Method to enhance the resolution of x-ray coherent diffraction imaging for non-crystalline bio-samples

Abstract

To circumvent the problem of radiation damage when using an x-ray coherent diffraction imaging experiment to resolve the structure of biological samples, we propose a method to add objects made of heavy atoms with the bio-samples or we load the samples on a template made of heavy atoms. This template method is shown by a numerical simulation (including shot noise) to be able to resolve the structure of a virus better than without the template. A counter-intuitive result is obtained, where heavier templates have a better resolution, even if the diffraction intensity of the bio-sample is much smaller than the noise intensity. In addition, the method also helps to greatly increase the efficiency of phase retrieval. We also provide a way to estimate the error to be expected if a particular experimental setting were chosen once the charge ratio between the sample and the template is estimated. Hence, this method will also help experiments choose the optimal setting for the best resolution with minimal radiation damage.

Signal enhancement and Patterson-search phasing for high-spatial-resolution coherent X-ray diffraction imaging of biological objects

“…1b) also shows a concentric ring pattern (Fig. 2b), but now dominated by the contribution from the CG particles141517. Each ring is composed of small speckles with an oversampling ratio σ 2 of ~12, where .…”

“…1b ). Interference between the strong diffraction waves from the CG particles and weak waves from the biological object can enhance the signals from the biological object to a detectable level 14 15 16 17 . The positions of the gold particles determined by Patterson analysis serve as the initial phase 18 19 .…”

Single-pulse enhanced coherent diffraction imaging of bacteria with an X-ray free-electron laser

“…In previous studies, references or templates were used to increase diffraction signal intensity and to improve the resolution of the reconstructions of low-scattering samples 42 43 . By introducing references or templates, reconstruction becomes easier, and resolution is improved at least by a factor of 2, depending on the simulation results 44 45 46 . Nanocluster labeling is widely used for cells for intercellular imaging and tracking.…”

In situ coherent diffractive imaging

“…Our numerical simulations suggest that the level of radiation dose reduction is related to the structure of the static pattern and the ratio of the coherent fluxes between the static and dynamic structure. Although template-based and phase diverse approachs have been introduced for radiation dose reduction in CDI 57 , 58 , with in situ CDI we have demonstrated the possibility of reducing the radiation dose by more than an order of magnitude, which we attribute mainly to the non-linearity of the phase retrieval process. If experimentally validated, this could be the most dose efficient X-ray imaging method to probe radiation sensitive systems.…”

“…One area currently being explored is the addition of a known diffusive structure to the sample to enhance the scattered signal. Placing a high atomic number element structure in the field of view has demonstrated the possibility of reducing the dose required for obtaining minimum reconstructable diffraction signal 57 – 62 . Since photons incident on the static region in in situ CDI do not hit the sample, those photons can enhance the measurable signal without inducing extra radiation damage to the sample.…”