Continuous-Flow Magnetic Fractionation of Red Blood Cells Based on Hemoglobin Content and Oxygen Saturation—Clinical Blood Supply Implications and Sickle Cell Anemia Treatment

Abstract

Approximately 36,000 units of red blood cells (RBCs) are used every day in the U.S. and there is a great challenge for hospitals to maintain a reliable supply, given the 42-day expiration period from the blood donation date. For many years, research has been conducted to develop ex vivo storage solutions that limit RBC lysis and maintain a high survival rate of the transfused cells. However, little attention is directed towards potential fractionation methods to remove unwanted cell debris or aged blood cells from stored RBC units prior to transfusion, which could not only expand the ex vivo shelf life of RBC units but also avoid adverse events in transfused patients. Such fractionation methods could also limit the number of transfusions required for treating certain pathologies, such as sickle cell disease (SCD). In this work, magnetic fractionation is studied as a potential technology to fractionate functional and healthy RBCs from aged or sickle cells. It has been reported that during ex vivo RBC storage, RBCs lose hemoglobin (Hb) and lipid content via formation of Hb-containing exosomes. Given the magnetic character of deoxygenated- or met-Hb, in this work, we propose the use of a quadrupole magnetic sorter (QMS) to fractionate RBCs based on their Hb content from both healthy stored blood and SCD blood. In our QMS, a cylindrical microchannel placed inside the center of the quadrupolar magnets is subjected to high magnetic fields and constant field gradients (286 T/m), which causes the deflection of the paramagnetic, Hb-enriched, and functional RBCs from their original path and their collection into a different outlet. Our results demonstrated that although we could obtain a significant difference in the magnetic mobility of the sorted fractions (corresponding to a difference in more than 1 pg of Hb per cell), there exists a tradeoff between throughput and purity. Therefore, this technology when optimized could be used to expand the ex vivo shelf life of RBC units and avoid adverse events in transfused individuals or SCD patients requiring blood exchange therapy.