The advent of highly-coherent x-ray light sources, such as those now available world-wide in modern third-generation synchrotrons and increasingly available in free-electron lasers, is driving the need for improved analytical and experimental techniques which exploit the coherency of the generated light. As the light illuminating a sample approaches full coherence, a simple Fourier transform describes the diffraction pattern generated by the scattered light in the far field; because the Fourier transform of an object is unique, coherent scattering can directly probe local structure in the scattering object instead of bulk properties. In this dissertation, we exploit the coherence of Advanced Light Source beamline 12.0.2 to build three types of novel coherent scattering microscopes. First, we extend the techniques of coherent diffractive imaging and Fourier transform holography, which uses iterative computational methods to invert oversampled coherent speckle patterns, into reflection geometry. This proof-of-principle experiment demonstrates a method by which reflection Bragg peaks, such as those from the orbitally-ordered phase of complex metal oxides, might eventually be imaged. Second, we apply a similar imaging method to the x-ray beam itself to directly image the mutual coherence function with only a single diffraction pattern. This technique supersedes the double-slit experiments commonly seen in the scattering literature to measure the mutual intensity function by using a set of apertures which effectively contains all possible double slit geometries. Third, we show how to evaluate the speckle patterns taken from a labyrinthine domain pattern for "hidden" rotational symmetries. For this measurement, we modify the iterative algorithms used to invert speckle patterns to generate a large number of domain configurations with the same incoherent scattering profile as the candidate pattern and then use these simulations as the basis for a statistical inference of the degree of ordering in the domain configuration. We propose extending this measurement to position-resolved speckle patterns, creating a symmetry-sensitive microscope. The three new techniques described herein may be employed at current and future light sources.

Fluorescence microscopy has revolutionized medicine and biological science with its ability to study the behavior and chemical expressions of living cells. Fluorescent probes can label cell components or cells of a particular type. Clinically the impact of fluorescence imaging can be seen in the diagnosis of cancers, AIDS, and other blood related disorders. Although fluorescence imaging devices have been established as a vital tool in medicine, the size, cost, and complexity of fluorescence microscopes limits their use to central laboratories. The work described in this thesis overcomes these limitations by developing a low cost integrated fluorescence microscope so single use fluorescence microscopy assays can be developed. These assays will enable at-home testing, diagnostics in resource limited settings, and improved emergency medicine.

Due to the ever-increasing demands of highly integrated optical devices in imaging, spectroscopy, communications, and so on, there is a compelling need to design and characterize novel compact photonic components. The traditional approaches to realizing compact optical devices typically result in large footprints and sizable optical thicknesses. Moreover, they offer few degrees of freedom (DOF), hampering on-demand functionalities, on-chip integration, and scalability. This thesis will address the design and development of ultracompact diffractive devices for imaging and spectroscopy, utilizing advanced machine learning techniques and optimization algorithms. I first present the inverse design of ultracompact dual-focusing lenses and broad-band focusing spectrometers based on adaptive diffractive optical networks (a-DONs), which combine optical diffraction physics and deep learning capabilities for the inverse design of multi-layered diffractive devices. I designed two-layer diffractive devices that can selectively focus incident radiation over well-separated spectral bands at desired distances and also optimized a-DON-based focusing spectrometers with engineered angular dispersion for desired bandwidth and nanometer spectral resolution. Furthermore, I introduced a new approach based on a-DONs for the engineering of diffractive devices with arbitrary k-space, which produces improved imaging performances compared to contour-PSF approaches to lens-less computational imaging. Moreover, my method enables control of sparsity and isotropic k-space in pixelated screens of dielectric scatterers that are compatible with large-scale photolithographic fabrication techniques. Finally, by combining adjoint optimization with the rigorous generalized Mie theory, I developed and characterize functionalized compact devices, which I called "photonic patches," consisting of ~100 dielectric nanocylinders that achieve predefined functionalities such as beam steering, Fresnel zone focusing, local density of states (LDOS) enhancement, etc. My method enables the inverse design of ultracompact focusing spectrometers for on-chip planar integration. Leveraging multiple scattering of light in disordered random media, I additionally demonstrated a novel approach to on-chip spectroscopy driven by high-throughput multifractal (i.e., multiscale) media, resulting in sub-nanometer spectral resolution at the 50×50 µm²-scale footprint.

State-of-the art Fourier transform holography (FTH) techniques use x-ray magnetic circular dichroism (XMCD) as a contrast mechanism for element-specfi c imaging of magnetic domains. With the soft x-ray Nanoscience beamline at Diamond Light Source in the UK, and the Dragon beamline at the European Synchrotron Radiation Facility (ESRF) in France, the possibility of new methods to study nanostructured magnetic systems has been demonstrated. The ability to record images without the use of lenses, in varying magnetic fi elds and with high spatial resolution down to 30 nm has been used to study in-plane magnetism of 50 nm thin permalloy (NiFe alloy) nanoelements. The holographic technique used extended reference objects rather than conventional pinhole references, which allowed a high flexibility on the direction of magnetisation that is probed. The element specific nature of the imaging, with the additional choice in the directions of magnetisation that are probed has been used to study dipolar interactions in a hard/Ta/soft [Co/Pt]30/Ta/Py multi-layered system. Images of the out-of-plane magnetised domains of [Co/Pt]30 were found to bare strong spatial resemblance to the in-plane domains of the permalloy. The domain structure is thought to be magnetostatically imprinted into permalloy during the growth stage of the lm, where stray elds generated by the adjacent Co/Pt multilayer influence the formation of domains in the permalloy. Strong resemblance between the two layers could be found at remanence within a pristine sample, however the similarities disappear after the sample was exposed to a saturating magnetic field. This disagreed with micromagnetic simulations performed in The Object Oriented MicroMagnetic Framework (OOMMF) program, and an explanation for the observations has been sought in the growth process of the multi-layered fi lm, with conditions that are diffi cult to recreate in the model. Optical holography has been used for preliminary insight into implementing a method of FTH in a reflective geometry at soft x-rays wavelength. With scattering chambers at BESSY II in Germany and at the Stanford Synchrotron Radiation Lightsource (SSRL) in California the possibility of reducing scattered noise in a hologram recorded in a reflective geometry has been investigated. Studies into specular and dif use reflections have been performed optically however the use of extended references alone may alleviate the current problem at x-ray wavelengths which lie in the weak signal given by a reflective point-like reference source.

Techniques for fast, 3D, quantitative microscopy are of great interest in many fields. In this context, in-line digital holography has significant potential due to its relatively simple setup (lensless imaging), its three-dimensional character and its temporal resolution. The goal of this thesis is to improve existing hologram reconstruction techniques by employing an "inverse problems" approach. For applications of objects with parametric shapes, a greedy algorithm has been previously proposed which solves the (inherently ill-posed) inversion problem of reconstruction by maximizing the likelihood between a model of holographic patterns and the measured data. The first contribution of this thesis is to reduce the computational costs of this algorithm using a multi-resolution approach (FAST algorithm). For the second contribution, a "matching pursuit" type of pattern recognition approach is proposed for hologram reconstruction of volumes containing parametric objects, or non-parametric objects of a few shape classes. This method finds the closest set of diffraction patterns to the measured data using a diffraction pattern dictionary. The size of the dictionary is reduced by employing a truncated singular value decomposition to obtain a low cost algorithm. The third contribution of this thesis was carried out in collaboration with the laboratory of fluid mechanics and acoustics of Lyon (LMFA). The greedy algorithm is used in a real application: the reconstruction and tracking of free-falling, evaporating, ether droplets. In all the proposed methods, special attention has been paid to improvement of the accuracy of reconstruction as well as to reducing the computational costs and the number of parameters to be tuned by the user (so that the proposed algorithms are used with little or no supervision). A Matlab® toolbox (accessible on-line) has been developed as part of this thesis

No description available.

L'objectif de ce mémoire est dedévelopper de nouvelles méthodes d'imageriesans lentille en simple tir 2D et 3D avec dessources harmoniques XUV. Un intérêt particulierest porté aux techniques d'imageries permettantl'imagerie des objets biologiques et de phase.Dans un premier temps, on introduit la théorie del'imagerie dans lentille et on détaille lesméthodes utilisées au cours de cette thèse pourreconstruire le champ diffracté par l'objet quel'on souhaite imager. Les techniques d'imageriessont séparées en deux catégories : itératifs etholographiques. On discute des conditionsexpérimentales nécessaires à la reconstruction del'image de l'objet et on compare les avantagesrespectifs des deux types de méthodes. Puis, ondétaille les aspects expérimentaux du faisceauXUV obtenu par HHG et on couvre brièvementla théorie associée à ce processus. La sectionsuivante traite des paramètres et des techniquesde traitement des données influant sur la qualitéde l'image reconstruite en imagerie sans lentille.On montre comment améliorer lesreconstructions HERALDO dans un régime defaible flux de photons. On présente ensuite lesrésultats d'une technique de caractérisationcomplète de la cohérence spatiale d’un faisceauXUV en simple tir. Cette dernière est unparamètre critique de l'imagerie sans lentille. Al'aide d'un tableau non redondant de référencesponctuelles, on mesure la cohérence spatialepour chaque distance entre les références, sansaucune mesure du profil spatial du faisceau. Onmontre que la distribution de la cohérence estgaussienne et que son diamètre dépend desconditions de génération du faisceauharmonique. On étudie aussi quantitativementcomment l'accumulation de plusieurs tirs dediffraction diminue la cohérence apparente dufaisceau. Une expérience d'imagerie d'objets dephase avec une source harmonique pouvant êtreappliquée à des objets biologiques est ensuiteprésentée.A notre connaissance c'est la premièrereconstruction par méthode CDI d'objets dephase avec une source harmonique. La suite dumanuscrit présente les résultats de deuxexpériences visant à réaliser de l'imagerie 3D àl'échelle nanométrique avec une sourceharmonique. Tout d’abord, on présente unetechnique d'imagerie 3D simple tir. C'est lapremière expérience permettant unereconstruction 3D à partir d'une seuleacquisition, avec une résolution spatialenanométrique et une résolution temporellefemtoseconde, sans utiliser de connaissances apriori sur l'objet étudié. Cette technique possèdeun vaste spectre d'application, particulièrementpour l'étude structurelle d'échantillonsbiologiques sensibles aux dégâts d'irradiation.De plus, cette technique peut être facilementapplicable à des FELs et des synchrontrons pourobtenir de meilleures résolutions. La deuxièmeexpérience d'imagerie 3D est une preuve deconcept validant la faisabilité de lacryptomographie avec une source harmonique.Pour reconstruire le volume 3D de l'échantillon,la cryptotomographie utilise des figures dediffraction qui sont acquises pour desorientations de l'échantillon inconnues. Lerégime de faible flux dans lequel on se place nouspermet de simuler les paramètres d'une sourceharmonique fonctionnant dans la fenêtre de l'eau.On conclut que, le niveau du signal de diffractionest suffisant pour pouvoir identifier l'orientationde l'objet à partir des figures de diffractionenregistrées, dans des conditions expérimentalesoptimisées. Ainsi, avec suffisamment de figuresde diffraction enregistrées et assez d'orientationsde l'objet, on peut reconstruire le volume 3D del'objet. Ces résultats impliquent qu'uneexpérience de cryptotomographie d'objetsbiologiques avec une source harmoniquefonctionnant dans la fenêtre de l'eau seraitréalisable. / The aim of this dissertation is todevelop new lensless single shot imagingtechnique in 2D and 3D with XUV harmonicsources which can be applied to study biologicalobjects and phase objects. Firstly, we introducethe theory underlying lensless imagingtechniques and we describe the methods usedduring this thesis to reconstruct the light fielddiffracted by the studied object. The imagingtechniques are split in two categories: iterativeand holographic. The iterative methodsreconstruct the phase of the diffracted wavefront using constraints in the Fourier space andthe reel space. With the holographic techniques,the phase is encoded directly in the interferencefringes between the reference and the objectwithin the diffraction pattern. We discuss theexperimental parameters required to achieve animage reconstruction and we compare therespective advantages of the two types ofmethod. Then, we describe the experimentalparameters of the XUV beam produced by highharmonic generation (HHG) and we brieflyexplain the theory of the HHG. The next sectiondiscusses the parameters the quality of thereconstructed image. We show how to improvethe resolution and the signal to noise ratio usingthe HERALDO technique in the low fluxregime.We then show the result of a new technique forthe single shot characterization of the spatialcoherence of XUV beams. Indeed, the spatialcoherence is a critical parameter for coherentdiffractive imaging techniques. Using a NRA ofreference holes, we measure the spatialcoherence for each distance between each pairof holes, without the knowledge of the intensitydistribution on the sample. We show that thespatial coherence has a gaussian distribution andthat its diameter varies according to thegeneration parameters of the harmonic beam.We also study quantitatively the effect of multishotsaccumulation of the diffraction pattern onthe apparent coherence of the beam. We alsoshow the result of phase object imaging usingcoherent diffractive imaging with a harmonicsource. To our knowledge, this if the first timesuch result has been achieved. The rest of thedissertation present new lensless imaging 3Dtechniques using harmonic sources. The first ofthe last two experiments shown is a lenslesssingle shot stereo 3D technique. It is the first oneallowing a 3D reconstruction from a singleacquisition, with a nanometer spatial resolutionand a femtosecond temporal resolution, withoutusing \textit{a priori} knowledge of the samplestudied. This method has a vast spectrum ofapplication and is particularly interesting for thestructural study of biological sample sensitive toradiation damage and for the study of nonreversibledynamical phenomena in 3D.Furthermore, this can easily be implemented inFELs and synchrotrons to reach even betterspatial resolution. The second 3D experimentshown in this thesis is a proof of concept ofcryptotomography using a high harmonic sourcein a low flux regime. To reconstruct the 3Dvolume of the sample, cryptotomographie usesdiffraction pattern acquired for unknown sampleorientations and therefore non-classified. Thelow flux regime used here simulate the flux of aharmonic source generated in the water window.We conclude from this experiment that, with theproper experimental conditions, the diffractionsignal is sufficient to allow the classification byorientation of the diffraction patterns. Withenough diffraction pattern and angles of thesample recorded, we can achieve a 3Dreconstruction of the sample. This result impliesthat the cryptotomography of biological objectsusing a water window harmonic source ispossible.

Coherent diffractive imaging (CDI) has become a very popular technique over the past two decades. CDI is a "lensless" imaging method which replaces the objective lens of a conventional microscope by a computational image reconstruction procedure. Its increase in popularity came together with the development of X-ray free-electron lasers (XFELs) which produce extremely bright and coherent X-rays. By facilitating these unique properties, CDI enables structure determination of non-crystalline samples at nanometre resolution and has many applications in structural biology, material science and X-ray optics among others. This work focuses on two specific CDI techniques, flash X-ray diffractive imaging (FXI) on biological samples and X-ray ptychography. While the first FXI demonstrations using soft X-rays have been quite promising, they also revealed remaining technical challenges. FXI becomes even more demanding when approaching shorter wavelengths to allow subnanometre resolution imaging. We described one of the first FXI experiments using hard X-rays and characterized the most critical components of such an experiment, namely the properties of X-ray focus, sample delivery and detectors. Based on our findings, we discussed experimental and computational strategies for FXI to overcome its current difficulties and reach its full potential. We deposited the data in the Coherent X-ray Database (CXIDB) and made our data analysis code available in a public repository. We developed algorithms targeted towards the needs of FXI experiments and implemented a software package which enables the analysis of diffraction data in real time. X-ray ptychography has developed into a very useful tool for quantitative imaging of complex materials and has found applications in many areas. However, it involves a computational reconstruction step which can be slow. Therefore, we developed a fast GPU-based ptychographic solver and combined it with a framework for real-time data processing which already starts the ptychographic reconstruction process while data is still being collected. This provides immediate feedback to the user and allows high-throughput ptychographic imaging. Finally, we have used ptychographic imaging as a method to study the wavefront of a focused XFEL beam under typical FXI conditions.  We are convinced that this work on developing strategies and algorithms for FXI and ptychography is a valuable contribution to the development of coherent diffractive imaging.

Le développement de techniques de microscopie quantitatives tridimensionnelles et résolues en temps est fondamental dans de nombreux domaines. Dans ce cadre, l’holographie numérique en ligne recèle un fort potentiel, en raison de sa relative simplicité de mise en œuvre (imagerie sans lentille), de son caractère tridimensionnel et de sa résolution temporelle. Le but de cette thèse est l’amélioration des algorithmes de reconstruction des hologrammes par une approche « problèmes inverses ». Dans le cadre de la reconstruction d’objets paramétriques, des travaux antérieurs ont permis de proposer un algorithme glouton permettant de résoudre le problème inverse de reconstruction (intrinsèquement mal posé) par une maximisation de la vraisemblance entre un modèle de formation d’hologramme et les données. Une première contribution de ce travail de thèse a été de réduire le temps de calcul de cet algorithme en utilisant une approche multi-résolution (algorithme FAST). Dans une deuxième contribution, une approche reconnaissance de forme de type « matching pursuit » est utilisée pour la reconstruction d’objets quelconques en recherchant les éléments d’un dictionnaire les plus proches des figures de diffraction composant l’hologramme. La réduction des dimensions du dictionnaire est proposée en utilisant une décomposition en valeurs singulières tronquée. La troisième contribution de cette thèse a été réalisée en collaboration avec le LMFA. L’algorithme glouton a été utilisé sur un cas réel : la reconstruction et le suivi de gouttelettes d’éther évaporantes en chute libre. Dans tous ces développements une attention particulière a été portée sur la précision des reconstructions, sur la réduction du nombre de paramètres à régler par l’utilisateur (algorithmes peu ou non supervisés). Une boîte à outils Matlab® (en ligne) a été développée dans le cadre de cette thèse / Techniques for fast, 3D, quantitative microscopy are of great interest in many fields. In this context, in-line digital holography has significant potential due to its relatively simple setup (lensless imaging), its three-dimensional character and its temporal resolution. The goal of this thesis is to improve existing hologram reconstruction techniques by employing an “inverse problems” approach. For applications of objects with parametric shapes, a greedy algorithm has been previously proposed which solves the (inherently ill-posed) inversion problem of reconstruction by maximizing the likelihood between a model of holographic patterns and the measured data. The first contribution of this thesis is to reduce the computational costs of this algorithm using a multi-resolution approach (FAST algorithm). For the second contribution, a “matching pursuit” type of pattern recognition approach is proposed for hologram reconstruction of volumes containing parametric objects, or non-parametric objects of a few shape classes. This method finds the closest set of diffraction patterns to the measured data using a diffraction pattern dictionary. The size of the dictionary is reduced by employing a truncated singular value decomposition to obtain a low cost algorithm. The third contribution of this thesis was carried out in collaboration with the laboratory of fluid mechanics and acoustics of Lyon (LMFA). The greedy algorithm is used in a real application: the reconstruction and tracking of free-falling, evaporating, ether droplets. In all the proposed methods, special attention has been paid to improvement of the accuracy of reconstruction as well as to reducing the computational costs and the number of parameters to be tuned by the user (so that the proposed algorithms are used with little or no supervision). A Matlab® toolbox (accessible on-line) has been developed as part of this thesis

The newly emerging technology of X-ray free-electron lasers (XFELs) has the potential to revolutionise molecular imaging. XFELs generate very intense X-ray pulses and predictions suggest that they may be used for structure determination to atomic resolution even for single molecules. XFELs produce femtosecond pulses that outrun processes of radiation damage and permit the study of structures at room temperature and of structural dynamics. While the first demonstrations of flash X-ray diffractive imaging (FXI) on biological particles were encouraging, they also revealed technical challenges. In this work we demonstrated how some of these challenges can be overcome. We exemplified, with heterogeneous cell organelles, how tens of thousands of FXI diffraction patterns can be collected, sorted, and analysed in an automatic data processing pipeline. We improved  image resolution and reduced problems with missing data. We validated, described, and deposited the experimental data in the Coherent X-ray Imaging Data Bank. We demonstrated that aerosol injection can be used to collect FXI data at high hit ratios and with low background. We reduced problems with non-volatile sample contaminants by decreasing aerosol droplet sizes from ~1000 nm to ~150 nm. We achieved this by adapting an electrospray aerosoliser to the Uppsala sample injector. Mie scattering imaging was used as a diagnostic tool to measure positions, sizes, and velocities of individual injected particles. XFEL experiments generate large amounts of data at high rates. Preparation, execution, and data analysis of these experiments benefits from specialised software. In this work we present new open-source software tools that facilitates prediction, online-monitoring, display, and pre-processing of XFEL diffraction data. We hope that this work is a valuable contribution in the quest of transitioning FXI from its first experimental demonstration into a technique that fulfills its potentials.