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

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.