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Developments in Mesoscale Correlative Multimodal X-ray Microscopy

Abstract

X-ray and electron microscopy are crucial tools that are widely used in basic and translational sciences to detect, understand, and treat diseases. Operating at length scales between molecular machineries and individual cells, those mesoscale imaging techniques enable studies into macromolecular assembly, biomechanics, biomaterials, and cellular engineering, among many others. As X-ray and electron techniques become more advanced, however, we have reached a point at which single modal imaging is asymptotically approaching its usefulness for solving challenging scientific and engineering problems.

Since most natural systems comprise hierarchical organizations with heterogeneous compositions, individual imaging methods do not have the scope to understand the comprehensive set of rules governing a system's mesoscale self-organization and to make predictions of its macroscopic behaviors. This necessitates the development of a hybrid imaging approach that integrates X-ray and electron microscopy, and presents an opportunity to leverage both modalities in a complementary fashion. The four studies presented in this dissertation demonstrates the use of intra- or intermodal X-ray and electron microscopy to study a variety of organic and inorganic samples with heterogeneous compositions and mesoscale morphologies. This hybrid microscopy approach reveals multidimensional and multiscale insights into the structural, chemical, and dynamic properties of the samples.

Study 1 integrates X-ray fluorescence microscopy and ptychography for 3D imaging of frozen hydrated green algae; it highlights the potential of such an intramodal method for non-destructive correlative imaging with nanometer spatial resolution and elemental specificity. Study 2 combines X-ray and electron microscopy in 2D and 3D to study highly heterogeneous meteoric grains with elemental and chemical identification; it is used to reveal the meteorite's mineralogical properties, and at the same time showcases the power of multimodal X-ray and electron imaging.

Study 3 leverages linearly polarized X-rays and electron scanning nanodiffraction to reveal crystal orientations in dichroic coral particles. This demonstration suggests the possibility of combining X-ray and electron methods to study optically anisotropic materials across multiple length scales. Finally, Study 4 presents a novel lensless in situ coherent diffractive imaging technique for generating high spatiotemporal resolution movies of ultrafast dynamics. This technique may be integrated into existing X-ray diffractive imaging microscopes to add a temporal dimension to the multimodal imaging paradigm.

Taken together, this dissertation promotes multidisciplinary thinking in hybrid X-ray and electron imaging---one that seeks to integrate the strengths of each microscopy technique into a comprehensive correlative imaging paradigm that can help solve today's most challenging problems.

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