Surface acoustic wave nebulization improves compound selectivity of low-temperature plasma ionization for mass spectrometry.

Mass spectrometry coupled to low-temperature plasma ionization (LTPI) allows for immediate and easy analysis of compounds from the surface of a sample at ambient conditions. The efficiency of this process, however, strongly depends on the successful desorption of the analyte from the surface to the gas phase. Whilst conventional sample heating can improve analyte desorption, heating is not desirable with respect to the stability of thermally labile analytes. In this study using aromatic amines as model compounds, we demonstrate that (1) surface acoustic wave nebulization (SAWN) can significantly improve compound desorption for LTPI without heating the sample. Furthermore, (2) SAWN-assisted LTPI shows a response enhancement up to a factor of 8 for polar compounds such as aminophenols and phenylenediamines suggesting a paradigm shift in the ionization mechanism. Additional assets of the new technique demonstrated here are (3) a reduced analyte selectivity (the interquartile range of the response decreased by a factor of 7)-a significant benefit in non-targeted analysis of complex samples-and (4) the possibility for automated online monitoring using an autosampler. Finally, (5) the small size of the microfluidic SAWN-chip enables the implementation of the method into miniaturized, mobile LTPI probes.

Analyte and matrix evaporability - key players of low-temperature plasma ionization for ambient mass spectrometry.

The introduction of ambient ionization at atmospheric pressure for mass spectrometry (AI-MS) attracted the interest of many researchers in the field and various ionization techniques have been described in recent years that allow a quick and easy-to-handle analysis of samples under ambient conditions without or with only minor sample preparation. Among those, plasma-based techniques including the low-temperature plasma probe require very little resources thereby providing great potential for implementation in mobile analytical devices. However, systematic studies on signal responsiveness with this technique, such as the influence of the analyte and matrix characteristics on relative signal intensity, are still rare. Therefore, we used a low-temperature plasma source based on dielectric barrier discharge with helium as process gas to assess influencing factors on signal intensity in mass spectrometry. Among 12 tested molecular descriptors, in particular a low vaporization enthalpy and a large molecular nonpolar surface area improve the relative signal intensity. In addition, we show that the impact of compound characteristics strongly outperforms the influence of simple sample matrices such as different organic solvents and water, with a weak trend that volatile solvents tend to decrease the signal responsiveness of the analytes. However, several specific solvent-analyte interactions occurred, which have to be considered in targeted applications of this method. Our results will help further in improving the implementation and standardization of low-temperature plasma ionization for ambient mass spectrometry and understanding the requirements and selectivity of this technique. Graphical abstract Influencing factors (analyte and matrix characteristics) on signal intensity in dielectric-barrier discharge plasma for ionization in mass spectrometry.

The requirements for low-temperature plasma ionization support miniaturization of the ion source.

Ambient ionization mass spectrometry (AI-MS), the ionization of samples under ambient conditions, enables fast and simple analysis of samples without or with little sample preparation. Due to their simple construction and low resource consumption, plasma-based ionization methods in particular are considered ideal for use in mobile analytical devices. However, systematic investigations that have attempted to identify the optimal configuration of a plasma source to achieve the sensitive detection of target molecules are still rare. We therefore used a low-temperature plasma ionization (LTPI) source based on dielectric barrier discharge with helium employed as the process gas to identify the factors that most strongly influence the signal intensity in the mass spectrometry of species formed by plasma ionization. In this study, we investigated several construction-related parameters of the plasma source and found that a low wall thickness of the dielectric, a small outlet spacing, and a short distance between the plasma source and the MS inlet are needed to achieve optimal signal intensity with a process-gas flow rate of as little as 10 mL/min. In conclusion, this type of ion source is especially well suited for downscaling, which is usually required in mobile devices. Our results provide valuable insights into the LTPI mechanism; they reveal the potential to further improve its implementation and standardization for mobile mass spectrometry as well as our understanding of the requirements and selectivity of this technique. Graphical abstract Optimized parameters of a dielectric barrier discharge plasma for ionization in mass spectrometry. The electrode size, shape, and arrangement, the thickness of the dielectric, and distances between the plasma source, sample, and MS inlet are marked in red. The process gas (helium) flow is shown in black.

Response in Ambient Low Temperature Plasma Ionization Compared to Electrospray and Atmospheric Pressure Chemical Ionization for Mass Spectrometry.

Modern technical evolution made mass spectrometry (MS) an absolute must for analytical chemistry in terms of application range, detection limits and speed. When it comes to mass spectrometric detection, one of the critical steps is to ionize the analyte and bring it into the gas phase. Several ionization techniques were developed for this purpose among which electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) are two of the most frequently applied atmospheric pressure methods to ionize target compounds from liquid matrices or solutions. Moreover, recent efforts in the emerging field of "ambient" MS enable the applicability of newly developed atmospheric pressure techniques to solid matrices, greatly simplifying the analysis of samples with MS and anticipating, to ease the required or even leave out any sample preparation and enable analysis at ambient conditions, outside the instrument itself. These developments greatly extend the range of applications of modern mass spectrometry (MS). Ambient methods comprise many techniques; a particular prominent group is, however, the plasma-based methods. Although ambient MS is a rather new field of research, the interest in further developing the corresponding techniques and enhancing their performance is very strong due to their simplicity and often low cost of manufacturing. A precondition for improving the performance of such ion sources is a profound understanding how ionization works and which parameters determine signal response. Therefore, we review relevant compound characteristics for ionization with the two traditional methods ESI and APCI and compare those with one of the most frequently employed representatives of the plasma-based methods, i.e., low temperature plasma ionization. We present a detailed analysis in which compound characteristics are most beneficial for the response of aromatic nitrogen-containing compounds with these three methods and provide evidence that desorption characteristics appear to have the main common, general impact on signal response. In conclusion, our report provides a very useful resource to the optimization of instrumental conditions with respect to most important requirements of the three ionization techniques and, at the same time, for future developments in the field of ambient ionization.

Electrospray Ionization Efficiency Is Dependent on Different Molecular Descriptors with Respect to Solvent pH and Instrumental Configuration.

Over the past decades, electrospray ionization for mass spectrometry (ESI-MS) has become one of the most commonly employed techniques in analytical chemistry, mainly due to its broad applicability to polar and semipolar compounds and the superior selectivity which is achieved in combination with high resolution separation techniques. However, responsiveness of an analytical method also determines its suitability for the quantitation of chemical compounds; and in electrospray ionization for mass spectrometry, it can vary significantly among different analytes with identical solution concentrations. Therefore, we investigated the ESI-response behavior of 56 nitrogen-containing compounds including aromatic amines and pyridines, two compound classes of high importance to both, synthetic organic chemistry as well as to pharmaceutical sciences. These compounds are increasingly analyzed employing ESI mass spectrometry detection due to their polar, basic character. Signal intensities of the peaks from the protonated molecular ion (MH+) were acquired under different conditions and related to compound properties such as basicity, polarity, volatility and molecular size exploring their quantitative impact on ionization efficiency. As a result, we found that though solution basicity of a compound is the main factor initially determining the ESI response of the protonated molecular ion, other factors such as polarity and vaporability become more important under acidic solvent conditions and may nearly outweigh the importance of basicity under these conditions. Moreover, we show that different molecular descriptors may become important when using different types of instruments for such investigations, a fact not detailed so far in the available literature.

Artifacts in amine analysis from anodic oxidation of organic solvents upon electrospray ionization for mass spectrometry.

Different phenylenediamines were used to explore anodic oxidation in solution during electrospray ionization (ESI) mass spectrometry analysis. In our experiments, a series of unknown ionic species was detected in the phenylenediamine solutions. Our results propose that reactions of phenylenediamines with species formed by anodic oxidation of typical ESI solvents during the electrospray ionization process such as formaldehyde are producing these peaks. Identification of these compounds inter alia suggests formal alkylation, a reaction not reported so far as a result of electrolytic oxidation in the prospective organic solvents.