Sickle cell vaso-occlusive episodes correlate with the magnetic heterogeneity of red blood cells

Sickle cell disease (SCD) is a complex condition that results in low oxygen affinity and oxidative damage within red blood cells (RBCs), which contributes to serious complications such as vaso-occlusive episodes (VOEs). Given the well-established theoretical and experimental evidence that oxygenated hemoglobin is diamagnetic, whereas deoxygenated hemoglobin and methemoglobin are paramagnetic, this study aims to investigate whether RBCs from patients with SCD exhibit progressively increased magnetic susceptibility in correlation with disease severity. In this study, we employed cell tracking velocimetry (CTV) to perform single-cell analysis of RBC magnetic properties under both oxygenated and deoxygenated states. CTV quantifies the oxygen saturation of each cell by measuring their magnetically induced cell velocities in conjunction with known cell properties. Subsequent statistical analysis revealed that although the mean oxygen saturation of the RBCs from patients with SCD did not differ significantly from that of healthy donors, the magnetic velocities at the 1st and 99th percentile of RBC samples from patients with SCD were significantly reduced and elevated, respectively. These elevated and reduced velocities correlate directly to the magnetic susceptibility of the cell, which corresponds to the hemoglobin state. Moreover, we identified a correlation (P< .01) between magnetic heterogeneity in the top and bottom 1% and pain severity, particularly in patients with SCD experiencing acute VOEs. This study underscores the potential of RBC magnetic properties as biophysical markers for identifying the pain severity in patients with SCD and opening avenues for personalized therapeutic interventions.