Presenter Bio: I am a trained colorectal surgeon from Taiwan. In my hospital we perform one-thousand colorectal cancer operations every year. In my clinical practice, I recognized the need for better strategy for non-invasive early detection of cancer. I am currently undertaking a PhD at the department of Surgery and Cancer at Imperial College London. My research focus on method development and integration of mass spectrometry methods within the field of breath research. In addition, I support the coordination of a major clinical study about colorectal cancer detection through breath testing. My research has helped me to develop new skills that are important to becoming an academic clinician, including: analytical mass spectrometry, critical thinking and multi-disciplinary team working. I hope to apply the knowledge gained during my PhD to improve cancer care in my home country.
Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
Introduction
Numerous studies have independently shown that the profile of volatile organic compounds (VOCs) within exhaled breath can predict presence of human disease, including cancer1. Significant variation in the way in which breath samples are collected and analysed has largely prevented validation of these findings. Under the correct circumstances different analytical approaches may be complementary in their ability to detect, identify and quantify biomarkers2. The purpose of this study was to perform multiplatform correlation of VOCs levels within standardised breath samples using the three principal analytical modalities within breath research.
Objectives
The primary objective of this study was to describe the correlation VOC levels detected within standardised breath sample analysed by Gas Chromatography-mass spectrometer (GC-MS), proton transfer reaction-Time on Flight-mass spectrometer (PTR-ToF-MS) and selected ion flow tube-mass spectrometer (SIFT-MS).
Methods
Twenty healthy subjects were required to provide a single six-litre breath sample by exhaling into a Nalophan bag of the same volume. Ten VOCs from six chemical classes were analysed by GC-MS, PTR-ToF-MS and SIFT-MS. Breath samples were first simultaneously analysed by direct injection (on-line) PTR-MS and SIFT-MS using the H3O+ precursor ion. Breath was subsequently transferred to thermal desorption (TD) tubes (500ml per tube). TD tubes would be analysed by PTR-MS (H3O+) and GC-MS. The results would be compared using Pearson’s correlation coefficient.
Results
Whilst measured concentrations were higher with the SIFT-MS compared to PTR-MS, a good correlation was maintained. Levels of acetone, isoprene, fatty acid (C2 to C6), alcohols, and phenol were strongly correlated (R2>0.8; P<0.001). Broadly equivalent results were achieved when breath was analysed by either direct injection- or TD- PTR-MS (R2>0.8; P<0.001). Comparison of TD-PTR-MS and TD-GC-MS determined acceptable correlation in the analysis of acetone (R2>0.8; P<0.001) and isoprene (R2>0.8; P<0.001).
Conclusion
Results are intended to provide better understanding of the variance seen in breath data in turn supporting recommendations for optimisation of future analytical strategies. Findings indicate good correlation of results for SIFT-MS and PTR-MS for direct and TD sampling. Further optimisation of GC-MS settings and column will be required for studies hoping to provide cross-platform validate the results of breath analysis.
Reference
1. Kumar, S., et al. (2015). "Mass Spectrometric Analysis of Exhaled Breath for the Identification of Volatile Organic Compound Biomarkers in Esophageal and Gastric Adenocarcinoma." Ann Surg 262(6): 981-990.
2. Tomasz Majchrzak, et al. (2018). “PTR-MS and GC-MS as complementary techniques for analysis of volatiles: A tutorial review.” Analytica Chimica Acta(1035): 1-13.
= Discovery stage.
= Translation stage.
= Clinically available.
