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Label‐free super‐resolution (LFSR) imaging relies on light‐scattering processes in nanoscale objects without a need for fluorescent (FL) staining required in super‐resolved FL microscopy. The objectives of this Roadmap are to present a comprehensive vision of the developments, the state‐of‐the‐art in this field, and to discuss the resolution boundaries and hurdles that need to be overcome to break the classical diffraction limit of the label‐free imaging. The scope of this Roadmap spans from the advanced interference detection techniques, where the diffraction‐limited lateral resolution is combined with unsurpassed axial and temporal resolution, to techniques with true lateral super‐resolution capability that are based on understanding resolution as an information science problem, on using novel structured illumination, near‐field scanning, and nonlinear optics approaches, and on designing superlenses based on nanoplasmonics, metamaterials, transformation optics, and microsphere‐assisted approaches. To this end, this Roadmap brings under the same umbrella researchers from the physics and biomedical optics communities in which such studies have often been developing separately. The ultimate intent of this paper is to create a vision for the current and future developments of LFSR imaging based on its physical mechanisms and to create a great opening for the series of articles in this field. [ABSTRACT FROM AUTHOR]

Liquid sample delivery systems are used extensively for serial femtosecond crystallography at X‐ray free‐electron lasers (XFELs). However, misalignment of the liquid jet and the XFEL beam leads to the X‐rays either partially or completely missing the sample, resulting in sample wastage and a loss of experiment time. Implemented here is an algorithm to analyse optical images using machine vision to determine whether there is overlap of the X‐ray beam and liquid jet. The long‐term goal is to use the output from this algorithm to implement an automated feedback mechanism to maintain constant alignment of the X‐ray beam and liquid jet. The key elements of this jet alignment algorithm are discussed and its performance is characterized by comparing the results with a manual analysis of the optical image data. The success rate of the algorithm for correctly identifying hits is quantified via a similarity metric, the Dice coefficient. In total four different nozzle designs were used in this study, yielding an overall Dice coefficient of 0.98.A novel strategy is presented for sample jet alignment using machine vision for liquid‐jet‐based sample delivery systems. Feedback using height‐resolution images from an optical microscope positioned perpendicular to the path of the X‐ray beam enables tracking of the relative alignment of the liquid jet and X‐ray beam. [ABSTRACT FROM AUTHOR]

Characterizing the properties of X-ray free-electron laser (XFEL) sources is a critical step for optimization of performance and experiment planning. The recent availability of MHz XFELs has opened up a range of new opportunities for novel experiments but also highlighted the need for systematic measurements of the source properties. Here, MHz-enabled beam imaging diagnostics developed for the SPB/SFX instrument at the European XFEL are exploited to measure the shot-to-shot intensity statistics of X-ray pulses. The ability to record pulse-integrated two-dimensional transverse intensity measurements at multiple planes along an XFEL beamline atMHz rates yields an improved understanding of the shot-to-shot photon beam intensity variations. These variations can play a critical role, for example, in determining the outcome of single-particle imaging experiments and other experiments that are sensitive to the transverse profile of the incident beam. It is observed that shot-to-shot variations in the statistical properties of a recorded ensemble of radiant intensity distributions are sensitive to changes in electron beam current density. These changes typically occur during pulse-distribution to the instrument and are currently not accounted for by the existing suite of imaging diagnostics. Modulations of the electron beam orbit in the accelerator are observed to induce a time-dependence in the statistics of individual pulses - this is demonstrated by applying radio-frequency trajectory tilts to electron bunch-trains delivered to the instrument. We discuss how these modifications of the beam trajectory might be used to modify the statistical properties of the source and potential future applications. [ABSTRACT FROM AUTHOR]

Optical metamaterials offer precise control over the properties and interactions of light at the nanoscale, attracting interest in many new fields of research including chemical and molecular sensing, magnetic antennas, and photovoltaic elements. By utilizing the phenomenon of extraordinary optical transmission (EOT) plasmonic devices enable the detection of minute changes in the local, near‐surface, dielectric properties of materials, opening up a wide range of different applications. Characterization of the optoelectronic properties of ultra‐thin films is of paramount importance for a wide range of electronic applications including integrated circuit production. However, it is often extremely difficult to achieve using conventional imaging techniques. Here, it is demonstrated that plasmonic color filters can be used for the direct optical imaging and characterization of ion implantation in thin films. A model system consisting of variable doses of gallium ions implanted within titanium oxide thin films is used. It is observed that the ion implantation dose leads to a variation in the measured plasmon resonance spectra, which can be further enhanced through the use of bimodal nanopixel arrays. Using Monte Carlo simulations and the Maxwell‐Garnett relation, the observed plasmon resonance spectra in terms of the gallium ion implantation dose is quantitatively interpreted. [ABSTRACT FROM AUTHOR]

A peak‐finding algorithm for serial crystallography (SX) data analysis based on the principle of 'robust statistics' has been developed. Methods which are statistically robust are generally more insensitive to any departures from model assumptions and are particularly effective when analysing mixtures of probability distributions. For example, these methods enable the discretization of data into a group comprising inliers (i.e. the background noise) and another group comprising outliers (i.e. Bragg peaks). Our robust statistics algorithm has two key advantages, which are demonstrated through testing using multiple SX data sets. First, it is relatively insensitive to the exact value of the input parameters and hence requires minimal optimization. This is critical for the algorithm to be able to run unsupervised, allowing for automated selection or 'vetoing' of SX diffraction data. Secondly, the processing of individual diffraction patterns can be easily parallelized. This means that it can analyse data from multiple detector modules simultaneously, making it ideally suited to real‐time data processing. These characteristics mean that the robust peak finder (RPF) algorithm will be particularly beneficial for the new class of MHz X‐ray free‐electron laser sources, which generate large amounts of data in a short period of time. [ABSTRACT FROM AUTHOR]

Abstract: Plasmonic devices offer the possibility of passively detecting changes in local chemistry that opens up a wide range of applications from molecular sensing to monitoring water quality. Conventional plasmonics have previously shown great promise as nanoscale chemical sensors through detection of small variations in the local refractive index (RI). The motivation behind using plasmonics for these applications includes the fact that detection is entirely passive and the devices themselves can be readily miniaturized. Previously, a lack of any control over the output of these devices, has fundamentally limited their application to chemicals which produce clearly identifiable resonances within the range of detection. Here it is demonstrated that microfluidic devices, incorporating polarization‐controlled plasmonic nanopixels, allow the device response to be tuned to the particular analyte of interest, anywhere within the visible spectrum. This dramatically increases the effective dynamic range and allows local variations in RI to be perceived directly as color changes by the human eye. Active control over the output of the device also enables clear differentiation between a number of different analytes, paving the way for plasmonics to be used for a wide range of real‐world chemical sensing applications. [ABSTRACT FROM AUTHOR]

The recent development of serial crystallography at synchrotron and X-ray free-electron laser (XFEL) sources is producing crystallographic datasets of ever increasing volume. The size of these datasets is such that fast and efficient analysis presents a range of challenges that have to be overcome to enable real-time data analysis, which is essential for the effective management of XFEL experiments. Among the blocks which constitute the analysis pipeline, one major bottleneck is `peak finding', whose goal is to identify the Bragg peaks within (often) noisy diffraction patterns. Development of faster and more reliable peak-finding algorithms will allow for efficient processing and storage of the incoming data, as well as the optimal use of diffraction data for structure determination. This paper addresses the problem of peak finding and, by extension, `hit finding' in crystallographic XFEL datasets, by exploiting recent developments in robust statistical analysis. The approach described here involves two basic steps: (1) the identification of pixels which contain potential peaks and (2) modeling of the local background in the vicinity of these potential peaks. The presented framework can be generalized to include both complex background models and alternative models for the Bragg peaks. [ABSTRACT FROM AUTHOR]

The recent availability of extremely intense, femtosecond X-ray free-electron laser (XFEL) sources has spurred the development of serial femtosecond nanocrystallography (SFX). Here, SFX is used to analyze nanoscale crystals of β-hematin, the synthetic form of hemozoin which is a waste by-product of the malaria parasite. This analysis reveals significant differences in β-hematin data collected during SFX and synchrotron crystallography experiments. To interpret these differences two possibilities are considered: structural differences between the nanocrystal and larger crystalline forms of β-hematin, and radiation damage. Simulation studies show that structural inhomogeneity appears at present to provide a better fit to the experimental data. If confirmed, these observations will have implications for designing compounds that inhibit hemozoin formation and suggest that, for some systems at least, additional information may be gained by comparing structures obtained from nanocrystals and macroscopic crystals of the same molecule. [ABSTRACT FROM AUTHOR]

Multi-reflection Bragg coherent diffraction imaging has the potential to allow three-dimensional (3D) resolved measurements of the full lattice strain tensor in specific micro-crystals. Until now such measurements were hampered by the need for laborious, time-intensive alignment procedures. Here a different approach is demonstrated, using micro-beam Laue X-ray diffraction to first determine the lattice orientation of the micro-crystal. This information is then used to rapidly align coherent diffraction measurements of three or more reflections from the crystal. Based on these, 3D strain and stress fields in the crystal are successfully determined. This approach is demonstrated on a focused ion beam milled micro-crystal from which six reflections could be measured. Since information from more than three independent reflections is available, the reliability of the phases retrieved from the coherent diffraction data can be assessed. Our results show that rapid, reliable 3D coherent diffraction measurements of the full lattice strain tensor in specific micro-crystals are now feasible and can be successfully carried out even in heavily distorted samples. [ABSTRACT FROM AUTHOR]

Owing to its extreme sensitivity, quantitative mapping of elemental distributions via X-ray fluorescence microscopy (XFM) has become a key microanalytical technique. The recent realisation of scanning X-ray diffraction microscopy (SXDM) meanwhile provides an avenue for quantitative super-resolved ultra-structural visualization. The similarity of their experimental geometries indicates excellent prospects for simultaneous acquisition. Here, in both step- and fly-scanning modes, robust, simultaneous XFM-SXDM is demonstrated. [ABSTRACT FROM AUTHOR]

An understanding of the mechanical response of modern engineering alloys to complex loading conditions is essential for the design of load-bearing components in high-performance safety-critical aerospace applications. A detailed knowledge of how material behaviour is modified by fatigue and the ability to predict failure reliably are vital for enhanced component performance. Unlike macroscopic bulk properties ( e.g. stiffness, yield stress, etc.) that depend on the average behaviour of many grains, material failure is governed by `weakest link'-type mechanisms. It is strongly dependent on the anisotropic single-crystal elastic-plastic behaviour, local morphology and microstructure, and grain-to-grain interactions. For the development and validation of models that capture these complex phenomena, the ability to probe deformation behaviour at the micro-scale is key. The diffraction of highly penetrating synchrotron X-rays is well suited to this purpose and micro-beam Laue diffraction is a particularly powerful tool that has emerged in recent years. Typically it uses photon energies of 5-25 keV, limiting penetration into the material, so that only thin samples or near-surface regions can be studied. In this paper the development of high-energy transmission Laue (HETL) micro-beam X-ray diffraction is described, extending the micro-beam Laue technique to significantly higher photon energies (50-150 keV). It allows the probing of thicker sample sections, with the potential for grain-level characterization of real engineering components. The new HETL technique is used to study the deformation behaviour of individual grains in a large-grained polycrystalline nickel sample during in situ tensile loading. Refinement of the Laue diffraction patterns yields lattice orientations and qualitative information about elastic strains. After deformation, bands of high lattice misorientation can be identified in the sample. Orientation spread within individual scattering volumes is studied using a pattern-matching approach. The results highlight the inability of a simple Schmid-factor model to capture the behaviour of individual grains and illustrate the need for complementary mechanical modelling. [ABSTRACT FROM AUTHOR]

The provision of palliative care for older people within the next decade will need to be substantially different to that provided today. In long-term care settings the achievement of quality palliative care will require attention to all levels of the health and social care system, in both its formal and informal manifestations. We suggest that long-term care facilities will become the hospices of the future, caring for older people with chronic conditions with a long trajectory to death, the most common being dementia. We see this progression as inevitable and appropriate if the right support is provided. We discuss the impact that transferability and sustainability has had on the present provision of palliative care for older people and how that may affect the future. Four forces which are important factors in public policy; leadership, a culture that supports learning throughout the care process, an emphasis on effective team development and the use of information technologies for quality activities are used as a framework for our vision of social planning. We then go on to discuss the impact of costs, workforce, service planning and public awareness as vital areas where progress needs to be carefully tackled. We suggest some likely poor outcomes if this planning does not occur, but indicate that if planning and implementation is effective then services can provide the kind of care the baby boomer generation seeks. [ABSTRACT FROM AUTHOR]