Applications of Proton Transfer Reaction and Selected Ion Flow Tube Mass Spectrometry in Health Monitoring

Lourenҫo, Célia Maria Farinha (2017). Applications of Proton Transfer Reaction and Selected Ion Flow Tube Mass Spectrometry in Health Monitoring. PhD thesis The Open University.

Abstract

This thesis investigates the use of Volatile Organic Compounds (VOCs) in disease diagnosis and monitoring. VOCs may be found in the human body, in exhaled breath, faecal matter, urine, and skin. Analysis of the volatile profile produced in the human body can provide an indicator of metabolic status, allowing the screening and monitoring of different diseases and conditions, non-invasively and painlessly.

In this thesis a range of highly sensitive analytical techniques have been adopted to measure such VOCs and demonstrate that such monitoring may be used as a disease diagnostic. For example breath samples may be analysed and calibrated against gas-phase standards prepared under physiologically representative concentrations as a tool for non-invasive disease monitoring, e.g. type 2 diabetes.

Detailed faecal headspace analyses of two different mouse models of type 2 diabetes (Cushing´s mice and Afmid) were made. The mouse model of Cushing’s syndrome develop excessive circulating glucocorticoid concentrations, which are associated with obesity, hyperglycaemia and insulin resistance. The Afmid knockout mice suffer inactivation of Afmid genes, which in part regulates many functions including pancreatic secretion. These mice show impaired glucose tolerance. The gut microbiota of diabetic mice appear to have a different composition when compared to wild-type littermates, i.e. significantly increased levels of short-chain fatty acids (SCFAs), ketones, alcohols and aldehydes were found in the faecal headspace of diabetic mice, and a possible link between gut microbiota and type 2 diabetes is demonstrated.

The use of VOCs as a screening tool of colorectal cancer was also explored. The current screening tools show lack of sensitivity and specificity for the screening of the disease. The volatile faecal profile of patients with colorectal cancer was investigated, and sulphide compounds, including hydrogen sulphide (H2S) are shown to have potential as biomarkers for screening of colorectal cancer.

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