NTA: Materials - General

The need to characterize different properties of nanomaterials continues to grow rapidly. Since the commercialization of the technique in 2004, Nanoparticle tracking Analysis (NTA) has become increasingly prevalent in a wide variety of different research fields and industrial applications. In this fourteenth chapter of the Nanoparticle Tracking Analysis (NTA) application and usage review, we review the use of Nanoparticle Tracking Analysis with materials not covered in other chapters, such as carbon and carbon nanotubes, composite material nanoparticles and magnetic nanoparticles.

Miscellaneous Materials

Binns et al. (2012) have reported on a new method to produce liquid suspensions of hydrosol suspensions of elemental and core–shell nanoparticles by co-deposition with water vapor from the gas-phase in ultra-high vacuum conditions. They extended the method to include core–shell nanoparticles, in which there was flexible control over the core size and shell thickness and free choice of the material in either. NTA was used to check for aggregation while DLS measured the primary particle size of approximately 5nm. Using a modified NTA system, Jakobi et al. (2011) have determined the stoichiometry of alloy nanoparticles from laser ablation of PtIr in acetone and their electrophoretic deposition on PtIr electrodes.

A model for metal spherical particle formation was proposed by Irizarry (2010) guided by optical kinetic data of monodisperse metal colloid synthesis. Using a new strategy, called simulated dynamic optical response, it was found that autocatalytic formation of primary particles followed by a zone of very fast aggregation mechanism can describe the dominant dynamics during early stages. In later stages, the dominant mechanism switches to slower aggregation modulated by a stability factor.

Capretto et al. (2011), through experimental and computational analysis, worked on the continuous-flow production of polymeric micelles in microreactors demonstrating that microfluidic reactors provide a useful platform for the continuous-flow production of polymeric micelles with improved controllability, reproducibility and homogeneity of the size characteristics. Capretto has also looked at the mechanism of co-nanoprecipitation of organic actives and block copolymers in a microfluidic environment (Capretto et al., 2012).

In their study on nanoscale clustering and nucleation in aqueous glycine solutions, Jawor-Baczynski et al. (2012) used several analytical techniques including small angle x-ray scattering and static and dynamic light scattering, NTA was used specifically to detect much larger clusters on the order of hundreds of nanometres, their presence confirmed by both SAXS and DLS. Wark et al. (2011) investigated the dynamic multimodal surface plasmon enhanced imaging of single nanoparticles and assembled clusters in suspension also using NTA for aggregate analysis.

Liposomes are artificially prepared vesicles consisting of natural and synthetic phospholipids that are widely used as a cell membrane mimicking platform to study protein-protein and protein-lipid interactions, monitor drug delivery and encapsulation and Morton et al. (2012a) have developed a constant pressure-controlled extrusion method for the preparation of nano-sized lipid vesicles. Manual extrusion using gas-tight syringes and polycarbonate membranes is a common practice but heterogeneity is often observed when using pore sizes <100 nm due to due to variability of manual pressure applied. They employed a constant pressure-controlled extrusion apparatus to prepare synthetic liposomes whose diameters range between 30 and 400 nm. DLS, EM and NTA were used to quantify the liposome sizes as described in their protocol, with commercial polystyrene beads used as a calibration standard.

Complexes of dyes and polyelectrolytes have found widespread use in a variety of functional materials and interfaces and Helseth (2012), in a study of pyranine-induced self-assembly of colloidal structures using poly(allylamine-hydrochloride, found that upon mixing the anionic dye pyranine and a cationic polyelectrolyte, poly(allylamine-hydrochloride), two different colloidal structures may form. NTA was used to follow changes in particle sizes with time. Combining fluorescence measurements with studies of the particle size with time, it was found that red-shift was related to the crosslinking of the dye and the polyelectrolyte and was not influenced significantly by the aggregation and particle growth.

In a most interesting variation on the conventional use of NTA, Wilson et al. (2012a) have tracked the autonomous movement of platinum-loaded stomatocytes. Polymer stomatocytes are bowl-shaped structures of nanosize dimensions formed by the controlled deformation of polymer vesicles. The stable nanocavity and strict control of the opening are ideal for the physical entrapment of nanoparticles which, when catalytically active, can turn the stomatocyte morphology into a nanoreactor. They reported the generation of autonomous movement of the polymer stomatocytes by selectively entrapping catalytically active platinum nanoparticles within their nanocavities and subsequently using catalysis as a driving force for movement. Hydrogen peroxide is free to access the inner stomatocyte cavity, where it is decomposed by the active catalyst (the entrapped platinum nanoparticles) into oxygen and water. This generates a rapid discharge, which induces thrust and directional movement. The design of the platinum-loaded stomatocytes resembles a miniature monopropellant rocket engine, in which the controlled opening of the stomatocytes directs the expulsion of the decomposition products away from the reaction chamber (inner stomatocyte cavity). NTA was used to detect and visualize the population of nanoparticles. Wilson et al. (2012b) have further extended this work to study, using NTA, the way in which the speed of these nanomotors can be controlled by varying the fuel concentration.

Finally, Jornada et al. (2012) have recently established the mechanism of self-assembly, control of size and loading capacity of lipid-core nanocapsules for use in drug delivery. Nanocarriers have been developed as drug delivery systems to be administered by different biological routes. To ensure the nanotechnological properties, pre-formulation studies are especially critical in determining the influence of the process parameters on the size and polydispersity of particles. Thus, the objective of this work was to establish the mechanism of self-assembly, by determining the influence of the critical aggregation concentration of the materials in the organic phase on the final average particle size and polydispersity of polymeric lipid-core nanocapsules obtained by interfacial deposition of polymer using NTA. Measurements of the surface tension and viscosity of the organic and aqueous phases were correlated with the particle size and the concentration of raw materials. They demonstrated that the lipid-core nanocapsules are formed on the nanoscopic scale as unimodal distributions but only if the aggregation state of raw materials in the organic phase tends to infinite dilution. The strategy for controlling the particle size distribution is a valuable tool in producing lipid-core nanocapsule formulations with different loading capacities intended for therapeutics.

Composite materials

Green et al. (2012) have recently developed multicomponent degradable cationic polymers that self-assemble with DNA to form particles that are effective for gene delivery while formulations of lipid-core nanocapsules, stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan (LNC and LNC-CS), were prepared and characterized by laser diffraction (D [4,3]: 129 and 134 nm), DLS (119 nm and 133 nm), NTA (D50: 124 and 139 nm) and particle mobility analysis (zeta potential: −15.1 mV and +9.3 mV).

Combining several different materials types, Fatisson et al. (2010) established the roles of solution chemistry and organic molecules on deposition of carboxymethylcellulose-coated zero-valent iron nanoparticles onto silica and Pazik et al. (2011) used BaTiO3 as a case study to investigate the surface functionalization of the metal oxide nanoparticles with biologically active molecules containing phosphonate moieties. Donati et al. (2011) have filed patents on nanocomposite materials based on metallic nanoparticles stabilized with branched polysaccharides.

Stevens et al. (2012) described nanosponge formation from organocatalytically synthesized poly(carbonate) copolymers and Guerrini et al. (2012), in tuning the interparticle distance in nanoparticle assemblies in suspension via DNA-triplex formation, established a correlation between plasmonic and SERS responses. They exploited the triplex-assembling ability of DNA-conjugated silver nanoparticles to engineer interparticle junctions with controlled interparticle distance and tuned the aggregation rate to allow accurate investigation into the correlation between the averaged time-dependent plasmonic and SERS responses within a complex ensemble of nanoparticles in suspension.

In reporting recent modelling and design work indicating that mixtures of nanoparticles in liquids can be used as an alternative to conventional optical filters Taylor et al. (2013) used NTA to show that the commercially available nanofluids they were assessing as the basis for producing long-pass, short-pass and band-pass optical filters contained larger particles than the manufactured stated mean.

Mariz et al. (2013) used NTA-analyzed hybrid nanoparticles dispersed in water prepared from selected polymers with two-photon excited fluorescence emission that competed with those of the best performing quantum dots during their study of the molecular architecture effect in two-photon absorption. In studying VI semiconductors as promising nanomaterials for applications as window layers in low-cost and high-efficiency thin film solar cells Tripathi (2013) reviewed the present status of nanoparticle-doped polymers as examples of types of inorganic/organic hybrid nanocomposite materials. He used NTA to characterize these nanocomposites.

In their description of a one-pot phase transfer and surface modification of CdSe/ZnS quantum dots by a synthetic functional copolymer which did not require coupling agents and multistep reactions, Finetti et al. (2013) used NTA to highlight that the particle distribution of in-house and commercial phase transferred QDs were very similar though they underlined that, for very small nanoparticles, such as those reported, the absolute size value measured with NTA is less accurate than that measured with DLS. However, they did employ NTA to generate concentration data which was not available from DLS and could only be surmised from an absorbance curve.

While colloidal scale mesospecies (nanodroplets) were previously reported in supersaturated solutions of glycine and DL-alanine amino acids and were implicated as intermediates species on a non-classical crystallization pathway, Jawor-Baczynska et al. (2013) used NTA, amongst other techniques, to show that the mesospecies are also present in significant numbers in undersaturated solutions even when the solute concentration is well below the solid-liquid equilibrium concentration.


Nanoparticles can be used for detection purposes for the quantification of nucleic acid. Thus, Wang and Vo-Dinh (2011) described using plasmonic coupling interference nanoprobes for nucleic acid detection using SERS in which NTA was needed to show the potential of nucleic acid diagnostic tools for biomedical diagnostics and biosensing applications. Similarly, Kell et al. (2011) developed a silica nanoparticle-based DNA biosensor capable of detecting Bacillus anthracis bacteria through the use of unlabelled ss-oligonucleotides. The biosensor makes use of the optical changes that accompany a nanoparticle-immobilized cationic conjugated polymer (polythiophene) interacting with single-stranded vs. hybridized oligonucleotides, where a fluorescence signal appears only when hybridized DNA is present (i.e. only when the ss-oligonucleotide interacting with the polymer has hybridized with its complement). NTA was used to show that the silica nanoparticle scaffold employed in this investigation was 188 ± 30 nm in diameter as measured by TEM and 196 ± 36 nm in diameter measured by NTA.

Schrittwieser et al. (2012) modelled and developed a biosensor based on optical relaxation measurements of hybrid nanoparticles using NTA to characterize their core asymmetric and magnetic nanoparticles. A range of different nanoparticles have been proposed as sensing structures. Thus Kumar et al. (2011) have reported the bioconjugation of InGaP quantum dots for molecular sensing, while Eremenko et al. (2012) describe the use of manganese dioxide nanostructures as a novel electrochemical mediator for thiol sensors. Finally, Jayapaul et al. (2012) described the preparation of riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors. NTA was used in all of these studies to characterize the materials employed.

Membrane curvature and lipid composition regulates important biological processes within a cell. Currently, several proteins have been reported to sense and/or induce membrane curvatures such as synaptotagmin-1 and amphiphysin (Saludes et al., 2012) and Morton et al. (2012) have identified a 25-mer peptide, MARCKS-ED, based on the effector domain sequence of the intracellular membrane protein myristoylated alanine-rich C-kinase substrate, that can recognize PS with preferences for highly curved vesicles in a sequence specific manner. These studies further contribute to the understanding of how proteins and peptides sense membrane curvature, as well as providing potential probes for membrane shape and lipid composition, NTA being used to monitor vesicle size.

Calò et al. (2012) have exploited natural vesicles produced from genetically engineered cells with tailored membrane receptor composition as promising building blocks for sensing biodevices. Using NTA to establish vesicle size, they then employed AFM to show that nanovesicles deposit and flatten without rupturing on glass substrates claiming this to be an important step in the practical realization of biosensor devices based on natural nanovesicles integrating G-protein coupled membrane receptors.

More recently, Sigolaeva et al. (2013) reported the use of co-assemblies of micelle-forming diblock copolymers and enzymes on a graphite substrate for an improved design of biosensor systems using NTA to characterize the diblock copolymers in aqueous solution which formed star-like micelles with a hydrophobic PB core and a cationic corona built up from either strong cationic PDMAEMAq or pH-sensitive PDMAEM.

In presenting a total internal reflection fluorescence microscopy based bioanalytical assay for the detection of whole viral particles with single virus sensitivity and specifically focussing on the detection of human norovirus, a highly infectious virus causing gastroenteritis, Bally et al. (2013) showed that NTA-estimated number concentrations of their virus samples matched well the titre reported by other methods.

Yang et al. (2013) have assessed transthyretin as both sensor and scavenger of abeta oligomers. Transthyretin (TTR) is a homotetrameric transport protein, assembled from monomers that each contains two four-stranded β-sheets and a short α-helix and loop. In the tetramer, the ‘inner’ β-sheet forms a hydrophobic pocket while the helix and loop are solvent-exposed. Beta-amyloid (Aβ) aggregates bind to TTR, and the binding is significantly reduced in mutants L82A (on the loop) and L110A (on the inner β-sheet). They exploited NTA, as a “novel technique”, to show that TTR arrests Aβ aggregation by both preventing formation of new aggregates and inhibiting growth of existing aggregates.

In another biosensor application, di Gennaro (2013) studied the tryptophan-terbium FRET pair interaction coupled to silver nanoprisms supporting the observation that while plasmonic coupling between fluorophores and metal surfaces has become a focal point of optical research during the last two decades, the interactions of FRET couples with metal surfaces remain relatively unexplored. NTA was used to measure silver nanoprism size and concentration. Silver nanoparticles were also used in the electrochemical detection of chloride levels in sweat as a basis for the preliminary screening for cystic fibrosis, NTA being used to size the silver nanoparticles in the solution-phase (Toh et al. (2013).

Similarly, Wang et al. (2013) have employed silver nanoparticles and Raman dye-labelled DNA hairpin probes as a SERS-based detection technique, referred to as “molecular sentinel”plasmonic nanoprobes, to detect an RNA target related to viral infection, the hydrodynamic size distribution of the bare nanoparticles being measured by NTA. They claimed that, with the use of a portable Raman spectrometer and total RNA samples, they had demonstrated for the first time the potential of the MS nanoprobe technology for detection of host-response RNA biomarkers for infectious disease diagnostics.

Nanoparticulate gold has also found increasing application in the sensing field and recent reports in which NTA has been used to help characterize such materials are summarized here.

The very strong optical resonances of plasmonic nanostructures can be harnessed for sensitive detection of chemical and biomolecular analytes in small volumes and Werts et al. (2013) have recently described an approach towards optical biosensing in microfluidic systems using plasmonic structures (functionalized gold nanoparticles) in colloidal suspension using NTA to address aspects of nanoparticle functionalization. Particle concentration was measured directly using NTA in the study by Lui et al. (2013) on quintuple-modality (SERS-MRI-CT-TPL-PTT) plasmonic gold nanostar nanoprobe for theranostics.

McLintock et al. (2013) described the preparation and characterization of stable and non-aggregated colloidal suspensions of gold nanorod–molecular dye complexes which exhibit very bright SERS signals. The polymer stabilized nanorod–dye conjugates were prepared without the added complexity of nanoparticle aggregation as well as having good control over the surface coverage and orientation of the dye molecules. Furthermore, they demonstrated that this new class of Raman nanotags greatly outperformed an approach based on quasi-spherical gold nanoparticles. Additional characterization of the particle concentrations and aggregation state of the NR–dye conjugate concentrations was performed using NTA.

More recently, Morasso et al. (2013) have undertaken the one-step synthesis of star-like gold nanoparticles for SERS. Using NTA to determine particle size and size distribution they showed that the particles exhibited excellent properties for SERS and, when compared with spherical nanoparticles with similar size and concentration, showed enhancing factors from 10 to 50 times higher depending on the dye and on the wavelength employed.

Gold was further employed for single particle luminescence imaging in cells when modified with high coatings of Ru(II) complexes. Using NTA to confirm sample uniformity, Pikramenou et al. (2013) showed that single 100 nm particles could be observed in whole cell luminescence imaging and which revealed their biomolecular association with chromatin in the nucleus of cancer cells.

In attempting to overcome the limitations inherent in in vivo monitoring system designs through invasive implantation procedures and biofouling, Cash and Clark (2013) recently demonstrated the first success in optically tracking histamine levels in vivo using a modular, injectable sensing platform based on diamine oxidase and a phosphorescent oxygen nanosensor in which NTA was used specifically to estimate particle concentration.

Olsson et al. (2013) resorted to NTA and TEM to confirm that their technique, based on quartz crystal microbalance with dissipation (QCM-D) monitoring, was capable of evaluating the size of nanoparticles deposited on surfaces. They showed that the mean nanoparticle sizes obtained by QCM-D were generally in closer agreement with the primary particle size determined by TEM and NTA than with the sizes obtained by DLS. Díaz (2013) also used NTA as well as DLS to confirm polymersome formation with the particular polymer in his production of water soluble photochromic fluorescent nanoprobes based on diheteroarylethenes and polymer coated quantum dots.

In characterizing the nonlinear optical properties of nanocrystals by hyper-Rayleigh scattering (HRS), Joulaud et al. (2013) investigated by HRS measurements the second harmonic properties of BaTiO3, KNbO3, KiTiOPO4, LiNbO3 and ZnO nanocrystals (NCs). It proved necessary to carefully analyze the nanocrystal suspensions and both DLS and NTA were used in this capacity. The data on two types of LiNbO3 NCs is of interest because the NTA plots match the DLS data only when it was plotted by a number distribution format. The usual, and recommended, format for presenting DLS data is to employ the intensity profile only but significant problems and misinterpretations frequently arise otherwise. The fact that, in this case, the extrapolation from intensity distribution to number distribution appears sound is probably due to the relative monodispersity of the sample in the first place. Even then, NTA data shows more structure in the distribution than is possible to obtain from the low resolution methods of DLS.

In a recent report, Jang et al. (2013) introduced a new surface-based sandwich assay for the direct detection of B-type natriuretic peptide (BNP), an important biomarker for cardiac failure, at concentrations ranging from 1 nM to 500 nM. NTA was used to establish the particle density of 1.07x1014 particles/L for a nanocube sample exhibiting a UV-vis extinction suitable for nanoparticle-enhanced surface plasmon resonance where a DNA aptamer is immobilized on a chemically modified gold surface in conjunction with the specific adsorption of antiBNP coated gold nanocubes in the presence of the biomarker target.

Finally, Rho et al. (2013) have described a magnetic nanosensor for detection and profiling of erythrocyte-derived microvesicles, using NTA to confirm the size of filtered MVs to be an average size of 167nm. This work was undertaken in an attempt to overcome the lack of sensitive, standardized MV assays which pose a significant barrier to implementing MV analyzes into clinical settings.

Carbon and Carbon Nanotubes

Following earlier and preliminary used of NTA to characterize various carbonaceous nanomaterials such as carbon nanotube-nematic liquid crystal composite materials (Trushkevych et al., 2007 and 2008) and the oxidative potential of a panel of carbonaceous and metallic nanoparticles.(Hohl et al., 2009), more recent work using NTA has focused on carbon nanotubes and nanocolloids.

To assess the removal efficiency of formaldehyde using nano-size carbon colloid, which was produced by a comparatively easy and cheap method, Kim et al. (2011) produced nano-size carbon colloid based on water by an electro-chemical method. NTA was used to monitor carbon particle size in production. Lv et al. (2011) used NTA to determine the size of graphene oxide nanoparticles in the design and production of graphene oxide membranes for possible use in new optical devices.

In the case of carbon nanotubes (CNTs), despite their highly asymmetric shape, NTA has been used to determine the sphere equivalent diameter as an indicator of sample monodispersity and behavior in different matrices. Thus, Schwyzer et al. (2011) have studied the influence of the initial state of carbon nanotubes on their colloidal stability under natural conditions over a period of many days. They showed that the initial state of the CNTs (dry vs. suspended) and the medium composition are critical determinants for the partitioning of CNTs between sediment and the water column. This work was subsequently extended into a more extended study on the long-term colloidal stability of 10 carbon nanotube types in the absence/presence of humic acid and calcium.

Recently, Zemanova has investigated the cytotoxicity of a water-soluble, radioprotective C60 fullerene derivative (DF) which had been obtained by a reaction of C60 fullerene with peracetic acid and subsequent hydrolysis. She used NTA to show monodisperse DF was less cytotoxic to cell cultures than an unfiltered, polydisperse equivalent which coagulated on cell surfaces (Zemanova et al., 2011). Clements (2013) has shown that while DLS data for a sample of a C60 colloids indicated a bimodal distribution and that the larger particles detected by DLS are beyond the range of the NTA instrument, the NTA particle size distribution for this sample picked up mainly the particles slightly larger than 100nm. The mode of the NTA particle size distribution for C60 agreed quite well with the number distribution data given by DLS.

The cellular toxicity of C60 fullerenes in RAW 264.7 immortalized macrophages has been studied by Russ (2013) and showed that exposure of immune cells to C60 fullerenes results in uptake of the nanoparticles and alterations in the normal functions of the cell. NTA was used to analyze the size of C60 Fullerene and terbium endohedral Fullerene aggregates.

In a study of the photoacoustic contrast imaging of biological tissues with radiation-damaged nanodiamonds fabricated for high near-infrared absorbance, Zhang et al. (2013) used NTA to carry out size determinations.

Reed et al. (2013) used using single particle-inductively coupled plasma-mass spectrometry (spICPMS) to detect single walled carbon nanotubes by monitoring embedded metals using trace catalytic metals intercalated in the CNT structure as proxies for the nanotubes. Interestingly, analysis of split samples by both spICPMS and NTA showed the quantification of particle number concentration by spICPMS to be several orders of magnitude lower than by NTA. They postulated that this was a consequence of metal content and/or size, caused by the presence of many CNTs that do not contain enough metal to be above the instrument detection limit, resulting in undercounting CNTs by spICPMS. However, they claimed that since the detection of CNTs at low ng L-1 concentrations is not possible by other techniques, spICPMS was still a more sensitive technique for detecting the presence of CNTs in environmental, materials, or biological applications. In a recent patent filing Fahmy et al. (2013) have described carbon nanotube-based compositions for activating cellular immune responses supporting their claims with NTA data on analysis of their magnetite and CL-2 loaded PLGA nanoparticles.

Finally, Sun et al. (2013) have investigated the adsorption of size-selected Pt colloidal nanoparticles on high-surface-area graphene powders for methanol oxidation reaction given graphene-supported nanoparticles are of tremendous interest for a variety of applications recently. They found that the adsorption of Pt colloidal nanoparticles on graphene surfaces is dramatically influenced by the process parameter in the mixing process and, specifically, the different solution volumes during the mixing process result in various catalyst morphologies.

Most recently, Chen et al. (2013) have used NTA to characterize the interactions between protein and carbon black (CB) in which they revealed that the CB can react with proteins (55kDa and 70kDa) after inhalation and may modify the functional structures of lung proteins, leading to the activation of acute-inflammatory responses in the lungs.


Superparamagnetic nanoparticles have potential applications in targeted drug delivery and as magnetic resonance imaging contrast agents. Magnetite clusters are of particular interest for these applications because they provide higher magnetic flux (under a magnetic field) than individual magnetite nanoparticles, are biocompatible and their size and compositions can be controlled. Mejia-Ariza (2010) described the design, synthesis, and characterization of magnetite clusters using a multi inlet vortex mixer. Following earlier work on superparamagnetic nanoparticles and non-oxidic iron core−shell nanomagnets (Yiu et al., 2008 and Herrmann et al., 2009 respectively), in which NTA was used to characterize nanoparticle suspension purity, the technique has found increasing use in this field of magnetic nanoparticle research.

Etgar et al. (2010) reported the trajectory control of PbSe–γ-Fe2O3 nanoplatforms under viscous flow and an external magnetic field. The flow behavior of nanostructure clusters, consisting of chemically bonded PbSe quantum dots and magnetic gamma-Fe(2)O(3) nanoparticles, was investigated. The clusters are regarded as model nanoplatforms with multiple functionalities, where the gamma-Fe(2)O(3) magnets serve as transport vehicles, manipulated by an external magnetic field gradient and the quantum dots act as fluorescence tags within an optical window in the near-infrared regime. The clusters' flow was characterized by an NTA instrument to visualize their trajectories within a viscous fluid (mimicking a blood stream). The trajectories were examined under various flow rates, viscosities and applied magnetic field strengths and the results revealed a control of the trajectories even at low magnetic fields (<1 T), validating the use of similar nanoplatforms as active targeting constituents in personalized medicine.

Paquet et al. (2011) developed a new form of particle generating a synergistic enhancement of the T2 relaxation using clusters of superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in a hydrogel using NTA to follow increase in particle diameter with progressive coatings and Song et al. (2011) prepared PANI/nano-ZnO composites prepared by in-situ polymerization under a magnetic field. NTA has also been used in to follow intermetallic magnetic nanoparticle precipitation by femtosecond laser fragmentation in liquids (Yamamoto et al. 2011).

The field of magnetic nanoparticles and their biomedical applications has been reviewed by Banerjee et al. (2010) and Rieger et al. (2012) have developed antibody-labelled superparamagnetic nanoparticles for the visualization of benzo[a]pyrene in porous media with magnetic resonance imaging in an attempt to achieve advanced visualization and quantification tools to link in vitro experiments with natural systems. The surface coatings of proteins on superparamagnetic iron oxide nanoparticles (SPIONs) that form immediately on contact with a biological milieu were assessed using a variety of techniques, including NTA, following stabilisation of the SPION with citric acid, poly(acrylic acid) or double layer oleic acid (Jedlovszky-Hajdú et al., 2012).

More recently, Bruckman et al. (2013) have reported on the development of supramolecular high-relaxivity MRI contrast agents using the plant viral nanoparticle tobacco mosaic virus (TMV). Rod-shaped TMV nanoparticles measuring 300×18 nm were loaded with up to 3500 or 2000 chelated paramagnetic gadolinium(III) ions selectively at the interior or exterior surface, respectively. Spatial control is achieved through targeting either tyrosine or carboxylic acid side chains on the solvent exposed exterior or interior TMV surface. Further, they showed that interior-labelled TMV rods can undergo thermal transition to form 170 nm-sized spherical nanoparticles containing 25 000 Gd chelates and a per particle relaxivity of almost 400 000 mM−1 s−1 (15.2 mM−1 s−1 per Gd). NTA was used to size the nanoparticles.

Finally, in showing that induced clustered nanoconfinement of superparamagnetic iron oxide in biodegradable nanoparticles enhances transverse relaxivity for targeted theranostics, Ragheb et al. (2013) used NTA to both visualize and analyze the sample allowing them to conclude that fatty acid modified iron oxide prolonged retention of the contrast agent in the polymer matrix during degradative release of drug. Antibody-fatty acid surface modification facilitated cellular targeting and subsequent internalization in cells while inducing clustering of encapsulated fatty-acid modified superparamagnetic iron oxide during particle formulation and that, accordingly, clustering of superparamagnetic iron oxide in poly(lactide-co-glycolide) did not affect the controlled release of encapsulated drugs such as methotrexate or clodronate and their subsequent pharmacological activity.


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