Perfluorinated polymer modified vertical silicon nanowires as ultra low noise laser desorption ionization substrate for salivary metabolites profiling.

Metabolites in the body fluid are becoming a rich source of disease biomarkers. Developing an effective and high throughput detection and analysis platform of metabolites is of great importance for potential biomarker discovery and validation. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been successfully applied in rapid biomolecules detection in large scale. However, non-negligible background interference in low molecule-weight region still constitutes a main challenge even though various nanomaterials have been developed as an alternative to traditional organic matrix. In this work, a novel composite chip, silicon nanowires loaded with fluorinated ethylene propylene (FEP@SiNWs) was fabricated. It can serve as an excellent substrate for nanostructure-initiator mass spectrometry (NIMS) detection with ultra-low background noise in low molecular weight region (<500 Da). Ion desorption efficiency and internal energy transfer of FEP@SiNWs were studied using benzylpyridinium salt and tetraphenylboron salt as thermometer chemicals. The results indicated that a non-thermal desorption mechanism might be involved in the LDI process on FEP@SiNWs. Owing to the higher LDI efficiency and low background interference of this novel substrate, the metabolic fingerprint of complex bio-fluids, such as human saliva, can be sensitively and stably acquired. As a proof of concept, FEP@SiNWs chip was successfully used in the detection of salivary metabolites. With the assistance of multivariate analysis, 22 metabolic candidates (p < 0.05) which can discriminate type 2 diabetes mellitus (2-DM) and healthy volunteers were found and identified. The role of these feature metabolites in the metabolic pathway involved in 2-DM was confirmed by literature mining. This work demonstrates that FEP@SiNWs-based NIMS might be served as an efficient and high throughput platform for metabolic biomarker exploration and clinical diagnosis.