Laser-Induced Microplasma as an Ambient Ionization Approach for the

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Laser-Induced Microplasma as an Ambient Ionization Approach for the Mass-Spectrometric Analysis of Liquid Samples Andreas Bierstedt, Yi You, Sebastian van Wasen, Gaby Bosc-Bierne, Michael G. Weller, and Jens Riedel Anal. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.analchem.9b00329 • Publication Date (Web): 01 Apr 2019 Downloaded from http://pubs.acs.org on April 2, 2019

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Analytical Chemistry

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Laser-Induced Microplasma as an Ambient Ionization Approach for the MassSpectrometric Analysis of Liquid Samples

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Andreas Bierstedt†, Yi You†, Sebastian van Wasen, Gaby Bosc-Bierne, Michael Weller, and Jens Riedel

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Abstract

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An airborne high repetition rate laser-induced plasma was applied as a versatile ambient ionization source for mass-spectrometric determinations of polar and nonpolar analytes in solution. The laser plasma was sustained between a homebuilt pneumatic nebulizer and the inlet capillary of an Orbitrap mass spectrometer. To maintain stable conditions in the droplet-rich spray environment, the plasma was directly fed by the fundamental output ( = 1064 nm) of a current state-of-the-art diode-pumped solid-state laser. Ionization by the laser-driven plasma resulted in signals of intact analyte ions of several chemical categories. The analyte ions were found to be fully desolvated since no further increase in ion signal was observed upon heating of the inlet capillary. Due to the electroneutrality of the plasma, both positive and negative analyte ions could be formed simultaneously without altering the operational parameters of the ion source. While, typically, polar analytes with pronounced gas phase basicities worked best, nonpolar and amphoteric compounds were also detected. The latter were detected with lower ion signals and were prone to a certain degree of fragmentation induced during the ionization process. All the described attests the laser-induced microplasma by a good performance in terms of stability, robustness, sensitivity, and general applicability as a self-contained ion source for the liquid sample introduction.

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Introduction

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One of the latest innovations in mass spectrometry is the ability to record mass spectra directly out of samples in their native environments with no or minimal sample preparation, commonly referred to ambient mass spectrometry.1 Under this unifying term, a multitude of ion sources have since been introduced, enabling convenient and direct mass-spectrometric analysis of molecules with a large range of masses and polarities.2 The individual designs mostly rely on well-established ionization schemes. Promising concepts include spray-based, plasma-based, and laser-based techniques.3–6 They all share the common denominator of an operation outside the vacuum region of the mass spectrometer. However, at some occasions, the intrinsic advantages of an operation at atmospheric pressure (i.e. fast and direct sampling, minimal sample preparation, and analysis of samples in their native state) come at the cost of reduced sensitivity and selectivity. Best obtained limits-of-detection range from ppm to the lower ppb level.

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Recently, these novel ion sources are also coupled to separation and purification techniques, such as liquid chromatography. A major motivation of this dual-purpose is to fully exploit the minor

Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter-Straße 11, 12489 Berlin, Germany † The authors contributed equally to this work Corresponding author: Jens Riedel, E-mail: [email protected], Tel. +493081041003, Fax: +4930810471003

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Analytical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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differences between the individual ionization schemes in terms of selectivity, softness, and robustness during liquid analyses. Most commonly, traditional electrospray ionization (ESI) has been adopted as the ionization technique of choice when interfacing liquid chromatographic systems and mass spectrometers. Even though it has become the ´gold standard´, this technique is not without shortcomings. Common limitations include a low ionization efficiency for less polar and nonpolar analytes. Additionally, ESI and ESI-like ionization approaches often suffer severely from competitive ionization (i.e. ionization matrix effect), which can result in significant ion suppression or source contamination.7 Despite these limitations, so far none of the developments in new ionization approaches was aiming at fully replacing it. Instead, newly designed ionization methods usually offer convenient alternatives by taking advantage of their unique attributes. As a side effect, the introduction of ever new ion sources led to a more general understanding of the effect of individual ion sources on the analytical performance.5 Among these novelties are the above-mentioned developments in ambient desorption/ionization approaches for rapid and direct mass-spectrometric analysis.

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Ambient ionization sources have demonstrated a lower susceptibility towards matrix effects and a higher salt tolerance.6 Thus far, liquid couplings relied predominantly on sprays and electrically driven plasmas, e.g., SSI8 and DESI,9 as well as DART,10 DBDI,11 and FAPA,12 respectively. For a more detailed overview of further online couplings in ambient mass spectrometry the reader is referred to Reference [13]. A similar variety of techniques can be found for the spray generation itself. In order to convert ions or molecules in a solution into the gas phase either an evaporation,14– 16 nebulization,17,18 piezoelectric devices,19–21 or a direct exposure of samples to the discharge region is feasible.22,23 On top of the individual ionization and nebulization steps of the liquid analyte, also the subsequent coupling of the two needs consideration. Even though most ambient techniques are built highly modular, not every possible combination of spray generation and ambient ionization is technically feasible. Especially large droplets or fumes of densely packed small droplets are challenging because in these cases an effective evaporation of the droplets requires a lot of energy. Consequently, ion sources that are unable to couple enough energy inside the sample volume get quenched and become unsuitable.

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Recently, an airborne high repetition rate laser-driven microplasma has been shown promising capabilities as a self-contained ionization method.24,25 Comparably, yet distinctively different from an electrically driven plasma, the introduction of analyte in the vicinity of a laser-induced micrometer-sized hot and dense plasma resulted in the predominant formation of intact molecular ions. As has been reported,24 the formation of molecular species is unlikely to occur in the hot plasma center itself. In specific, the spatially resolved optical emission of the laser-induced microplasma revealed the presence of N+* at the plasma core,26 indicating that the N-N triple bond of diatomic nitrogen is effectively dissociated into atoms. Instead, in the outer (colder) regions of the plasma an interaction of neutral analyte molecules with electrons, plasma-generated nascent species, e.g., [(H2O)nH]+, [(NH3)(H2O)nH]+, O2+, NO+, NO2+, etc., and/or VUV photons is feasible. Accordingly, the indirect plasma-based ionization scheme allows for rapid, non-contact mass spectrometric analysis with a wide versatility toward the analytes polarity or ionization potential. Given the open-air nature of the microplasma, mainly two sampling regimes have been exploited by now. The simplest option involves the analysis of samples already being present in the gas phase, using a headspace sampling technique.24 Further, the ion source can be used to perform rapid ambient desorption/ionization experiments, since the residual laser light not consumed to


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sustain the plasma is powerful enough to efficiently convert sample material from the condensed phase into the gas phase.25

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Although the previous work demonstrated the applicability of utilizing a laser-induced plasma for ionization purposes, whether the 532 nm laser output directly participated in terms of photoionization remains unclear up till this point. Moreover, the energy output of the 532 nm laser is severely restrained by the frequency doubling efficiency. With respect to a liquid coupling, the weaker 532 nm laser-induced plasma was found to be not capable of desolvating and ionizing sample-containing droplets. An efficient hybridization, combining the direct, continuous introduction of liquid samples and the flexibility of the laser-induced plasma-based ionization scheme is still pending.

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In the present work, the fundamental output ( = 1064 nm) of a 26 kHz pulsed diode-pumped solid-state (DPSS) laser is used to ignite a quasi-continuous microplasma in the open laboratory environment. In contrast to the previously described 532 nm setup, the new approach proved energetic enough to ionize non-volatile analyte sample solutions introduced as a spray on their way toward the inlet of an high-resolution Orbitrap mass spectrometer. Notably, the 1064 nm laserinduced plasma is formed through cascade electron impact.27 Even though each photon contributes only half the energy compared to 532 nm, the overall number of photons is more than doubled. In addition, the absorbance of the plasma increases towards longer wavelengths, so the infrared photons couple their energy more efficiently into the ionization region. The fraction of the laser power to maintain the plasma was determined to be 3.6 W and 8.2 W in case of the green laser and the infrared laser, respectively. Accompanying MS-experiments revealed this roughly two-fold increase in power consumption to result in a ten-fold increase in the ion count of ambient reactive species (data not shown). To introduce the liquid sample, a pneumatic nebulizer was built in-house, allowing a continuous and robust conversion of sample-containing bulk liquid into airborne droplets, while preserving simplicity in geometry and instrumentation.

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Experimental Section

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Safety Considerations. Special care is required when working with free laser beams to avoid potential dangers. The laser system used throughout these studies is classified as hazard class 4.

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Chemicals. All analytes used throughout this study were dissolved in a mixture of acetonitrile (HPLC grade, ≥99.93%, Sigma Aldrich, Steinheim, Germany), methanol (HPLC grade, ≥99.85%, Th. Geyer, Renningen, Germany), and water (UHPLC grade, Fisher Chemical, Fair Lawn, NJ, U.S.A.), with a volumetric ratio of 50:25:25. 3-aminoquinoline (99%, Merck, Darmstadt, Germany), 3-acetamidophenol (99%, J&K Scientific GmbH, Pforzheim, Germany), ferrocene (98%, Acros Organics, Geel, Belgium), caffeine (98.5%, Acros Organics, Geel, Belgium), Lalanine (98%, Sigma Aldrich, Steinheim, Germany), anthracene (97%, Sigma Aldrich, Steinheim, Germany), chlorpyrifos (analytical standard, Sigma Aldrich, Steinheim, Germany), diclofenac sodium (≥98.5%, Sigma Aldrich, Steinheim, Germany), and 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX, synthesized in-house) were used as model analytes. Unless otherwise specified, each solution was prepared containing a concentration of 10 µg mL-1. To further investigate the matrix effect for this liquid-coupled ionization approach, a five-component sample mixture was vaporized, consisting of diclofenac sodium, 3-aminoquinoline, caffeine, ferrocene, and anthracene. Within this mixture, each analyte remained the same concentration as they were individually prepared,



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i.e., 10 µg mL-1. Compressed nitrogen (99.999%, Air Liquide, Berlin, Germany) was used as nebulizing gas. All chemicals were used without further purification.

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Figure 1. Experimental setup including pneumatic nebulizer, laser plasma, and mass spectrometer inlet. a) Schematic. b) Side-view photograph of the real assembly.

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Laser and Optics. The procedure of igniting an airborne, quasi-continuous laser-driven microplasma as an ionization source for ambient mass spectrometry has been described earlier.24,25 Similar to these experiments, the compactness of the DPSS laser system allowed the laser head and the entire optical components to be assembled on a single optical breadboard on top of an Orbitrap mass spectrometer. The experimental setup is shown both schematically and as a closeup photograph in Figure 1. Following a top-down laser beam assembly, the fundamental wavelength (λ = 1064 nm) of the high repetition rate DPSS laser (Conqueror 3-LAMBDA, Nd:YVO4, 1–500 kHz, maximal pulse energy of 600 µJ/pulse, pulse width < 12 ns, average output power of 24 W at 50 kHz, Compact Laser Solutions GmbH, Berlin, Germany) was directed via three Nd:YAG laser line mirrors (NB1-K13, Thorlabs, Dachau, Germany) consecutively onto an antireflection-coated aspheric lens (C240TME-1064, f = 8 mm, NA = 0.50, Thorlabs, Dachau, Germany). Both the short focal length, as well as the large numerical aperture result in a tightly focused laser beam with a sufficient photon density to induce a breakdown in the ambient laboratory environment. The increase in plasma energy corresponding to the higher photon density at the fundamental wavelength was crucial to maintain the laser-driven plasma in the solvent-rich spray plume. Throughout the remainder of this study, the excitation laser was operated at a repetition rate of 26 kHz, at which the visual and audible plasma appearance was found to be the strongest. To monitor the temporal profiles of the incoming laser pulses, a 1 ns rise time photodiode (DET210, Thorlabs, Dachau, Germany) coupled to a digital oscilloscope (DL9140, 5 GS/s, 1 GHz, Yokogawa, Musashino, Japan) was used. Saturation of the detector was avoided by using two neutral density filters (Ne10a and NdUV10a, both Thorlabs, Dachau, Germany) to attenuate the laser energy. At the above-given operating conditions, the produced single pulse shape was found to be close to an ideal Gaussian of a full width at half maximum (FWHM) of 8 ns. Confirming the audiovisual adjustment, the maximum pulse peak height was detected at 26 kHz.

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Nebulizer. The spray source used within these studies was assembled based on the initial design of a Venturi nebulizer (similar to a sonic spray ionization (SSI) source, reported by Hirabayashi et al.28). Briefly, a fused-silica capillary (TSP-050192, i.d. 50 µm, o.d. 186 µm, BGB Analytik


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Vertrieb GmbH, Rheinfelden, Germany) was inserted into a flat polished disposable cannula (Sterican® 18, i.d. 270 µm, o.d. 450 µm, B. Braun Melsungen AG, Melsungen, Germany), with the fused-silica capillary tip protruding outwards for ~1.2 mm. Eventually, their center axes were coaxially aligned by fixing them into a brass mixing tee. Steady nebulization was sustained by feeding the sample solution to the fused-silica capillary at a flow rate of 10 µL min-1 with a dual syringe pump (Fusion 100T, CHEMYX Inc., Stafford, TX, U.S.A.), while the coaxial nitrogen gas flow was supplied at 0.36 L min-1 using a mass flow controller (Bronkhorst High Tech B.V., Ruurlo, The Netherlands).

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Mass Spectrometer. All mass spectra were recorded using an Orbitrap mass spectrometer (Exactive™, Thermo Fisher Scientific, Bremen, Germany). It should be noted that in contrast to the Q-Exactive™ orbitrap generation, this mass spectrometer is still equipped with a tube lens/skimmer assembly rather than the stacked ring ion guide (“S-lens”). Thus, the length of the initial ion transfer tube is almost doubled, when compared to the Q-Exactive™ instrument. The latter was held at a temperature of 250°C. For the analytes used within this study, the detection range was set to m/z 50-to-1000, with the maximum resolving-power of 100,000. The maximum injection time and scan number were set to 100 ms and 1, respectively. An instrument method that consecutively scanned in positive and negative ion mode was applied, allowing analyte ions to be detected in either polarity near-simultaneously.

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Geometry. To achieve maximum sensitivity of the proposed setup, at first, the sonic-spray-like nebulizer was positioned coaxially in front of the conical skimmer inlet of the Orbitrap mass spectrometer (cf. Figure 1). The alignment was carried out by maximizing the ion yield of the singly charged protonated monomer of caffeine (m/z 195.0875) in a SSI MS experiment, using the 10 µg mL-1 sample solution. The free space distance between the fused-silica capillary tip and the atmospheric pressure interface was set to 7 mm. Eventually, the plasma was ignited at the midpoint between the nebulizer and the MS inlet.



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Results and Discussion Under certain conditions, the Venturi nebulizer used within this study was capable of producing analyte ions out of the different sample solutions, even without the coupling of the laser-induced microplasma. At the nebulization gas flow and liquid feed-rate of 0.60 L min-1 and 10 μL min-1, respectively, the formation of singly charged protonated caffeine molecules [M+H]+ out of 10 µg mL-1 stock solution was in the order of 2-3×103 counts per second. The recorded mass spectrum is shown in the supplementary information (SI, cf. Figure S1). To exclude any ion signal contribution deriving from the nebulization process, prior to the analysis of further test solutions, the nebulizer gas flow was intentionally reduced. At the carrier gas flow rate of 0.36 L min-1, no ion signal was observed, while the nebulizer was found to produce uncharged droplets under stable conditions without accumulating liquid at the tip of the fused-silica capillary.

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Figure 2. Mass spectra obtained from single analyte solutions, including a) caffeine, b) 3aminoquinoline, and c) chlorpyrifos. The inset within a) displays the extracted ion chronogram of the protonated caffeine molecular ion [M+H]+ at m/z 195.0875.

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Under these spray conditions, only upon the combination of nebulization and the ignition of the laser-induced microplasma, a formation of ions can be followed. While in this paper only results for a solvent mixture of acetonitrile, methanol and water are shown, it is worth mentioning that the


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plasma was not found to be quenched by any other solvent. As can be seen in the inset in Figure 2a, immediately after the initial plasma formation, a steep increase in the signal abundance of the protonated caffeine ion signal at m/z 195.0875 is observed with a rise time of 1-3 seconds, roughly reflecting the time needed for ions to be transferred from the atmospheric detection volume onto the ion detector. Further analyte solutions containing 3-aminoquinoline (cf. Figure 2b) and chlorpyrifos (cf. Figure 2c) show a similar behavior. In both cases, the target analytes are detected as molecular ions in their protonated forms. However, in the case of chlorpyrifos, in addition to the [M+H]+ ion signal of the expected constituent, an [X-16]+ ion peak becomes visible. Considering the exact mass measurement and the isotopic distribution, this additional feature is most likely to be the transformation product [M+H-S+O]+.29 Such an oxidation is atypical and has not been observed before with other ambient ionization sources.30–32 The conclusion of a more oxidative environment in the vicinity of a 1064 nm laser-induced plasma goes along with the detection of different intermediate species formed by the plasma itself, including highly reactive oxygen containing ions, such as O2+, NO+, NO2+, and O3+ (cf. Figure S2).

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The formation of gas phase ions out of predominantly neutral droplets includes a charge separation, as well as a desolvation step. In principle, both can be driven by the hot plasma. However, whether the evaporation of the solvent occurs comprehensively, strongly depends on the available energy inside the plasma. Especially in the case of cold spray-based ion sources, this is why an additional heating of the ion transfer capillary was found to yield in an additional desolvation, resulting in a greater ion count.33 In other words, the completeness of the evaporation of solvent can be interrogated by studying the influence of the inlet capillary temperature on the total ion abundance. Therefore, the temperature of the inlet capillary was ramped from 110°C to 320°C while consecutive mass spectra were recorded. As can be seen, the ion signal of protonated caffeine at m/z 195.0875 exhibits no significant increase with temperature (cf. Figure 3). This observation suggests that under the given operational conditions, the target analyte caffeine is no longer present in the sprayed droplets, but already formed gas phase ions, when passing the atmospheric pressure interface.

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Figure 3. Response of the protonated caffeine molecular ion (m/z 195.0875) as a function of the inlet capillary temperature. The apparent segmentation (vertical-line feature) was due to the digitizing error of the instrument.

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Nonpolar Analytes. To probe the versatility of the introduced setup, additional analytes with distinctively different properties were vaporized, the first of which being the nonpolar polycyclic aromatic hydrocarbon anthracene. While, apart from the sulfur/oxygen exchange in the case of chlorpyrifos, all spectra of polar analytes are dominated by the formation of protonated molecular



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ions with hardly any fragment-ion contribution, nonpolar compounds, such as anthracene, are detected in the radical cation form (cf. Figure 4). Besides the [M]+ signal at m/z 178.0776, the spectrum exhibits a pronounced progression of peaks that are likely to originate from the formation of oxygenated anthracene molecules with up to three oxygen atoms. A comparable ozonolysis of aromatic hydrocarbons through plasma-based ionization techniques has been reported earlier to derive from the local presence of highly oxidizing intermediate species.34–36 The presence of oxidative species inside the plasma (e.g. O*) has been confirmed earlier via optical emission spectroscopy24 and is consistent with the mass spectrum of reactive species (cf. Figure S2). Therefore, the observed ion peak progression most likely corresponds to multiple degrees of oxidation.

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Figure 4. Recorded mass spectrum of anthracene.

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Source-Induced Fragmentation. Thus far, only spectra of analytes that are known to be readily accessible by other ambient ionization techniques have been shown. As an example of analytes, which has been rarely reported by now as a performance benchmark for ambient ion sources, the widely used nonsteroidal anti-inflammatory drug diclofenac was chosen. The acquired mass spectrum in positive ion mode for the laser-induced microplasma ionization scheme is depicted in Figure 5.

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Figure 5. Recorded mass spectrum of diclofenac.

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In this case, the identification of spectral features was facilitated due to the characteristic isotopic distribution of diclofenac, caused by the presence of the chlorine isotopes 35Cl and 37Cl. The spectrum is dominated by the presence of the protonated molecular ion [M+H]+, exhibiting isotopic peaks of X, X+2, and X+4 with relative intensities in a ratio of 9:6:1 at m/z 296, 298, and 300, respectively. However, in comparison to the spectra of more basic polar compounds (cf. Figure 2a, b), it can be seen to yield in relatively low overall signal, as well as a pronounced


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presence of fragmentation products similar to those obtained from performing collision-induced dissociation (CID) of the same molecule in an ion trap mass analyzer.37 While on first sight, a source-induced fragmentation appears as a drawback, it can be beneficial for structure elucidation purposes. For instance, source-induced fragmentation can sometimes offer a better fragmentation coverage.22 In the present work, the detected signals are identified as follows: The ion peaks at m/z 278 and 280 (ratio 3:2) correspond to the loss of water and formation of the protonated intramolecular cyclization product 1-(2,6-dichlorophenyl)indolin-2-one [M+H-H2O]+. Fragmentation of the latter results in the loss of CO, producing cations of the type [M+H-H2CO2]+ at m/z 250 and 252 (ratio 3:2). Eventually, the cleavage of a chlorine radical can be observed yielding the degradation product [M+H-H2CO2Cl]+ at m/z 215 and 217 (ratio 3:1). Moreover, the spectrum exhibits additional ion peaks at m/z 266 and 268. Based on their signal ratio of 3:2, which indicates the presence of 2 chlorine atoms, the mass difference of 30 mass units, and tandem MS analysis, these ion peaks have been identified earlier as the protonated 2-[(2,6dichlorophenyl)amino]benzaldehyde.37

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Negative Ion Mode. A characteristic feature of laser-induced plasmas is maintaining electroneutrality, because in a microcanonical ansatz there are approximately equal numbers of positively and negatively charged species. Consequently, it has no preferred polarity, which allows the ion source to produce positive and negative ions at the same time under the same experimental conditions. The reagent-ion background observed in the negative ion mode (cf. Figure S3) corroborates this assumption. Similar to ion sources based on an electrical discharge,38–40 the reagent-ion population in the mass range m/z 50-to-150 is dominated by a major abundant ion peak at m/z 62, indicating the formation of nitrate ions (NO3-). In addition, significantly lower ion abundances were obtained for CO3- (m/z 60), SiO2- (m/z 60), HCO3- (m/z 61), HCO4- (m/z 77), the deprotonated molecular ion of oxalic acid [(C2H2O4)-H]- (m/z 89), and H(NO3)2- (m/z 125). To assess the ionization capabilities of the laser-induced microplasma in the negative ion mode, the commercial explosive RDX was selected as a model analyte and introduced to the ionization volume. The recorded spectrum is shown in Figure 6. Given the chemical properties of the cyclic nitramine, the attachment of the reagent-ion NO3- to the analyte is invariably observed as the preferred reaction channel of producing the adduct ion [M+NO3]- (m/z 284) of RDX. This result is in good agreement with spectra obtained by other plasma-based ambient desorption/ionization sources.41–43 Further fragmentation products or the commonly formed adduct [M+NO2]- (m/z 268) were not detected.

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Figure 6. Mass spectrum recorded in negative ion mode for the detection of RDX.

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Cross Sensitivity. In another experiment, the capability of detecting analytes in a complex matrix was investigated by analyzing a mixture of five compounds, i.e., diclofenac, 3-aminoquinoline,



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caffeine, ferrocene, and anthracene. After ignition of the laser-induced microplasma, the formation of molecular ions could be monitored for all compounds simultaneously. However, the individual corresponding signal levels were found to change significantly compared to those of the neat sample solutions. The results are summarized in Figure 7, depicting the ion signal comparison of analytes within the mixture (blue bars, filled with horizontal lines), and those analyzed individually (red bars, filled with vertical lines). Notably, the detection efficiency of analytes that are preferably ionized by proton transfer was significantly enhanced, while radical cations were suppressed. For instance, the [M+H]+ signal of caffeine increased ~3.8 fold, while the [M]+ signal of anthracene was only detected with 17% of the signal intensity from the pure solution. This finding implies that, under the chosen operating conditions, the radical cation of anthracene [M]+ potentially acts as a dopant, inducing radical-mediated microenvironment interactions. Subsequent formation of proton-bound solvent clusters, followed by an incorporation of the analyte via ligandswitching/association and collision-induced decomposition, yields the protonated analyte [M+H]+, if the analyte has a higher proton affinity than the cluster constituents itself.44 Specifically, the presence of VUV photons within and near the laser-induced plasma, formation of the charge transfer promoting intermediates O2+, NO+, NO2+, and O3+, thermal ionization via adiabatic compression in a shock wave, electron impact ionization, and/or Penning ionization can promote the formation of [M]+ of analytes, such as ferrocene and anthracene. However, additional studies and deuteration experiments are needed to further deduce the underlying ionization mechanisms.

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Figure 7. Ion signal comparison of analytes within the mixture (blue bars, filled with horizontal lines), and those analyzed individually (red bars, filled with vertical lines).

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Tunability of the Ion Source. Through the interrogation of the five-component sample mixture, it was found that the abundance of different analyte ions produced by the laser-induced microplasma ion source, [M+H]+ and [M]+, can be altered by varying the output power of the excitation laser. Towards lower laser power, the plasma becomes weaker in terms of optical emission and sound level. At 75% of the maximum current provided to the pump laser diodes, the air breakdown is barely visible. Even though under these operating conditions, the visual inspection of the plasma implied that not all lasing events result in the formation of a laser-induced plasma, a spectrometric detection of ionic species was possible. Every lower current led to an output fluence below the plasma threshold, where otherwise ion formation was no longer observed. Thus, this value was chosen as the lower limit. Then, the laser power was ramped from 75% to 100% with a step size of 5%. Further, it should be noted that the nebulization was not interrupted


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while modifying the output power of the laser. The normalized ion counts (relative abundances) of the five individual analytes as a function of the laser power are depicted in Figure 8.

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Figure 8. Laser power dependency of analyte ion signals within the five-component mixture.

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The power dependency plot indicates the ionization efficiency of analytes detected as [M+H]+ to peak at around 80% of the full laser power (cf. Figure 8, solid traces in magenta, black, and blue). Concurrently, the ion signals corresponding to the radical cations of ferrocene and anthracene [M]+ are low (cf. Figure 8, dashed traces in red and green). As towards higher pulse energies the individual plasmas become more intense, the ion abundances observed for all [M+H]+ species decrease, until at 100% laser power, they only occur with ~30-40% of their maximum intensity. This decrement in ion signal for analytes that tend to be ionized via proton transfer may be caused by collision-induced charge loss. Conversely, the formation of intact molecular cations M+ scales with increasing laser power. As an increase in the laser power generally results in a more energetic plasma, a greater ionization probability for particular analytes along any of the above-mentioned reaction pathways for radical cation formation is feasible.

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Overall, these findings suggest that a selective ionization toward the detection of polar vs. nonpolar analytes is possible. Though this tunability in ionization chemistry might appear subtle, it increases the selectivity and, thus, leads to more efficient ionization which in some analytically complex situations can be important. Note for instance, how the caffeine ion signal at 80% laser power appears with roughly double the intensity compared to its equivalent at 100% (cf. Figure 8, solid, blue trace). In total, this data point corresponds to nearly eight times of the ion signal out of the neat caffeine solution. Vice versa, the signal of the nonpolar analytes increases by a factor of five throughout the laser power range depicted here.

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Conclusion

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The performance of a quasi-continuous laser-induced microplasma as an ambient ionization approach with liquid coupling was investigated. To achieve this, the driving laser was changed to the infrared fundamental wavelength, resulting in a two-fold increase in plasma power. The resulting more energetic plasma was found to be much more robust towards laboratory conditions



1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

and was not quenched upon the spray introduction. Specifically, different model analytes were tested in positive and negative ion mode and primarily detected in intact molecular forms. This preservation of molecular information allows for a more controlled molecular investigation of the target species, such as determining the structural identity via subsequent tandem-MS experiments. At the same time, the high temperature of the plasma and the heating effect of the laser light itself were found to positively affect the complete desolvation of the analyte-containing droplets prior to them entering the mass spectrometer. Unlike ESI, the capillary temperature was not crucial in this study. Consequently, atmospheric pressure chemical ionization and photoionization are suggested as the major contributors in the ionization process, combined with other possible reaction pathways, such as dopant-assisted atmospheric pressure photoionization, electron impact ionization, Penning ionization, and thermal ionization. As such, this ionization scheme shares the same limitations that have been observed for other electrically driven plasma-based ambient ionization sources: First, larger molecules cannot be efficiently detected. Second, ionization matrix effects were unavoidably observed when the laser-induced microplasma was used to analyze sample mixtures. However, the analyte signal suppression is not only related to competitive ionization in this case. Specifically, the complex ionization mechanisms underlying the laserinduced plasma can result in significant alternation of atmospheric reactions, which in turn are directly related to different ionization pathways of analytes. In this study, the presence of anthracene within a sample mixture amplified the caffeine ion signal by almost four times. On top of that, the observed laser power dependency implies that the ionization mechanism can be significantly altered. This observation potentially not only provides unique insights to ion-ion and ion-molecule interactions at atmospheric pressure, but also enhances the selectivity and, thus, sensitivity of future ion sources based on laser-induced plasmas.

24

Acknowledgements

25

Yi You is grateful for the fellowship provided by the Adolf-Martens fund.

26

Notes

27

The authors declare no competing financial interest.

28

Supporting Information

29 30 31

The Supporting Information is available free of charge on the ACS Publications website. Figure S1: Sonic spray spectrum of caffeine solution. Figure S2: Positive mode reagent-ion background. Figure S3: Negative mode reagent ion background.

32


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For Table of Contents Only.



Recorded mass spectrum of anthracene. 104x69mm (300 x 300 DPI)


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Ion signal comparison of analytes within the mixture (blue bars, filled with horizontal lines), and those analyzed individually (red bars, filled with vertical lines).



Laser power dependency of analyte ion signals within the five-component mixture. 105x111mm (300 x 300 DPI)


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Laser-Induced Microplasma as an Ambient Ionization Approach for the

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