Abstract

The endogenous volatile organic compounds (VOCs) in exhaled breath can be promising biomarkers for various diseases including cancers. An olfactory sensor has a possibility for extracting a specific feature from collective variations of the related VOCs with a certain health condition. For this approach, it is important to establish a feasible protocol for sampling exhaled breath in practical conditions to provide reproducible signal features. Here we report a robust protocol for the breath analysis, focusing on total expiratory breath measured by a Membrane-type Surface stress Sensor (MSS), which possesses practical characteristics for artificial olfactory systems. To assess its reproducibility, 83 exhaled breath samples were collected from one subject throughout more than a year. It has been confirmed that the reduction of humidity effects on the sensing signals either by controlling the humidity of purging room air or by normalizing the signal intensities leads to reasonable reproducibility verified by statistical analyses. We have also demonstrated the applicability of the protocol for detecting a target material by discriminating exhaled breaths collected from different subjects with pre- and post-alcohol ingestion on different occasions. This simple yet reproducible protocol based on the total expiratory breath measured by the MSS olfactory sensors will contribute to exploring the possibilities of clinical applications of breath diagnostics.

Highlights

  • Breath analysis has long been recognized as an ideal non-invasive diagnostic technique, which poses a potential for its future usage in disease detection and therapeutic monitoring [1]

  • It is rational to consider that patterns of volatile organic compounds (VOCs) in exhaled breath could be a predictive biomarker for disease detection

  • Numerous studies have far reported that some exhaled VOCs are associated with cancer in terms of exhalation kinetics of VOCs [7], sensing response patterns of artificially intelligent nanoarrays [8], and diagnostic accuracy of breath tests [9], as well as specific correlations such as 15 VOCs for colorectal cancer [10], 3 VOCs for head and neck cancer [11], 12 VOCs for esophageal and gastric adenocarcinoma [12], 14 VOCs for breast cancer [13], and 22 VOCs for hepatocellular carcinoma [14]

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Summary

Introduction

Breath analysis has long been recognized as an ideal non-invasive diagnostic technique, which poses a potential for its future usage in disease detection and therapeutic monitoring [1]. A pilot study analysing exhaled breath using MSS showed the possibility that patients with head and neck cancer can be discriminated from healthy volunteers [23] and patients before surgery from those after surgery as well as healthy control persons [24] These previous studies have demonstrated promising sensitivity and specificity of MSS, it is known that the conditions of samples (e.g., temperature, humidity, and interfering gases) affect the signals measured by artificial olfactory systems based on chemical sensor arrays, including MSS. In this study, we focus on this simple approach and evaluate its reproducibility by analysing the sensing data collected throughout more than a year and the applicability to the detection of a testing material in exhaled breath using a same MSS standard measurement module. Because of the simplicity and the possibility for standardization as well as the demonstrated reproducibility and applicability, the proposed artificial olfactory system based on the total expiratory breath measured by the MSS measurement module can be a promising candidate for future breath diagnostics

Study Design
Verification of Reproducibility
Detection of a Testing Material
Statistical Analysis
Results and Discussion
Analysis of Paired Samples with Close RH Conditions
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