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

Abstract

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).

High‐throughput polymer tip‐electrospray ionization mass spectrometry for enhanced detection of neopterin and biopterin in clinical urine samples

“…The signal of Neo ( m/z 254) in raw urine (0.1 μg/mL) was used for investing the responses of different substrate tips, as shown in Figure A. It can be seen that the hydrophilic Neo was obtained the best signal on the hydrophobic tip, ie, PE tip, because of the weak analyte‐substrate interactions on the tip‐ESI . Loading solvent could also be employed as the extraction and spray‐ionization solvent for tip‐ESI‐MS analysis of real samples.…”

“…However, both Bio and Neo are highly hydrophilic analytes; it is found that the interaction between analytes and hydrophilic tips (eg, wooden tip) could reduce the detection sensitivity . It is reported that high‐hydrophobic tips such as polyethylene (PE) allowed the better adsorption of hydrophobic compounds compared with low‐hydrophobic tip such as wooden tips, due to the analyte‐substrate interaction . Therefore, there is an expectation to seek hydrophobic materials for enhanced detection hydrophilic analytes from complex samples .…”

“…Recently, remarkable achievements of ambient tip-based ESI (tip ESI) have also been made with the developments and applications of paper spray ionization (PSI) 19 and probe ESI (PESI) 20 in which the paper tip and metal needle were used as ESI emitter for sampling and ionization of samples. So far, various substrates including metal materials, [20][21][22] porous materials, [23][24][25] functionalized materials, [26][27][28] and biological materials [29][30][31][32] have been successfully developed as tip-ESI for direct sample analysis. For example, wooden tip-ESI-MS has been used for direct analysis of biofluid samples such as blood, urine, and oral fluid.…”

Electrostatic field–induced tip‐electrospray ionization mass spectrometry for direct analysis of raw food materials

“…Recent years, the development of ambient desorption/ionization MS have greatly facilitated direct analysis of food samples with little or no sample pretreatment, and most of the ambient desorption/ionization techniques employ charged spray, gas jet, laser, or plasma beam to desorb and ionize analytes from complex matrices . More recently, various tip‐electrospray ionization (tip‐ESI) methods that employed tip‐based materials as ESI emitters included but not limited to paper tip, wooden tip, graphite sheet, swab tip, ballpoint tips, metal needle, metal foil, chip‐tip, and biological tissue have also been successfully developed for direct sample analysis, and the related mechanisms and applications have also been investigated in our previous work . In this kind of tip ESI methods, the food samples could be loaded on the tip, and then the solvent and high voltage are applied onto the tip for generating an electrospray.…”

“…8,9 More recently, various tip-electrospray ionization (tip-ESI) methods that employed tip-based materials as ESI emitters included but not limited to paper tip, wooden tip, graphite sheet, swab tip, ballpoint tips, metal needle, metal foil, chip-tip, and biological tissue have also been successfully developed for direct sample analysis, [10][11][12][13][14][15][16][17][18][19][20][21][22] and the related mechanisms and applications have also been investigated in our previous work. [22][23][24][25] In this kind of tip ESI methods, the food samples could be loaded on the tip, and then the solvent and high voltage are applied onto the tip for generating an electrospray. Particularly, various raw food materials including eggs, meats, bones, and vegetables, fruits, and herbs have been successfully analyzed by the tip ESI methods.…”