Abstract

Intense femtosecond x-ray pulses from free-electron laser sources allow the imaging of individual particles in a single shot. Early experiments at the Linac Coherent Light Source (LCLS) have led to rapid progress in the field and, so far, coherent diffractive images have been recorded from biological specimens, aerosols, and quantum systems with a few-tens-of-nanometers resolution. In March 2014, LCLS held a workshop to discuss the scientific and technical challenges for reaching the ultimate goal of atomic resolution with single-shot coherent diffractive imaging. This paper summarizes the workshop findings and presents the roadmap toward reaching atomic resolution, 3D imaging at free-electron laser sources.

Highlights

  • First single particle imaging (SPI) experiments performed at the Linac Coherent Light Source (LCLS) have been very successful, producing single-shot coherent diffraction images of viruses,3 bacteriophages,4 organelles,5 and cyanobacteria6 to name a few

  • The highly coherent x-ray beam produced by an X-ray free-electron lasers (XFEL) provides Coherent diffractive imaging (CDI) data much closer to the assumptions made in CDI

  • The ultimate impact and niche of CDI must be considered in the context of recent developments in cryo-electron microscopy (cryo-EM) analysis of single particles. cryo-EM is limited in scattered flux per exposure and in temporal resolution

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Summary

INTRODUCTION

One of the grand visions for X-ray free-electron lasers (XFEL) is the ability to image nonrepetitive and non-reproducible structures with single femtosecond x-ray pulses. The underlying concept is that the x-ray pulses are so intense that the imaging process is outrunning the sample damage. First single particle imaging (SPI) experiments performed at the Linac Coherent Light Source (LCLS) have been very successful, producing single-shot coherent diffraction images of viruses, bacteriophages, organelles, and cyanobacteria to name a few. To unlock the full potential of imaging experiments with free-electron lasers, including the ability to perform time-resolved studies, atomic resolution needs to be achieved. Currently, it is not clear if atomic resolution from single particles can be reached and if so, which technical and scientific problems have to be solved. It is not clear if atomic resolution from single particles can be reached and if so, which technical and scientific problems have to be solved In this spirit, LCLS has hosted a by-invitation workshop with renowned experts in the field of ultrafast radiation damage, imaging algorithm development, XFEL instrumentation, and sample issues. This paper summarizes the workshop findings and presents the road map

Our current picture of radiation damage
Resulting beam parameters
ALGORITHMS
The orientation challenge
The signal challenge
The noise challenge
The sample heterogeneity challenge
Desired beam parameters
Accelerator and X-ray beamline instrumentation
Detector development
Biological significance and other structural methods
Sample heterogeneity
Sample delivery
Recommendations
THE LCLS SINGLE PARTICLE IMAGING ROAD MAP
CONCLUSIONS
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