(97g) Label-Free Magnetic Isolation of Red Blood Cells Based on Their Differential Iron Cargo

Iron (Fe) is one of the top ten most abundant elements in the universe and an essential trace element for nearly all forms of life. Nature provides a wide range of proteins and prosthetic groups to tightly control Fe within cells, with hemoglobin (Hb) being the most well-known. Fe’s ability to accept or donate electrons (and in the case of Fe in Hb, the interchanging of a covalent bond with O₂ and an ionic form of Fe) results in the potential to transition to an unpaired electron state and acquisition of paramagnetic properties. In this work, we aim to develop novel tools to analyze the intracellular Fe/Hb content in red blood cells (RBCs) using magnetophoresis and to exploit the differential Hb state and Hb content of aged and dysfunctional RBCs to isolate these cells from healthy, normal, functional RBCs in blood. Our previous studies have demonstrated a relationship between the magnetic properties of RBCs and their maturity (ex vivo storage time) and to disease states (hematologic diseases like anemia and sickle cell disease) [1,2]. To achieve separation, we will use our Quadrupole Magnetic Sorter (QMS), featuring a 10.2 mm aperture and a quadrupole magnet array generating a 1.36 T field with a 286 T/m constant magnetic field gradient [3]. In the presence of the magnetic field, the healthier RBCs should experience a stronger magnetic force and be deflected into a buffer stream, allowing for their separation from non-healthy cells and further enrichment at the outlet. We will assess the influence of flow rate, flow ratio, and rod diameter on the efficiency of healthy RBC recovery using experimental and numerical modeling approaches. We aim to use this technology to: i) isolate healthy, Hb-enriched cells from damaged and Fe-deficient cells in stored RBC units, in order to extend their shelf life beyond the current 6 weeks; and ii) design novel transfusion therapies that can benefit patients requiring repeated RBC exchange transfusions, since this technique can discard detrimental RBCs with low/abnormal Hb from the patient and to recycle the healthy, endogenous RBCs back to the individual. This will also reduce the number and volume of RBC units transfused to patients for their treatment, increasing the availability of blood units for other therapies. Thus, this technology can revolutionize the separation science of blood components and can help increase the supply of high-quality blood products, potentially extend the ex vivo storage lifetime of aged RBC units and revolutionize transfusion therapies with minimal harmful consequences to patients.

[1] Weigand, M.; Gomez-Pastora, J.; Strayer, J.; Wu, X.; Choe, H.; Lu, S.; Plencner, E.; Landes, K.; Palmer, A.; Zborowski, M.; Desai, P.; Chalmers, J. The Unique Magnetic Signature of Sickle Red Blood Cells: A Comparison Between the Red Blood Cells of Transfused and Non-Transfused Sickle Cell Disease Patients and Healthy Donors. IEEE Transactions on Biomedical Engineering 69 (2022) 3582-3590.

[2] Gómez-Pastora, J.; Kim, J.; Weigand, M.; Palmer, A.F.; Yazer, M.; Desai, P.C.; Zborowski, M.; Chalmers, J.J. Potential of Cell Tracking Velocimetry as an Economical and Portable Hematology Analyzer. Scientific Reports 12 (2022) 1-12.

[3] Weigand, M.; Gomez-Pastora, J.; Palmer, A.; Zborowski, M.; Desai, P.; Chalmers, J. Continuous-Flow Magnetic Fractionation of Red Blood Cells Based on Hemoglobin Content and Oxygen Saturation—Clinical Blood Supply Implications and Sickle Cell Anemia Treatment. Processes 10 (2022) 927.