Magnetic nanoparticles

Magnetic single-core and multi-core particles

Magnetic nanoparticles (MNPs) have been studied from about 1930 when William Fuller Brown and Louis Néel discussed the concept of magnetic single-domain particles, since then, an active and large research field emerged. The definition of a single-domain particle implies that all spins in the particle have the same direction. MNPs of, for example, magnetite or maghemite are common iron oxides particles used in magnetic nanoparticle applications e.g. in biomedicine. Typically, a spherical magnetite particle with a core diameter below about 80 nm is in a single-domain state. Magnetic iron oxide nanoparticles with sizes from a few nanometers and multi-core composite particles with sizes up to several micrometers can be found in biomedical applications in the areas of diagnosis, therapy, actuating and imaging. Single-core magnetic nanoparticles can be coarsely divided into small particles that show internal magnetic relaxation (Néel relaxation) and larger particles that are thermally blocked. An ensemble of single-core particles, with a typical relaxation time shorter than the specific time scale of the measurement of the system, behaves as a superparamagnetic material and shows no hysteresis effect and no residual magnetization (remanence). On the other hand, an ensemble of thermally blocked particles has a magnetic relaxation time that is longer than the specific measurement time scale and both hysteresis and time dependent effects can be found in their response to an external magnetic field. Magnetic nanoparticles are often dispersed in a carrier liquid and in that case the particle magnetic moment can be decoupled from the physical particle rotation in the liquid (Néel relaxation) or have a particle moment that is physically locked in a specific particle direction. In the latter case, magnetic relaxation occurs at the same rate as the particle rotation in the liquid (Brownian relaxation). The parameters that determine whether we have Néel or Brownian relaxation of a nanoparticle system dispersed in the carrier liquid at given temperature, are the sizes and shapes of the nanoparticles, the magnetic material properties (through the magnetic anisotropy) and the viscous properties of the liquid. When the single core nanoparticles are physically anchored in a matrix of a multicore composite particle, Brownian relaxation of the individual nanoparticles is inhibited and magnetic relaxation is determined by the size (and shape) distribution of the single core nanoparticles via the mechanism of Néel relaxation. Both types of magnetic behaviour (Néel and Brownian relaxation) can be found in different biomedical applica-tions, such as in magnetic biosensor detection systems, or as local heat sources in magnetic hyperthermia to kill tumour cells, separation in immunoassay, drug delivery or as contrast substances in magnetic resonance imaging or magnetic particle imaging. Since the relaxation time and thereby the magnetic properties of magnetic nanoparticles can be changed by changing the size of the nanoparticles or using different kinds of magnetic materials, magnetic nanoparticles have been and will be very useful in many biomedical applications.

In order to optimise the use of nanoparticles it is of crucial importance to have a good control of the particle sizes for a specific used magnetic material and, equally, to understand how the structural and magnetic properties are interrelated with each other. Magnetic nanoparticles exhibit a dramatic change of properties when the dimensions are reduced to the nanoscale range. That reduction in size is responsible for new magnetic properties which are mainly determined by chemical composition, crystal structure, particle size and shape, magnetic inter-actions between particles and with the surrounding matrix. This justifies the importance of the nanoparticle size, shape and structural homogeneity, the robustness of the coatings and the preparation reproducibility. In the case of multi-core particles including several magnetic single-crystals, properties will also depend on the separation between particles and the degree of alignment, which will strongly affect the magnetic interactions.

In the NanoMag project we will synthesize different types of MNPs and analyse these particles with different characterization techniques. We will also study commercial magnetic nanoparticle systems that are already on the market today. We will then correlate the magnetic properties with the structural properties in order to get a self-consistent picture of the nanostructured materials and define standardization methods that can be used for analysing magnetic nanoparticle that shall be used in different applications.

Magnetic particle synthesis

Synthesis methods are nowadays focused on the preparation of nearly monodispersed nanoparticles with a relative size distribution width lower than 10%. One of these methods is the thermal decomposition in organic media of organic precursors that provides great size and shape control and allows fabrication of multifuntional single-core nanoparticles exhibiting different properties as a consequence of the combination of different materials in complex structures such as core/shell, heterodimers or with gradient composition. Recently, the synthesis of magnetic nanoparticles in water has achieved an important advance thanks to slight modifications of conventional methods such as the precipitation of Fe salts in base media or new methods such as the laser pyrolysis of aerosols that lead to a reduction in polydispersity from 40% down to 20%. Further modification of the nanoparticle surface is possible following different approaches depending on the shell composition (organic or inorganic) which is also determined by the nanoparticle application. Organic coatings are preferred for biomedical applications, covalently bonded to the nanoparticle surface to avoid loss during processing. Those particles consist of multi-core magnetic crystals surrounded by a polymer coating. However, commercial magnetic nanoparticle systems exist where the surface coatings are physically absorbed (for instance the Resovist and Endorem particle systems).

Single-core particles by definition contain only one single-domain crystal. The surface of the nano-particle is coated with stabilizing molecules and in many bio-medical applications also molecules that specifically can bind to different bio-targets. The mean sizes of a single-core nanoparticle are from a few nm’s up to about 50 nm depending on the surface layers. The magnetic crystal size can be from a few nm’s to about 30 nm (depending on the material in the single-core crystals and synthesis route). Crystal material in biomedical application is typical magnetite or maghemite or a mixture thereof. Particles with this size range can be obtained by thermal decomposition of organic precursors in organic media in the presence of a surfactant or by precipitation of an Fe(II) salt in water in the presence of a mild oxidant. A multi-core particle by definition contains several single-domain crystals positioned in different configurations. The single-domain crystals can be very densely packed in the particle, more loosely packed but homogenously distributed in the particle or in some cases positioned at the surface of the particles. The size of the single-core crystals is from a few nm’s up to 30 nm. The total particle size is from about 30 nm up to several microns. The material that surrounds the nanocrystals can be dextran or starch or other polymeric as well as monomeric material. The surface of the particles can further be modified by molecules for specific binding. Multi-core particles can be obtained directly by coprepitation of Fe salts in water in the presence of the stabilizing molecules (“one pot synthesis”) or by first synthesizing the uncoated MNPs and then coating them in a second step (“two pot synthesis”).

While the organic synthesis route intrinsically allows a more “controlled” formation of the nanoparticles leading to single crystalline particles with very narrow distribution in size and shape the nanoparticle formation from aqueous synthesis leads to broader size distributed particles with clustered cores due to the high local supersaturation at which particles formation occurs (i.e. in a “less controlled” way) which is intrinsically connected to this synthesis route. However, the aqueous synthesis route is fast, cheap and is conducted at room or slightly elevated temperature. If the process is optimized appropriately the synthesis of high quality magnetic nanoparticles is feasible and such particles are nowadays of practical relevance in biomedical applications, for example as contrast agents for diagnostic MR imaging. Further purification or separation steps after the synthesis allow obtaining narrow distributed particles with defined properties. In contrast, the organic synthesis is typically conducted at high temperatures and requires the use of toxic iron precursors. After the synthesis the nanoparticles have to be transferred into an aqueous phase under complete removal of any organic solvents or residues which is of outmost importance especially for most biomedical applications.

Project Partners

Project partners


	This project has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 604448