This thesis describes the development, characterisation and application of a portable spectroscopy system for ultra-sensitive, real-time detection of breath ethane. In healthcare, breath ethane is a widely accepted marker of free radical-induced cell damage and may be
used to indicate changes in oxidative stress.
The aim was to deliver a compact instrument capable of long-term, on-site use in a clinical environment, while also retaining the high performance previously achieved by lab-based systems at the University of Glasgow. The newly developed instrument has a sensitivity of 70 parts per trillion with a 1 Hz sampling rate. The system incorporates a cryogenicallycooled lead-salt laser and uses a second derivative wavelength modulation detection scheme.
A thermally-managed closed-loop refrigeration system has eliminated the need for liquid coolants.
The instrument has been field-tested to ensure target performance is sustained in a range of environments, both indoor and outdoor. It has since been used in a number of pilot clinical studies, both off-site and on-site, in which breath ethane was monitored as a marker of oxidative stress. The three main clinical areas investigated were dialysis, radiotherapy and intensive care. In the intensive care study, the instrument was modified to enable automatic
breath sampling of inspired and expired gases of ventilated patients. This technique proved highly successful and the instrument then remained at the Southern General hospital, where it continued to be used as part of a wider study into breath ethane in intensive care patients.
The use of the new spectroscopy system has enabled ultra-sensitive, rapid analysis of a large number of breath samples. The use of the new instrument, in particular for continual breath monitoring, has enabled the detection of short-lived fluctuations in breath ethane,
yielding some interesting findings in a number of pilot clinical studies. Our results suggest that breath ethane may be used as an indicator of dynamic changes in oxidative stress. Further studies will be required to determine if such monitoring is of clinical benefit.
Chapter 1 gives a general introduction to spectroscopy and some background to our project. A number of spectroscopic techniques and laser sources are discussed, along with a review of previous work in ethane detection. In chapter 2 some background theory of molecular spectroscopy is given, with a more detailed discussion of the wavelength modulation technique.
Chapter 3 describes in detail the development of the portable spectroscopy system. The achieved performance and factors contributing to this performance are discussed in
chapter 4. The field test of the instrument is reported on in chapter 5. In chapter 6 the application of the technology to breath analysis and the current challenges in this field are discussed. Example breath ethane measurements for healthy controls are provided. The
clinical pilot studies conducted using the new system in areas of dialysis, intensive care and radiotherapy are discussed in chapters 7, 8, and 9 respectively. Chapter 10 contains the thesis summary and conclusions, with suggestions for future work
