Advanced microcrystallisation techniques for serial crystallography

Lewis, Sam 2025. Advanced microcrystallisation techniques for serial crystallography. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

This PhD thesis details the development of small-molecule serial (multi-crystal) X-ray crystallography, a nascent research area that is quickly gaining considerable interest from the solid-state community, at Beamline I19 of the UK synchrotron facility Diamond Light Source. While serial techniques were originally spearheaded at ultrabright X-ray Free Electron Lasers to study macromolecular samples, current upgrades to synchrotron light sources around the world to become so-called “fourth-generation” light sources show great promise for small-molecule serial crystallography, and has emerged concurrently with this project. Serial data collection methodologies are particularly attractive to enable structure determination of X-ray sensitive samples, provide high-throughput bulk analysis, and to conduct challenging time-resolved measurements to observe dynamic processes in the crystalline state. This final point is the central motivation of the work conducted here and the progress achieved is broad in scope and relevant to a variety of applications. Chapter 1 seeks to review the literature surrounding time-resolved small-molecule crystallography and the development of serial crystallography from origins surrounding X-ray sensitive macromolecules to contemporary studies on small-molecule systems. Chapter 2 then outlines the fundamental principles of crystallisation, X-ray crystallography, and synchrotron operation before introducing the experimental aims of this project. Chapter 3 details the crystallisation studies that have been conducted to produce optimised microcrystal batches with desirable crystal habits and narrow crystal size distributions for use in serial experiments. Chapter 4 describes the development of small-rotative fixed-target serial synchrotron crystallography (SR-FT-SSX) techniques utilising novel small-wedge rotative methods that have been implemented on Beamline I19 at Diamond Light Source. Chapter 5 then outlines progress in the use of SR-FT-SSX for bulk analysis of microcrystal batches and the identification of new crystal forms. Then finally, Chapter 6 explores the use of SR-FT-SSX to conduct steady-state photocrystallographic experiments and comments on future research directions to achieve the ultimate goal of conducting time-resolved pump-probe experiments.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Chemistry
Date of First Compliant Deposit:	6 May 2026
Last Modified:	06 May 2026 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/186813

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