High-resolution FAIMS-mass spectrometry for breath analysis using atmospheric pressure chemical ionisation.

Exhaled breath containing volatile organic compounds (VOCs) can be analysed non-invasively and has potential applications in disease diagnosis. Previous FAIMS-based breath studies have primarily used low-resolution FAIMS with ion current detection rather than mass spectrometry (MS). Here, atmospheric pressure chemical ionisation (APCI) was coupled with high-resolution FAIMS-MS for direct breath analysis. APCI-FAIMS-MS increased the number of detected breath features by >200% compared with APCI-MS alone and consistently detected 60-130 breath features per sample. Within-participant heatmap consistency was comparable across the four participants based on structural similarity index (SSIM) analysis. Exploratory principal component analysis showed participant-associated clustering of breath profiles. These results demonstrate that high-resolution FAIMS substantially enhances breath feature detection and provides an orthogonal separation dimension for untargeted breath profiling. Future studies involving larger cohorts and disease-specific populations will determine whether the increased breath feature coverage afforded by high-resolution FAIMS can improve VOC-based classification and diagnostic performance.