Effective detection of bio-molecules relies on the precise design and preparation of materials, particularly in laser desorption/ionization mass spectrometry (LDI-MS). Despite significant advancements in substrate materials, the performance of single-structured substrates remains suboptimal for LDI-MS analysis of complex systems. Herein, designer Au@SiO@ZrO core-shell substrates are developed for LDI-MS-based early diagnosis and prognosis of pancreatic cancer (PC). Through controlling Au core size and ZrO shell crystallization, signal amplification of metabolites up to 3 orders is not only achieved, but also the synergistic mechanism of the LDI process is revealed. The optimized Au@SiO@ZrO enables a direct record of serum metabolic fingerprints (SMFs) by LDI-MS. Subsequently, SMFs are employed to distinguish early PC (stage I/II) from controls, with an accuracy of 92%. Moreover, a prognostic prediction scoring system is established with enhanced efficacy in predicting PC survival compared to CA19-9 (p < 0.05). This work contributes to material-based cancer diagnosis and prognosis.
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