Advancing Lung\nCancer Diagnosis through NH<sub>2</sub>‑MON-SPME-GC-MS/MS:\nEnhanced Sensitivity in Aldehyde Biomarker\nDetection from Exhaled Breath

The sensitive detection of trace biomarkers in exhaled\nbreath for\nlung cancer diagnosis represents a critical area of research in life\nanalytical chemistry, with profound implications for early disease\ndetection, therapeutic intervention, and prognosis monitoring. Despite\nits potential, the analytical process faces significant challenges\ndue to the ultratrace levels of disease biomarkers present and the\ncomplex, high-humidity composition of exhaled breath. This study introduces\na highly sensitive method for detecting aldehyde biomarkers in exhaled\nbreath by integrating the use of amino-functionalized microporous\norganic networks (NH<sub>2</sub>-MON) as a solid-phase microextraction\n(SPME) fiber coating with gas chromatography–triple quadrupole\nmass spectrometry (GC-MS/MS) analysis. The method innovatively combines\nsample collection and extraction, achieving a dual-step enrichment\nprocess that significantly enhances both the enrichment efficiency\nand reproducibility of biomarker detection while effectively mitigating\nthe interference caused by water vapor in exhaled breath. The NH<sub>2</sub>-MON, utilized as an SPME fiber coating, demonstrates exceptional\nenrichment capacity for five key aldehyde biomarkers, facilitating\nthe development of a highly sensitive detection approach for these\nbiomarkers in exhaled breath. Compared to previously reported methods,\nthe proposed technique exhibits significantly lower limits of quantification,\nranging from 0.77 to 11.89 pg mL<sup>–1</sup>, and achieves\nsubstantially higher enrichment factors, ranging from 9156- to 35723-fold.\nThe practicality and feasibility of the method were validated through\nthe analysis of exhaled breath samples from lung cancer patients,\nunderscoring its potential application in the early diagnosis and\nmonitoring of lung cancer.