Hybrid Analytical Platform Based on Field-Asymmetric Ion Mobility Spectrometry, Infrared Sensing, and Luminescence-Based Oxygen Sensing for Exhaled Breath Analysis

The reliable online analysis of volatile compounds in exhaled breath remains a challenge, as a plethora of molecules occur in different concentration ranges (i.e., ppt to %) and need to be detected against an extremely complex background matrix. Although this complexity is commonly addressed by hyphenating a specific analytical technique with appropriate preconcentration and/or preseparation strategies prior to detection, we herein propose the combination of three different detector types based on truly orthogonal measurement principles as an alternative solution: Field-asymmetric ion mobility spectrometry (FAIMS), Fourier-transform infrared (FTIR) spectroscopy-based sensors utilizing substrate-integrated hollow waveguides (iHWG), and luminescence sensing (LS). By carefully aligning the experimental needs and measurement protocols of all three methods, they were successfully integrated into a single compact analytical platform suitable for online measurements. The analytical performance of this prototype system was tested via artificial breath samples containing nitrogen (N₂), oxygen (O₂), carbon dioxide (CO₂), and acetone as a model volatile organic compound (VOC) commonly present in breath. All three target analytes could be detected within their respectively breath-relevant concentration range, i.e., CO₂ and O₂ at 3-5 % and at ~19.6 %, respectively, while acetone could be detected with LOQs as low as 165-405 ppt. Orthogonality of the three methods operating in concert was clearly proven, which is essential to cover a possibly wide range of detectable analytes. Finally, the remaining challenges toward the implementation of the developed hybrid FAIMS-FTIR-LS system for exhaled breath analysis for metabolic studies in small animal intensive care units are discussed.