Noble Metal Nanoparticle Assisted Mass Spectrometry for Metabolite-Based In Vitro Diagnostics

In vitro diagnostics (IVD) makes clinical diagnosis rapid, simple, and noninvasive to patients, playing a crucial role in the early diagnosis and monitoring of diseases. Metabolic biomarkers are closely correlated to the phenotype of diseases. However, most IVD platforms are constrained by the sensitivity and throughput of assay. In recent years, noble-metal-nanoparticle (NMNP)-assisted laser desorption/ionization mass spectrometry (LDI MS) has generated major advances in metabolite analysis, significantly improving the sensitivity, accuracy, and throughput of IVD due to the unique optical and electrical properties of NMNPs. This review systematically assesses the development of NMNPs as LDI MS matrices in the detection of metabolites for IVD application. The analysis of several NMNP structures, such as core-shell, porous, and 2D nanoparticles, elucidates their significant contribution to the enhancement of MS performance. Furthermore, the recent advancements in the application of NMNPs for diagnosing various systemic diseases are summarized. Finally, the prospects and challenges of NMNP-assisted MS for IVD are discussed. This review elucidates the roles of NMNPs' structure in enhancing MS-based metabolic detection and provides an overview of various IVD applications, consequently offering comprehensive insights for researchers and developers in this field.