An investigation into the viability of an infrared diagnostic instrument for measurement of CO2 isotope ratios in breath
Stable CO2 isotope ratio breath tests are established as a valuable tool in diagnostic and investigative medicine, with the potential to become more prominent in the future. The instrument conventionally used to measure the very small changes involved is an Isotope Ratio Mass Spectrometer however, the expense and complexity of such an instrument severely restricts the widespread and routine use of isotopic breath tests. Hence, to realise their full potential an alternative technique is required which is reliable, insensitive to environmental and component fluctuations, uncomplicated and affordable. We present a system that satisfies these criteria using broadband, non-dispersive, ground-state absorption infrared spectroscopy. Two isotopically distinct channels are created and their basal path length ratio recorded at the condition of transmitted intensity equilibrium. The change in channel path length ratios required to restore equilibrium in the 13C-enriched breath sample is directly related to the change in 13CO2 / 12CO2 concentration ratio. The system's novelty lies in this negative feedback loop balancing the signal by means of adjusting the path length of one of the channels. There is little evidence in the literature on infrared breath measurements that the possibility of interference from coincident infrared active breath trace compounds or various spectral effects that could lead to spurious results have been adequately assessed. Therefore, prior to the construction of a prototype instrument based upon this technique the question of its validity must be addressed. Furthermore, in addition to any instrument presenting a viable alternative it should also offer better reliability, long term stability and ideally be of lower cost than other emergent infrared instruments. Significant emphasis has therefore been placed upon evaluation of possible interferents, with the intention of providing an unambiguous assurance of the measurement's validity over a range of conceivable operating conditions and establishing operating tolerances that improve reliability over other infrared techniques. Also the prospect of using this technique to perform alternative isotope ratio breath tests was explored with the feasibility of using a novel filtering technique to enable measurement of 18O12O16O / 13C16O2 being investigated further. These aims were accomplished through the thorough evaluation of literature on breath trace compound's infrared spectra and by a series of theoretical computer instrument simulations, using detailed modelling of a breath sample's CO2 spectroscopy, capable of identifying, evaluating and quantifying the risks posed to a reliable measurement of 13CO2 / 12CO2 due to various spectral effects. The breath trace compound analysis revealed that 13C16O2 / 12C16O2 ratios can confidently be measured for isotopic breath tests using an instrument based on infrared absorption, the position of C02's n3 absorption band precluding any discernible risk. From the instrument simulations it has been possible to establish operating tolerances required to avoid or limit the generation of a spurious results and determine parameters necessary for the instrument's construction. Thus, we conclude that through the merits of its design and compliance to operating tolerances established the instrument described presents a viable alternative for providing highly accurate, reliable and low cost breath tests capable of being performed outside of a laboratory environment.