Abstract

Single-particle reconstruction can be used to perform three-dimensional (3D) imaging of homogeneous populations of nano-sized objects, in particular viruses and proteins. Here, it is demonstrated that it can also be used to obtain 3D reconstructions of heterogeneous populations of inorganic nanoparticles. An automated acquisition scheme in a scanning transmission electron microscope is used to collect images of thousands of nanoparticles. Particle images are subsequently semi-automatically clustered in terms of their properties and separate 3D reconstructions are performed from selected particle image clusters. The result is a 3D dataset that is representative of the full population. The study demonstrates a methodology that allows 3D imaging and analysis of inorganic nanoparticles in a fully automated manner that is truly representative of large particle populations.

Highlights

  • Developments in the single-particle reconstruction technique for obtaining three-dimensional (3D) images of viruses and proteins have revolutionized structural biology over the last decade

  • We recently reported a single-particle reconstruction approach to reveal the elemental distribution within a PtNi nanoparticle in three dimensions at the nanoscale (Wang et al, 2019)

  • We demonstrate that single-particle reconstruction can be applied to heterogeneous inorganic nanoparticle populations with almost all aspects fully automated

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Summary

Introduction

Developments in the single-particle reconstruction technique for obtaining three-dimensional (3D) images of viruses and proteins have revolutionized structural biology over the last decade. Protein structures determined by electron microscopy deposited to the protein data bank have risen from less than 1% of yearly deposits in 2009 to over 10% of yearly deposits in 2017 (Westbrook, 2017). The resolution of reconstructions is routinely at or below 3 Å and, can be used to determine atomic structures (Holubcová et al, 2015; Bartesaghi et al, 2018). The 3D visualization of structures at the atomic scale is a vital in physical sciences as it is in biology, for example, to understand the catalytic behavior, or the optical and electronic properties of nanomaterials (Bals et al, 2007; Nicoletti et al, 2013; Slater et al, 2014). While the use of single-particle reconstruction in structural biology has become pervasive, there has been very

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