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.
Highlights
Zeta potential, which is indicative of the particle surface charge, is an important and widely used characterisation method of nanometer-sized objects in liquids, such as pharmaceuticals, inks, foams, liposomes and exosomes
It was shown that tunable resistive pulse sensing (TRPS), using conical thermoplastic polyurethane pores, is able to measure the zeta potential of individual particles based on the duration of the resistive pulse signal[12,13,14,15]
From the inverse translocation time versus voltage dependency electrophoretic mobility and consecutively zeta potentials were calculated, which is comparable to the approach reported by Blundell et al.[15] and Sikora et al.[12]
Summary
Zeta potential, which is indicative of the particle surface charge, is an important and widely used characterisation method of nanometer-sized objects in liquids, such as pharmaceuticals, inks, foams, liposomes and exosomes. Ito et al used a comparable approach to determine the electrophoretic mobility of polystyrene nanoparticles using carbon-nanotube based pores[9,10,11]. From the inverse translocation time versus voltage dependency electrophoretic mobility and consecutively zeta potentials were calculated, which is comparable to the approach reported by Blundell et al.[15] and Sikora et al.[12]. There exist numerous advantages of this convection inclusive approach compared with the methods described above, where electrophoresis dominates particle motion. These include the measurement of a wider spectrum of zeta potentials, the evaluation of very dilute particle suspensions and an increase in measurement resolution and accuracy. The unique capability of TRPS to simultaneously measure particle size and zeta potential on a particle-by-particle basis represents a new approach for investigating and understanding the heterogeneous properties of particle dispersions
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