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Abstract

Outrunning radiation damage, femtosecond pulses of x-ray free electron laser (XFELs) open up the possibility of imaging the structure and dynamics of single-particles, frozen in time at room temperature, at ultrafast time-scales. Though atomic resolution single-particle imaging with XFELs is yet to be achieved, there has been a steady progress in three-dimensional imaging of isolated biological and inorganic single-particles with XFELs at modest resolution. Oftentimes, poor signal-to-noise ratio in experimental conditions lead to the requirement of several hundreds of thousands of diffraction patterns to reconstruct the target object in 3D at high-resolution, and it has been difficult to achieve such huge set of diffraction patterns with low-repetition rate FELs. With the advent of MHz repetition rate XFELs, such as the EuXFEL or LCLS-II, this has become attainable. Here we report our recent demonstration of collecting more than ten-million single-particle diffraction patterns of aerosolized small anisotropic gold nanoparticles—as small as the size of large macromolecules—at the EuXFEL with a micron focus hard-X-ray laser beam. The collected number of single-particle diffraction patterns is an order of magnitude more than in any SPI experiments carried out so far, to the best of our knowledge. Our analysis of the large dataset shows that a subset of nanoparticles in solution is highly monodisperse even at high-resolution, and it is possible to achieve sub-3 nm resolution 3D reconstruction of AuNPs. Such large-dataset studies, which were not previously possible, would shed light on the growth dynamics and heterogeneity of the anisotropic nanoparticles and provide new insights. Further, in line with the foundational goals of XFELs, these results indicate the potential of MHz XFELs in imaging the ultrafast dynamics and conformational landscape of macromolecules.

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