Development of a High-Throughput Magnetic Separation Device for Malaria-Infected Erythrocytes

Abstract

This study describes a non-dilutive high-gradient magnetic separation (HGMS) device intended to continuously remove malaria-infected red blood cells (iRBCs) from the circulation. A mesoscale prototype device with disposable photo-etched ferromagnetic grid and reusable permanent magnet was designed with a computationally-optimized magnetic force. The prototype device was evaluated in vitro using a non-pathogenic analog for malaria-infected blood, comprised of 24% healthy RBCs, 6% human methemoglobin RBCs (metRBCs), and 70% phosphate buffer solution (PBS). The device provided a 27.0 ± 2.2% reduction of metRBCs in a single pass at a flow rate of 77 μL min^-1. This represents a clearance rate over 380 times greater throughput than microfluidic devices reported previously. These positive results encourage development of a clinical scale system that would economize time and donor blood for treating severe malaria.

Keywords: Apheresis; Magnetics; Malaria; Microfluidic; Modeling; Separation; Treatment.

FIGURE 1

Schematic of mesoscale continuous HGMS device. (A) Assembly illustrating the construction of the main components (B) exploded view, (C) schematic of the flow passage (section A-A) indicating hRBC (red) and magnetic RBC (brown), and (D) the prototype used in this study.

FIGURE 2

Blood flow path within high-gradient magnetic separator (A) isometric, (B) side, and (C) top view.

FIGURE 3

Simulated magnetic field density field (B) for the mesoscale HGMS device with a single 76.2 mm wide × 25.4 mm thick N40 permanent magnet in cross-section. The black dashed box indicates the flow domain where magnetic force was calculated.

FIGURE 4

Simulation results comparing waste channel width of 1.0, 0.4, 0.1, 0.04, and 0.01 mm. Gray dots are hRBCs, black dots are iRBCs.

FIGURE 5

Velocity streamlines created via ANSYS within inlet manifold a) and b) bottom view.

FIGURE 6

Experimental setup for the mesoscale continuous HGMS prototype verification.

FIGURE 7

Comparison of treatment of hypothetical malaria patient with and without HGMS. Black line indicates conventional exchange transfusion with drug therapy (black). The blue curve indicates the addition of HGMS. Blood volume replacement adjusted to achieve the same final hematocrit of 30% (■). Solid circle (●) indicates parasitemia reduced to 1%.