Due to their negative effects to the human body (e.g. DMSO is considered to be toxic, glycerol is responsible for the osmotic lysis of cells when the glycerolized RBCs are directly transfused), CPAs must be removed before clinical transfusion to patients [4,5,6,7]. There are two major criteria to weigh a method for removing CPAs: one is the osmotic damage to RBCs (or the recovery rate of RBCs) and the other is the washing time or the removal efficiency of the CPAs. A high recovery rate of RBCs can improve the treatment, and a short washing time can significantly reduce the waiting time of patients, especially during emergency treatment. A dilution-filtration system was proposed to achieve the efficient clearance of cryoprotectants from the cryopreserved blood
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