Biomedical applications of mesoscale magnetic particles
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Introduction The use of magnetic micro- and nanoparticles in biological and biomedical applications goes back nearly 100 years. In the early 20th century, Heilbronn and Seifritz used magnetic forces on iron and nickel microparticles embedded within slime molds and cellular cytoplasm to probe their rheological properties.1,2 More than 60 years ago, Nobel Laureate Francis Crick, along with Arthur Hughes, expanded on these studies using wellcharacterized iron oxide microparticles.3 In the decades since, the use of magnetic micro- and nanoparticles in biomedical applications has undergone rapid growth, with exponential growth in both publications and citations in this field since the early 2000s. Research in this area is growing at a remarkable pace. Novel applications that exploit the most fundamental principle of magnetism and magnetic particles—action at a distance—are being developed that have the potential to revolutionize fields as diverse as cancer therapy, gene therapy, developmental biology, and tissue engineering. Most magnetic particles used in biomedical applications are superparamagnetic iron oxides, particularly for in vivo applications. Iron oxide is well tolerated by living organisms; in fact, virtually all living organisms, including humans, store iron in the form of iron oxide. However, aggregations of magnetic particles circulating within the bloodstream of a human or animal can have catastrophic consequences, as the clusters can block the flow of blood. By coating superparamagnetic iron oxides
with biocompatible polymers such as dextran or polyethyleneglycol or synthesizing multiple superparamagnetic crystallites within a polymer matrix, it is possible to prevent particle aggregation (and the associated potential for embolism formation when the particles are introduced intravenously) as well as attenuate any immune response, facilitating longer circulation times. Here we explore both established and emerging biomedical applications of mesoscale magnetic particles.
Magnetic cell separation One of the most widely used applications for mesoscale magnetic particles is magnetic cell separation to isolate a specific cell population from a heterogeneous sample. Cells are labeled with antibody-conjugated magnetic particles targeted to specific proteins or peptides (antigens) displayed on the surface of the desired cell population. Magnetically labeled cells can then be separated from the rest of the (non-labeled) cell population using a high gradient magnetic separator (Figure 1). In 1990, Miltenyi et al.4 introduced a magnetic cell separation system that employed fluorescently labeled, antibodyconjugated magnetic microparticles in combination with a separation column filled with steel wool. A static magnetic field magnetizes the steel wool, enabling trapping of the magnetically labeled cells. With the magnetic field in place, unlabeled cells are washed through the column. After removing the magnetic field, the labeled cells are released from the steel wool in
Bettina Kozissnik, University of Florida, Gainesville,
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