Why can't regular Dynamic Light Scattering (DLS) be used to accurately measure a flowing suspension? How can we tackle this problem?

If a flowing suspension of nanoparticles (i.e., LNPs) is measured by means of DLS, the measured particle size is inaccurate and can be completely misleading.

DLS is based on illuminating a particle dispersion and then analyzing the fluctuations of the scattered light. These fluctuations are directly related to the diffusing speed of the dispersed particles, which diffuse naturally by Brownian motion. Via the analysis of correlation functions of the scattered light signal, it is possible to infer the corresponding diffusion constant of the particles, which can be related to particle size by means of the Einstein-Stokes relation.

The problem with a flowing system is that particles have then a compounded velocity: Brownian diffusion plus the flow speed. If it were not convoluted enough, inside a tubing flow is not uniform: it has a boundary value of 0 at the wall, and increases towards the center of the tube. Therefore, inside the illuminated volume of a standard DLS system particles have a very complex distribution of velocities compounded by their Brownian behavior and the complex flow profile inside the tubing.

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How does flow affect the particle size measurement?

Particle size, as per Einstein-Stokes, is inversely proportional to the diffusion constant of the particles. In other words, bigger particles diffuse slowly, while smaller particles diffuse faster. Since particles in a flowing system have increased average velocities (Brownian diffusion plus flow speed), the measured diffusion constant via DLS is higher (faster) than it would be for a static system. This results in an inaccurate calculated particle size, with an average particle size lower than it would be measured for the same system in static conditions. For strong flows, errors can become very significant, producing totally unrepresentative results.

How does Spatially Resolved DLS (the NanoFlowSizer) tackle this problem?

Spatially Resolved DLS (SR-DLS, the base of the NanoFlowSizer) can slice the illuminated volume to get depth resolved data by exploiting Optical Coherence Tomography (OCT) principles. If the flow is then perpendicular to the illumination direction, the depth resolved data can be used to reconstruct the complex flow profile in the tubing and correct for flow effects. This effectively yields a flow-free measurement, from which the pure Brownian motion diffusion constant can be extracted, and thus the accurate particle size.

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For more technical information on SR-DLS: https://www.sciencedirect.com/science/article/abs/pii/S0928098719301332?via%3Dihub

More information on the NanoFlowSizer: www.inprocess-lsp.com

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