Magnetic nanoparticles

Magnetic nanoparticles are a class of nanoparticle which can be manipulated using magnetic field gradients. Such particles commonly consist of magnetic elements such as iron, nickel and cobalt and their chemical compounds. While nanoparticles are smaller than 1 micrometer in diameter (typically 5–500 nanometers), the larger microbeads are 0.5–500 micrometer in diameter. Magnetic nanoparticle clusters which are composed of a number of individual magnetic nanoparticles are known as magnetic nanobeads with a diameter of 50–200 nanometers. The magnetic nanoparticles have been the focus of much research recently because they possess attractive properties which could see potential use in catalysis including nanomaterial-based catalysts, biomedicine and tissue specific targeting, magnetically tunable colloidal photonic crystals, microfluidics, magnetic resonance imaging, magnetic particle imaging, data storage, environmental remediation, nanofluids, and optical filters, defect sensor and cation sensors.

Properties

The physical and chemical properties of magnetic nanoparticles largely depend on the synthesis method and chemical structure. In most cases, the particles range from 1 to 100 nm in size and may display superparamagnetism.

Types of magnetic nanoparticles

Oxides: ferrites

Ferrite nanoparticles or iron oxide nanoparticles (iron oxides in crystal structure of maghemite or magnetite) are the most explored magnetic nanoparticles up to date. Once the ferrite particles become smaller than 128 nm they become superparamagnetic which prevents self agglomeration since they exhibit their magnetic behavior only when an external magnetic field is applied. The magnetic moment of ferrite nanoparticles can be greatly increased by controlled clustering of a number of individual superparamagnetic nanoparticles into superparamagnetic nanoparticle clusters, namely magnetic nanobeads. With the external magnetic field switched off, the remanence falls back to zero. Just like non-magnetic oxide nanoparticles, the surface of ferrite nanoparticles is often modified by surfactants, silica, silicones or phosphoric acid derivatives to increase their stability in solution.

TEM image of a maghemite magnetic nanoparticle cluster with silica shell.

Ferrites with a shell

The surface of a maghemite or magnetite magnetic nanoparticle is relatively inert and does not usually allow strong covalent bonds with functionalization molecules. However, the reactivity of the magnetic nanoparticles can be improved by coating a layer of silica onto their surface. The silica shell can be easily modified with various surface functional groups via covalent bonds between organo-silane molecules and silica shell. In addition, some fluorescent dye molecules can be covalently bonded to the functionalized silica shell.

Ferrite nanoparticle clusters with narrow size distribution consisting of superparamagnetic oxide nanoparticles (~ 80 maghemite superparamagnetic nanoparticles per bead) coated with a silica shell have several advantages over metallic nanoparticles:

• Higher chemical stability (crucial for biomedical applications)
• Narrow size distribution (crucial for biomedical applications)
• Higher colloidal stability since they do not magnetically agglomerate
• Magnetic moment can be tuned with the nanoparticle cluster size
• Retained superparamagnetic properties (independent of the nanoparticle cluster size)
• Silica surface enables straightforward covalent functionalization

Metallic

Metallic nanoparticles may be beneficial for some technical applications due to their higher magnetic moment whereas oxides (maghemite, magnetite) would be beneficial for biomedical applications. This also implies that for the same moment, metallic nanoparticles can be made smaller than their oxide counterparts. On the other hand, metallic nanoparticles have the great disadvantage of being pyrophoric and reactive to oxidizing agents to various degrees. This makes their handling difficult and enables unwanted side reactions which makes them less appropriate for biomedical applications. Colloid formation for metallic particles is also much more challenging.

Cobalt nanoparticle with graphene shell (note: The individual graphene layers are visible)

Metallic with a shell

The metallic core of magnetic nanoparticles may be passivated by gentle oxidation, surfactants, polymers and precious metals. In an oxygen environment, Co nanoparticles form an anti-ferromagnetic CoO layer on the surface of the Co nanoparticle. Recently, work has explored the synthesis and exchange bias effect in these Co core CoO shell nanoparticles with a gold outer shell. Nanoparticles with a magnetic core consisting either of elementary Iron or Cobalt with a nonreactive shell made of graphene have been synthesized recently. The advantages compared to ferrite or elemental nanoparticles are:

• Higher magnetization
• Higher stability in acidic and basic solution as well as organic solvents
• Chemistry on the graphene surface via methods already known for carbon nanotubes

Synthesis

The established methods of magnetic nanoparticle synthesis include:

Co-precipitation

Main article: Co-precipitation

Co-precipitation is a facile and convenient way to synthesize iron oxides (either Fe₃O₄ or γ-Fe₂O₃) from aqueous Fe²⁺/Fe³⁺ salt solutions by the addition of a base under inert atmosphere at room temperature or at elevated temperature. The size, shape, and composition of the magnetic nanoparticles very much depends on the type of salts used (e.g.chlorides, sulfates, nitrates), the Fe²⁺/Fe³⁺ ratio, the reaction temperature, the pH value and ionic strength of the media, and the mixing rate with the base solution used to provoke the precipitation. The co-precipitation approach has been used extensively to produce ferrite nanoparticles of controlled sizes and magnetic properties. A variety of experimental arrangements have been reported to facilitate continuous and large–scale co–precipitation of magnetic particles by rapid mixing. Recently, the growth rate of the magnetic nanoparticles was measured in real-time during the precipitation of magnetite nanoparticles by an integrated AC magnetic susceptometer within the mixing zone of the reactants.

Thermal decomposition

Main article: Thermal decomposition

Magnetic nanocrystals with smaller size can essentially be synthesized through the thermal decomposition of organometallic compounds in high-boiling organic solvents containing stabilizing surfactants.

Microemulsion

Main article: Microemulsion

Using the microemulsion technique, metallic cobalt, cobalt/platinum alloys, and gold-coated cobalt/platinum nanoparticles have been synthesized in reverse micelles of cetyltrimethlyammonium bromide, using 1-butanol as the cosurfactant and octane as the oil phase.,

Flame spray synthesis

Using flame spray pyrolysis and varying the reaction conditions, oxides, metal or carbon coated nanoparticles are produced at a rate of > 30 g/h .

Various flame spray conditions and their impact on the resulting nanoparticles

Operational layout differences between conventional and reducing flame spray synthesis

Applications

A wide variety of applications have been envisaged for this class of particles which include:

Medical diagnostics and treatments

Magnetic nanoparticles are used in an experimental cancer treatment called magnetic hyperthermia in which the fact that nanoparticles heat when they are placed in an alternative magnetic field is used.

Affinity ligands such as epidermal growth factor (EGF), folic acid, aptamers, lectins etc. can be attached to the magnetic nanoparticle surface with the use of various chemistries. This enables targeting of magnetic nanoparticles to specific tissues or cells. This strategy is used in cancer research to target and treat tumors in combination with magnetic hyperthermia or nanoparticle-delivered cancer drugs.

Another potential treatment of cancer includes attaching magnetic nanoparticles to free-floating cancer cells, allowing them to be captured and carried out of the body. The treatment has been tested in the laboratory on mice and will be looked at in survival studies.

Magnetic nanoparticles can be used for the detection of cancer. Blood can be inserted onto a microfluidic chip with magnetic nanoparticles in it. These magnetic nanoparticles are trapped inside due to an externally applied magnetic field as the blood is free to flow through. The magnetic nanoparticles are coated with antibodies targeting cancer cells or proteins. The magnetic nanoparticles can be recovered and the attached cancer-associated molecules can be assayed to test for their existence.

Magnetic nanoparticles can be conjugated with carbohydrates and used for detection of bacteria. Iron oxide particles have been used for the detection of Gram negative bacteria like Escherichia coli and for detection of Gram positive bacteria like Streptococcus suis

In an online news story article from Harvard Medical School posted by Jake Miller on Wednesday, March 21, 2012,:

"Researchers from Harvard Medical School and Massachusetts General Hospital have developed a magnetic nanoparticle-based MRI technique for predicting whether—and when—subjects with a genetic predisposition for diabetes will develop the disease. While done initially in mice, preliminary data show that the platform can be used in people as well, so far to distinguish patients that do or do not have pancreas inflammation. “This research is about predicting Type-1 diabetes, and using that predictive power to figure out what is different between those who get it and those who don’t get it,” said Diane Mathis, Morton Grove-Rasmussen Professor of Immunohematology in the Department of Microbiology and Immunobiology and, along with Christophe Benoist, Morton Grove-Rasmussen Professor of Immunohematology, co-senior author of the paper. The results were published online in Nature Immunology on Feb. 26, 2012. According to first author Wenxian Fu, a research fellow in the Mathis-Benoist lab, the group was surprised that the diagnostic window—from six to 10 weeks of age— was so early, and so brief. This shows that the progression of the disease, at least in this animal model, is determined very early in life, and that diabetes does not require an additional trigger such as a secondary infection or environmental stress ..."

Magnetic immunoassay

Magnetic immunoassay (MIA) is a novel type of diagnostic immunoassay utilizing magnetic nanobeads as labels in lieu of conventional, enzymes, radioisotopes or fluorescent moieties. This assay involves the specific binding of an antibody to its antigen, where a magnetic label is conjugated to one element of the pair. The presence of magnetic nanobeads is then detected by a magnetic reader (magnetometer) which measures the magnetic field change induced by the beads. The signal measured by the magnetometer is proportional to the analyte (virus, toxin, bacteria, cardiac marker,etc.) quantity in the initial sample.

Waste water treatment

Thanks to the easy separation by applying a magnetic field and the very large surface to volume ratio, magnetic nanoparticles have a good potential for treatment of contaminated water. In this method, attachment of EDTA-like chelators to carbon coated metal nanomagnets results in a magnetic reagent for the rapid removal of heavy metals from solutions or contaminated water by three orders of magnitude to concentrations as low as micrograms per Litre. Magnetic nanobeads or nanoparticle clusters composed of FDA-approved oxide superparamagnetic nanoparticles (e.g. maghemite, magnetite) hold much potential for waste water treatment since they express excellent biocompatibility which concerning the environmental impacts of the material is an advantage compared to metallic nanoparticles.

Chemistry

Magnetic nanoparticles are being used or have the potential use as a catalyst or catalyst supports. In chemistry, a catalyst support is the material, usually a solid with a high surface area, to which a catalyst is affixed. The reactivity of heterogeneous catalysts occurs at the surface atoms. Consequently great effort is made to maximize the surface area of a catalyst by distributing it over the support. The support may be inert or participate in the catalytic reactions. Typical supports include various kinds of carbon, alumina, and silica.

Biomedical imaging

There are many applications for iron-oxide based nanoparticles in concert with magnetic resonance imaging. Magnetic CoPt nanoparticles are being used as an MRI contrast agent for transplanted neural stem cell detection.

Information storage

Research is going into the use of using MNPs for magnetic recording media. The most promising candidate for high-density storage is the face-centered tetragonal phase FePt alloy. Grain sizes can be as small as 3 nanometers. If it's possible to modify the MNPs at this small scale, the information density that can be achieved with this media could easily surpass 1 Terabyte per square inch.

Genetic engineering

Magnetic nanoparticles can be used for a variety of genetics applications. One application is the isolation of mRNA. This can be done quickly – usually within 15 minutes. In this particular application, the magnetic bead is attached to a poly T tail. When mixed with mRNA, the poly A tail of the mRNA will attach to the bead's poly T tail and the isolation takes place simply by placing a magnet on the side of the tube and pouring out the liquid. Magnetic beads have also been used in plasmid assembly. Rapid genetic circuit construction has been achieved by the sequential addition of genes onto a growing genetic chain, using nanobeads as an anchor. This method has been shown to be much faster than previous methods, taking less than an hour to create functional multi-gene constructs in vitro.

See also

• Magnetic chemistry
• Iron oxide nanoparticles

External links

• FML – Functional Materials Laboratory of the ETH Zürich
• Properties and use of magnetic nanoparticle clusters (magnetic nanobeads)
• Magnetic nanoparticles target human cancer cells
• Magnetic Nanoparticles Remove Ovarian Cancer Cells from the Abdominal Cavity
• Wiedwald, U. and Ziemann, P. (Ed.): Properties and applications of magnetic nanoparticles, Thematic Series in the Open Access Beilstein Journal of Nanotechnology.