Gain Deeper Insights with High-Precision Zeta Potential Measurement

Distinguish Subpopulations with High-Resolution Insights

Simultaneous measurements of size and zeta potential enable in-depth sample comparisons and allow you to identify subpopulations within a multimodal sample. This powerful TRPS capability is illustrated particularly well in a Scientific Reports study by Vogel et al (2017), whereby subpopulations of particles in a multimodal sample were clearly distinguished – both when analysed separately (pink/blue/purple) and together (peach). The high-resolution nature of TRPS lends itself to detecting subtle shifts in sample stability.

Obtain Valuable Single-Particle Measurements, Not Averages

Without detailed data that shows you what’s really going on with your sample, physical characterisation can essentially become a ‘box-ticking exercise’. With TRPS, however, you characterise your particles and arm yourself with information that informs your next move. For example, to optimise and refine your production protocols, compare storage conditions for extracellular vesicle research, or compare lipid nanoparticle formulations.

This unique capability is illustrated through a comparison of tunable resistive pulse sensing (TRPS, top) and phase analysis light scattering (PALS, bottom) analysis. Here, TRPS could resolve the two particle populations, while an average value was provided through PALS.

Measure Size & Zeta Potential Simultaneously

Measuring size and zeta potential of particles simultaneously has incredible benefits for a wide range of applications and industries. Tunable Resistive Pulse Sensing (TRPS) is able to do this on a particle-by-particle basis with high reliability and reproducibility. It represents a new approach for understanding and researching the intrinsic behaviour of nanoscale distributions. Since these nanoparticle properties have been seen to play a central role in biological interactions, including influencing, their uptake by the target tissues/cells, TRPS allows for the investigation and better understanding of things such as nanoparticle-based delivery of microRNA. This in turn could be used for many therapeutic applications, such as overcoming drug resistance, in cancer therapy and in diagnostics. TRPS instruments are also the only devices on the market that can do this simultaneously and accurately. The high-resolution single particle size and zeta potential characterisation will positively impact developmental nanomedicine by providing a better understanding of nano-bio interactions.

Charge Measurement in Physiological-Strength Buffer

Particle dispersions and formulations are stabilized by electrostatic repulsion, steric hindrance, or a combination of these two forces. Particles will eventually aggregate in the absence of sufficient stabilisation. Researchers use zeta potential as an indicator of electrostatic stabilisation of particles. Zeta potential is a modelled quantity derived by measuring electrophoretic mobility of particles in suspension. Electrophoretic mobility is critically dependent on particle and solution properties (ionic strength, ionic composition, and viscosity). Thus, it’s important to perform zeta analysis for nanoparticles or nano-formulations in physiological buffer(s) designed for biological applications.

High-resolution single particle zeta analysis will provide an advanced understanding of particle behaviour in different pH and salt conditions and aid in monitoring particle corona evolution over time for biokinetic studies. Moreover, determination of accurate charge on each particle could provide potential insights into nano-bio interactions in varying physiological buffers, critical for determining particle stability and uptake; impacting the overall delivered particle dosage.

Final Scale Precision

Tunable Resistive Pulse Sensing (TRPS) alone provides the means to distinguish particles through fine scale mapping of zeta potential of individual particles. The surface charge of membranous vesicles arise from the combined net charge of extrinsic moieties on the vesicle surface. Using TRPS, subtle changes in surface charge can be resolved as the membrane composition is altered.  

TRPS can also be used to monitor changes in zeta potential through particle-ligand interaction in real time. This is demonstrated below in the binding of biotinylated single stranded DNA (35 bases) to the surface of a streptavidin coated particle. The diffusion dependent binding reaction goes to completion within approximately 170 sec after the addition of DNA at 30 sec, the binding of the DNA coincides with a reduction in the zeta potential. The resolution limit was 10% of the oligo coverage. For example, the resolution limit was 44 oligos per particle for particles with a DNA/particle ratio of 400. The control reaction which uses streptavidin that has been enzymatically inactivated by proteinase K shows no DNA interaction. With longer oligos the sensitivity is increased. TRPS provides researchers with the tool for advanced charge studies of particle-particle interactions, zeta based vesicle characterisation, receptor-ligand interactions that may result in altered charge of the carrier particle, charge reporting antibody-antigen reactions and aptamer based detection technologies.