Development and integration of chemical imaging methods for applications in biomedical and pharmaceutical research

Randall, Elizabeth Claire (2017). Development and integration of chemical imaging methods for applications in biomedical and pharmaceutical research. University of Birmingham. Ph.D.

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Abstract

Imaging of biomolecules in biological substrates by mass spectrometry or spectroscopic imaging techniques plays a major role in biomedical, clinical, and pharmaceutical research. The work presented in this thesis investigates the capabilities of three imaging techniques, liquid extraction surface analysis (LESA) mass spectrometry imaging (MSI), matrix assisted laser desorption ionisation (MALDI) MSI and stimulated Raman scattering (SRS) microscopy. A method for combined LESA and MALDI analysis was developed and results provided high resolution imaging of multiple analyte classes (proteins, lipids and small molecule drugs) in thin tissue sections. SRS microscopy was used for the quantitative imaging of
MALDI sampling effects and sample preparation, providing insight into fundamental processes of MALDI MS. Multimodal SRS, LESA and MALDI imaging was executed on a single tissue sample revealing the complementarity between the three approaches. Specific challenges for LESA were further explored, namely quantification, improved spatial resolution and alternative biological substrates. A quantitative LESA method based on the production of mimetic tissue models containing stable isotope-labelled proteins was developed. An alternative platform, the Flow-Probe™, with the potential to achieve higher spatial resolution was assessed. Finally, a LESA method for the direct analysis of proteins from live bacterial colonies was developed.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):