A Cross-Method Comparison of Sub-10 nm Nanoparticle Size Distribution

27 September 2019, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Accurate nanoparticle (NP) size determination is essential across research domains, with many functions in nanoscience and biomedical research being size-dependent. Although transmission electron microscopy (TEM) is capable of resolving a single NP down to the sub-nm scale, the reliable representation of entire populations is plagued by challenges in providing statistical significance, predominantly due to limited sample counts, suboptimal preparation procedures and operator bias during image acquisition and analysis. Meanwhile alternative techniques exist, but reliable implementation requires a detailed understanding of appendant limitations. Herein, conventional TEM is compared to the size determination of sub-10 nm gold NPs in solution by small-angle X-ray scattering and analytical ultracentrifugation. Form-free Monte Carlo fitting of scattering profiles offers access to a direct representation of the core size distribution while ultracentrifugation sedimentation velocity analysis provides information of the hydrodynamic size distribution. We report a comparison of these three methods in determining the size of quasi-monodisperse, polydisperse and bimodal gold nanoparticles of 2 – 7 nm and discuss advantages and limitations of each technique.


Monte Carlo
Size Determination

Supplementary materials

SI Cross-method size determination final(v7)


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