Surface-Transfer Mass Spectrometry Imaging on a Monoisotopic Silver

Nov 19, 2013 - A new method for both high-resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging is described. The met...
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Surface-Transfer Mass Spectrometry Imaging on a Monoisotopic Silver Nanoparticle Enhanced Target Joanna Nizioł and Tomasz Ruman* Rzeszów University of Technology, Faculty of Chemistry, Bioorganic Chemistry Laboratory, 6 Powstańców Warszawy Ave., 35-959 Rzeszów, Poland S Supporting Information *

ABSTRACT: A new method for both high-resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging is described. The method could be considered as matrix-less because no additional matrix is needed for MS measurements and also because of surface-assisted laser desorption/ionization due to the nanoparticle-rich surface. The standard matrix-assisted laser desorption/ionization target containing unique monoisotopic cationic 109Ag nanoparticles (109AgNPs) was used for high-resolution mass spectrometry imaging of fingermarks and also plant flower and plant stem cross sections with high mass accuracy. The methodology presented in this work allowed visualization of two drugsantiinflammatory ibuprofen and anticancer 5-fluorouracilalong with many other compounds found on the finger. Moreover, visualization of herbicide localization inside of the plant stem is also shown. The simple inorganic ions ionized by silver nanoparticles were also found and may be used for their localization in biological material. In addition, the methodology presented here does not require freezing of species or slice-making equipment.

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Laser desorption/ionization (LDI) mass spectrometry imaging is described almost exclusively as a method where the traditional organic matrices such as α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydroxybenzoic acid (DHB) are used. These matrices are best-suited for ionic substances such as peptides, proteins, and some polymers with preferable measurement range higher than 1500 Da due to (i) the large amount of matrix peaks in the low-mass region, (ii) unreliable calibration, (iii) low mass accuracy due to relatively high thickness of measured regions, (iv) low mass accuracy with external calibration, (v) low ionization efficiency for neutral organic compounds, and (v) inhomogeneous matrix crystallization. Crystalline matrices were widely used in biological and biomedical sciences, a subject that has been covered by a few excellent reviews.22−27 One of the most interesting applications of LDI MS imaging is the fingermark analysis for its physical pattern as well as endo- and exogenous compounds, a subject reviewed recently by Francese and co-workers.28 LDI mass spectrometry imaging of plant material was recently discussed in a review by Kaspar et. al.29 We have recently shown a new method for the preparation of a modified MALDI target by covering it with cationic, monoisotopic silver-109 nanoparticles (109AgNPET). The

atrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was developed by Tanaka et al. in 1988,1 and it belongs to the most selective, sensitive, and efficient mass spectrometry methods. However, it has been rarely applied to detect low molecular weight (LMW) compounds (MW < 1000 Da) because common MALDI matrices, being low molecular weight organics, produce a variety of matrix-related ions, thus causing interfering signals in the low-mass-spectrum range.2,3 Some of above-mentioned problems were solved with the development of surface-assisted desorption/ionization (SALDI) techniques, in which the target plate contains various organic or inorganic micro- or nanoscale structures.4−11 It is clear that one of the most important directions of development of MALDI and other LDI MS methods is imaging mass spectrometry (IMS). It is worth mentioning that the imaging mass spectrometry term was initially associated with the secondary-ion mass spectrometry (SIMS) method.12 A few years later, matrix-assisted laser desorption/ionization (MALDI) 13,14 and desorption electrospray ionization (DESI)15,16 methods were used for imaging purposes. Laserbased methods were especially intensively developed in recent years mainly due to the very broad applicability range of the LDI (laser desorption/ionization) system. New laser-based imaging methods such as laser ablation electrospray ionization (LAESI),17−19 electrospray-assisted laser desorption/ionization (ELDI),20 and desorption atmospheric pressure photoionization (DAPPI)21 are also known. © 2013 American Chemical Society

Received: October 2, 2013 Accepted: November 19, 2013 Published: November 19, 2013 12070

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contains sodium laureth sulfate, cocamide DEA, lanolin, glycerin, citric acid, pH 5.5), and 100 mL of water. Ibuprofen solution (0.5 μL; 1 mg/mL in methanol) was then placed on the finger (roughly in two regions of finger). Additionally, 1 μg of 5-fluorouracil (5 μL of water solution) was placed on the finger and smeared on the whole fingertip. (b) The Crepis mollis flower (diameter approximately 10 mm) was used approximately 24 h after collection (24 h storing in ambient temperature) of the 30 cm stem and the flower part of plant. The flower was then cut with a steel razor blade and held on the 109AgNPET for 2−3 s. (c) A Mentha piperita stem (diameter approximately 4 mm) was collected from a 2-methyl4-chlorophenoxyacetic acid (MPCA)-polluted plant (average 30 cm height, 3−5 mm diameter of stems). The plant was held for 4 days in soil which was watered daily with 20 mL of MCPA water solution (1 μg/mL). The stem was collected by cutting (razor blade) at approximately 5 cm above the soil level, followed by 24 h of storing in ambient temperature, and cutting again with the blade (5 cm above the previous cut). The blade was moved laterally while cutting (1 cm for every 1 mm of stem diameter). The stem was then gently touched to the filtration paper and then to the 109AgNPET (less than 1 s). (d) The starting materialfingermarks on a glass surfacewas obtained by gentle touching of a glass surface with the fingertip, which was previously washed with water and acetone followed by touching of the forehead to cover the finger with a thin layer of skin compounds. The transferring material (Vinyl duct tape, 0.13 mm thickness, TESA, Germany, or two layers of nitrile glove material, Nugard Nitril, powder-free medical gloves, Malaysia) was then touched to the fingermark and gently pressed, followed by touching and pressing to the 109 AgNPET surface. The target was then directly analyzed with an MS apparatus. Spatial resolutions used were 250 × 250 and 150 × 150 μm for nitrile and vinyl materials, respectively.

method was found to be very efficient for cationization of various LMW compounds.11 The next logical step was to develop an imaging methodology utilizing 109AgNPET for visualization of natural compound distribution in various samples. For this purpose, examples of applications of 109AgNPET in LDI MS imaging of plant tissue and fingermark were prepared. The plant material that was used in the present work included flower and stem cross sections, the latter was used for visualization of toxic herbicide as well as endogenous compound distribution. Other experiments were prepared for the visualization of both physical and chemical properties of fingermarks, and also fingermark copies were transferred with the use of duct tape and nitrile rubber. Two drugs of low polarity placed on the fingertip were chosen as examples of the possibility of foreign substance visualization.

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EXPERIMENTAL SECTION Materials. Silver-109 (min 99.75% of 109Ag) isotope was purchased from BuyIsotope (Sweden) and transformed to trifluoroacetate salt by commonly known methods (involving dissolving in HNO3, followed by 109AgOH formation and dissolving in trifluoroacetic acid) and recrystallized from the THF/hexane system. The compound 2,5-dihydroxybenzoic acid (DHB) was purchased from Bruker Daltonics Gmbh (Germany). Steel targets (MTP 384 type) for imaging were machined from carbon (1050 steel) or stainless steel. The surface of targets was polished to a mirror-like appearance with P150 to P2000 grit (ISO/FEPA grit designation), followed by mechanical polishing with polishing paste. All other chemicals were purchased from Sigma-Aldrich (97−99% purity). All solvents were of HPLC quality, except for water (Ultrapure Water, Merck) and methanol (LCMS grade, Fluka). The silver109 nanoparticles were synthesized on the surface of steel targets as described in our recent publication.11 Optical photographs were made with the use of an Olympus SZ10 microscope equipped with an 8 MPix Olympus digital camera. LDI MS Imaging Experiments. Measurements were performed using a Bruker Autoflex Speed time-of-flight mass spectrometer in reflectron mode. The apparatus was equipped with a SmartBeam II 1000 Hz 355 nm laser. Laser impulse energy was approximately 100−190 μJ, laser repetition rate was 1000 Hz, and deflection was set on m/z lower than 80 Da. The m/z range was 80−1490 for the Crepis mollis flower experiment (200 × 200 μm spatial resolution), 80−990 for the Mentha piperita stem experiment (50 × 50 μm spatial resolution), and 80−560 Da for the pixel fingermark measurements (150 μm spatial resolution), with an exception for the 50 × 50 μm spatial resolution experiment of m/z = 80−700. The experiments were made with 500 laser shots per individual spot (except for fingermarks1500 shots in 300 random walk steps) with a default random walk applied (FlexImaging 4.0). All spectra were calibrated with the use of silver ions (109Ag+ − 109Ag12+, 5−10 calibration points depending on the measurement range). The first accelerating voltage was held at 19 kV, and the second ion source voltage was held at 16.7 kV. Reflector voltages used were 21 kV (the first) and 9.55 kV (the second). All of the analyzed imaging m/z values were within ±0.02 Da range. TIC normalization was used for all of the shown results. Imaging Sample Preparation. The following protocols (a−d) describe the sample preparation for the experiments: (a) Ungroomed fingermarks for mass spectrometry imaging were obtained by touching the 109AgNPET for approximately 1 s. The finger was previously washed with simple liquid soap (e.g.,

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RESULTS AND DISCUSSION The preparation, characterization, and examples of applicability of the silver-109 nanoparticle enhanced steel target (109AgNPET) for LDI (laser desorption/ionization) mass spectrometry were presented in our recent papers.11,30,31 It was shown that this method is capable of fast and reliable determination of pure compounds as well as analysis of complicated biological mixtures such as blood plasma or urine with very high mass accuracy. These results suggested that 109 AgNPET could be perfectly suitable for mass spectrometry imaging for all measured objects that are having some degree of elasticity and could be directly touched to the target. The direct contact of the measured object permits direct, surface transfer of chemical compounds from the object to silver-109 nanoparticles, thus making this region of the target a “chemical photograph” of the object. Moreover, mirror-like, polished 109 AgNPET allows visual characterization of the analyzed object, which also helps with the proper localization of the object’s “chemical photograph” with mass images. The main advantages of this new method are (i) high precision of calibration and thus high mass accuracy, (ii) reliable and very narrow peak window being in the ±0.005−0.02 m/z range, which minimizes risk of visualization of overlapped peaks, (iii) high resolution, (iv) lack of sweet spots, and (v) large degree of applicability as 109AgNPET can detect simple inorganic ions and a wide variety of organic compounds. Moreover, the presented MS imaging methods do not require liquid nitrogen 12071

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Figure 1. Latent fingermark MSI analysis (150 μm pixel size) on 109AgNPET. (A, B) Optical microscope images of a 109AgNPET surface without (A) and with fingermark (B). (C−J) Graphical representations (TIC normalization) of fingermark compounds at m/z: 131.895 (C), 315.036 (D), 312.301 (E), 240.259 (F), 147.864 (G), 396.150 (H), 284.286 (I), 311.303 (J), and 168.982 (N). The K (m/z 96.922), L (m/z 80.948), and M (m/z 83.022) representations are from another experiment of 50 × 50 μm spatial resolution. All representations are within ±0.02 m/z.

exogenous compounds, which are often present on the finger tips, should not interfere with visualization of small amounts of endogenous compounds, as the latter may be used for visualization of the fingermark physical pattern. The endogenous compounds found on the skin are lipids, proteins, peptides, amino acids, but also larger quantities of urea, simple inorganic (NaCl, KCl), and organic (sodium and potassium lactate) salts may be found. The compounds mentioned in the last sentence are produced mainly by sweat pores, which are located on the ridges. The method allowing localization of sweat-pore-excreted compounds should be essential in this field because it would allow direct localization of ridges and also sweat pores. The 109AgNPET method was used for visualization of fingermarks left directly on the target plate. The presented experiment (Figure 1) was made with 150 × 150 μm spot/pixel size, but more detailed results from a 50 × 50 μm pixel size experiment are presented in insets K−M. It should be noted that a detailed experiment was performed on the same fingermark. The application of the fingermark on the 109AgNPET is extremely simple and requires only simple touching of the finger to the target surface (Figure 1A). Similarly, fingermarks from other sources may be transferred to 109AgNPET with duct tape or nitrile rubber. We have also found that the amount of endogenous substances on 109AgNPET should

freezing of biological samples and also could be used without preparation of ultrathin slices, which is both expensive and time-consuming. The method is also compatible with very highresolution mass spectrometry imaging as a 10 μm (above 25 000 points per inch) pixel size can be used, depending on the spectrometer. It is noteworthy that the target surface which was already measured in the imaging run can be used again for highresolution MS or MS/MS measurements. There are a few examples of imaging applications of the mentioned target described below. Latent Fingermark Analysis on 109AgNPET. It is wellknown that fingermarks are one of the most important means of biometric identification. The physical information obtainable from fingermarks include level 1 details (i.e., ridge pattern), level 2 details (i.e., local shape of the ridge pattern called minutiae, which contain information about ridge endings, bifurcations, islands, spurs, etc.), and level 3 details (i.e., sweat pores’ geometry, placement, and size). The perfect fingermark analysis method should give information about, at least, level 1 and 2 details and also about endogenous and exogenous chemical compounds existing on the fingers. Exogenous substances of interest that may be on the finger include drugs, explosives, toxins, poisons and also less dangerous substances, including cosmetics, toiletry products, and so forth. It is important to remember that relatively large amounts of 12072

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Figure 2. MSI analysis of the cross-sectional surface of the Crepis Mollis flower (200 μm pixel size) on 109AgNPET. (A) Photograph of measured cross-section, (B) photograph of the 109AgNPET surface, and (C−L) graphical representations (TIC normalization) of flower compounds at m/z: 147.868 (C), 387.178 (D), 389.158 (E), 271.131 (F), 104.076 (G), 219.063 (H), 463.141 (I), 131.895 (J), 533.037 (K), 287.126 (L). All representations are within ±0.02 m/z.

image. The finger used in our experiment was washed with liquid soap containing sodium laureth sulfate (and other sulfates of different aliphatic chain length), cocamide DEA (cocamide diethanolamine), lanolin (mixture of esters), glycerin, and citric acid. We have also applied on the finger 5 μg of a very popular nonsteroidal anti-inflammatory drug (ibuprofen (2-(4-(2methylpropyl)phenyl)propanoic acid)), which methanol sol-

be kept rather low as an active layer of nanoparticles should not be covered by too thick a layer of finger lipids. The optimal procedure should be done after cleaning the finger with paper tissue, after handwashing, or when applying the fingermark from another source (duct tape, foil, etc.). The obtained “chemical photograph” of the fingermark ridge pattern may be visible using the correct angle of light (Figure 1B) or it could be developed by dusting after the MSI measurement for a better 12073

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ution was placed mainly on the fingertip. The ibuprofen was found as a silver-109 adduct at m/z 315.036 (Figure 1D) exactly where it was applied. In the same experiment, a solution containing a total amount of 1 μg of a polar anticancer drug (5fluorouracil (5FU)) was distributed on the forward part of the finger (Figure 1N). The local concentration of this drug was lower than 10 ng/mm2 (77 pmol/mm2), which is 25 pg (192 fmol) of 5FU per one measured spot. At this level of concentration, mass accuracy (m/zexperimental − m/zcalculated difference) from measured spots was approximately m/z 0.003−0.004 (m/zexperimental directly from imaging data). As can be seen, mass accuracy is better than that required for compound identification. The graphical representations shown in Figure 1E,F,H−J are for m/z of 312.301, 240.259, 396.150, 284.286, and 311.303, respectively. The mentioned five m/z values were assigned to detergent [C18H37N3O + H]+ (E), isomers of hexadecenylamine [C16H33N + H]+ (F), [laurylamide DEA + 109Ag]+ (H), antifoam [N-ethylhexadecanamide + H]+ (I), and oleic acid ethyl ester [C20H38O2 + H]+ from lanoline mixture (J), respectively. The C and G insets (Figure 1) present graphical representations of the distribution of [109AgNa]+ (m/z 131.895) and [109AgK]+ (m/z 147.864) ions. These ions may be used for precise estimation of local potassium and sodium ion concentrations. As can be seen in Figure 1C,G, the mentioned two ions are presenting very clear representations of fingermark ridges. It is important to remember that sodium and potassium ions are excreted from sweat pores in relatively large quantities and should be considered as direct sweat pore and ridge localization method. Further examination of small ion visualization possibilities led us to a detailed, 50 × 50 μm spatial resolution experiment (Figure 1K−M. The mentioned experiment allowed us to focus on visualization of sweat-poreexcreted compounds such as NaCl, KCl, or urea in form of ions, including [KNaCl]+ (Figure 1K), [Na2Cl]+ (Figure 1L), and [urea + Na]+ (Figure 1M). As can be seen, these ions are found in close proximity to sweat pores, the latter are round, dark structures encompassed by ring-like structures of areas rich in the mentioned ions. In conclusion, visual localization of the mentioned three ions can be used for reliable visualization of ridges and also sweat pores. The mass accuracy in this methodology is very high, mainly because of a very thin layer of compounds that are present on the target which do not contain any additional matrix. The mass accuracy calculated as m/zexperimental − m/zcalculated, for the experiment calibrated before the imaging measurement, was, for example, 0.0005 for [109AgNa]+, 0.0045 for [ibuprofen+109Ag]+, and 0.0004 for [Na2Cl]+ ion in 50 μm pixel size experiment. To our knowledge, the 109AgNPET method is the most precise method for MS imaging known and is limited primarily by the instrument. It is important to remember that the discussed mass accuracy is based directly on peak parameters found in the post-MS-imaging data, which have a much lower resolution than normal MS measurements. For objects as large as fingermarks, data reduction and lower resolution is necessary as detailed experiments (pixels smaller than 100 μm) produce a vast amount of data, require great computing power, and also are time-consuming. As can be seen, this method has mass accuracy similar to the nonimaging, full-resolution MS analysis and therefore could be used for preliminary and also, in many cases, final identification of unknown compounds. Naturally,

measured spots may be further analyzed in higher resolution with the same LDI apparatus. As the described methodology could be of interest to forensic specialists, other experiments were performed. The fingermarks on the glass surface were lifted with various materials and then transferred to the 109AgNPET target plate. The vinyl duct tape and nitrile glove material were found to effectively transfer fingermark substances with visible physical structure (Figures S35−S39, Supporting Information), even with applied lower spatial resolutions. It is reasonable to state that other transferring materials, especially those utilized by forensic experts, should give a level of quality at least as good as shown in the mentioned experiments. Plant Flower Cross Section on 109AgNPET. To find out if this method is suitable for analysis of biological samples, another two experiments were conducted. Biological samples, and especially plant samples, are very difficult to analyze because of the high amount of simple organic and inorganic ions which drastically lower the sensitivity of the mass spectrometer’s detector. A cross section of the Crepis mollis flower (perennial flowering plants of the family Asteraceae; Figure 2A) was made with a razor blade without any freezing step. The touching of the cross section to the target plate left a “chemical image” (Figure 2B), similarly as described for the fingermark analysis. To our knowledge, the literature does not contain any information about similar methodology for direct surface compound transfer suitable for analysis of plant material. A similar method where a plant leaf was pressed onto a Teflon plate was presented for the DESI imaging method.32,33The analysis made with a pixel size of 200 × 200 μm gave very interesting results. As can be seen in Figure 2C, potassium−silver-109 adduct ions were found only within the flower cross-sectional area. The [109AgNa]+ ions (Figure 2 J) were found in very low concentrations in most of the measured area, but higher intensity points are only within the flower cross-sectional area. Additional examples of ions found are (m/ z): 387.178 (D), 389.158 (E), 271.131 (F), 104.076 (G), 219.063 (H), 463.141 (I), 533.037 (K), and 287.126 (L), which were assigned to [gibberellin GA97 + Na]+, [16,17-dihydro16,17-dihydroxygibberellin GA4 + Na]+, [abscisic aldehyde + Na]+, [valeric/isovaleric acid + H]+, [5-hydroxyconiferyl alcohol + Na]+, [11,15-dihydroxy-9-oxoprost-13-enoate + 109 Ag]+, [salicortin + 109Ag]+ and [9α-hydroxy-4β,15,11β,13tetrahydrodehydrozaluzanin C+Na]+ ions, respectively. It should be noted that many more peaks were found, and just 10 of them were chosen for presentation. MCPA-Polluted Plant Stem on 109AgNPET. In order to study the possibility of using 109AgNPET for MSI analysis of plant stems, another experiment was conducted. Plant stems are responsible, for example, for water and inorganic compound transport from roots to other parts of the plant. Therefore, stem liquids are rather difficult to analyze with MS methods due to the high concentration of simple inorganic ions. In this experiment, the plant Mentha piperita was watered with water containing 2-methyl-4-chlorophenoxyacetic acid (MCPA, 1 μg/ mL) which is a potent and selective herbicide. The U.S. EPA (1989) concluded that MCPA is nononcogenic and nonmutagenic at low doses; however, at high doses, it may cause mutations and tumors.34 After four days of MCPA application, the stem was collected, air-dried for 24 h, and cut with a razor blade. The cross-section was then touched to 109AgNPET, and the target was air-dried. The compounds that were transferred in this process left a chemical image with very good visibility 12074

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Figure 3. MSI analysis of the cross-sectional surface of the MCPA-polluted Mentha piperita stem (50 μm pixel size) on 109AgNPET. (A) Photograph of the 109AgNPET surface. (B−I) Graphical representations (TIC normalization) of stem compounds at m/z: 96.922 (B), 381.064 (C), 112.896 (D), 131.889 (E), 223.014 (F), 186.035 (G), 481.179 (H), 147.878 (I). All representations are within ±0.02 m/z.

a potassium adduct (Figure 3G), and also 7-methylthioheptylhydroximoylglutathione as a proton adduct (H in Figure 3).

(Figure 3A) and allows optical localization of the epidermis, cortex, xylem, and pith. The mass spectrometry imaging of this chemical image allowed us to visualize the distribution of simple inorganic ions such as sodium and potassium in the form of [109AgK]+, [109AgNa]+, and [KNaCl]+ ions (Figure 3, I,E,B, respectively). The potassium−silver-109 and sodium−silver-109 adducts, whose intensities are correlated with potassium and sodium local concentrations, were found mainly in the inner (xylem vessels) area of the stem (Figure 3I). Dipotassium chloride cation was found to ionize very efficiently in the outer part of stem as it contains a high concentration of chloride ions (Figure 3D). The MCPA was found as a sodium adduct (Figure 3F), mainly in the outer parts of stem’s cross section. The calculated/experimental m/z difference (m/z experimental value originating directly from imaging data) for the [MCPA + Na]+ adduct was 0.0028. Other examples of ions found are robustaquinone G in the form of a sodium adduct (Figure 3C), a metabolite of the herbicide 5-methylthiopentanaldoxime K as

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CONCLUSION

We have shown mass spectrometry imaging as a methodology applicable to a wide range of objects. The examples shown contain the results of analysis of fingermarks with various exoand endogenous compounds, including two drugs of different polarity. The methodology shown could be used in forensic science for the localization of a fingermark’s physical and chemical information. It was also shown that a fingermark may be also lifted from a glass surface and transferred onto 109 AgNPET for analysis. Other imaging experiments allowed analysis of plant flower and also plant stem containing herbicide. Mass accuracy obtained directly from reduced, low resolution imaging data is comparable with high-resolution mass spectrometry results. The applied methods do not require freezing and slicing equipment. 12075

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(25) Alberici, R. M.; Simas, R. C.; Sanvido, G. B.; Romão, W.; Lalli, P. M.; Benassi, M.; Cunha, I. B. S.; Eberlin, M. N. Anal. Bioanal. Chem. 2010, 398, 265−294. (26) Lietz, C. B.; Gemperline, E.; Li, L. Adv. Drug Delivery Rev. 2013, 65, 1074−1085. (27) Chughtai, K.; Heeren, R. M. A. Chem. Rev. 2010, 110, 3237− 3277. (28) Francese, S.; Bradshaw, R.; L. Ferguson, S.; Wolstenholme, R.; Clench, M. R.; Bleay, S. Analyst 2013, 138, 4215−4228. (29) Kaspar, S.; Peukert, M.; Svatos, A.; Matros, A.; Mock, H.-P. Proteomics 2011, 11, 1840−1850. (30) Nizioł, J.; Ruman, T. Int. J. Chem. Eng. Appl. 2013, 2, 46−49. (31) Nizioł, J.; Zielinśki, Z.; Rode, W.; Ruman, T. Int. J. Mass Spectrom. 2013, 335, 22−32. (32) Thunig, J.; Hansen, S. H.; Janfelt, C. Anal. Chem. 2011, 83, 3256−3259. (33) Müller, T.; Oradu, S.; Ifa, D. R.; Cooks, G. R.; Kraütler, B. Anal. Chem. 2011, 83, 5754−5761. (34) USEPA (U.S. Environmental Protection Agency). Drinking water health advisory: Pesticides. USEPA, Office of Drinking Water Health Advisories: Washington, DC, 1989.

ASSOCIATED CONTENT

S Supporting Information *

Additional information as noted in the text. Full-resolution images from Figures (S2−S39). This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest

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ACKNOWLEDGMENTS Supported by the Ministry of Education and Science, Poland, Grant No. N N204 226940. We also thank German and Polish Bruker-Daltonics for FlexImaging 4.0.

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REFERENCES

(1) Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida, Y.; Yoshida, T. Rapid Commun. Mass Spectrom. 1988, 2, 151−153. (2) Hatsis, P.; Brombacher, S.; Corr, J.; Kovarik, P.; Volmer, D. A. Rapid Commun. Mass Spectrom. 2003, 17, 2303−2309. (3) Kang, M.-J.; Tholey, A.; Heinzle, E. Rapid Commun. Mass Spectrom. 2000, 14, 1972−1978. (4) Sunner, J.; Dratz, E.; Chen, Y. C. Anal. Chem. 1995, 67, 4335− 4342. (5) Law, K. P.; Larkin, J. R. Anal. Bioanal. Chem. 2011, 399, 2597− 622. (6) Black, C.; Poile, C.; Langley, J.; Herniman, J. Rapid Commun. Mass Spectrom. 2006, 20, 1053−1060. (7) Xu, S. Y.; Li, Y. F.; Zou, H. F.; Qiu, J. S.; Guo, Z.; Guo, B. C. Anal. Chem. 2003, 75, 6191−6195. (8) Chen, Y. C.; Shiea, J.; Sunner, J. J. Chromatogr., A 1998, 826, 77− 86. (9) Tang, H.-W.; Ng, K.-M.; Lu, W.; Che, C.-M. Anal. Chem. 2009, 81, 4720−4729. (10) Dong, X.; Cheng, J.; Li, J.; Wang, Y. Anal. Chem. 2010, 82, 6208−6214. (11) Nizioł, J.; Rode, W.; Laskowska, B.; Ruman, T. Anal. Chem. 2013, 85, 1926−1931. (12) Liebl, H. J. Appl. Phys. 1967, 38, 5277−5283. (13) Spengler, B.; Hubert, M.; Kaufmann, R. Proceedings of the 42nd Annual Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 29−June 3, 1994; American Society for Mass Spectrometry: Santa Fe, NM, 1994; p 1041. (14) Caprioli, R. M.; Farmer, T. B.; Gile, J. Anal. Chem. 1997, 69, 4751−4760. (15) Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. Science 2004, 306, 471−473. (16) Wiseman, J. M.; Ifa, D. R.; Song, Q. Y.; Cooks, R. G. Angew. Chem., Int. Ed. 2006, 45, 7188−7192. (17) Shiea, J.; Huang, M. Z.; Hsu, H. J.; Lee, C. Y.; Yuan, C. H.; Beech, I.; Sunner, J. Rapid Commun. Mass Spectrom. 2005, 19, 3701− 3704. (18) Nemes, P.; Vertes, A. Anal. Chem. 2007, 79, 8098−8106. (19) Nemes, P.; Barton, A. A.; Li, Y.; Vertes, A. Anal. Chem. 2008, 80, 4575−4582. (20) Nemes, P.; Barton, A. A.; Vertes, A. Anal. Chem. 2009, 81, 6668−6675. (21) Pol, J.; Vidova, V.; Kruppa, G.; Kobliha, V.; Novak, P.; Lemr, K.; Kotiaho, T.; Kostiainen, R.; Havlicek, V.; Volny, M. Anal. Chem. 2009, 81, 8479−8487. (22) Rubakhin, S. S.; Jurchen, J. C.; Monroe, E. B.; Sweedler, J. V. Drug Discovery Today 2005, 10, 823−837. (23) Norris, J. L.; Caprioli, R. M. Chem. Rev. 2013, 113, 2309−2342. (24) Sun, N.; Walch, A. Histochem. Cell Biol. 2013, 140, 93−104. 12076

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