Synthesis of Surface-Functionalized Molybdenum Disulfide Nanomaterials for Efficient Adsorption and Deep Profiling of the Human Plasma Proteome by Data-Independent Acquisition

Blood is one of the most important clinical samples for protein biomarker discovery, as it provides rich physiological and pathological information and is easy to obtain with low invasiveness. However, the discovery of protein biomarkers in the blood by mass spectrometry (MS)-based proteomic strategies has been shown to be highly challenging due to the particularly large concentration range of proteins and the strong interference by the high-abundant proteins in the blood. Therefore, developing sensitive methods for low-abundant biomarker protein identification is a key issue that has received great attention. Here, we report the synthesis and characterization of surface-functionalized magnetic molybdenum disulfide (MoS₂) for the large-scale adsorption of low-abundant plasma proteins and deep profiling by MS. MoS₂ nanomaterials resulted in the coverage of more than 3400 proteins (including a single-peptide hit) in a single LC-MS analysis without peptide prefractionation using pooled plasma samples, which were five times more than those obtained by the direct analysis of the plasma proteome. A detection limit in the low ng L^-1 range was obtained, which is rare compared with previous reports.