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A Hierarchical Etched Grid for Correlative Chemical Imaging

Lookup NU author(s): Dr Christopher MorrisORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2026 The Authors. Co-published by Nanjing University and American Chemical Society.Correlative microscopy linking synchrotron X-ray fluorescence (SXRF) with optical imaging is valuable for contextualizing chemical element distributions in biology. The spatial correlation necessary to achieve this presents fundamental challenges and can be a significant constraint on accuracy and data interpretation. We present a technical solution based on a finder grid concept, optimized for SXRF correlative studies of metals in biological tissues, with scope for wider adaptation and application. A hierarchically patterned fiducial system was directly etched onto spectroscopically clean quartz substrates via femtosecond laser ablation. This design enables improved correlation among SXRF, optical imaging, and histological staining over a greater range of length scales than conventional registration methods such as the use of tissue architecture from serial sections and the use of electron-microscopy-resolution finder grids and applied fiduciary markers that can introduce XRF-signal-dominating levels of elements such as copper, nickel, gold, and titanium. We present two quartz finder grid formats: a microgrid and a nanogrid design. We demonstrate their utility for rapid ROI relocalization and same-section correlative workflows using human brain tissue. The etched quartz finder grid approach facilitates rapid and reproducible ROI relocalization and alignment across instruments, particularly where integral fiducial markers are sparse or ambiguous.


Publication metadata

Author(s): Arigundiya NSW, Brooks J, Sykes P, Lee S, Visanji NP, Morris CM, Geraki K, Collingwood JF

Publication type: Article

Publication status: Published

Journal: Chemical and Biomedical Imaging

Year: 2026

Volume: 4

Issue: 7

Pages: 1538-1546

Print publication date: 27/07/2026

Online publication date: 04/03/2026

Acceptance date: 10/02/2026

Date deposited: 10/08/2026

ISSN (electronic): 2832-3637

Publisher: American Chemical Society

URL: https://doi.org/10.1021/cbmi.5c00231

DOI: 10.1021/cbmi.5c00231

Data Access Statement: The data that support the findings in this study are available in the Warwick Research Archive Portal (WRAP) repository at [https://wrap.warwick.ac.uk/id/eprint/197379/]


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