Correlative Spectromicroscopy and Tomography for Biomedical Applications Involving Electron, Ion, and Soft X-ray Microscopies


Adam P. Hitchcock,1 * Xiaoyue Wang,2 Kathryn Grandfield,2 Joanna F. Collingwood,4 and Neil D. Telling3


1Chemistry and Chemical Biology, McMaster University, Hamilton, L8S 4M1 Canada 2Materials Science and Engineering, McMaster University, Hamilton, L8S 4L7 Canada


3Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, Staffordshire ST4 7QB, UK 4School of Engineering, University of Warwick, Coventry, CV4 7AL, United Kingdom


*aph@mcmaster.ca


Abstract: Many important scientific and technical problems are best addressed using multiple, microscopy-based analytical techniques that combine the strengths of complementary methods. Here, we provide two examples from biomedical challenges: unravelling the attachment zone between dental implants and bone, and uncovering the mecha- nism of Alzheimer’s disease. They combine synchrotron-based scan- ning transmission X-ray microscopy (STXM) with transmission electron microscopy ((S)TEM), electron tomography (ET), EELS tomography, and/or atom probe tomography (APT). STXM provides X-ray absorption based chemical sensitivity at mesoscale resolution (10–30 nm), which complements higher spatial resolution electron microscopy and APT.


Keywords: scanning transmission X-ray microscopy, scanning transmission electron microscopy, atom probe tomography, titanium implants, Alzheimer’s disease


Introduction Correlative microscopy refers to coordinated use of com-


plementary techniques to study the same specimen, ideally on exactly the same area [1]. For biomedical applications correlative methods are oſten critical. Due to the hierarchically structured nature of bone and the inhomogeneous topographical quality of implant surfaces, multiple-length-scale 3D characterization techniques are needed to visualize bone–implant interfaces [2]. Similarly, multiple techniques probing at different length scales are required to begin to understand the complexity of eukary- otic cells in both healthy and diseased states. Tus, correlative microscopy is an efficient way to complement and validate indi- vidual characterization techniques and to improve data analysis [3]. Figure 1 shows the relative capabilities, in terms of spatial resolution and elemental/chemical sensitivity of some microana- lytical methods, including those employed in the work described in this article. For biomedical and health challenges, gaining a view of the full structural and chemical details at multi-length scales is essential for understanding the evolution of disease, proper diagnosis, and determining best treatment options. In this article we highlight two recent examples that used correla- tive microscopy methods in biomedical contexts. Implants. Bone interfacing implants are used worldwide in


the form of hip joint replacements and dental implants. Despite being generally successful, there is still an appreciable frequency of implant failures that demand revision surgeries. Degrada- tion of the bonding between living bone and the implant device, called osseointegration, is the cause of many of these failures [4]. Te physical and chemical properties of an implant surface, such as porosity, morphology, and chemical composition, are thought


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to play a crucial role in forming long-lasting load-bearing bonds [3,5,6]. Te understanding of osseointegration has evolved as a consequence of many different microscopy and analytical stud- ies of ever finer structures at the interface. Human bone has complex hierarchical structures with nanoscale building units of type I collagen and carbonated hydroxyapatite crystals. Aſter a titanium implant is placed in vivo, new bone forms along the implant surface to generate a biomechanically functional inte- gration. However, the mechanism of bone integration with nanostructured surfaces is not well understood. State-of-the-art research in this area has been generally limited to micro-scale morphological evaluations, with little compositional or nano- scale mapping at the interface. Correlative spectrometry and tomography can enable a deeper understanding of the hierar- chical attachment mechanism of bone to implant. Alzheimer’s disease. Te accumulation of the peptide frag- ) within the brain is a characteristic


ment amyloid-beta (Aβ1−42 James Everett,3


Figure 1: Spatial resolution and relative chemical sensitivity of certain micro- analytical methods, including those used for correlative studies in this work. Note that techniques that are higher vertically correspond to methods that are more chemically sensitive.


doi:10.1017/S1551929518001256 www.microscopy-today.com • 2019 March


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