Reference materials and representative test materials to develop nanoparticle characterization methods: the NanoChOp project case

This paper describes the production and characteristics of the nanoparticle test materials prepared for common use in the collaborative research project NanoChOp (Chemical and optical characterization of nanomaterials in biological systems), in casu suspensions of silica nanoparticles and CdSe/CdS/ZnS quantum dots (QDs). This paper is the first to illustrate how to assess whether nanoparticle test materials meet the requirements of a "reference material" (ISO Guide 30, 2015) or rather those of the recently defined category of "representative test material (RTM)" (ISO/TS 16195, 2013). The NanoChOp test materials were investigated with small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and centrifugal liquid sedimentation (CLS) to establish whether they complied with the required monomodal particle size distribution. The presence of impurities, aggregates, agglomerates, and viable microorganisms in the suspensions was investigated with DLS, CLS, optical and electron microscopy and via plating on nutrient agar. Suitability of surface functionalization was investigated with attenuated total reflection Fourier transform infrared spectrometry (ATR-FTIR) and via the capacity of the nanoparticles to be fluorescently labeled or to bind antibodies. Between-unit homogeneity and stability were investigated in terms of particle size and zeta potential. This paper shows that only based on the outcome of a detailed characterization process one can raise the status of a test material to RTM or reference material, and how this status depends on its intended use

An interlaboratory comparison on the characterization of a sub-micrometer polydisperse particle dispersion

The measurement of polydisperse protein aggregates and particles in biotherapeutics remains a challenge, especially for particles with diameters of ≈ 1 µm and below (sub-micrometer). This paper describes an interlaboratory comparison with the goal of assessing the measurement variability for the characterization of a sub-micrometer polydisperse particle dispersion composed of five sub-populations of poly(methyl methacrylate) (PMMA) and silica beads. The study included 20 participating laboratories from industry, academia, and government, and a variety of state-of-the-art particle-counting instruments. The received datasets were organized by instrument class to enable comparison of intralaboratory and interlaboratory performance. The main findings included high variability between datasets from different laboratories, with coefficients of variation from 13 % to 189 %. Intralaboratory variability was, on average, 37 % of the interlaboratory variability for an instrument class and particle sub-population. Drop-offs at either end of the size range and poor agreement on maximum counts of particle sub-populations were noted. The mean distributions from an instrument class, however, showed the size-coverage range for that class. The study shows that a poly-disperse sample can be used to assess performance capabilities of an instrument set-up (including hardware, software, and user settings) and provides guidance for the development of polydisperse reference materials.Drug Delivery Technolog

Validation of a particle tracking analysis method for the size determination of nano- and microparticles.

&lt;p&gt;Particle tracking analysis (PTA) is an emerging technique suitable for size analysis of particles with external dimensions in the nano- and sub-micrometre scale range. Only limited attempts have so far been made to investigate and quantify the performance of the PTA method for particle size analysis. This article presents the results of a validation study during which selected colloidal silica and polystyrene latex reference materials with particle sizes in the range of 20 nm to 200 nm were analysed with NS500 and LM10-HSBF NanoSight instruments and video analysis software NTA 2.3 and NTA 3.0. Key performance characteristics such as working range, linearity, limit of detection, limit of quantification, sensitivity, robustness, precision and trueness were examined according to recommendations proposed by EURACHEM. A model for measurement uncertainty estimation following the principles described in ISO/IEC Guide 98-3 was used for quantifying random and systematic variations. For nominal 50 nm and 100 nm polystyrene and a nominal 80 nm silica reference materials, the relative expanded measurement uncertainties for the three measurands of interest, being the mode, median and arithmetic mean of the number-weighted particle size distribution, varied from about 10% to 12%. For the nominal 50 nm polystyrene material, the relative expanded uncertainty of the arithmetic mean of the particle size distributions increased up to 18% which was due to the presence of agglomerates. Data analysis was performed with software NTA 2.3 and NTA 3.0. The latter showed to be superior in terms of sensitivity and resolution.&lt;/p&gt;</p

A comparison of techniques for size measurement of nanoparticles in cell culture medium

Four common size analysis techniques were applied to engineered silica nanoparticles suspended in purified water, in physiological buffer and in cell culture medium, and the results were compared using uncertainty estimates.</p

Hydrophilization of Magnetic Nanoparticles with Modified Alternating Copolymers. Part 2: Behavior in Solution

Aqueous solutions of iron oxide nanoparticles (NPs) stabilized by poly(maleic acid-alt-1-octadecene) (PMAcOD) modified with the 5,000 Da poly(ethylene glycol) (PEG) or the short ethylene glycol (EG) tails were analyzed by small-angle X-ray scattering (SAXS). Advanced SAXS data analysis methods were employed to systematically characterize the structure and interactions between the NPs. Depending on the type of the grafted tail and the grafting density all NPs can be separated into three groups. All the samples contain mixtures of individual nanoparticles, their dynamic clusters and aggregates, and the fractions of these species are different in the different groups. The first group consists of NPs coated with PMAcOD modified with the long PEG tails with the maximal grafting density, and the content of dynamic clusters and aggregates in the samples of this group does not exceed 4%. The samples from the second group with less dense coatings demonstrate a larger amount (5-7%) of the aggregates and dynamic clusters. The samples from the third group consisting of the NPs protected by EG modified PMAcOD contain mostly individual NPs and some amount of dumbbell dimers without noticeable aggregation. Importantly, the solution behavior of the NPs is independent on the iron oxide core size. Our results therefore provide means of predicting stabilization and avoiding aggregation of NPs based on the type of a protective shell