Novel Green Silver Nanoparticles as Matrix in the Detection of Small Molecules Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS)

Abstract

The number of studies utilizing the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has significantly increased over the past years. This technique features excellent sensitivity and speed of analysis for ionic compounds such as proteins, peptides, nucleic acids and small metabolites. Detection of small metabolites by MALDI-MS is essential for early diagnosis and monitoring of various diseases and understanding their pathogenesis. For metabolic analysis, conventional matrix and designed materials have certain limitations in terms of undesired aggregations, synthetic chemicals, low reproducibility and high cost. Herein, we report a novel application for enhanced MALDI-MS detection of small metabolites (MW < 500 Da) using biosynthesized silver nanoparticles (Ag-NPs) from the leaf parts of Cudrania tricuspidata as a green metal matrix. We were able to detect standard molecules (glucose, lysine, sucrose and glutamic acid) at a low detection limit (4–20 nmol) and achieve MALDI-MS profiling of these molecules at different dosages utilizing green metal matrix. The subsequent peaks were of higher intensity and with low background noise in comparison with those obtained using conventional α-cyano-4-hydroxycinnamic acid (CHCA) matrix and other nanomaterials. The tolerance assessment further demonstrated the analytical sensitivity of the green metal matrix in complex protein/salt mixture. In addition, we were able to detect 13 low molecular weight metabolites in 10× delude human healthy serum samples and another distinct 18 low molecular weight compounds in pancreatic cancer serum samples. Furthermore, the commonly used matrix, CHCA and other nanomaterial matrices, including silver, gold, SiO2@Ag and TiO2 nanoparticles, were also used in this study to compare with green noble metals (Ag) for the detection of small metabolites. Our work highlights the enhancement of green substrates as a matrix in the real-case analysis of small metabolites, besides the successful detection of the standard molecules using MALDI-MS. The green metal matrix offers future prospects in systems biology and disease detection and will have an industrial application for being economic, eco-friendly and rapid over the large scale chemical synthesis matrix.