Advances in nanomaterials based laser desorption/ionization mass spectrometry for metabolic analysis

Laser desorption/ionization mass spectrometry (LDI-MS) has emerged as a promising analytical tool for biomolecules analysis due to its high throughput, fast analysis speed, and simple sample preparation. The emerging of nanomaterials substrates make it a pivotal technique for metabolic analysis which overcome the limitations of traditional organic matrices by providing a non-interference background, enhanced desorption/ionization efficiency, and superior thermal and chemical stability, and ease of functionalization. In recent years, a variety of nanomaterials including noble metals, silicon/carbon-based nanomaterials, metal oxides, metal/covalentorganic frameworks, and hybrids nanomaterials have been explored. This review, with a focus on an overview of nanomaterial substrates, highlights the mechanism of LDI-MS, its applications in biofluids/exosomes metabolic analysis for disease diagnosis, and MALDI-MS imaging. Furthermore, the integration of advanced machine learning algorithms and metabolic fingerprints has significantly improved the diagnostic performance in specificity, sensitivity, accuracy, etc. Finally, we discussed the prospects of nanomaterial-based LDI-MS for metabolic analysis, emphasizing both its potential and challenges in clinical applications.