Interlayer spray ionization mass spectrometry for the simple direct analysis of low amounts of sample

Abstract

Interlayer spray is proposed as a convenient ionization source for direct analysis by mass spectrometry. Two slices of non-absorbent substrate hold the liquid sample to form a sandwich structure. By applying a high voltage to the sample, spray is generated at the tip of the substrate. The sampling procedure can be operated easily in an open condition and the spray is processed in a semi-enclosed condition, which leads to a relatively stable process. An ultralow amount (<2 μL) of the liquid sample can be analyzed without dilution, which ensures that the natural concentration and properties of the target are maintained. Less influence from the substrate is achieved compared with the spray methods based on porous absorbent materials, which results in a sensitivity enhancement of large molecule samples. It is demonstrated that the interlayer spray is applicable for the analysis of various compounds, including therapeutic drugs, peptides, and proteins. Good linearity can be obtained at a concentration as low as 50 ng/mL in the quantitative analysis for imatinib. We also show the ability to identify the chemical residuals on surfaces with high sensitivity by the "wipe-spray" method, which is useful for the fast screening of illicit substances. Interlayer spray working with mass spectrometry provides a promising method for direct analysis in an ambient environment. Graphical Abstract The schematic of the interlayer spray ionization source.

Advances in Ionization for Mass Spectrometry

“…Forbes et al acoustically actuated droplet ejection combined with extractive ESI for the rapid detection of inorganic compounds . Interlayer spray ionization for analysis of small volumes of liquid (<2 μL) with no pretreatment was proposed by Chen and co-workers . The method places the sample between two nonporous substrates and applies voltage to form a plume (with no additional solvent).…”

“…96 Interlayer spray ionization for analysis of small volumes of liquid (<2 μL) with no pretreatment was proposed by Chen and co-workers. 97 The method places the sample between two nonporous substrates and applies voltage to form a plume (with no additional solvent). Sensitivity compared to a porous substrate was improved for large molecules.…”

Induced Self-aspiration Electrospray Ionization Mass Spectrometry for Flexible Sampling and Analysis

“…Two typical representatives derived from electrospray technology are nanoelectrospray ionization (nano-ESI) and paper spray (PS) . Nano-ESI can produce nanoscale droplets with extremely low sample consumption and high tolerance to salts. , PS has the characteristics of ambient ionization methods, allowing direct analysis of complex mixtures without sample preparation. , Besides, electrospray of analytes can also be carried out in a variety of other creative ways, such as probe electrospray, leaf spray, membrane electrospray, and so on. − For these techniques, the transfer and spray of the solution rely mainly on the electrostatic field between the spray tip and the MS sampling interface, and both the sample injection system and the nebulization gas are eliminated. Since low flow-rate electrospray is generated and the dead volume in tubing is minimized, the total sample consumption can be significantly reduced in these cases …”

Developing a Vacuum Electrospray Source To Implement Efficient Atmospheric Sampling for Miniature Ion Trap Mass Spectrometer

“…In fact, internal ionization (e.g., electron impact ionization , and ultraviolet photoionization) coupled with direct sampling interface, such as the membrane and capillary inlet, has consistently been an efficient introduction strategy for small MS instruments. ,,, Typical utility of these devices lies in the detection of volatile organic compounds with low molecular mass (usually less than several hundred atomic mass units), but this has yet become an application limitation. Electrospray ionization (ESI) is one of the most widely used techniques that can ionize a wide variety of polar compounds in solutions. , Many variants on ESI have been reported, , and these devices are traditionally marked as atmospheric pressure ion sources. By coupling with a DAPI, nano-ESI and ESI sources have been successfully used in miniature mass spectrometers. ,, However, a conventional ESI system generally needs a bulky injection pump to drive liquid transport, and this may limit its application in in situ measurements.…”

“…Electrospray ionization (ESI) is one of the most widely used techniques that can ionize a wide variety of polar compounds in solutions. 29,30 Many variants on ESI have been reported, 31,32 and these devices are traditionally marked as atmospheric pressure ion sources. By coupling with a DAPI, nano-ESI and ESI sources have been successfully used in miniature mass spectrometers.…”