MOF-Derived Erythrocyte-like CuO/Cu2O@ZnO–CN Nanomaterials for Enhanced Laser Desorption/Ionization Mass Spectrometric Detection of Saccharides and Glucose Quantification in Diabetic Patient Serum

Enhancing the ionization efficiency of saccharides remains a significant challenge in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Herein, novel MOF-derived erythrocyte-like CuO/Cu2O@ZnO–CN nanomaterials were designed as a MALDI matrix for various saccharides’ detection. The ZIF-8-derived ZnO framework maintained its intrinsic porosity while gaining uniformly distributed C/N-doped catalytic sites. Copper oxides integration further induced an erythrocyte-like morphology with a substantially larger surface area. The CuO/Cu2O@ZnO–CN matrix demonstrated superior performance over conventional CHCA and DHB in LDI-MS analysis of saccharides (Xyl, Glc, and Malt), featuring the advantages of excellent conductivity and stability, minimum background interference, excellent ionization efficiency, high salt and protein tolerance, and remarkable specificity. The developed method enabled accurate glucose quantification in human serum (0.5–9 mM linear range, R2 = 0.998) with a low limit of detection (LOD) of 0.28 mM via internal standardization. Good reproducibility and reliability of the method were verified by intraday (1.7–5.6%) and interday precision (2.2–8.2%) and accuracy (93.8 to 101.6%). Analysis of glucose of human serum from healthy people and diabetes patients indicated the matrix’s potential application in clinical analysis.