Plasmonic array assisted mass spectrometry for preferential metabolite detection

Metabolites, depicting physiological and pathophysiological state, underpin diverse disease-associated phenomena. Metabolite detection offers insights for identifying disease biomarkers and monitoring treatment responses, thereby facilitating early disease diagnosis and personalized medicine. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) holds promise in molecular profiling, with advanced materials emerging as efficient matrices for metabolite detection. Yet, their preferences in analyzing various metabolites have not been systematically explored, hindering the development of matrices for suitable clinical practice. Herein, we report plasmonic array assisted MS for fast and direct quantification of specific metabolites in human biofluids. Plasmonic array is prepared by self-assembling hybrid bimetallic alloys at liquid–liquid interfaces. Large scale screening of 37 metabolites exhibited LDI preferences of plasmonic array especially for nucleosides. Plasmonic array enables sensitive and selective detection of nucleosides, due to the synergistic effect via alloy composition and chemical interactions without the use of costly antibodies. Consequently, accurate quantification is achieved with a recovery rate of 103.18 % ± 3.78 % for inosine, consuming a trace amount of serum as low as 4 μL within seconds. This work provides useful guidelines for matrix design in the MALDI MS analysis of metabolites toward biomedical applications.