X-ray ptychographic and fluorescence microscopy using virtual single-pixel imaging based deconvolution with accurate probe images.

Simultaneous measurement of X-ray ptychography and fluorescence microscopy allows high-resolution and high-sensitivity observations of the microstructure and trace-element distribution of a sample. In this paper, we propose a method for improving scanning fluorescence X-ray microscopy (SFXM) images, in which the SFXM image is deconvolved via virtual single-pixel imaging using different probe images for each scanning point obtained by X-ray ptychographic reconstruction. Numerical simulations confirmed that this method can increase the spatial resolution while suppressing artifacts caused by probe imprecision, e.g., probe position errors and wavefront changes. The method also worked well in synchrotron radiation experiments to increase the spatial resolution and was applied to the observation of S element maps of ZnS particles.

High-resolution and high-sensitivity X-ray ptychographic coherent diffraction imaging using the CITIUS detector.

Ptychographic coherent diffraction imaging (PCDI) is a synchrotron X-ray microscopy technique that provides high spatial resolution and a wide field of view. To improve the performance of PCDI, the performance of the synchrotron radiation source and imaging detector should be improved. In this study, ptychographic diffraction pattern measurements using the CITIUS high-speed X-ray image detector and the corresponding image reconstruction are reported. X-rays with an energy of 6.5 keV were focused by total reflection focusing mirrors, and a flux of ∼2.6 × 1010 photons s-1 was obtained at the sample plane. Diffraction intensity data were collected at up to ∼250 Mcounts s-1 pixel-1 without saturation of the detector. Measurements of tantalum test charts and silica particles and the reconstruction of phase images were performed. A resolution of ∼10 nm and a phase sensitivity of ∼0.01 rad were obtained. The CITIUS detector can be applied to the PCDI observation of various samples using low-emittance synchrotron radiation sources and to the stability evaluation of light sources.

Nanoscale domain imaging of Li-rich disordered rocksalt-type cathode materials with X-ray spectroscopic ptychography.

Lithium-rich disordered rocksalt-type cathode materials are promising for high-capacity and high-power lithium-ion batteries. Many of them are synthesized by mechanical milling and may have heterogeneous structures and chemical states at the nanoscale. In this study, we performed X-ray spectroscopic ptychography measurements of Li-rich disordered rocksalt-type oxide particles synthesized by mechanical milling before and after delithiation reaction at the vanadium K absorption edge, and visualized their structures and chemical state with a spatial resolution of ∼100 nm. We classified multiple domains with different chemical states via clustering analysis. A comparison of the domain distribution trends of the particles before and after the delithiation reaction revealed the presence of domains, suggesting that the delithiation reaction was suppressed.

Development and application of a tender X-ray ptychographic coherent diffraction imaging system on BL27SU at SPring-8.

Ptychographic coherent diffraction imaging (CDI) allows the visualization of both the structure and chemical state of materials on the nanoscale, and has been developed for use in the soft and hard X-ray regions. In this study, a ptychographic CDI system with pinhole or Fresnel zone-plate optics for use in the tender X-ray region (2-5 keV) was developed on beamline BL27SU at SPring-8, in which high-precision pinholes optimized for the tender energy range were used to obtain diffraction intensity patterns with a low background, and a temperature stabilization system was developed to reduce the drift of the sample position. A ptychography measurement of a 200 nm thick tantalum test chart was performed at an incident X-ray energy of 2.500 keV, and the phase image of the test chart was successfully reconstructed with approximately 50 nm resolution. As an application to practical materials, a sulfur polymer material was measured in the range of 2.465 to 2.500 keV including the sulfur K absorption edge, and the phase and absorption images were successfully reconstructed and the nanoscale absorption/phase spectra were derived from images at multiple energies. In 3 GeV synchrotron radiation facilities with a low-emittance storage ring, the use of the present system will allow the visualization on the nanoscale of the chemical states of various light elements that play important roles in materials science, biology and environmental science.

Visualization of Structural Heterogeneities in Particles of Lithium Nickel Manganese Oxide Cathode Materials by Ptychographic X-ray Absorption Fine Structure.

A heterogeneous phase/structure distribution in the bulk of spinel lithium nickel manganese oxides (LNMOs) is the key to maximizing the performance and stability of the cathode materials of lithium-ion batteries. Herein, we report the use of two-dimensional ptychographic X-ray absorption fine structure (XAFS) to visualize the density and valence maps of manganese and nickel in as-prepared LNMO particles and unsupervised learning to classify the three-phase group in terms of different elemental compositions and chemical states. The described approach may increase the supply of information for nanoscale characterization and promote the design of suitable structural domains to maximize the performance and stability of batteries.

Demonstration of single-frame coherent X-ray diffraction imaging using triangular aperture: Towards dynamic nanoimaging of extended objects.

Coherent diffraction imaging (CDI) is a powerful method for visualizing the structure of an object with a high spatial resolution that exceeds the performance limits of the lens. Single-frame CDI in the X-ray region has potential use for probing dynamic phenomena with a high spatiotemporal resolution. Here, we experimentally demonstrate a general method for single-frame X-ray CDI using a triangular aperture and a Fresnel zone plate. Using 5 keV synchrotron radiation X-rays, we reconstructed the object image of the locally illuminated area with a spatial resolution of higher than 50 nm and an exposure time of more than 0.1 s without prior information about the sample. After a 10 s exposure, a resolution of 17 nm was achieved. The present method opens new frontiers in the study of dynamics at the nanoscale by using next-generation synchrotron radiation X-rays/free-electron lasers as light sources.

Single-frame coherent diffraction imaging of extended objects using triangular aperture.

We propose a method of single-frame coherent diffraction imaging using a triangular aperture, which can not only reconstruct the projection image of extended objects from a single-frame coherent diffraction pattern, but also improve the image of the wavefield of the probe. In this method, a plane-wave illuminates a triangular aperture. An object is placed immediately after the aperture or in the image plane of the aperture through a lens. A far-field coherent diffraction pattern is collected by a two-dimensional detector. The object image is reconstructed from the single-frame diffraction pattern using a phase retrieval algorithm without support constraints. We simulate feasible experimental setups in the hard X-ray regime and show that this method can be practical use for single-frame coherent diffraction imaging. The present method has the potential exploring dynamic phenomena in materials science and biology with high spatiotemporal resolution using synchrotron radiation/free-electron lasers.

Nanoscale Visualization of Phase Transition in Melting of Sn-Bi Particles by In situ Hard X-ray Ptychographic Coherent Diffraction Imaging.

The phase transition in the melting of Sn­Bi eutectic solder alloy particles was observed by in situ hard X-ray ptychographic coherent diffraction imaging with a pin-point heating system. Ptychographic diffraction patterns of micrometer-sized Sn­Bi particles were collected at temperatures from room temperature to 540 K. The projection images of each particle were reconstructed at a spatial resolution of 25 nm, showing differences in the phase shifts due to two crystal phases in the Sn­Bi alloy system and the Sn/Bi oxides at the surface. By quantitatively evaluating the Bi content, it became clear that the nonuniformity of the composition of Sn and Bi at the single-particle level exists when the particles are synthesized by centrifugal atomization.

Nanoscale determination of interatomic distance by ptychography-EXAFS method using advanced Kirkpatrick-Baez mirror focusing optics.

This work demonstrates a combination technique of X-ray ptychography and the extended X-ray absorption fine structure (ptychography-EXAFS) method, which can determine the interatomic distances of bulk materials at the nanoscale. In the high-resolution ptychography-EXAFS method, it is necessary to use high-intense coherent X-rays with a uniform wavefront in a wide energy range, hence a ptychographic measurement system installed with advanced Kirkpatrick-Baez mirror focusing optics is developed and its performance is evaluated. Ptychographic diffraction patterns of micrometre-size MnO particles are collected by using this system at 139 energies between 6.504 keV and 7.114 keV including the Mn K absorption edge, and then the EXAFS of MnO is derived from the reconstructed images. By analyzing the EXAFS spectra obtained from a 48 nm × 48 nm region, the nanoscale bond lengths of the first and second coordination shells of MnO are determined. The present approach has great potential to elucidate the unclarified relationship among the morphology, electronic state and atomic arrangement of inhomogeneous bulk materials with high spatial resolution.

Multibeam ptychography with synchrotron hard X-rays.

We report the first demonstration of multibeam ptychography using synchrotron hard X-rays, which can enlarge the field of view of the reconstructed image of objects by efficiently using partially coherent X-rays. We measured the ptychographic diffraction patterns of a Pt test sample and MnO particles using three mutually incoherent coherent beams with a high intensity that were produced by using both the multiple slits and a pair of focusing mirrors. We successfully reconstructed the phase map of the samples at a spatial resolution of 25 nm in a field of view about twice as wide as that in the single-beam ptychography. We also computationally simulated a feasible experimental setup using random modulators to further enlarge the field of view by increasing the number of available beams. The present method has the potential to enable the high spatial resolution and large field-of-view observation of specimens in materials science and biology.

Exposure-response analysis of drug-induced QT interval prolongation in telemetered monkeys for translational prediction to human.

INTRODUCTION: The preclinical in vivo assay for QT prolongation is critical for predicting torsadogenic risk, but still difficult to extrapolate to humans. This study ran preclinical tests in cynomolgus monkeys on seven QT reference drugs containing the drugs used in the IQ-CSRC clinical trial and applied exposure-response (ER) analysis to the data to investigate the potential for translational information on the QT effect. METHODS: In each of six participating facilities in the J-ICET project, telemetered monkeys were monitored for 24 h following administration of vehicle or 3 doses of test drugs, and pharmacokinetic profiles at the same doses were evaluated separately. An individual rate-corrected QT interval (QTca) was derived and the vehicle-adjusted change in QTca from baseline (∆∆QTca) was calculated. Then the relationship of concentration to QT effect was evaluated by ER analysis. RESULTS: For QT-positive drugs in the IQ-CSRC study (dofetilide, dolasetron, moxifloxacin, ondansetron, and quinine) and levofloxacin, the slope of the total concentration-QTca effect was significantly positive, and the QT-prolonging effect, taken as the upper bound of the confidence interval for predicted ∆∆QTca, was confirmed to exceed 10 ms. The ER slope of the negative drug levocetirizine was not significantly positive and the QTca effect was below 10 ms at observed peak exposure. DISCUSSION: Preclinical QT assessment in cynomolgus monkeys combined with ER analysis could identify the small QT effect induced by several QT drugs consistently with the outcomes in humans. Thus, the ER method should be regarded as useful for translational prediction of QT effects in humans.

Three-dimensional iterative multislice reconstruction for ptychographic X-ray computed tomography.

Ptychographic X-ray computed tomography (PXCT) is a potential tool for visualizing three-dimensional (3D) structures of large-volume samples at high spatial resolution. Currently, both the requirement of a large number of views and the narrow depth of field limit the range of applications of PXCT. Here, we propose an improved 3D reconstruction algorithm for PXCT that is based on 3D iterative reconstruction and multislice phase retrieval calculation. Computer simulations showed that the proposed algorithm can reduce the number of required views without degrading the spatial resolution. In a synchrotron experiment, ptychographic diffraction data sets of a flat and thick processor specimen were collected under a limited-angle condition, and then high-resolution multislice images of the Cu multilevel interconnects were clearly reconstructed using the proposed algorithm. The proposed algorithm is expected to open up a new frontier of large-volume 3D nanoimaging in various fields.

Visualization of Heterogeneous Oxygen Storage Behavior in Platinum-Supported Cerium-Zirconium Oxide Three-Way Catalyst Particles by Hard X-ray Spectro-Ptychography.

The cerium density and valence in micrometer-size platinum-supported cerium-zirconium oxide Pt/Ce2 Zr2 Ox (x=7-8) three-way catalyst particles were successfully mapped by hard X-ray spectro-ptychography (ptychographic-X-ray absorption fine structure, XAFS). The analysis of correlation between the Ce density and valence in ptychographic-XAFS images suggested the existence of several oxidation behaviors in the oxygen storage process in the Ce2 Zr2 Ox particles. Ptychographic-XAFS will open up the nanoscale chemical imaging and structural analysis of heterogeneous catalysts.

Multislice imaging of integrated circuits by precession X-ray ptychography.

A method for nondestructively visualizing multisection nanostructures of integrated circuits by X-ray ptychography with a multislice approach is proposed. In this study, tilt-series ptychographic diffraction data sets of a two-layered circuit with a ∼1.4 µm gap at nine incident angles are collected in a wide Q range and then artifact-reduced phase images of each layer are successfully reconstructed at ∼10 nm resolution. The present method has great potential for the three-dimensional observation of flat specimens with thickness on the order of 100 µm, such as three-dimensional stacked integrated circuits based on through-silicon vias, without laborious sample preparation.

Modulation of Electron-Phonon Coupling in One-Dimensionally Nanorippled Graphene on a Macrofacet of 6H-SiC.

Local electron-phonon coupling of a one-dimensionally nanorippled graphene is studied on a SiC(0001) vicinal substrate. We have characterized local atomic and electronic structures of a periodically nanorippled graphene (3.4 nm period) prepared on a macrofacet of the 6H-SiC crystal using scanning tunneling microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES). The rippled graphene on the macrofacets distributes homogeneously over the 6H-SiC substrate in a millimeter scale, and thus replica bands are detected by the macroscopic ARPES. The STM/STS results indicate the strength of electron-phonon coupling to the out-of-plane phonon at the K̅ points of graphene is periodically modified in accordance with the ripple structure. We propose an interface carbon nanostructure with graphene nanoribbons between the surface rippled graphene and the substrate SiC that periodically modifies the electron-phonon coupling in the surface graphene.

Use of Kramers-Kronig relation in phase retrieval calculation in X-ray spectro-ptychography.

Coherent diffraction imaging (CDI) is a method for reconstructing the complex-valued image of an object from diffraction intensities by using iterative phasing methods. X-ray ptychography is a scanning type of CDI using X-rays, allowing us to visualize the complex transmission function of an extended specimen. We here propose the use of the Kramers-Kronig relation (KKR) as an additional constraint in phase retrieval algorithms for multiple-energy X-ray ptychography using the absorption edge of a specific element. A numerical simulation showed that the speed of convergence was increased by using the improved algorithm with the KKR. We successfully demonstrated its usefulness in a proof-of-principle experiment at SPring-8. The present algorithm is particularly useful for imaging X-ray absorption fine structures of a specific element buried within thick samples by hard X-ray spectro-ptychography.

Dark-field X-ray ptychography: Towards high-resolution imaging of thick and unstained biological specimens.

The phase shift of light or electrons in objects is now necessary for probing weak-phase objects such as unstained biological specimens. Optical microscopy (OM) and transmission electron microscopy (TEM) have been used to observe weak-phase objects. However, conventional OM has low spatial resolution and TEM is limited to thin specimens. Here, we report on the development of dark-field X-ray ptychography, which combines X-ray ptychography and X-ray in-line holography, to observe weak-phase objects with a phase resolution better than 0.01 rad, a spatial resolution better than 15 nm, and a field of view larger than 5 µm. We apply this method to the observation of both the outline and magnetosomes of the magnetotactic bacteria MO-1. Observation of thick samples with high resolution is expected to find broad applications in not only biology but also materials science.

Multiple defocused coherent diffraction imaging: method for simultaneously reconstructing objects and probe using X-ray free-electron lasers.

The sample size must be less than the diffraction-limited focal spot size of the incident beam in single-shot coherent X-ray diffraction imaging (CXDI) based on a diffract-before-destruction scheme using X-ray free electron lasers (XFELs). This is currently a major limitation preventing its wider applications. We here propose multiple defocused CXDI, in which isolated objects are sequentially illuminated with a divergent beam larger than the objects and the coherent diffraction pattern of each object is recorded. This method can simultaneously reconstruct both objects and a probe from the coherent X-ray diffraction patterns without any a priori knowledge. We performed a computer simulation of the prposed method and then successfully demonstrated it in a proof-of-principle experiment at SPring-8. The prposed method allows us to not only observe broad samples but also characterize focused XFEL beams.

Room-temperature local ferromagnetism and its nanoscale expansion in the ferromagnetic semiconductor Ge(1-x)Fex.

We investigate the local electronic structure and magnetic properties of the group-IV-based ferromagnetic semiconductor, Ge(1-x)Fex (GeFe), using soft X-ray magnetic circular dichroism. Our results show that the doped Fe 3d electrons are strongly hybridized with the Ge 4p states, and have a large orbital magnetic moment relative to the spin magnetic moment; i.e., morb/mspin ≈ 0.1. We find that nanoscale local ferromagnetic regions, which are formed through ferromagnetic exchange interactions in the high-Fe-content regions of the GeFe films, exist even at room temperature, well above the Curie temperature of 20-100 K. We observe the intriguing nanoscale expansion of the local ferromagnetic regions with decreasing temperature, followed by a transition of the entire film into a ferromagnetic state at the Curie temperature.

Dark-field X-ray ptychography.

The dynamic range of X-ray detectors is a key factor limiting both the spatial resolution and sensitivity of X-ray ptychography as well as the coherent flux of incident X-rays. Here, we propose a method for high-resolution and high-sensitivity X-ray ptychography named "dark-field X-ray ptychography", which compresses the dynamic range of intensities of diffraction patterns. In this method, a small reference object is aligned upstream of the sample. The scattered X-rays from the object work as a reference beam for in-line holography. Ptychographic diffraction patterns including the in-line hologram are collected, and then the image of the sample is reconstructed by an iterative phasing method. This method allows us to obscure the low-Q region of the diffraction patterns using a beamstop since the in-line hologram complements structural information in the low-Q region, resulting in the compression of the dynamic range of intensities of diffraction patterns. A numerical study shows that the dynamic range of intensities of diffraction patterns is decreased by about three orders of magnitude.