Rapid detection of monoamine neurotransmitters by carboxyl ionic organic crystal-functionalized paper spray mass spectrometry

The development of a mass spectrometry-based workflows for monoamine neurotransmitters (NTs) detection in biological samples is crucial for the accurate diagnosis of adrenal tumor. In this study, a carboxyl ionic organic crystal (CIOC) was synthesized via ion self-assembly of cationic and anionic monomers, featuring abundant carboxyl active sites for selective monoamine NTs capture. The CIOC-functionalized paper strips significantly enhance the sensitivity of direct capillary spray miniature mass spectrometry (DCS-mini MS) for monoamine NTs analysis. For biofluid analysis, the CIOC-functionalized paper strips were immersed in samples, washed with ACN to remove interferents, and analyzed by DCS-mini MS. Compared to unmodified paper strips, the CIOCfunctionalized paper strips exhibited significantly enhanced sensitivity, with signal amplification factors of 7.6-fold for dopamine, 3.4-fold for norepinephrine, 4.6-fold for 5-hydroxytryptamine, and 5.6-fold for epinephrine in plasma, and corresponding increases of 10.9-fold, 4.0-fold, 6.3-fold, and 7.5-fold in urine. The CIOC@DCS-mini MS platform enables rapid (3 min), label-free clinical monoamine NTs monitoring, offering a precise solution for diagnosing monoamine NTs-related disorders.

Conventional methods are unsuitable for continuous monitoring or point-of-care testing, while clinical practice necessitates simultaneous detection of multiple monoamine neurotransmitters to facilitate disease diagnosis.

This approach achieves direct detection of monoamine NTs in complex biofluids with a low detection limit and rapid assay time, demonstrating superior performance for point-of-care applications. The ease of fabrication and   mass producibility of CIOC-functionalized paper strips ensure robustness and reliability, while the integrated DCS device simplifies operation and allows for neurotransmitter measurement from minimally processed samples. Given its high sensitivity, selectivity, and rapid analysis, the CIOC@DCS-mini MS platform holds great promise for real-time monitoring of neurotransmitter imbalances, facilitating early diagnosis of neurological disorders and improving personalized patient care. Future work will focus on expanding this technology to multiplexed detection and clinical validation for broader diagnostic applications.