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Title: Metabolite profiling of biological specimens using small molecular weight volatile organic compounds by proton transfer reaction time-of-flight mass spectrometry
Author: Kuppusami, Sharmilah
ISNI:       0000 0004 6348 5340
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2017
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Metabolite profiling is an analytical study of metabolites that are of low molecular weight which results from normal and pathological cellular processes, using high throughput analytical technologies. This thesis documents the development of the analytical technique of proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS) for the analysis of small molecular weight volatile organic compounds (VOCs) in different biological specimens. The work explored the challenges associated with sampling, analysis, and metabolite profiling and identification in microbiology and clinical studies. Initial work focused on the VOCs produced in the headspace of ten Clostridium difficile ribotypes in an attempt to metabolically profile C. difficile at the ribotype level. The C. difficile ribotypes were successfully distinguished from one another. The metabolite profiles suggested that VOC profiling may provide a useful indicator for the identification of the ribotypes. The PTR-ToF-MS system was applied to two clinical trials. The first was a genitourinary clinical trial of patients with sexually transmitted infections (STI), which explored the VOCs emitted from vaginal, cervical and throat swabs to support the hypothesis that metabolite profiling has the potential to identify the presence of infection. The second involved the analysis of exhaled breath to examine the VOCs in the breath of individuals with ovarian cancer (7 female cancer patients, 12 healthy female controls, 5 female with benign cysts) using offline breath collection technique. The premise is that the VOCs in the breath are representative of the VOCs in blood; therefore specific VOCs may be produced in the body caused by tumour cells and these can be detected in breath. Within these applications, the PTR-ToF-MS was able to demonstrate that metabolite profiles are promising biomarkers for disease/infection identification, as well as providing information of cell mechanism and alterations in cells.
Supervisor: Ellis, Andrew ; Monks, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available