title: Miniaturisation and testing of an optical interference block for fluorescence imaging in capsule endoscopy
Creators: name: Melino, Gianluca
Publisher: name: University of Glasgow
Year: 2021
Subjects: subject: Fluorescence imaging, endoscopy, capsule endoscopy, colon cancer.

description: Early detection of gastrointestinal cancer is crucial to increase the life span of patients. The implementation of new imaging modalities, such as fluorescence imaging, in traditional endoscopy is the key in the detection of early signs of cancer. Fluorescence imaging techniques for clinical applications can be divided in two groups defined as autofluorescence imaging and fluorescence-labelling imaging. The former exploits the natural green fluorescence emitted by human tissues when excited by blue or ultra-violet light. Detection of cancer through autofluorescence imaging relies on the fact that cancer tissues have a much lower autofluorescence signal than healthy tissues. On the other hand, fluorescence-labelling imaging is used when the difference in autofluorescence between cancer and healthy surroundings is too weak to detect. Therefore, external fluorescence agents are used to target and label cancer lesions. Although traditional endoscopy has been successfully equipped with fluorescence imaging capabilities, the discomfort caused in patients and the incapability to reach the small intestine represent two main limitations. Fluorescence capsule endoscopy can enhance diagnostic accuracy with less inconvenience for patients. The optical components in traditional endoscopes are bulky and implemented outside the body of the patients. Therefore, there is a demand to develop highly miniaturised optical components for integration in capsule endoscopy. This thesis describes the design, fabrication, characterisation, and testing of a 5 mm x 6 mm x 6 mm optical interference block with the capability of fluorescence imaging in capsule endoscopy. The block accommodates ultrathin filters for optical isolation and was successfully integrated with a sensitive 64 x 64 pixels complementary metal oxide semiconductor single photon avalanche diode array to detect green fluorescence from Flavin Adenine Dinucleotide. This coenzyme is among the fluorophores responsible for autofluorescence in human tissues. The fluorescence-labelling capabilities of the imaging system were also tested to detect fluorescence from the cancer selective molecular probe ProteoGREEN-gGluTM which was used to label colorectal cancer cells. In vitro studies were also validated using a commercial ModulusTM Microplate reader. The potential use of the miniaturised block in capsule endoscopy was further demonstrated by imaging healthy and malignant resected human tissues from the colon to detect changes in autofluorescence signal that are crucial for cancer diagnosis. The results obtained demonstrated that the system successfully imaged the differences in the autofluorescence signal from resected healthy and malignant human tissues from the colon. Moreover, results from the in vitro tests showed that the system detected changes in the fluorescence signal induced in colorectal cancer cells after labelling with ProteoGREEN-gGluTM.