Aggregation of gold nanoparticles followed by methotrexate release enables Raman imaging of drug delivery into cancer cells

A certified reference material, ERM-FD100, for quality assurance and validation of various nanoparticle sizing methods, was developed by the Institute for Reference Materials and Measurements. The material was prepared from an industrially sourced colloidal silica containing nanoparticles with a nominal equivalent spherical diameter of 20?nm. The homogeneity and stability of the candidate reference material was assessed by means of dynamic light scattering and centrifugal liquid sedimentation. Certification of the candidate reference material was based on a global interlaboratory comparison in which 34 laboratories participated with various analytical methods (DLS, CLS, EM, SAXS, ELS). After scrutinising the interlaboratory comparison data, 4 different certified particle size values, specific for the corresponding analytical method, could be assigned. The good comparability of results allowed the certification of the colloidal silica material for nanoparticle size analysis.     

Characterisation of nanoparticle size and state prior to nanotoxicological studies

Before commencing any nanotoxicological study, it is imperative to know the state of the nanoparticles to be used and in particular their size and size distribution in the appropriate test media is particularly important. Particles satisfying standards can be commercially purchased; however, these invariably cannot be used directly and need to be dispersed into the relevant biological media. Often such changes in the environment or ionic strength, or a change in the particle concentration, results in some aggregation or a shift in the particle size distribution. Such unexpected aggregation, dissolution or plating out, if unaccounted for, can have a significant effect on the available nanoparticle dose and on interpretation of any results obtained thereafter. Here, we demonstrate the application of characterisation instrumentation that sizes nanoparticles based on their Brownian motion in suspension. Unlike classical light-scattering techniques, the nanoparticle tracking and analysis (NTA) technique allows nanoparticles to be sized in suspension on a particle-by-particle basis allowing higher resolution and therefore better understanding of aggregation than ensemble methods (such as dynamic light scattering (DLS) and differential centrifugation sedimentation (DCS)). Results will be presented from gold (standard) nanoparticles in biologically relevant media that emphasise the importance of characterisation of the nanoparticle dispersion. It will be shown how the NTA technique can be extended to multi-parameter analysis, allowing for characterization of particle size and light scattering intensity on an individual basis. This multi-parameter measurement capability allows sub-populations of nanoparticles with varying characteristics to be resolved in a complex mixture. Changes in one or more of such properties can be followed both in real time and in situ.     

Interlaboratory comparison for the measurement of particle size and zeta potential of silica nanoparticles in an aqueous suspension

The Institute for Reference Materials and Measurements has organised an interlaboratory comparison (ILC) to allow the participating laboratories to demonstrate their proficiency in particle size and zeta potential measurements on monomodal aqueous suspensions of silica nanoparticles in the 10–100 nm size range. The main goal of this ILC was to identify competent collaborators for the production of certified nanoparticle reference materials. 38 laboratories from four different continents participated in the ILC with different methods for particle sizing and determination of zeta potential. Most of the laboratories submitted particle size results obtained with centrifugal liquid sedimentation (CLS), dynamic light scattering (DLS) or electron microscopy (EM), or zeta potential values obtained via electrophoretic light scattering (ELS). The results of the laboratories were evaluated using method-specific z scores, calculated on the basis of consensus values from the ILC. For CLS (13 results) and EM (13 results), all reported values were within the ±2 |z| interval. For DLS, 25 of the 27 results reported were within the ±2 |z| interval, the two other results were within the ±3 |z| interval. The standard deviations of the corresponding laboratory mean values varied between 3.7 and 6.5%, which demonstrates satisfactory interlaboratory comparability of CLS, DLS and EM particle size values. From the received test reports, a large discrepancy was observed in terms of the laboratory’s quality assurance systems, which are equally important for the selection of collaborators in reference material certification projects. Only a minority of the participating laboratories is aware of all the items that are mandatory in test reports compliant to ISO/IEC 17025 (ISO General requirements for the competence of testing and calibration laboratories. International Organisation for Standardization, Geneva, 2005b). The absence of measurement uncertainty values in the reports, for example, hindered the calculation of zeta scores.     

Size measurement uncertainties of near-monodisperse,near-spherical nanoparticles using transmission electron microscopy and particle-tracking analysis

Particle-tracking analysis (PTA) in combination with systematic imaging, automatic image analysis, and automatic data processing is validated for size measurements. Transmission electron microscopy (TEM) in combination with a systematic selection procedure for unbiased random image collection, semiautomatic image analysis, and data processing is validated for size, shape, and surface topology measurements. PTA is investigated as an alternative for TEM for the determination of the particle size in the framework of the EC definition of nanomaterial. The intra-laboratory validation study assessing the precision and accuracy of the TEM and PTA methods consists of series of measurements on three gold reference materials with mean area-equivalent circular diameters of 8.9 nm (RM-8011), 27.6 nm (RM-8012), and 56.0 nm (RM-8013), and two polystyrene materials with modal hydrodynamic diameters of 102 nm (P1) and 202 nm (H1). By obtaining a high level of automation, PTA proves to give precise and non-biased results for the modal hydrodynamic diameter in size range between 30 and 200 nm, and TEM proves to give precise and non-biased results for the mean area-equivalent circular diameter in the size range between 8 and 200 nm of the investigated near-monomodal near-spherical materials. The expanded uncertainties of PTA are about 9 % and are determined mainly by the repeatability uncertainty. This uncertainty is two times higher than the expanded uncertainty of 4 % obtained by TEM for analyses on identical materials. For the investigated near-monomodal and near-spherical materials, PTA can be used as an alternative to TEM for measuring the particle size, with exception of 8.9 nm gold, because this material has a size below the detection limit of PTA.     

Agglomeration,isolation and dissolution of commercially manufactured silver nanoparticles in aqueous environments

The increasing use of manufactured nanoparticles ensures these materials will make their way into the environment. Silver nanoparticles in particular, due to use in a wide range of applications, have the potential to get into water systems, e.g., drinking water systems, ground water systems, estuaries, and/or lakes. One important question is what is the chemical and physical state of these nanoparticles in water? Are they present as isolated particles, agglomerates or dissolved ions, as this will dictate their fate and transport. Furthermore, does the chemical and physical state of the nanoparticles change as a function of size or differ from micron-sized particles of similar composition? In this study, an electrospray atomizer coupled to a scanning mobility particle sizer (ES-SMPS) is used to investigate the state of silver nanoparticles in water and aqueous nitric acid environments. Over the range of pH values investigated, 0.5–6.5, silver nanoparticles with a bimodal primary particle size distribution with the most intense peak at 5.0 ± 7.4 nm, as determined from transmission electron microscopy (TEM), show distinct size distributions indicating agglomeration between pH 6.5 and 3 and isolated nanoparticles at pH values from 2.5 to 1. At the lowest pH investigated, pH 0.5, there are no peaks detected by the SMPS, indicating complete nanoparticle dissolution. Further analysis of the solution shows dissolved Ag ions at a pH of 0.5. Interestingly, silver nanoparticle dissolution shows size dependent behavior as larger, micron-sized silver particles show no dissolution at this pH. Environmental implications of these results are discussed.     

Effect of the particle temperature on lift force of nanoparticle in a shear rarefied flow

The nanoparticles suspended in a shear flow are subjected to a shear lift force, which is of great importance for the nanoparticle transport. In previous theoretical analysis on the shear lift, it is usually assumed that the particle temperature is equal to the temperature of the surrounding gas media. However, in some particular applications, the particle temperature can significantly differ from the gas temperature. In the present study, the effect of particle temperature on the shear lift of nanoparticles is investigated and the corresponding formulas of shear lift force are derived based on the gas kinetic theory. For extremely small nanoparticles(with radius R 2 nm) or large nanoparticles(R 20 nm), the influence of the particle temperature can be neglected. For the intermediate particle size, the relative error induced by the equal gas–particle temperature can be significant. Our findings can bring an insight into accurate evaluation of the nanoparticle transport properties.     

Characterisation of Grinding‐Relevant Particle Properties by Inverting a Population Balance Model

An approach for the quantitative characterisation of feed materials in impact grinding is presented. With the help of dimensional reasoning and a fracture mechanic model two material parameters can be derived which describe the breakage probability quantitatively. The influence of stress intensity (impact energy), stress number, initial particle size and material are separated clearly. The two derived material parameters can be determined by single particle impact experiments with narrow size fractions of the feed material. A single mastercurve for the selection function of five different polymers, limestone and glass describes the breakage behaviour for two decades of initial particle size. The procedure using narrow feed size fractions can be simplified by using feed material with a broad particle size distribution. Then the appropriate population balance has to be inverted in order to determine the particle properties. Both, the population balance and the inversion are presented and validated with experimental results.     

Multi-lognormal soot particle size distribution for time-resolved laser induced incandescence in diesel engines

In-cylinder and exhaust soot particle size measurements were carried out using time-resolved laser induced incandescence and electrical mobility spectrometer techniques in a single cylinder optical diesel engine and multi-cylinder high-speed diesel engine. The temporal decay of the laser induced incandescence signal from a polydisperse nanoparticle ensemble of soot during transient diesel combustion is shown to be described by both a single-lognormal distribution as well as multi-lognormal size distribution. However, a multi-lognormal particle size distribution is introduced in the existing model for a comprehensive characterisation and realistic reconstruction of the size distribution. Detailed theoretical analysis of multi-lognormal size distribution along with its application to the experimentally measured soot particle size is validated in this work. These results were also qualitatively compared and independently verified by the experimental results obtained by the electrical mobility spectrometer and published transmission electron microscopy data. These findings reveal that the in-cylinder and the exhaust soot particle size distributions in engines are better represented by a multi-lognormal size distribution.     

Task-based exposure assessment of nanoparticles in the workplace

Although task-based sampling is, theoretically, a plausible approach to the assessment of nanoparticle exposure, few studies using this type of sampling have been published. This study characterized and compared task-based nanoparticle exposure profiles for engineered nanoparticle manufacturing workplaces (ENMW) and workplaces that generated welding fumes containing incidental nanoparticles. Two ENMW and two welding workplaces were selected for exposure assessments. Real-time devices were utilized to characterize the concentration profiles and size distributions of airborne nanoparticles. Filter-based sampling was performed to measure time-weighted average (TWA) concentrations, and off-line analysis was performed using an electron microscope. Workplace tasks were recorded by researchers to determine the concentration profiles associated with particular tasks/events. This study demonstrated that exposure profiles differ greatly in terms of concentrations and size distributions according to the task performed. The size distributions recorded during tasks were different from both those recorded during periods with no activity and from the background. The airborne concentration profiles of the nanoparticles varied according to not only the type of workplace but also the concentration metrics. The concentrations measured by surface area and the number concentrations measured by condensation particle counter, particulate matter 1.0, and TWA mass concentrations all showed a similar pattern, whereas the number concentrations measured by scanning mobility particle sizer indicated that the welding fume concentrations at one of the welding workplaces were unexpectedly higher than were those at workplaces that were engineering nanoparticles. This study suggests that a task-based exposure assessment can provide useful information regarding the exposure profiles of nanoparticles and can therefore be used as an exposure assessment tool.     

Information Content of Acoustic Attenuation Spectra

In recent years ultrasonic attenuation spectroscopy has gained much attention as a method for the characterisation of concentrated dispersions. Several publications have shown, that this method allows the accurate determination of particle size. In particular for submicron dispersions there is, however, some uncertainty to which degree the details of a size distribution can be resolved by acoustic attenuation measurements. Ideally the inversion of an attenuation spectrum into a size distribution would yield as much distribution parameters as sound frequencies. In practice, however, the measurement errors affect the inversion very strongly and may result in multiple solutions for the size distribution. The maximum number of distribution parameters, for which a unique solution exists, can be therefore regarded as the information content. For a given ultrasonic spectrometer and material system it is possible to quantify the information content. Such an information analysis has been conducted with selected material systems in the submicron range. The investigation shows that the information content of acoustic attenuation spectra with regard to particle size analysis in the submicron range is relatively low. On the other hand, the results imply that the number of frequencies can be reduced significantly without loss of information content or stability of inversion algorithms.     

Fiber optic sensor based on surface plasmon resonance with nanoparticle films

This paper reports on a novel design of a fiber optic surface plasmon resonance (SPR) sensor based on nanoparticle metal film. The performance of the proposed sensor in terms of its signal-to-noise ratio (SNR) and sensitivity under different conditions related to the film with spherical gold nanoparticles embedded in a host material is theoretically analyzed. In particular, the effect of the parameters such as gold particle size, film thickness, and refractive index of host material is studied and the possible explanation, whenever required, is given. The numerical results presented in this paper leads to fulfill the requirement of significant optimization of the important design parameters to achieve a high SNR and sensitivity of a fiber optic SPR sensor with nanoparticle films.     

Morphological and elemental characterisation with the high-energy ion-nanoprobe LIPSION

This contribution deals with the morphological and elemental characterisation with high-energy (MeV) focused ion beams (in particular protons) with special emphasis on high spatial resolution in the sub-micrometer regime and very low minimum detection limits (sub-ppm) in trace element analysis. The most important methods like particle induced X-ray emission (PIXE), Rutherford backscattering spectrometry (RBS), as well as scanning transmission ion microscopy (STIM) and STIM-tomography will be illustrated by examples from material and life sciences.     

Self-assembled silver nanoparticles: correlation between structural and surface plasmon resonance properties

We report a facile method for controllable fabrication of high-density silver nanoparticle films with a widely adjustable surface plasmon resonance (SPR) frequency, based on the gas phase cluster beam deposition. On the one hand, we can control the particle size by depositing clusters on silica substrate. Light extinction spectra of the self-assembled Ag nanoparticles with various particle sizes are characterized and show two SPRs, in which a SPR exhibits a redshift from less 400 nm to more than 570 nm with an increase in the particle size, whereas the other shows a slight position shifting. On the other hand, the inter-particle distance of the self-assembled Ag nanoparticles can also be controlled by depositing clusters on silica glass coated with Formvar film, and the SPR wavelength shows a redshift from <400 nm to more than 560 nm, which can be attributed to the increase of the fraction of closely spaced nanoparticle pairs that are near-field coupled with the deposition mass. The size and coverage-dependent SPR properties are also compared with the results from the discrete dipole approximation calculations. The present method of tailoring metallic microstructures could find important applications in plasmonics.     

Efficient adsorption and photocatalytic degradation of Congo red onto hydrothermally synthesized NiS nanoparticles

The influence of the length of the cation alkyl chain on the dispersibility by ultrasonic treatment of TiO₂ nanopowders in hydrophilic imidazolium-based room temperature ionic liquids was studied for the first time by dynamic light scattering and advanced rheology. TiO₂ nanopowders had been synthesized by chemical vapor synthesis (CVS) under varied conditions leading to two different materials. A commercial nanopowder had been used for comparison. Characterizations had been done using transmission electron microscopy, X-ray diffraction, nitrogen adsorption with BET analysis, and FT-IR spectroscopy. Primary particle sizes were about 6 and 8 nm for the CVS-based and 26 nm for the commercial materials. The particle size distribution in the dispersion was strongly influenced by the length of the cation alkyl chain for all the investigated powders with different structural characteristics and concentrations in the dispersion. It was found that an increase of the alkyl chain length was beneficial, leading to a narrowing of the particle size distribution and a decrease of the agglomerate size in dispersion. The smallest average nanoparticle sizes in dispersion were around 30 nm. Additionally, the surface functionality of the nanoparticles, the concentration of the solid material in the liquid, and the period of ultrasonic treatment control the dispersion quality, especially in the case of the ionic liquids with the shorter alkyl chain. The influence of the nanopowders characteristics on their dispersibility decreases considerably with increasing cation alkyl chain length. The results indicate that ionic liquids with adapted structure are candidates as absorber media for nanoparticles synthesized in gas phase processes to obtain liquid dispersions directly without redispergation.     

Effects of Al(OH)O nanoparticle agglomerate size in epoxy resin on tension,bending, and fracture properties

Several epoxy Al(OH)O (boehmite) dispersions in an epoxy resin are produced in a kneader to study the mechanistic correlation between the nanoparticle size and mechanical properties of the prepared nanocomposites. The agglomerate size is set by a targeted variation in solid content and temperature during dispersion, resulting in a different level of stress intensity and thus a different final agglomerate size during the process. The suspension viscosity was used for the estimation of stress energy in laminar shear flow. Agglomerate size measurements are executed via dynamic light scattering to ensure the quality of the produced dispersions. Furthermore, various nanocomposite samples are prepared for three-point bending, tension, and fracture toughness tests. The screening of the size effect is executed with at least seven samples per agglomerate size and test method. The variation of solid content is found to be a reliable method to adjust the agglomerate size between 138–354 nm during dispersion. The size effect on the Young’s modulus and the critical stress intensity is only marginal. Nevertheless, there is a statistically relevant trend showing a linear increase with a decrease in agglomerate size. In contrast, the size effect is more dominant to the sample’s strain and stress at failure. Unlike microscaled agglomerates or particles, which lead to embrittlement of the composite material, nanoscaled agglomerates or particles cause the composite elongation to be nearly of the same level as the base material. The observed effect is valid for agglomerate sizes between 138–354 nm and a particle mass fraction of 10 wt%.     

Comparison of nanoparticle measurement instruments for occupational health applications

Nanoparticles are used in many applications because of their novel properties compared to bulk material. A growing number of employees are working with nanomaterials and their exposure to nanoparticles trough inhalation must be evaluated and monitored continuously. However, there is an ongoing debate in the scientific literature about what are the relevant parameters to measure to evaluate exposure to level. In this study, three types of nanoparticles (ammonium sulphate, synthesised TiO₂ agglomerates and aerosolised TiO₂ powder, modes in a range of 30–140 nm mobility size) were measured with commonly used aerosol measurement instruments: scanning and fast mobility particle sizers (SMPS, FMPS), electrical low pressure impactor (ELPI), condensation particle counter (CPC) together with nanoparticle surface area monitor (NSAM) to achieve information about the interrelations of the outputs of the instruments. In addition, the ease of use of these instruments was evaluated. Differences between the results of different instruments can mainly be attributed to the nature of test particles. For spherical ammonium sulphate nanoparticles, the data from the instruments were in good agreement while larger differences were observed for particles with more complex morphology, the TiO₂ agglomerates and powder. For instance, the FMPS showed a smaller particle size, a higher number concentration and a narrower size distribution compared with the SMPS for TiO₂ particles. Thus, the type of the nanoparticle was observed to influence the data obtained from these different instruments. Therefore, care and expertise are essential when interpreting results from aerosol measurement instruments to estimate nanoparticle concentrations and properties.     

Characterisation of silica nanoparticles prior to in vitro studies: from primary particles to agglomerates

The size, surface charge and agglomeration state of nanoparticles under physiological conditions are fundamental parameters to be determined prior to their application in toxicological studies. Although silica-based materials are among the most promising candidates for biomedical applications, more systematic studies concerning the characterisation before performing toxicological studies are necessary. This interest is based on the necessity to elucidate the mechanisms affecting its toxicity. We present here TEM, SAXS and SMPS as a combination of methods allowing an accurate determination of single nanoparticle sizes. For the commercial material, Ludox TM50 single particle sizes around 30 nm were found in solution. DLS measurements of single particles are rather affected by polydispersity and particles concentration but this technique is useful to monitor their agglomeration state. Here, the influence of nanoparticle concentration, ionic strength (IS), pH and bath sonication on the agglomeration behaviour of silica particles in solution has been systematically investigated. Moreover, the colloidal stability of silica particles in the presence of BSA has been investigated showing a correlation between silica and protein concentrations and the formation of agglomerates. Finally, the colloidal stability of silica particles in standard cell culture medium has been tested, concluding the necessity of surface modification in order to preserve silica as primary particles in the presence of serum. The results presented here have major implications on toxicity investigations because silica agglomeration will change the probability and uptake mechanisms and thereby may affect toxicity.     

Particle size prediction of magnesium nanoparticle produced by inert gas condensation method

Properties of nanoparticles are normally depending on particle size; therefore, developing a model to predict particle size is of vital importance. This paper established an energy analysis model to predict average particle size of magnesium nanoparticles fabricated by inert gas condensation method. Predictions of average particle size ranging from 20 to 50 nm by energy analysis model have relative errors of less than 10% compared with experimental research. Further, the model is applied to investigate operation conditions to decrease the average particle size of magnesium nanoparticles. It is found that decreasing the absolute pressure in the condensation room and increasing the temperature rise of the inert gas can both produce nanoparticles with smaller average particle sizes. Temperature rise of the inert gas plays a more important role in effect on average nanoparticle size than the absolute pressure in the condensation room. Energy transformed by collision bonding and dissipated by convection are the dominant processes for particle growth when number of atoms in one particle is greater than 2000 atoms.     

Influence of synthesis parameters on iron nanoparticle size and zeta potential

Zero valent iron nanoparticles are of increasing interest in clean water treatment applications due to their reactivity toward organic contaminants and their potential to degrade a variety of compounds. This study focuses on the effect of organophosphate stabilizers on nanoparticle characteristics, including particle size distribution and zeta potential, when the stabilizer is present during nanoparticle synthesis. Particle size distributions from DLS were obtained as a function of stabilizer type and iron precursor (FeSO₄·7H₂O or FeCl₃), and nanoparticles from 2 to 200 nm were produced. Three different organophosphate stabilizer compounds were compared in their ability to control nanoparticle size, and the size distributions obtained for particle volume demonstrated differences caused by the three stabilizers. A range of stabilizer-to-iron (0.05–0.9) and borohydride-to-iron (0.5–8) molar ratios were tested to determine the effect of concentration on nanoparticle size distribution and zeta potential. The combination of ferrous sulfate and ATMP or DTPMP phosphonate stabilizer produced stabilized nanoparticle suspensions, and the stabilizers tested resulted in varying particle size distributions. In general, higher stabilizer concentrations resulted in smaller nanoparticles, and excess borohydride did not decrease nanoparticle size. Zeta potential measurements were largely consistent with particle size distribution data and indicated the stability of the suspensions. Probe sonication, as a nanoparticle resuspension method, was minimally successful in several different organic solvents.