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1.
Sci Rep ; 7(1): 17479, 2017 12 12.
Article in English | MEDLINE | ID: mdl-29234015

ABSTRACT

Physicochemical properties of nanoparticles, such as size, shape, surface charge, density, and porosity play a central role in biological interactions and hence accurate determination of these characteristics is of utmost importance. Here we propose tunable resistive pulse sensing for simultaneous size and surface charge measurements on a particle-by-particle basis, enabling the analysis of a wide spectrum of nanoparticles and their mixtures. Existing methodologies for measuring zeta potential of nanoparticles using resistive pulse sensing are significantly improved by including convection into the theoretical model. The efficacy of this methodology is demonstrated for a range of biological case studies, including measurements of mixed anionic, cationic liposomes, extracellular vesicles in plasma, and in situ time study of DNA immobilisation on the surface of magnetic nanoparticles. The high-resolution single particle size and zeta potential characterisation will provide a better understanding of nano-bio interactions, positively impacting nanomedicine development and their regulatory approval.


Subject(s)
Chemistry Techniques, Analytical/methods , Nanoparticles/chemistry , Nanotechnology/methods , DNA/chemistry , Extracellular Vesicles/chemistry , Humans , Kinetics , Light , Liposomes/chemistry , Models, Theoretical , Nanopores , Particle Size , Polystyrenes/chemistry , Reproducibility of Results , Scattering, Radiation
2.
J Extracell Vesicles ; 5: 31242, 2016.
Article in English | MEDLINE | ID: mdl-27680301

ABSTRACT

BACKGROUND: Understanding the pathogenic role of extracellular vesicles (EVs) in disease and their potential diagnostic and therapeutic utility is extremely reliant on in-depth quantification, measurement and identification of EV sub-populations. Quantification of EVs has presented several challenges, predominantly due to the small size of vesicles such as exosomes and the availability of various technologies to measure nanosized particles, each technology having its own limitations. MATERIALS AND METHODS: A standardized methodology to measure the concentration of extracellular vesicles (EVs) has been developed and tested. The method is based on measuring the EV concentration as a function of a defined size range. Blood plasma EVs are isolated and purified using size exclusion columns (qEV) and consecutively measured with tunable resistive pulse sensing (TRPS). Six independent research groups measured liposome and EV samples with the aim to evaluate the developed methodology. Each group measured identical samples using up to 5 nanopores with 3 repeat measurements per pore. Descriptive statistics and unsupervised multivariate data analysis with principal component analysis (PCA) were used to evaluate reproducibility across the groups and to explore and visualise possible patterns and outliers in EV and liposome data sets. RESULTS: PCA revealed good reproducibility within and between laboratories, with few minor outlying samples. Measured mean liposome (not filtered with qEV) and EV (filtered with qEV) concentrations had coefficients of variance of 23.9% and 52.5%, respectively. The increased variance of the EV concentration measurements could be attributed to the use of qEVs and the polydisperse nature of EVs. CONCLUSION: The results of this study demonstrate the feasibility of this standardized methodology to facilitate comparable and reproducible EV concentration measurements.

3.
Pharm Res ; 29(9): 2578-86, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22638870

ABSTRACT

PURPOSE: To explore the application of scanning ion occlusion sensing (SIOS) as a novel technology for characterization of nanoparticles. METHODS: Liposomes were employed as model nanoparticles. The size distribution of the liposomes was measured by both SIOS and dynamic light scattering (DLS). Particle number concentration was determined based on particle translocation rate. The ability of SIOS and DLS to resolve bimodal samples was evaluated by measuring a mixture of 217 and 355 nm standard nanoparticles. Opsonization of liposomes by plasma was also studied using SIOS. RESULTS: SIOS was shown to measure the size of different liposomes with higher sensitivity than DLS and it requires a smaller sample volume than DLS. With appropriate calibration, SIOS could be used to determine particle number concentrations. In comparison, SIOS analysis of the mixture showed accurate resolution of the population as a bimodal distribution over a wide range of number ratios of the particles. SIOS could detect plasma opsonization of liposomes by demonstrating a increase in particle size and also changes in the particle translocation rate. CONCLUSION: SIOS is a useful technology for nanoparticle characterization. It shows some advantages over DLS and is clearly a useful tool for the study of nanoparticle drug delivery systems.


Subject(s)
Drug Delivery Systems , Nanoparticles , Particle Size , Scattering, Radiation
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