Enhanced Breath Aldehyde Analysis by Dual-Membrane-Assisted Charge Tagging, Enrichment, and Onsite Elution NanoESI-MS

Aldehydes, crucial volatile organic compounds present in exhaled breath, have been established as promising biomarkers for cancer diagnosis. However, their rapid and sensitive detection through widely employed spray-based ionization mass spectrometry is still challenging. To address this, we introduce a charged "iridium isotopic signature" probe tailored for efficient capture and unambiguous identification of ubiquitous aldehydes in the gas phase. This ^191/193Ir-tagged mass spectrometric probe, equipped with a reactive amine moiety capable of interacting with aldehydes, is immobilized on the porous Nylon-6 membrane that facilitates efficient gas transport and enriches aldehydes from the complex breath matrix. Following a rapid solvent extraction, the Ir-tagging aldehyde derivatives were successfully eluted with efficient removal of excess probes by the oxidized cellulose membrane, yielding a purified sample ideally suited for direct, rapid, and ultrasensitive (with a detection limit below 0.1 ppt) nanoelectrospray ionization mass spectrometry (nanoESI-MS) analysis. By utilizing an analogous iridium complex as an internal standard, our method precisely identified and quantified 12 aldehydes in exhaled breath (EB), with several exhibiting significant elevations in esophageal cancer patients compared with healthy controls. This highlights its efficacy as a rapid and accurate tool for detecting breath aldehyde biomarkers, offering promising avenues for cancer diagnosis.