A Combined Chemical Ionization and Photoelectron Ionization Source for TOFMS: Application to Online Detection of Aldehydes in End-Tidal Exhaled Breath

Abstract

In conventional exhaled breath analysis, a CO2 sensor is typically deployed separately from a biomarker detection instrument. Herein, we developed an all-in-one ionization source that integrates chemical ionization (CI) and photoelectron ionization (PEI) within a single hardware system, with the CI stage enabling highly sensitive detection of organic compounds and the PEI stage facilitating accurate quantification of inorganic species. NO+ was adopted as the reagent ion in the CI stage for efficient ionization of aldehydes to form [M + H]+ characteristic ions. The five-stage differential vacuum system and inverted-funnel high-pressure ion molecule reactor design introduced into the CI module enhanced the detection sensitivity toward dehydrated aldehydes by 1.63–24.13 times compared with the previously developed chemical ionization focusing integrated ionization source. Under optimal conditions, the limits of quantification for 10 aldehydes were as low as 0.28 to 86.77 pptv with a single analysis time of 1 s, and both intraday and interday relative standard deviations are below 11%. In exhaled breath analysis, CI and PEI stages are used for the simultaneous detection of aldehydes and CO2, respectively, enabling rapid determination of aldehyde biomarkers in exhaled breath combined with the CO2 conditions. Ultimately, the system was successfully deployed for the end-tidal breath analysis of healthy controls, smokers, and drinkers, accurately capturing distinct aldehyde signatures across different exposure cohorts, demonstrating its practicability and reliability in noninvasive medical diagnostics and metabolomic screening.