Tunable Resistive Pulse Sensing (TRPS) and Dynamic Light Scattering (DLS) are two particle measurement techniques based on very different principles. Both TRPS and DLS are used to varying degrees to assess the physical parameters and polydispersity of particle populations across many disciplines, including the nanomedicine/pharmaceutical industry (e.g. lipid nanoparticles and liposomes), virology, and the study of exosomes and other extracellular vesicles. How Does TRPS Measure Nanoparticles? Tunable Resistive Pulse Sensing (TRPS) monitors current flow through a tunable nanopore. Particles crossing the nanopore cause transient changes in the flow of an ionic current, which can be detected and analysed via the resulting blockades. Each particle size is determined for individual particles; blockade magnitude is proportional to particle size, and particle concentration is calculated from the particle flow rate measured at several different applied pressures. Zeta potential (a measure of the effective surface charge) is derived by measuring electrophoretic mobility, which is calculated based on the speed at which the particle traverses the nanopore. Why Choose TRPS over DLS? For those looking to gain real insights into the size and concentration, or size and zeta potential, of particles in their sample, Tunable Resistive Pulse Sensing (TRPS) is a far superior technique. Unlike Dynamic Light Scattering (DLS), which is an ensemble technique that measures the average intensity of light scattered by particles in a solution, TRPS is a single-particle analytical method and uses more direct measurements of physical characteristics. This allows you to detect subtle differences between subpopulations of particles in your sample – differences which may be critical indicators of sample stability, aggregation, or differences in drug loading efficiency. With DLS, these subtle differences can easily be missed. TRPS enables high-resolution particle measurement (40 nm to > 11 µm), allowing a wide range of particle types to be characterised. Unlike DLS, TRPS measurements are independent of the particle or dispersant's optical properties, allowing you to confidently measure samples with heterogenous optical densities. With DLS, larger particles tend to be overestimated, distorting the particle distribution and obscuring smaller particles due to the sextic dependence of light-scattering intensity. The ensemble approach of DLS limits subpopulation identification; a recent study showed Multi-Angle Dynamic Light Scattering (MADLS) failing to identify subpopulations within quadrimodal samples, whereas TRPS could identify all four subpopulations. Finally, whilst TRPS measures actual diameter, DLS can only measure hydrodynamic radius. Whilst this is not inherently inferior in many circumstances, the actual diameter may be favoured by some regulatory bodies in the nanomedicine space. Contrasting TRPS and DLS Abilities in Different Applications Given its ability to accurately and reproducibly resolve samples to a high level of resolution, Tunable Resistive Pulse Sensing (TRPS) lends itself to a wide range of applications across biological and pharmaceutical research and development. TRPS has filled the unmet need for precise characterisation for a range of particle types. In the context of measuring exosomes and other extracellular vesicles (EVs), TRPS is commonly used to identify differences in EV concentration under different physiological conditions, verify the presence of EVs via measurements of particle size distribution, and identify changes to zeta potential under different conditions (e.g. studies of EV storage conditions). In nanomedicine, TRPS has far-reaching applications, enabling stability and characterisation studies across the development of monoclonal antibodies, lipid nanoparticles, virus-like particle vaccines, and virus preparations. In summary, compared to DLS, TRPS can offer far deeper insights into the properties of your nanoparticles. Tunable Resistive Pulse Sensing (TRPS) - Single-particle technique - Using appropriately sized nanopores, particles can be measured across a wide size range (40 nm–11 µm) - Automated data processing with user-friendly data visualisation interface. - Single-particle resolution - Number-weighted analysis - Diameter is directly proportional to blockade size - Can resolve populations in multimodal samples - Not dependent on optical properties of particles and dispersant
