Imaging the Unimaginable: Desorption Electrospray Ionization – Imaging Mass Spectrometry (DESI-IMS) in Natural Product Research

Abstract

Imaging mass spectrometry (IMS) has recently established itself in the field of “spatial metabolomics.” Merging the sensitivity and fast screening of high-throughput mass spectrometry with spatial and temporal chemical information, IMS visualizes the production, location, and distribution of metabolites in intact biological models. Since metabolite profiling and morphological features are combined in single images, IMS offers an unmatched chemical detail on complex biological and microbiological systems. Thus, IMS-type “spatial metabolomics” emerges as a powerful and complementary approach to genomics, transcriptomics, and classical metabolomics studies. In this review, we summarize the current state-of-the-art IMS methods with a strong focus on desorption electrospray ionization (DESI)-IMS. DESI-IMS utilizes the original principle of electrospray ionization, but in this case solvent droplets are rastered and desorbed directly on the sample surface. The rapid and minimally destructive DESI-IMS chemical screening is achieved at ambient conditions and enables the accurate view of molecules in tissues at the µm-scale resolution. DESI-IMS analysis does not require complex sample preparation and allows repeated measurements on samples from different biological sources, including microorganisms, plants, and animals. Thanks to its easy workflow and versatility, DESI-IMS has successfully been applied to many different research fields, such as clinical analysis, cancer research, environmental sciences, microbiology, chemical ecology, and drug discovery. Herein we discuss the present applications of DESI-IMS in natural product research.

Key words

DESI-IMS - imaging mass spectrometry - chemical imaging - metabolomics - natural products

• References

• 1 Jarmusch AK, Cooks RG. Emerging capabilities of mass spectrometry for natural products. Nat Prod Rep 2014; 31: 730-738
• 2 Fenn J, Mann M, Meng C, Wong S, Whitehouse C. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989; 246: 64-71
• 3 Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T, Matsuo T. Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 1988; 2: 151-153
• 4 Aksenov AA, da Silva R, Knight R, Lopes NP, Dorrestein PC. Global chemical analysis of biology by mass spectrometry. Nat Rev Chem 2017; 1: 1-20
• 5 Petras D, Jarmusch AK, Dorrestein PC. From single cells to our planet-recent advances in using mass spectrometry for spatially resolved metabolomics. Curr Opin Chem Biol 2017; 36: 24-31
• 6 Chabala JM, Soni KK, Li J, Gavrilov KL, Levi-Setti R. High-resolution chemical imaging with scanning ion probe SIMS. Int J Mass Spectrom Ion Process 1995; 143: 191-212
• 7 Chaurand P, Schwartz SA, Billheimer D, Xu BJ, Crecelius A, Caprioli RM. Integrating histology and imaging mass spectrometry. Anal Chem 2004; 76: 1145-1155
• 8 Caprioli RM, Farmer TB, Gile J. Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 1997; 69: 4751-4760
• 9 Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM. Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 2001; 7: 493-496
• 10 Masumori N, Thomas TZ, Chaurand P, Case T, Paul M, Kasper S, Caprioli RM, Tsukamoto T, Shappell SB, Matusik RJ. A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Cancer Res 2001; 61: 2239-2249
• 11 Caldwell RL, Caprioli RM. Tissue profiling by mass spectrometry. Mol Cell Proteomics 2005; 4: 394-401
• 12 Dunham SJB, Ellis JF, Li B, Sweedler JV. Mass spectrometry imaging of complex microbial communities. Acc Chem Res 2016; 50: 96-104
• 13 Esquenazi E, Dorrestein PC, Gerwick WH. Probing marine natural product defenses with DESI-imaging mass spectrometry. Proc Natl Acad Sci 2009; 106: 7269-7270
• 14 Li LP, Feng BS, Yang JW, Chang CL, Bai Y, Liu HW. Applications of ambient mass spectrometry in high-throughput screening. Analyst 2013; 138: 3097-3103
• 15 McDonnell AL, Heeren RM. Imaging mass spectrometry. Mass Spectrom Rev 2007; 26: 606-643
• 16 Ho YN, Shu LJ, Yang YL. Imaging mass spectrometry for metabolites: technical progress, multimodal imaging, and biological interactions. Wiley Interdiscip Rev Syst Biol Med 2017; 9: 1-32
• 17 Castaing R, Slodzian G. Microanalyse par émission secondaire. J Microsc (Paris) 1962; 1: 395-410
• 18 Smentkowski VS. Trends in sputtering. Prog Surf Sci 2000; 64: 1-58
• 19 Liebl H. Ion microprobe mass analyzer. J Appl Phys 1967; 38: 5277-5283
• 20 Boxer SG, Kraft ML, Weber PK. Advances in imaging secondary ion mass spectrometry for biological samples. Annu Rev Biophys 2009; 38: 53-74
• 21 Fletcher JS, Vickerman JC. Secondary ion mass spectrometry: characterizing complex samples in two and three dimensions. Anal Chem 2013; 85: 610-639
• 22 Chandra S, Smith DR, Morrison GH. Peer reviewed: a subcellular imaging by dynamic SIMS ion microscopy. Anal Chem 2000; 72: 104A-114A
• 23 Wu K, Jia F, Zheng W, Luo Q, Zhao Y, Wang F. Visualization of metallodrugs in single cells by secondary ion mass spectrometry imaging. JBIC J Biol Inorg Chem 2017; 22: 653-661
• 24 Chandra S, Tjarks W, Lorey DR, Barth RF. Quantitative subcellular imaging of boron compounds in individual mitotic and interphase human glioblastoma cells with imaging secondary ion mass spectrometry (SIMS). J Microsc 2008; 229: 92-103
• 25 Tian H, Six DA, Krucker T, Leeds JA, Winograd N. Subcellular chemical imaging of antibiotics in single bacteria using C60-secondary ion mass spectrometry. Anal Chem 2017; 89: 5050-5057
• 26 Dekas AE, Poretsky RS, Orphan VJ. Deep-sea Archaea fix and share nitrogen in methane-consuming microbial consortia. Science 2009; 326: 422-426
• 27 Lechene CP, Luyten Y, McMahon G, Distel DL. Quantitative imaging of nitrogen fixation by individual bacteria within animal cells. Science 2007; 317: 1563-1566
• 28 Vidal A, Remusat L, Watteau F, Derenne S, Quenea K. Incorporation of 13C labelled shoot residues in Lumbricus terrestris casts: a combination of transmission electron microscopy and nanoscale secondary ion mass spectrometry. Soil Biol Biochem 2016; 93: 8-16
• 29 Karas M, Bachmann D, Bahr U, Hillenkamp F. Matrix-assisted ultraviolet laser desorption of non-volatile compounds. Int J Mass Spectrom Ion Process 1987; 78: 53-68
• 30 Watrous JD, Dorrestein PC. Imaging mass spectrometry in microbiology. Nat Rev Microbiol 2011; 9: 683-694
• 31 Simmons TL, Coates RC, Clark BR, Engene N, Gonzalez D, Esquenazi E, Dorrestein PC, Gerwick WH. Biosynthetic origin of natural products isolated from marine microorganism-invertebrate assemblages. Proc Natl Acad Sci U S A 2008; 105: 4587-4594
• 32 Moree WJ, Yang JY, Zhao X, Liu WT, Aparicio M, Atencio L, Ballesteros J, Sanchez J, Gavilan RG, Gutiarrez M, Dorrestein PC. Imaging mass spectrometry of a coral microbe interaction with fungi. J Chem Ecol 2013; 39: 1045-1054
• 33 Moree WJ, Phelan VV, Wu CH, Bandeira N, Cornett DS, Duggan BM, Dorrestein PC. Interkingdom metabolic transformations captured by microbial imaging mass spectrometry. Proc Natl Acad Sci 2012; 109: 13811-13816
• 34 Li B, Bhandari DR, Römpp A, Spengler B. High-resolution MALDI mass spectrometry imaging of gallotannins and monoterpene glucosides in the root of Paeonia lactiflora . Sci Rep 2016; 6: 36074
• 35 Shiono K, Hashizaki R, Nakanishi T, Sakai T, Yamamoto T, Ogata K, Harada K, Ohtani H, Katano H, Taira S. Multi-imaging of cytokinin and abscisic acid on the roots of rice (Oryza sativa) using matrix-assisted laser desorption/ionization mass spectrometry. J Agric Food Chem 2017; 65: 7624-7628
• 36 Wu W, Liang Z, Zhao Z, Cai Z. Direct analysis of alkaloid profiling in plant tissue by using matrix-assisted laser desorption/ionization mass spectrometry. J Mass Spectrom 2007; 42: 58-69
• 37 Shroff R, Vergara F, Muck A, Svatos A, Gershenzon J. Nonuniform distribution of glucosinolates in Arabidopsis thaliana leaves has important consequences for plant defense. Proc Natl Acad Sci 2008; 105: 6196-6201
• 38 Anderson DMG, Carolan VA, Crosland S, Sharples KR, Clench MR. Examination of the distribution of nicosulfuron in sunflower plants by matrix-assisted laser desorption/ionisation mass spectrometry imaging. Rapid Commun Mass Spectrom 2009; 23: 1321-1327
• 39 Li B, Bhandari DR, Janfelt C, Römpp A, Spengler B. Natural products in Glycyrrhiza glabra (licorice) rhizome imaged at the cellular level by atmospheric pressure matrixassisted laser desorption/ionization tandem mass spectrometry imaging. Plant J 2014; 80: 161-171
• 40 Gonzalez DJ, Haste NM, Hollands A, Fleming TC, Hamby M, Pogliano K, Nizet V, Dorrestein PC. Microbial competition between Bacillus subtilis and Staphylococcus aureus monitored by imaging mass spectrometry. Microbiology 2011; 157: 2485-2492
• 41 Yang YL, Xu Y, Straight P, Dorrestein PC. Translating metabolic exchange with imaging mass spectrometry. Nat Chem Biol 2009; 5: 885-887
• 42 Esquenazi E, Coates C, Simmons L, Gonzalez D, Gerwick WH, Dorrestein PC. Visualizing the spatial distribution of secondary metabolites produced by marine cyanobacteria and sponges via MALDI-TOF imaging. Mol Biosyst 2008; 4: 562-570
• 43 Genji T, Fukuzawa S, Tachibana K. Distribution and possible function of the marine alkaloid, norzoanthamine, in the zoanthid Zoanthus sp. using MALDI imaging mass spectrometry. Mar Biotechnol 2010; 12: 81-87
• 44 Elnaggar MS, Ebada SS, Ashour ML, Ebrahim W, Singab A, Lin W, Liu Z, Proksch P. Two new triterpenoids and a new naphthoquinone derivative isolated from a hard coral-derived fungus Scopulariopsis sp. Fitoterapia 2017; 116: 126-130
• 45 Waters AL, Peraud O, Kasanah N, Sims JW, Kothalawala N, Anderson MA, Abbas SH, Rao KV, Jupally VR, Kelly M, Dass A, Hill RT, Hamann MT. An analysis of the sponge Acanthostrongylophora igens microbiome yields an actinomycete that produces the natural product manzamine A. Front Mar Sci 2014; 1: 1789-1802
• 46 Yarnold JE, Hamilton BR, Welsh DT, Pool GF, Venter DJ, Carroll AR. High resolution spatial mapping of brominated pyrrole-2-aminoimidazole alkaloids distributions in the marine sponge Stylissa flabellata via MALDI-mass spectrometry imaging. Mol Biosyst 2012; 8: 2249-2259
• 47 Nemes P, Vertes A. Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal Chem 2007; 79: 8098-8106
• 48 Nemes P, Vertes A. Laser Ablation Electrospray Ionization Mass Spectrometry: Mechanisms, Configurations and imaging Applications. In: Domin M, Cody R. eds. Ambient Ionization Mass Spectrometry. London: Royal Society of Chemistry; 2014: 348-371
• 49 Bartels B, Kulkarni P, Danz N, Bocker S, Saluz HP, Svatos A. Mapping metabolites from rough terrain: laser ablation electrospray ionization on non-flat samples. RSC Adv 2017; 7: 9045-9050
• 50 Nemes P, Barton AA, Li Y, Vertes A. Ambient molecular imaging and depth profiling of live tissue by infrared laser ablation electrospray ionization mass spectrometry. Anal Chem 2008; 80: 4575-4582
• 51 Dean SN, Walsh C, Goodman H, Van Hoek ML. Analysis of mixed biofilm (Staphylococcus aureus and Pseudomonas aeruginosa) by laser ablation electrospray ionization mass spectrometry. Biofouling 2015; 31: 151-161
• 52 Nemes P, Vertes A. Atmospheric-pressure molecular imaging of biological tissues and biofilms by LAESI mass spectrometry. J Vis Exp 2010; 43: pii:2097 doi:10.3791/2097
• 53 Bartels B, Svatoš A. Spatially resolved in vivo plant metabolomics by laser ablation-based mass spectrometry imaging (MSI) techniques: LDI-MSI and LAESI. Front Plant Sci 2015; 6: 1-7
• 54 Etalo D, de Vos RC, Joosten MH, Hall R. Spatially-resolved plant metabolomics: some potentials and limitations of laser-ablation electrospray ionization (LAESI) mass spectrometry metabolite imaging. Plant Physiol 2015; 169: 1424-1435
• 55 Motley JL, Stamps BW, Mitchell CA, Thompson AT, Cross J, You J, Powell DR, Stevenson BS, Cichewicz RH. Opportunistic sampling of roadkill as an entry point to accessing natural products assembled by bacteria associated with non-anthropoidal mammalian microbiomes. J Nat Prod 2017; 80: 598-608
• 56 Takáts Z. Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 2004; 306: 471-472
• 57 Perez CJ, Tata A, de Campos ML, Peng C, Ifa DR. Monitoring toxic ionic liquids in zebrafish (Danio rerio) with desorption electrospray ionization mass spectrometry imaging (DESI-MSI). J Am Soc Mass Spectr 2017; 28: 1136-1148
• 58 Takáts Z, Wiseman JM, Cooks RG. Ambient mass spectrometry using desorption electrospray ionization (DESI): instrumentation, mechanisms and applications in forensics, chemistry, and biology. J Mass Spectrom 2005; 40: 1261-1275
• 59 Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cooks GR. Desorption electrospray ionization mass spectrometry for lipid characterization and biological tissue imaging. Biochim Biophys Acta 2011; 1811: 946-960
• 60 Wiseman JM, Ifa DR, Zhu Y, Kissinger CB, Manicke NE, Kissinger PT, Cooks RG, Wiseman JM, Ifa DR, Zhu Y, Kissinger CB, Manicke NE, Kissinger PT, Cooks RG. Desorption electrospray ionization mass spectrometry: imaging drugs and metabolites in tissues. Proc Natl Acad Sci U S A 2008; 105: 18120-18125
• 61 Manicke NE, Wiseman JM, Ifa DR, Cooks RG. Desorption electrospray ionization (DESI) mass spectrometry and tandem mass spectrometry (MS/MS) of phospholipids and sphingolipids: ionization, adduct formation, and fragmentation. J Am Soc Mass Spectrom 2008; 19: 531-543
• 62 Harris GA, Nyadong L, Fernandez FM. Recent developments in ambient ionization techniques for analytical mass spectrometry. Analyst 2008; 133: 1297-1301
• 63 Venter A, Sojka PE, Cooks RG. Droplet dynamics and ionization mechanisms in desorption electrospray ionization mass spectrometry. Anal Chem 2006; 78: 8549-8555
• 64 Green FM, Salter TL, Gilmore IS, Stokes P, OʼConnor G. The effect of electrospray solvent composition on desorption electrospray ionisation (DESI) efficiency and spatial resolution. Analyst 2010; 135: 731
• 65 Badu-Tawiah A, Bland C, Campbell DI, Cooks RG. Non-aqueous spray solvents and solubility effects in desorption electrospray ionization. J Am Soc Mass Spectrom 2010; 21: 572-579
• 66 Jackson AU, Talaty N, Cooks RG, Van Berkel GJ. Salt tolerance of desorption electrospray ionization (DESI). J Am Soc Mass Spectrom 2007; 18: 2218-2225
• 67 Collins RT, Jones JJ, Harris MT, Basaran OA. Electrohydrodynamic tip streaming and emission of charged drops from liquid cones. Nat Phys 2008; 4: 149-154
• 68 Sigmund P, Bitensky IS, Jensen J. Molecule and cluster bombardment: energy loss, trajectories, and collision cascades. Nucl Instruments Methods Phys Res Sect B 1996; 112: 1-11
• 69 Kasi SR, Kang H, Sass CS, Rabalais JW. Inelastic processes in low-energy ion-surface collisions. Surf Sci Rep 1989; 10: 1-104
• 70 Cooks RG, Jo SC, Green J. Collisions of organic ions at surfaces. Applied Surface Science 2004; 231: 13-21
• 71 Gologan B, Green JR, Alvarez J, Laskin J, Cooks RG. Ion/surface reactions and ion soft-landing. Phys Chem Chem Phys 2005; 7: 1490-1500
• 72 Costa AB, Graham Cooks R. Simulated splashes: elucidating the mechanism of desorption electrospray ionization mass spectrometry. Chem Phys Lett 2008; 464: 1-8
• 73 Badu-Tawiah AK, Eberlin LS, Ouyang Z, Cooks RG. Chemical aspects of the extractive methods of ambient ionization mass spectrometry. Annu Rev Phys Chem 2013; 64: 481-505
• 74 Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY, Kersten RD, van der Voort M, Pogliano K, Gross H, Raaijmakers JM, Moore BS, Laskin J, Bandeira N, Dorrestein PC. Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci U S A 2012; 109: E1743-E1752
• 75 Lanekoff I, Geydebrekht O, Pinchuk GE, Konopka AE, Laskin J. Spatially resolved analysis of glycolipids and metabolites in living Synechococcus sp. PCC 7002 using nanospray desorption electrospray ionization. Analyst 2013; 138: 1971-1978
• 76 Watrous J, Roach P, Heath B, Alexandrov T, Laskin J, Dorrestein PC. Metabolic profiling directly from the Petri dish using nanospray desorption electrospray ionization imaging mass spectrometry. Anal Chem 2013; 85: 10385-10391
• 77 Wiseman JM, Ifa DR, Venter A, Cooks RG. Ambient molecular imaging by desorption electrospray ionization mass spectrometry. Nat Protoc 2008; 3: 517-524
• 78 Bodzon-Kulakowska A, Drabik A, Ner J, Kotlinska JH, Suder P. Desorption electrospray ionisation (DESI) for beginners – how to adjust settings for tissue imaging. Rapid Commun Mass Spectrom 2014; 28: 1-9
• 79 Tillner J, Wu V, Jones EA, Pringle SD, Karancsi T, Dannhorn A, Veselkov K, McKenzie JS, Takáts Z. Faster, more reproducible DESI-MS for biological tissue imaging. J Am Soc Mass Spectrom 2017; 28: 2090-2098
• 80 Campbell DI, Ferreira CR, Eberlin LS, Cooks RG. Improved spatial resolution in the imaging of biological tissue using desorption electrospray ionization. Anal Bioanal Chem 2012; 404: 389-398
• 81 Thunig J, Hansen SH, Janfelt C. Analysis of secondary plant metabolites by indirect desorption electrospray ionization imaging mass spectrometry. Anal Chem 2011; 83: 3256-3259
• 82 Laskin J, Heath BS, Roach PJ, Cazares L, Semmes OJ. Tissue imaging using nanospray desorption electrospray ionization mass spectrometry. Anal Chem 2012; 84: 141-148
• 83 Schwartz SA, Reyzer ML, Caprioli RM. Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. J Mass Spectrom 2003; 38: 699-708
• 84 Hemalatha RG, Pradeep T. Understanding the molecular signatures in leaves and flowers by desorption electrospray ionization mass spectrometry (DESI MS) imaging. J Agric Food Chem 2013; 61: 7477-7487
• 85 Müller T, Oradu S, Ifa DR, Cooks GR, Kräutler B, Müller T, Oradu S, Ifa DR, Cooks RG, Kräutler B. Direct plant tissue analysis and imprint imaging by desorption electrospray ionization mass spectrometry. Anal Chem 2011; 83: 5754-5761
• 86 Ifa DR, Manicke NE, Rusine AL, Cooks RG. Quantitative analysis of small molecules by desorption electrospray ionization mass spectrometry from polytetrafluoroethylene surfaces. Rapid Commun Mass Spectrom 2008; 22: 503-510
• 87 Li B, Knudsen C, Hansen NK, Jorgensen K, Kannangara R, Bak S, Takos A, Rook F, Hansen SH, Moller BL, Janfelt C, Bjarnholt N. Visualizing metabolite distribution and enzymatic conversion in plant tissues by desorption electrospray ionization mass spectrometry imaging. Plant J 2013; 74: 1059-1071
• 88 Oetjen J, Veselkov K, Watrous J, McKenzie JS, Becker M, Hauberg-Lotte L, Kobarg JH, Strittmatter N, Mróz AK, Hoffmann F, Trede D, Palmer A, Schiffler S, Steinhorst K, Aichler M, Goldin R, Guntinas-Lichius O, von Eggeling F, Thiele H, Maedler K, Walch A, Maass P, Dorrestein PC, Takáts Z, Alexandrov T. Benchmark datasets for 3D MALDI- and DESI-imaging mass spectrometry. Gigascience 2015; 4: 20
• 89 Inglese P, Mckenzie JS, Mroz A, Kinross J, Veselkov K, Holmes E, Takáts Z, Nicholson JK, Glen RC. Deep learning and 3D-DESI imaging reveal the hidden metabolic heterogeneity of cancer. Chem Sci 2017; 8: 3500-3511
• 90 Rübel O, Greiner A, Cholia S, Louie K, Bethel EW, Northen TR, Bowen BP. OpenMSI: a high-performance web-based platform for mass spectrometry imaging. Anal Chem 2013; 85: 10354-10361
• 91 Song Y, Talaty N, Datsenko K, Wanner BL, Cooks RG. In vivo recognition of Bacillus subtilis by desorption electrospray ionization mass spectrometry (DESI-MS). R Soc Chem 2009; 134: 838-841
• 92 Zhang JI, Talaty N, Costa AB, Xia Y, Tao WA, Bell R, Callahan JH, Cooks RG. Rapid direct lipid profiling of bacteria using desorption electrospray ionization mass spectrometry. Int J Mass Spectrom 2011; 301: 37-44
• 93 Angolini CFF, Vendramini PH, Araújo FDS, Araújo WL, Augusti R, Eberlin MN, De Oliveira LG. Direct protocol for ambient mass spectrometry imaging on agar culture. Anal Chem 2015; 87: 6925-6930
• 94 Figueroa M, Jarmusch AK, Raja HA, El-Elimat T, Kavanaugh JS, Horswill AR, Cooks RG, Cech NB, Oberlies NH. Polyhydroxyanthraquinones as quorum sensing inhibitors from the guttates of Penicillium restrictum and their analysis by desorption electrospray ionization mass spectrometry. J Nat Prod 2014; 77: 1351-1358
• 95 Jackson AU, Werner SR, Talaty N, Song Y, Campbell K, Cooks RG, Morgan JA. Targeted metabolomic analysis of Escherichia coli by desorption electrospray ionization and extractive electrospray ionization mass spectrometry. Anal Biochem 2008; 375: 272-281
• 96 Tata A, Perez C, Campos ML, Bayfield MA, Eberlin MN, Ifa DR. Imprint desorption electrospray ionization mass spectrometry imaging for monitoring secondary metabolites production during antagonistic interaction of fungi. Anal Chem 2015; 87: 12298-12305
• 97 Sica VP, Raja HA, El-Elimat T, Oberlies NH. Mass spectrometry imaging of secondary metabolites directly on fungal cultures. RSC Adv 2014; 4: 63221-63227
• 98 Araújo FDS, Vieira RL, Molano EPL, Maximo HJ, Dalio RJD, Vendramini PH, Araújo WL, Eberlin MN. Desorption electrospray ionization mass spectrometry imaging reveals chemical defense of Burkholderia seminalis against cacao pathogens. RSC Adv 2017; 7: 29953-29958
• 99 Watrous J, Hendricks N, Meehan M, Dorrestein PC. Capturing bacterial metabolic exchange using thin film desorption electrospray ionization-imaging mass spectrometry. Anal Chem 2010; 82: 1598-1600
• 100 Tata A, Perez CJ, Hamid TS, Bayfield MA, Ifa DR. Analysis of metabolic changes in plant pathosystems by imprint imaging DESI-MS. J Am Soc Mass Spectrom 2015; 26: 641-648
• 101 Li B, Bjarnholt N, Hansen H, Janfelt C. Characterization of barley leaf tissue using direct and indirect desorption electrospray ionization imaging mass spectrometry. J Mass Spectrom 2011; 46: 1241-1246
• 102 Li B, Hansen SH, Janfelt C. International Journal of Mass Spectrometry direct imaging of plant metabolites in leaves and petals by desorption electrospray ionization mass spectrometry. Int J Mass Spectrom 2013; 348: 15-22
• 103 Cabral EC, Mirabelli MF, Perez CJ, Ifa DR. Blotting assisted by heating and solvent extraction for DESI-MS imaging. J Am Soc Mass Spectrom 2013; 24: 956-965
• 104 Mohana Kumara P, Srimany A, Ravikanth G, Uma Shaanker R, Pradeep T. Ambient ionization mass spectrometry imaging of rohitukine, a chromone anti-cancer alkaloid, during seed development in Dysoxylum binectariferum Hook.f (Meliaceae). Phytochemistry 2015; 116: 104-110
• 105 Lane AL, Nyadong L, Galhena AS, Shearer TL, Stout EP, Parry RM, Kwasnik M, Wang MD, Hay ME, Fernandez FM, Kubanek J. Desorption electrospray ionization mass spectrometry reveals surface-mediated antifungal chemical defense of a tropical seaweed. Proc Natl Acad Sci 2009; 106: 7314-7319
• 106 Andras TD, Alexander TS, Gahlena A, Parry RM, Fernandez FM, Kubanek J, Wang MD, Hay ME. Seaweed allelopathy against coral: surface distribution of a seaweed secondary metabolite by imaging mass spectrometry. J Chem Ecol 2012; 38: 1203-1214
• 107 Eberlin LS, Norton I, Dill AL, Golby AJ, Ligon KL, Santagata S, Cooks RG, Agar NYR. Classifying human brain tumors by lipid imaging with mass spectrometry. Mol Cell Pathobiol 2012; 72: 645-655
• 108 Banerjee S, Zare RN, Tibshirani RJ, Kunder CA, Nolley R, Fan R, Brooks JD, Sonn GA. Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids. PNAS 2017; 114: 3334-3339
• 109 Miyamoto S, Hsu CC, Hamm G, Darshi M, Diamond-Stanic M, Declèves AE, Slater L, Pennathur S, Stauber J, Dorrestein PC, Sharma K. Mass spectrometry imaging reveals elevated glomerular ATP/AMP in diabetes/obesity and identifies sphingomyelin as a possible mediator. EBioMedicine 2016; 7: 121-134
• 110 Naraoka H, Hashiguchi M. In-situ organic compound analysis of the meteorite surface by desorption electrospray ionization coupled with an orbitrap mass spectrometer. In: 79th Annual Meeting of the Meteoritical Society August 7–12, 2016. Meteorit Planet Sci 2016; 51: 6169
• 111 Woolman M, Tata A, Bluemke E, Dara D, Ginsberg HJ, Zarrine-Afsar A. An assessment of the utility of tissue smears in rapid cancer profiling with desorption electrospray ionization mass spectrometry (DESI-MS). J Am Soc Mass Spectrom 2017; 28: 145-153
• 112 Eberlin LS, Norton I, Orringer D, Dunn IF, Liu X, Ide JL, Jarmusch AK, Ligon KL, Jolesz FA, Golby AJ, Santagata S, Agar NYR. Ambient mass spectrometry for the intraoperative molecular diagnosis of human brain tumors. PNAS 2013; 110: 1611-1616
• 113 Woolman M, Tata A, Dara D, Meens J, DʼArcangelo E, Perez C, Prova S, Bluemke E, Ginsberg H, Ifa D, McGuigan A, Ailles L, Zarrine-Afsar A. Rapid determination of tumour stroma ratio in squamous cell carcinomas with desorption electrospray ionization mass spectrometry (DESI-MS): a proof-of-concept demonstration. Analyst 2017; 142: 3250-3260
• 114 Lisboa A, Alves-júnior M, Vilczaki N, Nogueira M, Almeida A, Sussulini A. Lipid mapping by desorption electrospray ionization mass spectrometry in a murine breast DMBA carcinogenesis model. Int J Mass Spectrom 2016; 418: 86-91
• 115 Sans M, Gharpure K, Tibshirani R, Zhang J, Liang L, Liu J, Young JH, Dood RL, Sood AK, Eberlin LS. Metabolic markers and statistical prediction of serous ovarian cancer aggressiveness by ambient ionization mass spectrometry imaging. Cancer Res 2017; 77: 2903-2913
• 116 Cooks RG, Manicke NE, Dill AL, Ifa DR, Eberlin LS, Costa AB, Wang H, Guangming H, Ouyang Z. New ionization methods and miniature mass spectrometers for biomedicine: DESI imaging for cancer diagnostics and paper spray ionization for therapeutic drug monitoring. R Soc Chem 2011; 149: 247-267
• 117 Kauppila TJ, Talaty N, Kuuranne T, Kotiaho T, Cooks RG. Rapid analysis of metabolites and drugs of abuse from urine samples by desorption electrospray ionization-mass spectrometry. Analyst 2007; 132: 868-875
• 118 Zhang J, Feider CL, Nagi C, Yu W, Carter SA, Suliburk J, Cao HST, Eberlin LS. Detection of metastatic breast and thyroid cancer in lymph. J Am Soc Mass Spectrom 2017; 28: 1166-1174
• 119 Ferreira CR, Pirro V, Eberlin LS, Hallett JE, Cooks RG. Developmental phases of individual mouse preimplantation embryos characterized by lipid signatures using desorption electrospray ionization mass spectrometry. Anal Bioanal Chem 2012; 404: 2915-2926
• 120 González-Serrano AF, Pirro V, Ferreira CR, Oliveri P, Eberlin LS, Heinzmann J, Lucas-Hahn A, Niemann H, Cooks RG. Desorption electrospray ionization mass spectrometry reveals lipid metabolism of individual oocytes and embryos. PLoS One 2013; 8: 1-11