The magnetic beads (MBs) technology is a burgeoning method that uses modified magnetic microspheres as carriers for targeted capture and enrichment. The key point of this technology is the preparation of specific MBs. Up to date, this technology has been widely used in immunoassays, cell separation, purification of biological macromolecules and molecular biology.
Structure and Components of Magnetic Beads (MBs)
MBs is a kind of artificially synthesized small spherical composite particles, containing polymer and iron components, which can be attracted by magnetic force. The particles impart the magnetic properties to the beads, allowing rapid and easy separation by the application of an external magnetic field. On the other hand, as to the polymer component, it stabilizes the magnetic particles and offers swelling ability and elasticity to the beads. Likewise, the polymer endows the particles with functional groups required for the desired applications.
The magnetic cores have different structures (Fig. 1). In one kind of beads, the magnetic core is homogeneously distributed in the volume of polymer matrix (Fig. 1c). Other kinds of cores are characterized by core–shell structure (polymer core–magnetic shell (Fig. 1a) or magnetic core–polymer shell (Fig. 1b)).
Fig.1 Schematic illustration of different structures of magnetic cores of MBs. (European Polymer Journal 2011, 47 (4), 542-559)
As regards to the components, metal oxides like γ-Fe2O3 or Fe3O4, are often preferred over pure metals (Fe, Co, and Ni) for the use as embedded magnetic particles because they are more stable. The polymer layer is always composed of natural polymer materials (such as gelatin, agarose), or synthetic polymer materials (such as polystyrene, polyvinyl chloride). Moreover, in order to fix the magnetic beads in/on the polymer matrix, various of functional groups like -NH2, -COOH, -OH, -CHO can be introduced into polymer chains to obtain different properties such as hydrophobicity/hydrophilicity, non-polarity/polarity and positive/negative charge, thus it can bind to different immune ligands for further applications.
Synthetic Methods
The magnetic properties of MBs are strongly influenced by the morphology and structure, thus the synthesis methods are dramatically important. By now, various physical, chemical and biological methods have been already developed. Among these, physical methods such as ball milling, plasma deposition, lithography etc. are mostly used for electronics and engineering applications. Chemical and biological synthesis methods are often used for biomedical applications. Most chemical synthesis methods are briefly listed as follows:
- Co-precipitation
- Thermal Decomposition
- Microemulsion
- Hydrothermal Synthesis
- Polyol method
- Sol-gel
Characteristics of Magnetic Beads (MBs)
- Uniformity
The size and shape of MB are uniform, the target substance can be effectively bound to the MB and behave consistently, ensuring strong enough magnetic responsiveness without sedimentation.
- Ferrimagnetic cores or Superparamagneticcores
Ferrimagnetic magnetic cores have a strong magnetic moment. They could retain this magnetic moment even the magnetic field is removed. As regards to superparamagnetic cores, they allow the MBs to appear strong magnetism for separation and purification under the action of external magnetic field. In contrast, when there is no magnetic field, the magnetism will disappear quickly and will not be magnetized.
- Versatility
Copolymerization or modification can be used to give a variety of reactive functional groups to the surface of MBs. The functional groups can be further connected to a variety of biologically active substances like immune proteins, biological enzymes and cells.
- Recognition Specificity
In most cases, there are two combination ways of MB and protein/antibody: covalent binding and adsorption binding. Covalent binding relies on the active groups on the surface of MB, such as -NH2, -CHO. The MB covalently react with -COOH on the Fc section of the antibody, showing good specificity and less non-specific adsorption.
Applications of Magnetic Beads (MBs)
MBs technology is an appealing technique developed in 1980s. Based on immunology, it combines the unique merits of curing reagents with the high specificity of immunological reaction. It covers pathology, physiology, pharmacology, microbiology, biochemistry, molecular genetics and other fields.
- Bio-separation
In biomedical and biological research, it is often advantageous to separate specific biological entities from their native environment so that concentrated samples may be prepared for subsequent analysis or other use, while the magnetic beads separation using biocompatible nanoparticles is one way to achieve this. With the aid of magnetic absorbents, the isolation of various macromolecules such as enzymes, enzyme inhibitors, DNA, RNA, antibodies, antigens, etc. and cells from different sources can be performed. The cells or biomolecules which are non-magnetic in nature can be attached to MBs and thus can be manipulated. This technique is more effective when using superparamagnetic cores because they only exhibit magnetic properties in a magnetic field.
- Immunoassay
Immunoassay is one of the most important analytical methods applied in pharmaceutical, clinical chemistry, and environmental fields. The main use of superparamagnetic MBs in the development of immunoassays and immunosensors is mainly beacause MBs possess various advantages that can improve the performance of this technique. For example, because of their small particle size and large specific surface area, MBs can capture more analytes and directly display enzyme color, fluorescence or isotope displayed on their surface. Antibody-coated MBs are freely suspended in the antigen containing milieu, leading to a faster detection speed, higher specificity and sensitivity.
- Magnetic resonance imaging
MRI is considered to be one of the most powerful techniques in diagnostics, clinical medicine and biomedical research. As contrasting agent, superparamagnetic iron oxide or paramagnetic macromolecule with different polymer coatings may be used.
- Targeted drug delivery
Targeted drug delivery through a magnetic field is an innovative new approach for drug release. The MBs are precisely accumulated only in the area to which the magnetic field is applied, such as the tumor location. Shortly after accumulation, drug molecules are gradually released, thus improving the therapeutic efficiency of the drugs by lowering the collateral toxic side effects on the healthy cells or tissues.
- Hyperthermia
Hyperthermia is a treatment aimed at raising the temperature of tumor cells to 40–43◦C. The key problem in hyperthermia is the difficulty to realize a uniform heating, that is, only the tumor region can be heated while the other healthy regions are not be affected. A recent modality is the magnetic beads-based hyperthermia, in which the MBs can be accumulated only in the tumor tissue and then be heated by applying an external AC magnetic field.
References
1. Philippova, O.; Barabanova, A.; et al.Magnetic polymer beads: Recent trends and developments in synthetic design and applications. European Polymer Journal 2011, 47 (4), 542-559.
2. Pankhurst, Q. A.; Connolly, J.; et al. Applications of magnetic nanoparticles in biomedicine. Journal of Physics D: Applied Physics 2003, 36 (13), R167-R181.
3. Blanco-Andujar, C.; Walter, A.; et al.Design of iron oxide-based nanoparticles for MRI and magnetic hyperthermia. Nanomedicine 2016, 11 (14), 1889-1910.
4. Salunkhe, A. B.; Khot, V. M.; et al.Magnetic hyperthermia with magnetic nanoparticles: a status review. Current topics in medicinal chemistry 2014, 14 (5), 572-594.