Energy band engineered nanomatrix assisted mass spectrometry for metabolite detection

Metabolites participate in the regulation of various physiological and pathophysiological processes in organisms. Metabolite detection can identify disease biomarkers, facilitating early disease diagnosis. Laser desorption/ionization mass spectrometry (LDI MS) holds promise in metabolite detection, but the performance of mass spectrometry depends on the precise design and preparation of matrix materials. The lack of clear understanding of LDI mechanisms hinders the rational design of matrices. This paper proposes a matrix design strategy by developing an energy band engineered Indium-doped CuCrO₂ (ICCO), thereby achieving hole regulation, for precisely controlling charge-driven desorption to enhance LDI performance. Furthermore, by integrating density functional theory (DFT), this strategy is capable of enhancing the charge transfer ability at the matrix-glucose interface, to the consequent improvement in LDI performance. Compared to CCO, other concentrations of ICCO and traditional organic matrices, 2.5 % ICCO could achieve ≈2-500-fold signal enhancement. The optimized ICCO-assisted laser desorption ionization mass spectrometry platform can quantify glucose concentration in diabetic patient serum samples with only 1 μL of serum. This method has been validated to exhibit high accuracy (Pearson's r = 0.997 compared with the clinical gold standard) and good reproducibility (CV < 7 %). This work has facilitated the development of advanced substrates and underscored the potential of metabolite quantification in practical clinical applications going forward.