**5.1 Biomedical applications**

Magnetite nanoparticles represent an intriguing material for various researchers, due to their biomedical applications in the treatment of solid tumours (Gomez-Lopera, 2006) or contrast agents (Frija et al., 2004). In order to be efficient in biological applications, colloidal suspensions of magnetic particles must have long-time stability and the magnetic core must respond to an external magnetic field that directs the particle to a desired location. Colloidal stability is influenced by the size, structure and composition of the particle with a narrow dimensional controlled polydispersity. All these requirements lead to magnetic fluids that flow through the capillaries that provide a maximum diameter of 1.4 µm. The colloidal stability of magnetite particles is insured by coating the magnetic core with a monomer or (co)polymer, as surfactant, to have the particles dispersed in a carrier fluid.

Magnetite (Fe3O4) nanoparticles that exhibit excellent magnetic saturation (~78 emu/g) are desirable for these applications due to the strong ferromagnetic behaviour, lower sensitivity to oxidation and relatively low toxicity as compared to many other materials (e.g., iron, nickel and cobalt) (O'Brien, 2003). Magnetite has been intensively studied in the past decades due to its application in biotechnology and biomedicine: cancer treatment (Jordan et al, 2001, Jordan et al., 1999, Herrera et al., 2008), sensors, catalysis, storage media, clinical diagnosis and treatment of some diseases (Torchilin et al., 2001, Jordan et al., 2001).

Especially for biomedical application, the particles must present some specific properties like:

1. Magnetic properties

156 Materials Science and Technology

The synthesis methods for magnetic particles with magnetite core and monomer/polymer shell, named core-shell magnetic particles, are presented in the literature (Table 1). The surfactant used must have functional groups to interact by hydrogen or covalent bonds (Figure 4) with the hydroxilic groups from pre-formed magnetite surface (trialkoxysilanes or compounds with carboxylic groups) (Kazufumi et al., 2008; Wormuth, 2001; Mondini et al., 2008; Shukla et al., 2007; Wilson et al., 2005) and other functional groups to permit their

dispersing in a transport fluid (aminic, epoxy, vinyl groups, etc.).

(a) (b)

**5. Applications of micro- and nanomagnetite particles** 

treatment and as drug and nucleic acids carriers (Lubbe et al., 1996).

are biomedical applications, catalysis and industrial applications.

(co)polymer, as surfactant, to have the particles dispersed in a carrier fluid.

and shell.

**5.1 Biomedical applications** 

Fig. 4. Schematic representation of hydrogen bond (a) and covalent bond (b) between core

The high interest for magnetic particles (ferrofluids, nanospheres and microspheres) can be explained due to their various applications, e.g., in magnetic storage devices or magnetic cell separations (Goya et al., 2003). The magnetic particles were also tested for cancer

Top domains for multiple applications of micro- and nanoparticles with magnetic properties

Magnetite nanoparticles represent an intriguing material for various researchers, due to their biomedical applications in the treatment of solid tumours (Gomez-Lopera, 2006) or contrast agents (Frija et al., 2004). In order to be efficient in biological applications, colloidal suspensions of magnetic particles must have long-time stability and the magnetic core must respond to an external magnetic field that directs the particle to a desired location. Colloidal stability is influenced by the size, structure and composition of the particle with a narrow dimensional controlled polydispersity. All these requirements lead to magnetic fluids that flow through the capillaries that provide a maximum diameter of 1.4 µm. The colloidal stability of magnetite particles is insured by coating the magnetic core with a monomer or

Magnetite (Fe3O4) nanoparticles that exhibit excellent magnetic saturation (~78 emu/g) are desirable for these applications due to the strong ferromagnetic behaviour, lower sensitivity to oxidation and relatively low toxicity as compared to many other materials (e.g., iron, In order to respond to an external magnetic field magnetic particles must have a large saturation magnetization, an important characteristic for targeted drug delivery systems and contrast agents for MRI (magnetic resonance imaging) (Bulte, 2006, Modo et al., 2005, Burtea et al., 2005, Boutry et al., 2006, Babes et al., 1999, Sonvico et al., 2005, Corot et al., 2006, Corot et al., 2007)). In the presence of an external magnetic field the magnetic moments are oriented with the field (Figure 5). Magnetic nanoparticles modified with organic molecules and used for biomedical applications can be magnetically controlled by applying an external magnetic field.

2. Stability in colloidal dispersions

The stability of the particles can be enhanced by coating with biocompatible surfactants (Ma et al., 2003) capable of interactions with hydroxyl groups on the magnetite surface and ensuring the ferrofluid stability. The coating agent should have specific functional groups for further functionalization for specific applications.

3. Nano- sized dimensions

The magnetic particles with biomedical applications must have controllable sizes ranging from a few nanometres up to tens of nanometres, smaller than those of a cell (10–100 μm) (Pankhurst et al., 2003), a virus (20–450 nm), a protein (5–50 nm) or a gene (2 nm wide and 10–100 nm long) because they can 'get close' to a biological entity of interest. Magnetic particles encapsulated into a polymer matrix with dimensions more than 1 µm or submicron is more effective in the bloodstream through the veins or arteries (Lazaro et al., 2005).

4. Oxidation stability

Metals such as Fe, Co and Ni, which oxidize easily, are not recommended in biomedical uses due to the higher probability of oxidizing inside human bodies. This problem can be solved using magnetite particles that not only present a greater stability to oxidation, but can be coated with different specific surfactants, increasing their resistance to oxidation.

The polymers used as surfactants can be synthetic or natural molecules able to yield stable colloidal suspensions designed for drug delivery. Nevertheless, synthetic polymers have the advantage of high purity and reproducibility over natural polymers.

The colloidal magnetic particles obtained for biomedical application (Asmatulu et al., 2005) as targeted drug delivery will have to pass through a few mechanisms of releasing drug molecules: diffusion, degradation of polymeric shell, swelling of the shell followed by diffusion of active principle outside the magnetic particle. The diffusion involves drug

Tailored and Functionalized Magnetite Particles for Biomedical and Industrial Applications 159

particles (Mosso et al., 1973, Rand et al., 1976, Gordon et al., 1979, Rand et al., 1981, Borrelli et al., 1984, Hase et al., 1990, Suzuki et al., 1990, Chan et al., 1993, Matsuki et al., 1994, Mitsumori et al., 1994, Suzuki et al., 1995, Moroz et al., 2001, Jones et al., 2002). The hyperthermia procedure involves the dispersion of the magnetic particles throughout the target tissue, followed by applying an AC magnetic field with specific parameters (frequency, strength); the magnetization of the particles is continuously reversed, which translates into a conversion from magnetic to thermal energy and causes the heating of particles. The tumour is destroyed if the temperature is maintained above the therapeutic

The bisphosphonate modified magnetite nanoparticles were used as agents to remove uranyl ions (e.g., UO22+) in vivo from water or blood (Wang et al., 2006). The authors synthesized a bisphosphonate derivative, DA-BP, which modifies the magnetite nanoparticles for the successful decorporation of the radioactive metal from blood due to the chelating effect (Fukuda, 2005). Starting from this study, a protocol that allows the detection and recovery of other heavy metal toxins from the biological systems has been

Coated magnetite particles with magnetic resonance, fluorescent imaging and drug delivery applications were obtained (Kim et al., 2008). The particles obtained are monodisperse, with dimensions smaller than 100 nm, coated with silica shell using cetyltrimethylammonium bromide as surfactant for the transfer of hydrophobic nanocrystals to aqueous media and also as organic template in the sol-gel reaction. The silica-Fe3O4 particles were functionalized

Magnetite particles (nanoparticles with 5–300 nm or microparticles with 300–5,000 nm) have been surface functionalized and used as biosensors to recognize specific molecular targets. Three types of biosensors, (i) magnetic relaxation witches, (ii) magnetic particle relaxation sensors, and (iii) magnetoresistive sensors, were coated with different biosensing principles and magnetic materials for instrumentation (Josephson, 2009). Magnetic relaxation switch assay-sensors are based on the effects of the magnetic particles exert on water proton relaxation rates. Magnetic particle relaxation sensors determine the relaxation of the magnetic moment within the magnetic particle. Magnetoresistive sensors detect the presence of magnetic particles on the surface of electronic devices and are sensitive to

Magnetic resonance imaging (MRI) is a non-invasive technique without radiations exposure that can provide cross-sectional images from inside the solid materials and living organisms (Kim et al., 2003, Richardson et al., 2005). Magnetite nanoparticles are suitable for MRI contrast (Bean et al., 1959, Koenig et al., 1987). Magnetite particles have been proposed for oral use as magnetic resonance contrast agents and magnetic markers to study the gastrointestinal motility (Briggs et al., 1997, Ferreira et al., 2004). The gastric secretions include pepsin, mucus, and HCl (Paulev, 1999-2000) and magnetite particle dissolution may take place during their passing through the stomach. This could reduce the signal for MRI or for monitoring gastrointestinal motility. The problem that appears in this domain is to protect compounds from gastric environment and the xylan is a good candidate for this issue. Xylans are polysaccharides made from units of xylose and can be found as structural components in the cell walls of some green algae. Xylan-coated

with PEG for further biomedical applications in cancer diagnosis and therapy.

threshold of 420C for 30 min or more.

changes in magnetic fields on their surface.

developed and perfected.

molecules dissolving in body fluids around or within the particles and migration of the drug away from the particles. The degradation mechanism occurs when the polymer chains are hydrolysed into lower molecular weight species and release the drug trapped by the polymer chains. The coated particles, when inside the body, swell to increase pressure, and the drug diffuses from the polymer network into the body.

Fig. 5. Magnetite particles in presence/in absence of magnetic field.

Magnetic nanoparticles coated with different organic compounds offer a high potential for numerous biomedical applications, such as cell separation (Kuhara et al., 2004), automated DNA extraction (Yoza et al., 2003), gene targeting (Plank et al., 2003), drug delivery (Lazaro et al., 2005), magnetic resonance imaging (Glech et al., 2005), and hyperthermia (Pardoe et al., 2003). After coating with an antibody, they can be used for immunoassays (Chemla et al., 2000) or small substance recovery (Tanaka et al., 2004). DNA or oligonucleotides immobilized on magnetic particles have been used for DNA hybridization analyses to identify organisms (Matsunaga et al., 2001) and single-nucleotide polymorphism analyses for human blood (Maruyama et al., 2004).

Magnetic particles coated with immunospecific agents have been successfully bound to red blood cells (Molday et al., 1982, Tibbe et al., 1999), lung cancer cells (Kularatne et al., 2002), bacteria (Morisada et al., 2002), urological cancer cells (Zigeuner et al., 2003). Coupling of homing peptide labeled with 5-carboxyl-fluorescein (FAM-A54) and magnetite coated with starch chains functionalized with homing peptide was performed by Schiffs' reaction (Jiang et al., 2009). This magnetic fluid has great potential applications in diagnostics and therapeutics of human tumours.

Nano-sized iron oxide particles (Fe3O4) were coated with a lipid layer and then functionalized with biotin for further protein ligands. These particles were then used for binding streptavidin–fluorescein isothiocyanate generating a conjugate used to investigate their magnetic and fluorescent activity into cells (Beckera et al., 2007).

The magnetic particle application for hyperthermia goes back to 1957 (Gilchrist et al., 1957). The authors heated up various damaged tissue samples with 20–100 nm size particles of γ -Fe2O3 exposed to a 1.2 MHz magnetic field. Since then the scientists have been developing numerous methods and schemes using different types of magnetic materials, different field strengths and frequencies of encapsulation and delivery of the

molecules dissolving in body fluids around or within the particles and migration of the drug away from the particles. The degradation mechanism occurs when the polymer chains are hydrolysed into lower molecular weight species and release the drug trapped by the polymer chains. The coated particles, when inside the body, swell to increase pressure, and

Magnetic nanoparticles coated with different organic compounds offer a high potential for numerous biomedical applications, such as cell separation (Kuhara et al., 2004), automated DNA extraction (Yoza et al., 2003), gene targeting (Plank et al., 2003), drug delivery (Lazaro et al., 2005), magnetic resonance imaging (Glech et al., 2005), and hyperthermia (Pardoe et al., 2003). After coating with an antibody, they can be used for immunoassays (Chemla et al., 2000) or small substance recovery (Tanaka et al., 2004). DNA or oligonucleotides immobilized on magnetic particles have been used for DNA hybridization analyses to identify organisms (Matsunaga et al., 2001) and single-nucleotide polymorphism analyses

Magnetic particles coated with immunospecific agents have been successfully bound to red blood cells (Molday et al., 1982, Tibbe et al., 1999), lung cancer cells (Kularatne et al., 2002), bacteria (Morisada et al., 2002), urological cancer cells (Zigeuner et al., 2003). Coupling of homing peptide labeled with 5-carboxyl-fluorescein (FAM-A54) and magnetite coated with starch chains functionalized with homing peptide was performed by Schiffs' reaction (Jiang et al., 2009). This magnetic fluid has great potential applications in diagnostics and

Nano-sized iron oxide particles (Fe3O4) were coated with a lipid layer and then functionalized with biotin for further protein ligands. These particles were then used for binding streptavidin–fluorescein isothiocyanate generating a conjugate used to investigate

The magnetic particle application for hyperthermia goes back to 1957 (Gilchrist et al., 1957). The authors heated up various damaged tissue samples with 20–100 nm size particles of γ -Fe2O3 exposed to a 1.2 MHz magnetic field. Since then the scientists have been developing numerous methods and schemes using different types of magnetic materials, different field strengths and frequencies of encapsulation and delivery of the

their magnetic and fluorescent activity into cells (Beckera et al., 2007).

the drug diffuses from the polymer network into the body.

Fig. 5. Magnetite particles in presence/in absence of magnetic field.

for human blood (Maruyama et al., 2004).

therapeutics of human tumours.

particles (Mosso et al., 1973, Rand et al., 1976, Gordon et al., 1979, Rand et al., 1981, Borrelli et al., 1984, Hase et al., 1990, Suzuki et al., 1990, Chan et al., 1993, Matsuki et al., 1994, Mitsumori et al., 1994, Suzuki et al., 1995, Moroz et al., 2001, Jones et al., 2002). The hyperthermia procedure involves the dispersion of the magnetic particles throughout the target tissue, followed by applying an AC magnetic field with specific parameters (frequency, strength); the magnetization of the particles is continuously reversed, which translates into a conversion from magnetic to thermal energy and causes the heating of particles. The tumour is destroyed if the temperature is maintained above the therapeutic threshold of 420C for 30 min or more.

The bisphosphonate modified magnetite nanoparticles were used as agents to remove uranyl ions (e.g., UO22+) in vivo from water or blood (Wang et al., 2006). The authors synthesized a bisphosphonate derivative, DA-BP, which modifies the magnetite nanoparticles for the successful decorporation of the radioactive metal from blood due to the chelating effect (Fukuda, 2005). Starting from this study, a protocol that allows the detection and recovery of other heavy metal toxins from the biological systems has been developed and perfected.

Coated magnetite particles with magnetic resonance, fluorescent imaging and drug delivery applications were obtained (Kim et al., 2008). The particles obtained are monodisperse, with dimensions smaller than 100 nm, coated with silica shell using cetyltrimethylammonium bromide as surfactant for the transfer of hydrophobic nanocrystals to aqueous media and also as organic template in the sol-gel reaction. The silica-Fe3O4 particles were functionalized with PEG for further biomedical applications in cancer diagnosis and therapy.

Magnetite particles (nanoparticles with 5–300 nm or microparticles with 300–5,000 nm) have been surface functionalized and used as biosensors to recognize specific molecular targets. Three types of biosensors, (i) magnetic relaxation witches, (ii) magnetic particle relaxation sensors, and (iii) magnetoresistive sensors, were coated with different biosensing principles and magnetic materials for instrumentation (Josephson, 2009). Magnetic relaxation switch assay-sensors are based on the effects of the magnetic particles exert on water proton relaxation rates. Magnetic particle relaxation sensors determine the relaxation of the magnetic moment within the magnetic particle. Magnetoresistive sensors detect the presence of magnetic particles on the surface of electronic devices and are sensitive to changes in magnetic fields on their surface.

Magnetic resonance imaging (MRI) is a non-invasive technique without radiations exposure that can provide cross-sectional images from inside the solid materials and living organisms (Kim et al., 2003, Richardson et al., 2005). Magnetite nanoparticles are suitable for MRI contrast (Bean et al., 1959, Koenig et al., 1987). Magnetite particles have been proposed for oral use as magnetic resonance contrast agents and magnetic markers to study the gastrointestinal motility (Briggs et al., 1997, Ferreira et al., 2004). The gastric secretions include pepsin, mucus, and HCl (Paulev, 1999-2000) and magnetite particle dissolution may take place during their passing through the stomach. This could reduce the signal for MRI or for monitoring gastrointestinal motility. The problem that appears in this domain is to protect compounds from gastric environment and the xylan is a good candidate for this issue. Xylans are polysaccharides made from units of xylose and can be found as structural components in the cell walls of some green algae. Xylan-coated

Tailored and Functionalized Magnetite Particles for Biomedical and Industrial Applications 161

NASA (Kodama) (http://www.interactivearchitecture.org/ferrofluid-sculptures-bysachiko-kodama.html) choose to use the dynamic qualities of these fluids. Thus, Kodama models their shape using a computer to control the electro-magnetic fields and creating different forms that continually reinvent themselves without the help of video effect. In the printing industry, special inks are used to protect valuable documents, labels, packaging or brand. Magnetic ink contains a pigment that produces magnetic pulses detected by magnetic reading devices, and messages can be read only by exposure to the equipment

Magnetite particles coated by different Si-containing compounds (monomers and polymers) were prepared using co-precipitation method or a free-solvent synthesis. The covered magnetite particles were obtained in one step by co-precipitation of iron chloride salts in presence of monomers or (co)polymers adequately functionalized, as surfactants. When the co-precipitation was in the absence of surfactant, the covered particles were obtained in two steps, the first step consisting in the obtaining of magnetite particles and in the second step, the magnetite particles being covered with an adequate monomer or (co)polymer, specific for the desired application. The magnetite particles covered with aminosilane were obtained by replacement of the shell of magnetite-oleic acid particles which were synthesised by a free-solvent method. The average diameters of magnetic nanoparticles are depending on the synthesis method, are less than 1 µm and the smallest dimensions are obtained by free-

In this chapter we focused on the characterization of core-shell magnetic nanoparticles as determined by X-ray photoelectron spectroscopy (XPS). XPS, also known as Electron Spectroscopy for Chemical Analysis (ESCA), is an elemental analysis technique and used to determine quantitatively the atomic composition and surface chemistry. XPS spectra are obtained by irradiating a material with a beam of X-rays while simultaneously measuring the kinetic energy and number of electrons that escape from the top 1 to 10 nm of the material being analysed (Watts et al., 2003; http://en.wikipedia.org/wiki/X-

The surface of the magnetite particles modified with aminosilane (Ma-APTES) or with polydimethylsiloxane–carboxy-terminated poly(ethylene oxide) graft copolymer (Ma-

a. Co-precipitation of Fe2+ and Fe3+ ions in presence of ammoniacal solution according to the Massart method (Massart, 1981). The organic-inorganic "core-shell" magnetic particles (core: magnetite, shell: aminosilane monomer) were obtained by the condensation reaction between the hydroxyl groups on the magnetite surface and the ethoxyl groups from silane structure (Figure 6) (Durdureanu-Angheluta et al., 2008); b. The replacing, with aminosilane, of oleic acid of magnetite-oleic acid particles which were obtained by free-solvent method (Figure 7, Table 2) (Durdureanu-Angheluta et al.,

DLS, SEM and AFM analysis indicated the formation of low polydispersity particles, with a

Hydrophilic magnetite particles (Ma-APTES) were prepared by two methods:

(http://www.pricon.ro/ro/special.php).

solvent method (Table 2).

ray\_photoelectron\_spectroscopy).

2011b).

**6. XPS results for core-shell magnetic nanoparticles** 

PDMSgPEO-COOH) was carefully followed using XPS data.

spherical morphology and dimensions of nanometers (Table 2).

magnetic microparticles were obtained (Andriola Silva et al., 2007) to protect magnetite from gastric dissolution.

#### **5.2 Applications in catalysis**

The aim of the catalysis is to search new catalysts that can be recovered when their activity is ended (Sankaranarayanapillai et al., 2010). The magnetic dispersions are attractive in separation applications as they offer high surface area and can be functionalized to apply to different molecular or cellular species. The magnetic fluids can be used as magnetically separable nanocatalytic systems that combine the advantages of homogeneous and heterogeneous catalysis (Lu et al., 2004). Novel thermoreversible magnetic fluids based on magnetite (Fe3O4) coated with a covalently anchored polymeric shell of poly(2-methoxyethyl methacrylate) (PMEMA) were synthesized by surface-initiated ATRP (Gelbrich et al., 2006). The coated particles form stable dispersions in methanol at temperatures above an upper critical solution temperature.

Magnetically recoverable heterogenized nanoparticle supported chiral Ru complexes were obtained and used in highly enantioselective asymmetric hydrogenation of aromatic ketones (Hu et al., 2005). The catalysts can be recycled by magnetic decantation and used for asymmetric hydrogenation for up to 14 times without loss of activity and enantioselectivity.

#### **5.3 Industrial applications**

Ferofluids have numerous applications in rotary and linear seals as magneto transformers, sensors and pressure transducers (flow speed), inertial sensors (acceleration, inclination, and gravity) (Vekas, 2008), passive and active bearings, vibration dampers, linear and rotary drives, and chemical industry (microtechnologies) as chips, etc. Among the most important and commercial applications are developed magnetofluids rotating seals, which are found today in a variety of equipments, in electronics, nuclear industry, biotechnology, aeronautics and space applications.

Magnetofluids sealing advantages compared with mechanical seals are: sealing without leaking, life time (~ 5 years), only viscous friction, zero contamination, field operation (high vacuum (10-8 mbar) at approx. 10 bar), relatively simple construction and low manufacturing cost (www.roseal.topnet.ro).

For seals in dynamic regime, ferrofluids must obey a series of requirements (www.roseal.topnet.ro): high saturation magnetization (up to 50 kA/m (approx. 600 g)), physical properties adapted to operating conditions, especially in gas pressure and temperature sealed, high colloidal stability in intense and powerful magnetic field, Newtonian flow properties even in intense magnetic field.

Ferrofluids should operate at 1500C in continuous system or at temperatures of 2000C in intermittent system. They should also work in winter conditions (-200C) or in space environment (-550C) and to resist at nuclear radiation.

Researchers at NASA (Rosensweig et al., 1985) experienced ferrofluids in a spacecraft control system. While ferrofluids are used often in commercial processes, for the manufacture of CDs to create sophisticated suspension systems for cars, a researcher at NASA (Kodama) (http://www.interactivearchitecture.org/ferrofluid-sculptures-bysachiko-kodama.html) choose to use the dynamic qualities of these fluids. Thus, Kodama models their shape using a computer to control the electro-magnetic fields and creating different forms that continually reinvent themselves without the help of video effect. In the printing industry, special inks are used to protect valuable documents, labels, packaging or brand. Magnetic ink contains a pigment that produces magnetic pulses detected by magnetic reading devices, and messages can be read only by exposure to the equipment (http://www.pricon.ro/ro/special.php).
