S. Palmisano, A. R. Anderson, Z. J. Sasiene, E. Schaller, R. M. Taylor, R. Chitale1, P. T. McMahon, P. M. Mach, T. G. Glaros, J. Baca and E. M. McBride

Linking breath and blood metabolomics: advancing noninvasive biomarker discovery

Breath analysis offers a promising noninvasive alternative to blood-based diagnostics, but the relationship between breath and plasma metabolites remains poorly understood. This study integrates real-time SESI-MS breath analysis with LC-MS plasma profiling to systematically compare volatile and semi-volatile compounds across both matrices. By optimizing sample preparation and data processing workflows, including methanol-based extraction and the BreathXplorer pipeline, the study enhances feature detection and overlap between breath and plasma. The identification of shared metabolic signatures highlights the potential of breath analysis as a surrogate for systemic metabolomics, paving the way for more reliable, noninvasive diagnostic strategies.

D. García, A. Ballester, M. E. Fernández

SESI-MS for volatile analysis: overcoming challenges toward clinical and industrial adoption
Secondary electrospray ionization mass spectrometry (SESI-MS) is a powerful platform for real-time, noninvasive analysis of volatile compounds in complex matrices such as breath and microbial systems. This review examines the key methodological challenges limiting its broader adoption,including quantification, compound identification, and standardization, and highlights emerging solutions such as advanced fragmentation strategies, spectral stitching, and improved quality control approaches. By addressing these critical gaps, SESI-MS is positioned to transition from a research tool to a robust technology for clinical diagnostics, volatilomics, and industrial applications.

F. Schmidt, D. M. Baur, P. Baumgartner, J. Herth, K. Fricke, N.A. Sievi, K. Dev Singh, T. Gaisl, A. Huang, D. Franzen, S. Ulrich, P Sinues, M. Kohler

Real-time breath metabolomics: a new frontier in personalized lung cancer diagnostics
Real-time breath analysis is emerging as a powerful, non-invasive strategy for lung cancer detection and metabolic phenotyping. In this prospective matched case-control study, SESI-HRMS enabled rapid breath profiling and identified distinct metabolic signatures that differentiated lung cancer patients from matched controls with promising accuracy. Beyond detection, the study revealed subtype-specific metabolic patterns, highlighting the potential of breath metabolomics to complement imaging and genomic profiling in a more personalized, multi-omics approach to lung cancer diagnosis and care.

H.S. Shepard, J.C. May, J.A. McLean

Ambient mass spectrometry: rapid, in situ insights into microbial systems
Ambient ionization mass spectrometry is transforming microbial analysis by enabling rapid, high-throughput, and in situ chemical characterization with minimal sample preparation. This overview highlights key ambient MS platforms, including DESI-MS, DART-MS, paper spray MS, and SESI-MS,and their growing impact on microbial profiling and imaging of complex, fragile substrates. By capturing microbial biochemistry in real time, ambient MS is opening new avenues for fast diagnostics, spatially resolved analysis, and advanced microbiological research.