| dc.description.abstract | In times of economic constraint, an ageing population and antimicrobial
resistance, medical challenges must be met by exploring new pathways to
improve diagnostics, prevention and specialised treatments. Lung diseases
include a wide range of conditions and exhibit high morbidity and mortality
rates, especially for actively ventilated patients in intensive care units.
The aim of this PhD is to develop systems for endoscopic sensing in size
restricted regions such as the alveolar space in the distal lung. The systems are
based on miniaturised and disposable single optical fibres and a custom CMOS
SPAD line sensor capable of time-resolved single photon detection. Standard
optical fibres are suitable for single-use medical devices and allow access
to remote locations in the lung. Applying advanced time-resolving detector
technology has the potential to overcome common limitations of intensity-based
spectroscopy. Two common sensing technologies – Raman and fluorescence
spectroscopy – are investigated. Fluorescence spectroscopy is a powerful tool
for tissue diagnostics providing insight into the molecular composition and
local environment through changes in the fluorescence intensity, spectral
properties, and lifetime. Raman spectroscopy reveals the chemical ‘fingerprint’
of molecules under investigation, but is impeded by an inherently weak signal.
The visibility of the Raman signal can be significantly enhanced by utilising
the different time profiles of unwanted background signals and the Raman
signal. The systems are exemplified for differentiating normal and abnormal
tissue, detecting pathogens and measuring key physiological parameters such
as pH, facilitated by fluorescent markers and Raman reporters. Time-resolved
fluorescence lifetime spectroscopy successfully demonstrates its potential for
pH-sensing, distinguishing between normal and tumorous tissue, and detecting
fluorescent labelled bacteria, all through a miniaturised optical fibre. Time-gated
Raman spectroscopy enables pH-sensing with Raman reporters, functionalised
gold nanoshells deposited on the fibre tip, with an improved pH sensitivity of
0.06 pH units | en |
