Analyte-substrate interactions at functionalized tip electrospray ionization mass spectrometry: Molecular mechanisms and applications.

Conventional electrospray ionization mass spectrometry (ESI-MS) commonly uses capillary tip for sample introduction and ionization. In recent years, ESI-MS using noncapillary substrate tips has attracted growing interest as it allows separation and enrichment of analytes from complex samples due to analytes-substrate interactions. In this work, model mixtures and functionalized tips were employed to investigate the molecular mechanism of the analyte-substrate interactions. The mixtures were directly loaded on substrate tips, and then temporal responses of analytes were investigated by monitoring selected ion chromatogram (SIC) responses of each analyte. It is found that all analytes are sprayed out together when bulk solution loaded substrate surface and then sequential ionization of analytes were observed. Sequential ionization of analytes was affected by the analytes-substrate interactions which caused analytes of weaker-interaction to be faster moved and the analytes of stronger-interactions to be retained on the substrate. The main molecular mechanisms of analyte-substrate interactions were revealed to be hydrophobic interactions and electrostatic interactions. Furthermore, based on the mechanistic insights, functionalized tips were further applied for rapid extractive sampling of target analytes from complex samples with good analytical performances. Overall, this study on the mechanism and applications of analyte-substrate interactions is useful for understanding the fundamental principles and further developments of functionalized tip electrospray ionization (TESI).