Article pubs.acs.org/ac
Exploration of Microplasma Probe Desorption/Ionization Mass Spectrometry (MPPDI-MS) for Biologically Related Analysis Zhongjun Zhao,†,∥ Bo Wang,‡,∥ and Yixiang Duan*,§ †
College of Chemical Engineering, ‡College of Chemistry, §College of Life Science, Sichuan University, Chengdu 610064, P. R. China S Supporting Information *
ABSTRACT: To expand the applications of glow discharge microplasma into biological analysis, an innovative ambient ion source for mass spectrometry, microplasma probe desorption/ ionization mass spectrometry (MPPDI-MS), has been developed and demonstrated. Electrodes and a sampling tube were creatively combined using a stainless steel syringe needle, and efficient methods of introduction for biological samples in solid, liquid, and gaseous phases like phospholipid and amino acids were specially designed. Based on the active species generated by glow discharge plasma, simplified protonated spectra were obtained without extra solvent spray assistance. The method is easy to operate and versatile and especially has the ability to distinguish the isomeric compounds of ketone and aldehyde. Quantitative results of this method for different biological samples in different phases were also performed well. It was proved that with further improvement, this sensitive and selective analysis using MPPDI-MS with minimal invasiveness will be an ingenious tool in disease diagnosis and single-cell detections in the future.
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which has little or no sample prepreparation and is high throughput, promoted these analyses, making them much faster and simpler.10−12 It was a kind of noninvasive analysis and has been applied to living samples such as bacteria,9,13 cell lines,14,15 and investigation of biomarkers and the levels of therapy so far.16 Quickly sorting and detecting diseases has been achieved in clinical diagnosis using ambient mass spectrometry. AMS was equipped with atmospheric ionization sources such as direct analysis in real time (DART),17 desorption electrospray ionization (DESI),12 electrospray ionization (ESI),18 dielectric barrier discharge ionization (DBDI),10 microwave induced plasma desorption/ionization (MIPDI),19 and so on. In vitro analyses were attained with the technology of ESI,6 DESI, 1 2 matrix-assisted laser desorption/ionization (MALDI),20−22 paper spray (PS),23 and electrospray-assisted laser desorption/ionization (ELDI).24 However, in vivo analyses were more difficult because they were limited by the vulnerable structure of animal or human bodies and the size of the target cells. Therefore, probes used to collect samples from tissues or cells were introduced into AMS. In 2012, Mandal and co-workers25 introduced a MS probe based on electrospray ionization (ESI), named solid-probe-assisted nano electrospray ionization (SPA-nanoESI). In that method, sample was captured on the tip of the acupuncture needle by stabbing the needle into the biological tissue and then inserting the
or a long period of time, analytical chemistry has been used to explore the macroscopic world. Targets were almost always composed of visible objects. Nowadays, scientists have made it possible to distinguish millions of compounds in different phases based on the physicochemical properties and the interactions using analytical tools. The microscopic world can also be seen with the help of advanced technologies such as microtechnique, and therefore, analytical chemistry broke the boundary of the sample sizes and types, and the target chemicals became living things, such as organs of plants and animals, cells, single cells, and so on.1 Mostly, these studies were combined with genomics, transcriptomics, proteomics, and metabolomics in order to investigate the relations between biomarkers and the degree of diseases, the result of therapy and so on.2 Biomarkers were brought up with the trends of molecular biology and immunology. They were the markers that represent the growth and proliferation of cells and were used to explain pathogenesis at the molecular level. What’s more, biomarkers played an important role in early disease diagnosis because the dynamic changes in the biomarkers in tissues, fluid, breath, and cells by analytical instruments can indicate the status of the human body.3 From this perspective, the requirements for the analytical methods were more critical. They must provide noninvasive analysis and use avirulent chemical solvents.4 Among the analytical methods to detect tissues and cells in vitro and in vivo, mass spectrometry (MS) was one of the powerful tools because there have been many reports about the applications of MS in biosample detections.5−9 In particular, a booming technique named ambient mass spectrometry (AMS), © XXXX American Chemical Society
Received: September 29, 2015 Accepted: January 12, 2016
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DOI: 10.1021/acs.analchem.5b03671 Anal. Chem. XXXX, XXX, XXX−XXX
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Thomas glue, and a Teflon conversion interface was used as the joint to connect the outer gas to the plasma channel. Helium was used as the discharge gas and transported the ions toward the MS skimmer. The ion intensity increased first as the flow rate increased. However, it began to decrease after the signal reached the highest due to the high-speed discharge gas jet. The turbulence blew away the ions which were supposed to enter into the ion transfer capillary. Therefore, the gas flow rate was set to be 500 mL min−1 controlled by a mass flow controller (D07-19B, Sevenstar, Beijing, China). The outside dimension of our device was 20.0 mm × 10.0 mm × 3.0 mm. Usually the electrodes in the plasma-based ion source were symmetric and made from the same metal. However, the electrodes in our device were different in both size and material. Instead, one of the copper chip electrodes was exchanged into a stainless steel syringe needle with the inner diameter about 1.0 mm. The interior structure of microplasma probe was shown in Figure 1.
needle into the solvent-preloaded nanoESI capillary to analyze the sample. The method was successfully used to detect phospholipids and triacylglycerol in human kidney tissues and the liver of a living mouse. In a more microscopic view, metabolites at the cellular and subcellular levels were detected by probe ESI-MS (PESI-MS).26 In that work, tungsten probes with a tip diameter of about 1 μm were directly inserted into live cells for 30 s to enrich the metabolites. Assisted by a high voltage and the solvent spray, 6 fructans, 4 lipids, and 8 flavone derivatives in single Allium cepa cells were detected. Moreover, an ambient probe combined with mass spectrometry or electrosurgical technique was also active in breath gas analysis or clinical operations.27 These applications demonstrated the possibility to apply the probe mass spectrometry into life science. However, all of the techniques mentioned above were relevant to droplet spray ionization which meant solvents were necessary in these methods.28 Those chemicals can contaminate living samples, and the spray device made the cooperation of the instrument more difficult. In this paper, we described a newly designed microplasma probe (MPP) based on direct current glow discharge technique. Different from the droplet spray ionization, the proposed method ionizes samples with the various radicals in the plasma gas generated by glow discharge, so there was no need to use a solvent spray device. As a new source for ambient mass spectrometry, MPP also takes the advantages of microfabricated glow discharge plasma (MFGDP)29 source such as portability, low-temperature usability, and stability. In addition, a stainless steel syringe needle is creatively introduced and used as both the electrode and the sample tube, which reduced the dependence of the source position to the mass inlet. Biosamples in gaseous, liquid, and solid phases were selected to initially evaluate the capability of our microplasma probe. The performance was found to be acceptable. The thermal effect on the probe assisted the desorption of biological compounds with large molecules and also provided the energy to break the chemical bonds in polysaccharide. Especially, isomers of ketone and aldehyde were significantly distinguished by our method using N2 to prepare the samples. With further development, we believe that our microplasma probe will play an important role in detecting breath gas, tissues, and even cells and may enable the development of therapies in the future.
Figure 1. (a) Cross-sectional view of the interior structure of microplasma probe and (b) the photograph of the MPPDI-MS.
The needle was bent to 90° in the middle and set face to face with a 1.0 mm × 1.0 mm copper electrode in the horizontal direction inside the 2 mm wide discharge chamber. The front of the needle, ≈4−5 mm long, was extended out of the chamber, which was used as the sample tube, and the wedge-shaped tip lay tangent with the chamber outlet. The other end of the needle was used to connect an additional sample syringe. When applying a direct current (DC) voltage of 280 V, 11 mA onto the electrodes by a stabilized power source (WWL-LDG, Topower, Yangzhou, China), a stable glow discharge plasma was generated with the flame adhered to the needle electrode because of the gas flow. Therefore, comparing with the symmetric discharge which generated a plasma like a flame, our device discharged more concentrated to the sample because all the samples were loaded on the needle. Additionally, the outside diameter of the needle (1.6 mm) made the distance of the discharge chamber less than 1 mm, which made the plasma more stable. Microplasma Probe Mass Spectrometry. The mass spectrometer used in this experiment is a commercial ion trap mass spectrometer (LCQ Fleet, Thermal fisher, San Jose, CA). Data were acquired from the instrument software Xcalibur (version 1.4RS1). The analysis with MPPDI-MS was performed in positive-ion mode, and spectra were collected under automatic gain mode, where the maximum ion injection time was set to be 100 ms at 3 microscans per spectrum. The mass spectrometer parameters were optimized as follows: capillary temperature, 200 °C; tube lens (V), 78 V; capillary voltage, 18 V; multipole RF amplitude (Vp-p): 660 V. The microplasma
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EXPERIMENTAL SECTION Chemicals and Reagents. Methanol and acetone were purchased from Kermel (Tianjin, China). Biosamples like L-αphosphatidyl choline (PC), α-cyclohexapentylose and hexanal were obtained from Sigma-Aldrich Co. LLC. Butyraldehyde was purchased from Aladdin Industrial Inc. All of the solvents were HPLC grade and used without further purification. The powder-formed amino acid L-serine and glutathione reduced were bought from Sangon Biotech Engineering Technology & Services Co. Ltd., (Shanghai, China). N2 (99%), Ar (99.9%) and He (99.999%) used as the sample and plasma gases were all provided by Qiao Yuan Gas Company. Solutions were prepared by water and a UPHIV-10Y series UP water purification system (ULPURE, Chengdu, China) was used to produce ultrapure water (18 MΩ cm−3). Microplasma Probe Desorption/Ionization Mass Spectrometry (MPPDI-MS) System. Structure of the Microplasma Probe (MPP). The discharge chamber was assembled by four pieces of rectangular ceramic chips using B
DOI: 10.1021/acs.analchem.5b03671 Anal. Chem. XXXX, XXX, XXX−XXX
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Analytical Chemistry device was placed in front of the MS inlet with the distance about 2 mm. It is particularly worth mentioning that there was no limit to the angle of the source position to the mass spectrometer. The investigator must ensure that the probe outlet is focused on the MS inlet, and the experiment should proceed well. Selection and Introduction of the Samples. For the purpose application in life science, solid samples like αphosphatidyl choline (PC) and α-cyclohexapentylose and solutions of L-serine and reduced glutathione, acetone, butyraldehyde, and hexanal gas were chosen. Obviously, they were all biologically relevant compounds. The reason to investigate the analytical potential of α-cyclohexapentylose was because fructan and other saccharides with the molecular weight from 700 to 1500 widely exist in plant cells.30 With respect to PC, it abundantly exists in the membrane, myelin sheath, and yolk in animal cells, and amino acids and peptides are all essential for living organisms. Besides, gaseous acetone, butyraldehyde, and hexanal have been discovered as biomarkers to diabetes, breast cancer, and some other diseases.2,31 Thus, with the ambition of practical application in life-related analysis, the ability of our MPPDI probe with these samples were examined. Because the probe can be used as the sampling tube besides the electrode, there was no need to employ an extra sample plate. Different introduction methods were designed for samples in different phases. For gaseous samples, solvents (acetone, butyraldehyde, and hexanal) with different volumes were injected into aluminum foil gas collecting bags filled with 500 mL of N2 and diffused for 24 h to obtain the balanced gas samples. After that, gas was extracted from the gas bags by a 1 mL syringe and connected with the probe pin and then injected at a constant speed about 1 mL s−1. Therefore, gas samples were transported into the probe and separated from the discharge gas and the ambient air outside. Molecule−ion reactions between the gas sample and the active particles produced by discharge happened at the probe tip where the plasma was blown out. Gaseous samples with different concentrations were prepared by injecting different volumes of solvents into the gas bags. Liquid samples can be introduced with the same method as gaseous samples. However, unlike with gas-phase samples, solutions were difficult to be completely excited because only the small drop held in the tip was ionized, and most remained in the probe tube. This phenomenon directly affected the quantitative accuracy because the amounts of injection and detection were different. Therefore, a pipet was used to drip 1 μL solutions into the groove of the probe tip. Solid samples were swabbed onto the probe tip surface using a swab soaked with methanol. Safety Considerations. The MPPDI probe calls for DC voltage up to several hundred volts to generate the plasma, and thus, care should be taken in order to avoid electric shot.
Figure 2. Influence of the probe position to the intensity using 10 nL mL−1 acetone gas.
between the ion source and MS inlet did not affect the analysis. It was due to the desorption and ionization processes occurring on the probe and the ion products transported into the analyzer relying on force from the carrier gas and the electric field of the capillary in the mass spectrometer. Thus, as long as the microplasma probe sets closely to the sampling capillary, the ions will be led into MS efficiently. By modifying the length of the plasma and the intensity of the signal, we set the probe tip to the MS inlet at a distance of 1 mm. Additionally, in comparison with the probe electrospray ionization (PESI) using charged droplets created by an electrospray emitter to ionize, MPPDI utilized the positive and negative ions and metastable particles produced by discharge to ionize samples. Therefore, the structure of the source system was much simpler and easier to build. Analytical Performance of the MPPDI-MS for Solid and Liquid Samples. Because the mechanism was the same with MFGDP, MPPDI was also a kind of soft ionization source.28 The interactions between the discharge gas and the sample molecules were typically proton transfer reactions, and the main signal was observed at [M + H]+ as the protonated molecule in the positive-ion mode. The processes were listed below: e− + He → He+ + 2e−or He+∗ + 2e− +
He ∗ + N2 → He ∗ + N2 +
+
(1) (2)
+
H3O (H 2O)n − 1 + H 2O → H3O (H 2O)n
(3)
H3O+(H 2O)n + M → (H 2O)n + 1 + [M + H]+
(4)
The protonated water clusters were produced from the following chain reactions: the metastable He generated from the glow discharge plasma interacted with N2 at the outlet of the discharge chamber, and then N2 was excited to N2+ state, in which energy finally passed onto the water molecules in the ambient air. These protonated water molecules can be found in the background spectra (see the Supporting Information, Figure S1). They played significant roles in the process of ionizing sample molecules following eq 4, so that the protonated mass spectrum can be observed. As shown in Figure 3, protonated L-serine molecule with m/z 106 is the main peak. Quantitative behavior of the liquid sample was tested using the standard curve method, and the calibration curve is shown in Figure 3. The calibration curves were plotted from five multiplied concentrations of each targeted analyte,
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RESULTS AND DISCUSSION Performance of MPPDI-MS. Benefiting from the probe regarded as discharge needle and sampling system, the most obvious advantage was that the position of the ionization source was unconstrained. Unlike another ambient ion source which was also based on the glow discharge plasma, MFGDP,32 there was no need to make the source aim to the sample in order to desorb the deposit on the plate. As shown in Figure 2, the intensities of 10 nL mL−1 acetone changing with the different positions of the probe indicated that the angles C
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Figure 3. Mass spectrum of L-serine and the quantitative curve.
sensitivity of the method to differentiate the intensities of the target compounds contained in the experimental group and the control group, or distinguishing diseases by principle component analysis (PCA). Although the heating effect on the probe was limited to liquid detection, the ability of MPPDI-MS to detect solid samples, on the contrary, benefitted from the limited heating. Because the solid samples selected contained high molecular weights (MW > 700 Da), the mass spectra were usually more complex. As shown in Figure 4a, the mass spectra of different types of PC mixture with similar charge-to-mass ratio were discriminative in MPPDI-MS. It is worthwhile to mention that in our previous research,29 momentum desorption was tested to be difficult to desorb compounds with high MW, so the efficient desorption in this method was mainly caused by the thermal probe assistance. Without using an extra heating plate or a heating gun, the ionization source itself can supply enough energy for thermal desorption. Besides, this heat can also provide the energy to dehydrate in α-cyclodextrin molecule. In the mass spectrum of Figure 4b, the molecular ring was broken into three types of fragments, forming two, three, and four protonated glucose units. The dehydration temperature for αcyclodextrin was about 200−300 °C, and obviously, the plasma gas temperature of the MPPDI based on the plasma technique cannot reach that high.33 Thus, it was the heated probe that enhanced the desorption performance of traditional glow discharge microplasma. Analytical Performance of MPPDI-MS for Gaseous Samples. There were two conventional ways to inject gaseous samples into ambient mass spectrometry. One was to place the solvents at a certain distance with the MS source and relied on the free diffusion to detect the volatile sample in the environment,34 and the other one was to inject the sample gas into the gas channel of the source system or connected the sample gas with the carrier gas outlet.35 Even though the first method was able to detect the volatile organic compounds in the environment online, it was not suitable to detect offline gas such as breath gas. The second one was more common in AMS, but the sample was diluted and mixed by the carrier gas, which leads to a lower sensitivity. Besides, as the sample contacted with the electrodes directly, if water vapor or corrosive gas was introduced, the electrodes could be corroded. In this point of view, the sampling performance between piercing injection mode and our probe injection mode was compared, and the results are shown in Figure 5. We found that our method obtained a better signal, mainly because the probe separated the
and the corresponding signal intensities were recorded through three parallel injections of each concentration. The correlation coefficients (r2) of 0.966 were quite gratifying with the limits of detection (LOD) calculated to be 1.875 ng mL−1, which means the method could be a relatively accurate and dependable semiquantitative candidate. Another liquid sample, reduced glutathione, was tested with the similar result as L-serine. The correlation coefficient was 0.953 and the LOD was calculated to be 3.780 ng mL−1. Other peaks at m/z 149 and 167 in all of the spectrum in our experiment corresponded to the fragmentation of the peak at 279, which were confirmed by CID. The peak at m/z 279 was identified as protonated dibutyl phthalate, a kind of plasticizer. The plasticizers were probably derived from the degradation of the polyethylene tube and/or the Thomas Glue that was used, or it may have been in the air in the laboratory. However, compared with the quantitative results of other methods, MPPDI-MS was less accurate than MFGDP-MS.29 Considering the desorption mechanisms that comprised principally thermal desorption, laser desorption, and momentum desorption, these two kinds of glow discharge plasma source mainly showed momentum desorption caused by the flow of the carrier gas. Even though thermal desorption and momentum desorption were involved in almost all sources, the low temperature of MFGDP and MPPDI plasma gas showed less dependence on heat. However, the special structure of MPPDI source and the sampling method have changed this normal desorption process. In our previous experiment,32 a sample plate adhered to a piece of filter paper was introduced to suck solutions. The solvents like methanol, which were used to dissolve samples, were easy to be diffused and volatilized because the carrier gas blew onto the large sample point and the samples were desorbed and ionized immediately. In this experiment, the efficiency of the momentum desorption was insufficient to desorb samples because the solutions prepared by water were more concentrated holding in the probe and because the carrier gas cannot blow onto the solvent directly. However, the probe used as both sampling tube and electrode was heated after a period of ignition because of the discharge. The solvent in the needle was then quickly volatilized into the air, as well as the solute, without ionizing. The intensity of low concentration was especially effected because of such loss. Therefore, the linearity of the standard curves was not comparable with that of MFGDP-MS. However, in biological analysis, especially in disease screenings, relative quantity was more important than absolute quantitation. In addition, our method can achieve the goal in biological use, relying on the D
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tube. Without corroding the electrodes, the working life of our device can be prolonged as a result. Besides, the radicals generated in the plasma gas and the target molecules reacted just at the outlet of the probe, where most of the particles preferred to participate in the interactions and the ion products were flown into the analyzer directly rather than react inside the narrow chamber, as well as disperse and annihilate by collision before introduction into MS, which occurred in the pierced injection mode. Therefore, the signal intensity was stronger because of the reduction of ion loss. In addition, the discharge status was disturbed and changed when injecting the gas sample through the rubber gas tube. Also in Figure 5, the color of the plasma flame was also changed from red for normal He discharge to purple for N2 discharge. In order to simulate the components of human breath, N2 was introduced to prepare the gas sample like acetone and butyraldehyde. They were homodispersed in the N2 gas bag, and then N2 was extracted into the injection syringe and mixed with the carrier gas through injection. Considering the ingredients and the properties of plasma were managed by the discharge status, the intervention of N2 often made the plasma unstable in regular plasmas. However, in our newly established system, N2 was totally isolated in the probe injection mode, in which the discharge stayed the same all the time. Differentiating from the liquid detection, the quantitative analysis to gaseous sample was much better. As depicted in Figure 6, thanks to the direct sampling, the linear correlation coefficient was 0.999, and the limits of detection was calculated as low as 30 nL L−1 and 130 nL L−1 for acetone and butyraldehyde, respectively. During the six parallel analyses, the relative standard deviations (RSDs) were 1.34% and 1.50%. It means that the results using our method to detect gas sample were pretty stable. However, two different kinds of mass spectrum for these two compounds were observed. Owing to the proton-transfer reaction in the ionization process, protonated [M + H]+ appeared. However, the main peak in butyraldehyde mass spectrum was assigned to [M + NO] + instead. Because the ionization energy (IE) of He* is significantly higher than that of N2,36 NO+ came from the ionized production between these two species. Therefore, in further work, Ar was used to replace N2 to prepare butyraldehyde gas in order to eliminate the influence from the N2 gas in the bag. Interestingly, the protonated molecule dominated in the spectrum again in the Ar atmosphere (see the Supporting Information, Figure S2). [M + NO]+ was also found in the detection of hexanal (see the Supporting Information, Figure S3). However, it is important to note that at the same condition, acetone did not generate any [M +NO]+ peak as butyraldehyde and hexanal did. This phenomenon might be associated with the different reactions between NO+ with ketone and aldehyde. As described below, NO+ and aldehyde interacted as additional reaction while as charge transfer reaction with ketone:37
Figure 4. (a) Mass spectra of α-cyclodextrin and (b) the mass spectra of L-α-phosphatidylcholine.
NO+ + MH(aldehyde) → M·NO+ − H
(5)
NO+ + H 2O + M(ketone) → [M + H]+ + NO + OH (6)
Figure 5. Analytical performance for two gas sample introductions: (a) Piercing mode and (b) Probe mode.
It was not the first time to use this property of N2. In proton transfer reaction mass spectrometry (PTR-MS), N2 was one of the switchable reaction ions to identify the isomers of keytone and aldehyde.38 Thus, it revealed that besides accurate and
sample gas from the carrier gas into two channels, there was minimal dilution and air contamination in this independent E
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Figure 6. Mass spectra and quantitative curves for gaseous samples: Acetone (up) and butyraldehyde (down).
stable, MPPDI-MS has the ability to discriminate the unknown isomer samples utilizing N2 in the sample preparation.
breath gas or single-cell detection. We expected that microplasma probe mass spectrometry might be a powerful candidate in life science in future.
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CONCLUSIONS In summary, we have demonstrated a newly designed microplasma probe as an ambient mass spectrometry ion source named MPPDI for biological sample analysis. Direct sampling was allowed for solid, liquid, and gaseous biological samples by the probe that was used as both electrode and sampling tube. With the assistance of the thermal effect on the probe, molecules with high weights can be desorbed and extra energy used to break the circular compounds into pieces can be provided by the probe, which made the determination of heavy molecules possible and clearer. What’s more, compared with the common injection method, the sensitivity was greatly improved using the probe introduction method to detect gaseous samples with the LOD of about 30 nL L−1. Selective detection of ketones and aldehyde was achieved utilizing N2 as background gas to prepare samples. With a simplified structure, our MPPDI-MS offered a distinct way of sampling and detecting life-related samples. Beyond the present work, further improvements on analytical efficiencies are still needed. For example, coating the enrichment material onto the probe surface may consequently strengthen the sampling efficiency, or enhance the transmission and reaction efficiency utilizing voltage or magnet to guide the particles, thus significantly perfecting the analysis in practical terms. Because minimal invasiveness is an important merit in clinic, our probe could also be further miniaturized so that more applications could be possible for disease diagnosis using
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.5b03671. Background mass spectra of MPPDI-MS using He as discharge gas and mass spectra of butyraldehyde prepared in Ar atmosphere and the spectrum and quantitative analysis of hexanal (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. Phone: (+86) 028-85418180. Fax: (+86) 028-85418180. Author Contributions ∥
These authors contributed equally to this work and should be considered co-first authors (Z.Z. and B.W.). Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS The authors are grateful for the financial support from the National Recruitment Program of Global Experts (NRPGE), the Hundred Talents Program of Sichuan Province (HTPSP). They also thank to the support from the Research Center of F
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(34) Symonds, J. M.; Galhena, A. S.; Fernández, F. M.; Orlando, T. M. Anal. Chem. 2009, 82, 621−627. (35) Li, D.; Tian, Y. H.; Zhao, Z.; Li, W.; Duan, Y. J. Mass Spectrom. 2015, 50, 388−395. (36) Blake, R. S.; Monks, P. S.; Ellis, A. M. Chem. Rev. 2009, 109, 861−896. (37) Jordan, A.; Haidacher, S.; Hanel, G.; Hartungen, E.; Herbig, J.; Märk, L.; Schottkowsky, R.; Seehauser, H.; Sulzer, P.; Märk, T. D. Int. J. Mass Spectrom. 2009, 286, 32−38. (38) Inomata, S.; Tanimoto, H.; Yamada, H. Chem. Lett. 2014, 43, 538−540.
Analytical Instrumentation of Sichuan University for providing all of the devices and materials demanded in this work.
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DOI: 10.1021/acs.analchem.5b03671 Anal. Chem. XXXX, XXX, XXX−XXX
