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Cavity Amplified Scattering Spectroscopy reveals the dynamics of proteins and nanoparticles in quasi-transparent and miniature samples

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posted on 2023-01-10, 02:23 authored by Guillaume Graciani, John T. King, Francois Amblard
Dynamic light scattering techniques are routinely used for numerous industrial and research applications, because they can give access to the motion spectrum of micro- and nano-objects, and therefore to particle sizes or visco-elastic properties. However, measurements are impossible when samples do not scatterer light enough, i.e. when there are too few scattering events due to excessively small scattering cross-sections and/or low concentrations of scatterers. Here, we propose to amplify light scattering efficiency by placing weakly scattering samples inside a Lambertian cavity with high reflectance walls. It produces a 3D isotropic and homogeneous light field that effectively elongates the scattering pathlength by 2 to 3 orders of magnitude, and leads to a dramatic increase in sensitivity. We could indeed measure the diffusion coefficient and size of particles ranging from 5nm to 20 microns with volume fractions as low at 10^(-9) in volumes as low as 100 microliters, and in solvents with refractive index mismatches down to 0.01. With a 10^(4) fold increase in sensitivity compared to classical techniques, we considerably expand the applications of light scattering to highly diluted samples, miniaturized microfluidics samples, and samples practically deemed non-scattering. Beyond the realm of current applications of light scattering techniques, our Cavity Amplified Scattering Spectroscopy method (CASS) and its outstanding sensitivity represent a major methodological step towards the study of problems such as the ballistic limit of Brownian motion, the internal dynamics of proteins, or the low frequency dielectric dynamics of liquids.

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