Richard A. Kirian, P. Lourdu Xavier, Chun Hong Yoon, Henry N. Chapman, and Anton Barty'
bibliography:
- 'refs.bib'
title: 'Low-signal limit of X-ray single particle diffractive imaging'
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\[sec:intro\]Introduction
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The potential of X-ray free electron lasers (XFELs) to image biomolecular structures at room temperature without the need for crystallisation has been one of the goals driving their development. For many years, theoretical studies backed by simulated data have suggested that near-atomic resolution of isolated non-crystalline proteins should be possible with currently available XFEL sources [@Neutze:2000; @Ayyer:2016]. To date, published results have focused on large or symmetric particles such as viruses in the 60-500nm size range where the higher signal levels from larger particles is ideal for methods development [@Loh:2010; @Kassemeyer:2013; @Ekeberg:2015; @Aquila:2018]. Results from the single particle imaging initiative at the Linac Coherent Light Source (LCLS) [@Aquila:2015] have been in a similar size range [@Munke:2016; @Reddy:2017].

Imaging individual proteins has so far proven more elusive due to the lower signal-to-background from smaller sized particles and a lower than expected rate of single particle diffraction pattern acquisition [@Aquila:2018]. While theoretical studies indicate that molecular imaging should be achievable using Bayesian algorithms such as the EMC algorithm [@Loh:2009] for near-perfect data 