Engineered metal organic frameworks-assisted LDI MS for metabolic analysis in in vitro diagnosis: From functional design to applications.

High-throughput and highly sensitive detection of small-molecule metabolites are the key in in vitro diagnosis (IVD). Laser desorption/ionization mass spectrometry (LDI MS), as a rapid analytical technology, has attracted much attention in IVD. The regulation of the LDI MS matrix can significantly enhance the throughput and sensitivity of small-molecular detection. Metal-organic frameworks (MOFs), characterized by their tunable porosity, high surface area, and structural diversity, have emerged as promising nanomatrices for LDI MS. However, pristine MOFs have insufficient light absorption, low conductivity, and poor energy transfer, which limit their capability as LDI MS matrices for detection of metabolites. Engineered MOFs address these limitations but systematic summaries are lacked. This work comprehensively reviewed the design principles and classification of engineered MOFs as LDI MS matrices, with a focus on modulating the adsorption and photoelectronic/photothermal conversion properties. Recent targeted and untargeted IVD applications using engineered MOFs matrices are also discussed. Finally, the further trends and challenges of engineered MOFs-assisted LDI MS for small-molecule detection are outlined. We believe this review can provide a forward-looking perspective on engineered MOFs as next-generation LDI MS matrices, and provides effective engineered strategies of nanomaterials to promote their application in clinical metabolic analysis and precision diagnosis.