TL;DR: The interference signal of sugar-containing solutions in DLS and NTA is due to the presence of nanoparticulate impurities, and nanoparticles present in sucrose were found to be responsible for the interference.
Abstract: Purpose
In the present study we investigated the root-cause of an interference signal (100–200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products.
TL;DR: The effects of product and instrument parameters on NTA results for nanoparticle standards and therapeutic protein samples, and the effects of protein concentration on nanoparticle characterization, were investigated.
TL;DR: Thorough characterization of particulate matter present in protein therapeutics is limited by the lack of analytical methods for particles in the sub-micron size range, and Nanoparticle Tracking Analysis is evaluated as a potential tool for biologic development.
Abstract: Nanoparticle Tracking Analysis (NTA) is an emerging analytical technique developed for detection, sizing, and counting of sub-micron particles in liquid media. Its feasibility for use in biopharmaceutical development was evaluated with particle standards and recombinant protein solutions. Measurements of aqueous suspensions of NIST-traceable polystyrene particle standards showed accurate particle concentration detection between 2 × 107 and 5 × 109 particles/mL. Sizing was accurate for particle standards up to 200 nm. Smaller than nominal value sizes were detected by NTA for the 300–900 nm particles. Measurements of protein solutions showed that NTA performance is solution-specific. Reduced sensitivity, especially in opalescent solutions, was observed. Measurements in such solutions may require sample dilution; however, common sample manipulations, such as dilution and filtration, may result in particle formation. Dilution and filtration case studies are presented to further illustrate such behavior. To benchmark general performance, NTA was compared against asymmetric flow field flow fractionation coupled with multi-angle light scattering (aF4-MALS) and dynamic light scattering, which are other techniques for sub-micron particles. Data shows that all three methods have limitations and may not work equally well under certain conditions. Nevertheless, the ability of NTA to directly detect and count sub-micron particles is a feature not matched by aF4-MALS or dynamic light scattering. LAY ABSTRACT: Thorough characterization of particulate matter present in protein therapeutics is limited by the lack of analytical methods for particles in the sub-micron size range. Emerging techniques are being developed to bridge this analytical gap. In this study, Nanoparticle Tracking Analysis is evaluated as a potential tool for biologics development. Our results indicate that method performance is molecule-specific and may not work as well under all solution conditions, especially when testing opalescent solutions. Advantages and disadvantages of Nanoparticle Tracking Analysis are discussed in comparison to other analytical techniques for particles in the sub-micron size range.
TL;DR: The combination of NTA and MFI provided novel insight into the kinetics and mechanism of protein-polyelectrolyte complex formation, which was validated by studying particle growth kinetics in IgG:DS mixtures of different concentrations.
TL;DR: Direct observations of changes in absolute particle size distributions from NTA enhance both qualitative and quantitative understanding of particle separation processes of nano-sized particles.
TL;DR: In this article, the authors presented some advantages of nanoparticle tracking analysis (NTA) method in comparison to DLS, which is the most popular technique for particle size characterization.
Abstract: The most popular technique for particle size characterization is the dynamic light scattering (DLS). In recent years new advanced method based on counting each single particle movement was introduced giving perspective for measurement of each component of mixture. This study presents some advantages of nanoparticle tracking analysis (NTA) method in comparison to DLS. For tests standard polystyrene beds were chosen vary diameter of 22, 61 and 150 nm and its mixtures. Experiments showed that the particles size resolution allows to distinguish each population in two population suspension opposed to DLS. The NTA method permits to eliminate the negative effects i.e. dust or aggregates in sample during post processing, that permits to use it in a variety of studies.
TL;DR: The NTA technique is suitable for characterization of submicron particles in a studied therapeutic protein, however, the NTA can only be used as a semiquantitative methodology, because frequent sample dilution is required to achieve optimal particle concentration.
TL;DR: In this paper, the authors carried out tests on columns with soil collected in the landfill Volta Redonda located in the state of Rio de Janeiro, Brazil, and analyzed the concentrations of TiO2, as well as the distribution of the size of its aggregates by Nanoparticle Tracking Analysis.
Abstract: RESUMO – The study of nanoparticles involves a new bias research in various areas of technology, whose production and use have been offering multiple benefits to society. However, the uncontrolled emission to the environment of nanoparticles is growing exponentially over the last decade. Thus, knowledge of the influence of nanoparticles and how they can modify the ecosystem is extremely important and an area currently limited. Therefore, it is of fundamental importance to increase the knowledge of the fate and transport of nanoparticles in soil, in particular this research will study the TiO2 nanoparticles (TiNPs). This study will carry out tests on columns with soil collected in the landfill Volta Redonda located in the state of Rio de Janeiro, Brazil. The concentrations are analyzed TiO2, as well as the distribution of the size of its aggregates by Nanoparticle Tracking Analysis (NTA).