Breath Collection Equipment for Clinical Applications with SIFT-MS Instruments

Real time detection of Volatile Organic Compounds (VOCs) using Selected Ion Flow Tube – Mass Spectrometry (SIFT-MS) provides a unique opportunity for research into breath testing for clinical diagnosis. However, before engaging in research into breath analytes as markers of disease, appropriate breath collection methods are required. Collection of breath for SIFT-MS instruments fall into two categories, direct breath collection into the instrument and the remote breath collection onto a storage medium. This thesis describes the development and validation of both methods of breath collection equipment for SIFT-MS analysis. Development of the direct breath collection device involved standardising and optimising the way in which breath is sampled by SIFT-MS. Design considerations include ergonomics, patient safety, breathing resistance, materials, and appropriate operating conditions of the device. Results from materials testing showed that all materials emit VOCs and the best approach is to minimise VOC emission by careful material selection. To minimise flow resistance experienced by the patient, the capillary from which the SIFT-MS instrument samples, is placed as close as possible to the users mouth. The optimal operating temperature of the device was found to be 100°C - 120°C, which ensures that water vapour will not condense inside the capillary causing blockage. In order to ensure patient safety the device is adequately insulated using stagnant air which also minimises VOC emission from insulation materials. Because a SIFT-MS instrument is large and cannot be easily shifted around a hospital, a system of remote sample collection is required. It is also important to separately collect and analyse breath from the respiratory alveolar region. For this reason the remote breath collection device designed also fractionates collected breath samples into the breath from the upper airways and alveolar breath. The storage medium chosen for the collected breath samples is a gas sampling bag made from Tedlar™. Collection of breath into Tedlar™ bags allows breath to be stored as a whole air sample, the ideal form for analysis with the SIFT-MS technique. Alveolar breath is fractionated from deadspace gasses by measuring a subject's exhalation and collecting the portion of interest. The breath exhalation is measured by an averaging Pitot tube and pressure transducer. Signal processing and automation of the remote breath collection device is controlled by a Cypress Microsystems PSoC microcontroller. To validate the device isoprene and acetone concentrations in fractionated breath samples were compared with a whole breath sample. Results showed that the alveolar breath fraction had a higher concentration of acetone than the upper airway fraction, indicating that the breath was successfully fractioned. However, isoprene concentrations were lower in both fractions due to hyperventilation of the subject causing a dilution effect of alveolar VOCs. Therefore, a higher sample collection volume is required per exhalation, and regulating subjects' breathing rate will avoid the dilution effect observed in collected breath samples. Overall, this thesis had designed, developed and validated two forms of breath collection systems for use with SIFT-MS technology