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 non-capillary substrate tips has attracted growing interest as it allows separation and enrichment of analytes from complex samples due to the 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 movements of bulk solution on substrate surface was firstly occurred that all analytes are sprayed out together, and then sequential ionization of analytes were observed on substrate surface which were affected by the analytes-substrate interactions in which weaker interaction were easier to be faster moved on substrate tips and the stronger interactions caused the target analyte 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 of the fundamental principles and further developments of functionalized TESI.