摘要： Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is widely used in the biomedical field for the label-free analysis of molecules such as drugs, lipids, peptides, proteins, and biological tissues for molecular imaging. However, organic matrices used in traditional MALDI-MS applications introduce excessive interferences in the low m/z range. For this reason, nanostructured materials—and in particular silicon-based LDI strategies—have become a promising alternative, since they provide a much weaker background. Herein, the recent developments in fabrication, functionalization, and practical applications of silicon-based LDI-MS methods are reviewed. Also the basic requirements of silicon-based substrates for optimal LDI analysis by providing an overview of the LDI mechanisms that use silicon-based substrates instead of organic matrices are reported. Finally, the considerable potential of silicon-based substrates is discussed, giving suggestions for topics for future research.