Electronic nose technology as a point-of-care solution for the detection of colorectal cancer

Abstract

This thesis presents a comparative study of electronic nose technologies for the detection of colorectal cancer from healthy and disease controls using gases/volatiles in urine headspace. A review is made of the clinical features of lower gastro-intestinal diseases and the sensing technologies available to electronic noses. The literature surrounding the detection of cancers and other diseases by sensing of gases and volatiles is also reviewed. An investigation into the common volatile components of urine headspace is conducted experimentally using a gas chromatograph – mass spectrometer (451 Scion SQ, Bruker Corp), resulting in 10 candidate chemicals with links to gut bacteria and diet. A humidity generation unit was developed and integrated with a volatile testing rig to aid in assessing the response of different electronic nose technologies to volatile chemical groups. Four electronic nose systems were tested in parallel studies using urine headspace samples from patients of colorectal cancer (CRC) and irritable bowel syndrome (IBS), as well as healthy volunteers. This involved pre-classified multivariate analysis techniques followed by K-Nearest-Neighbour validation for sensitivity and specificity. A commercial electronic nose based on metal oxide sensors (Fox 4000, AlphaMOS Ltd) analysed 93 urine samples giving a sensitivity and specificity to colorectal cancer of 54% and 48%. A field asymmetric ion mobility spectrometer that is commercially available (Lonestar, Owlstone Ltd) was tested using 133 samples of CRC and volunteer samples, yielding 88% disease sensitivity and 60% specificity. A new electronic nose system was developed using state-of-the-art ampere-metric and optical sensors and tested against 92 urine samples, giving a respective sensitivity and specificity to CRC against IBS controls of 78% and 79%. A final instrument was developed that includes a micro-packed GC column and an array of micro-hotplate metal oxide sensors, which analysed 49 samples to give a 92% sensitivity and 77% specificity to CRC against IBS