Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has become a workhorse technique and an indispensable tool in bioanalysis. Despite its success, it is rarely used for the analysis of small molecules (<500 Da) because MALDI mass spectra suffer from high chemical background noise in the low mass region (m/z<500) due to the formation of clusters of matrix ions or matrix degradation products. Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) using nanomaterials (inorganic nanoparticles and nanostructured surfaces) has been reported for the LDI-MS analysis of small molecules as an organic matrix-free approach. Compared to MALDI-MS, SALDI-MS affords certain advantages, such as easy sample preparation, low background noise, high salt tolerance, and high throughput analysis for drug discovery. We have developed SALDI-MS method using functionalized nanoparticles, such as platinum-based nanomaterials, layer-by-layer (LBL) self-assembled multilayer films of gold nanoparticles, and magnetic nanoparticles, has been further improved in terms of the detection sensitivity, detection mass range from the low- to the high-mass region, a soft LDI process, the detection of both polar and nonpolar compounds, the selective detection of analytes from a complex mixture using functionalized NPs, and various applications, including imaging mass spectrometry.
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