Size distributions of gold nanoparticles in solution measured by single-particle mass photometry

Abstract

Measurements of nanoparticle size distributions are crucial for many advanced applications. Detection efficiency often scales non-linearly with diameter and this diminishes the accuracy of determinations in a range smaller than tens of nanometers.As a result, the accurate classification of broadly distributed systems requires very large numbers of measurements. This presents a problem for conventional techniques, which are labour intensive, and so have low throughput. Progress in many areas of nanotechnology requires a faster, lower-cost and more accurate measure of particle size distributions, particularly for diameters smaller than 20 nm. Here, we present a tailored interferometric microscope system, combined with a high-speed image-processing strategy, optimized for real-time particle tracking that determines accurate size distributions in nominal 5, 10 and 15 nm colloidal gold nanoparticle systems by automatically sensing and classifying thousands of single particles in solution at rates as high as 4,000 particles per minute. We demonstrate this method by sensing the irreversible binding of gold nanoparticles to poly-D-lysine functionalized coverslips. Variations in the single particle signal as a function of mass and time show clear evidence for the presence of diffusion-limited transport that most affects larger particles in solution.