Fig. 1. Potential role of ferritin during inflammation following COVID-19 infection. Active ferritin production by macrophages and cytokines may lead to hyperferritinemia, which in turn, might promote the production of several pro-inflammatory (IL-1β) and anti-inflammatory cytokines (IL-10) [9,10].

Magnetic cell separation has become a popular technique to enrich or deplete cells of interest from a heterogeneous cell population. One important aspect of magnetic cell separation is the degree to which a cell binds paramagnetic material. It is this paramagnetic material that imparts a positive magnetophoretic mobility to the target cell, thus allowing effective cell separation. A mathematical relationship has been developed to correlate magnetic labeling to the magnetophoretic mobility of an immunomagnetically labeled cell. Four parameters have been identified that significantly affect magnetophoretic mobility of an immunomagnetically labeled cell: the antibody binding capacity (ABC) of a cell population, the secondary antibody amplification (psi), the particle-magnetic field interaction parameter (DeltachiV(m)), and the cell diameter (D(c)). The ranges of these parameters are calculated and presented along with how the parameters affect the minimum and maximum range of magnetophoretic mobility. A detailed understanding of these parameters allows predictions of cellular magnetophoretic mobilities and provides control of cell mobility through selection of antibodies and magnetic particle conjugates.

The optimization of a purely negative depletion, enrichment process for circulating tumor cells, CTC's, in the peripheral blood of Head and Neck cancer patients is presented. The enrichment process uses a red cell lysis step followed by immunomagnetic labeling, and subsequent depletion, of CD45 positive cells. A number of relevant variables are quantified, or attempted to be quantified, which control the performance of the enrichment process. Six different immunomagnetic labeling combinations were evaluated as well as the significant difference in performance with respect to the blood source: buffy coats purchased from the Red Cross, fresh, peripheral blood from normal donors, and fresh peripheral blood from human cancer patients. After optimization, the process is able to reduce the number of normal blood cells in a cancer patient's blood from 4.05 × 109 to 8.04 × 103 cells/ml and still recover, on average, 2.32 CTC per ml of blood. For all of the cancer patient blood samples tested in which CTC were detected (20 out of 26 patients) the average recovery of CTCs was 21.7 per ml of blood, with a range of 282 to 0.53 CTC per ml of blood. Unlike a majority of other published studies, this study focused on quantifying as many factors as possible to facilitate both the optimization of the process as well as provide information for future performance comparisons. The authors are not aware any other reported study which has achieved the performance reported here (a 5.76 log10) in a purely negative enrichment mode of operation. Such a mode of operation of an enrichment process provides significant flexibility in that it has no bias with respect to what attributes define a CTC; thereby allowing the researcher or clinician to use any maker they choose to define whether the final, enrich product contains CTC's or other cell type relevant to the specific question (i.e. does the CTC have predominately epithelia or mesenchymal characteristics?).

The existence of unpaired electrons in the four heme groups of deoxy and methemoglobin (metHb) gives these species paramagnetic properties as contrasted to the diamagnetic character of oxyhemoglobin. Based on the measured magnetic moments of hemoglobin and its compounds, and on the relatively high hemoglobin concentration of human erythrocytes, we hypothesized that differential migration of these cells was possible if exposed to a high magnetic field. With the development of a new technology, cell tracking velocimetry, we were able to measure the migration velocity of deoxygenated and metHb-containing erythrocytes, exposed to a mean magnetic field of 1.40 T and a mean gradient of 0.131 T/mm, in a process we call cell magnetophoresis. Our results show a similar magnetophoretic mobility of 3.86 x 10(-6) mm(3) s/kg for erythrocytes with 100% deoxygenated hemoglobin and 3.66 x 10(-6) mm(3) s/kg for erythrocytes containing 100% metHb. Oxygenated erythrocytes had a magnetophoretic mobility of from -0.2 x 10(-6) mm(3) s/kg to +0.30 x 10(-6) mm(3) s/kg, indicating a significant diamagnetic component relative to the suspension medium, in agreement with previous studies on the hemoglobin magnetic susceptibility. Magnetophoresis may open up an approach to characterize and separate cells for biochemical analysis based on intrinsic and extrinsic magnetic properties of biological macromolecules.