Analytical and Bioanalytical Chemistry

, Volume 404, Issue 2, pp 389–398 | Cite as

Improved spatial resolution in the imaging of biological tissue using desorption electrospray ionization

  • Dahlia I. Campbell
  • Christina R. Ferreira
  • Livia S. Eberlin
  • R. Graham Cooks
Original Paper


Desorption electrospray ionization imaging allows biomarker discovery and disease diagnosis through chemical characterization of biological samples in their native environment. Optimization of experimental parameters including emitter capillary size, solvent composition, solvent flow rate, mass spectrometry scan-rate and step-size is shown here to improve the resolution available in the study of biological tissue from 180 μm to about 35 μm using an unmodified commercial mass spectrometer. Mouse brain tissue was used to optimize and measure resolution based on known morphological features and their known relationships to major phospholipid components. Features of approximately 35 μm were resolved and correlations drawn between features in grey matter (principally PS (18:0/22:6), m/z 834) and in white matter (principally ST (24:1), m/z 888). The improved spatial resolution allowed characterization of the temporal changes in lipid profiles occurring within mouse ovaries during the ovulatory cycle. An increase in the production of phosphatidylinositol (PI 38:4) m/z 885 and associated fatty acids such as arachidonic acid (FA 20:4) m/z 303 and adrenic acid (FA 22:4) m/z 331was seen with the postovulatory formation of the corpus luteum.


Ambient ionization Tissue imaging Electrospray ionization Imaging mass spectrometry High-resolution imaging Morphologically friendly solvents Histology Ovulation Corpus luteum 



This work was funded by the National Science Foundation (CHE NSF 0848650).

Supplementary material

216_2012_6173_MOESM1_ESM.pdf (858 kb)
ESM 1 (PDF 858 kb)


  1. 1.
    Seeley EH, Schwamborn K, Caprioli RM (2011) Imaging of intact tissue sections: moving beyond the microscope. J Biol Chem 286:25459–25466CrossRefGoogle Scholar
  2. 2.
    Rompp A, Guenther S, Schober Y, Schulz O, Takats Z, Kummer W, Spengler B (2010) Histology by mass spectrometry: label-free tissue characterization obtained from high-accuracy bioanalytical imaging. Angew Chem Int Ed 49:3834–3838CrossRefGoogle Scholar
  3. 3.
    Passarelli MK, Winograd N (2011) Lipid imaging with time-of-flight secondary ion mass spectrometry (ToF-SIMS). Biochim Biophys Acta 1811:976–990CrossRefGoogle Scholar
  4. 4.
    Harris GA, Galhena AS, Fernandez FM (2011) Ambient sampling/ionization mass spectrometry: applications and current trends. Anal Chem 83:4508–4538CrossRefGoogle Scholar
  5. 5.
    Ovchinnikova OS, Kertesz V, Van Berkel GJ (2011) Molecular surface sampling and chemical imaging using proximal probe thermal desorption/secondary ionization mass spectrometry. Anal Chem 83:598–603CrossRefGoogle Scholar
  6. 6.
    Nemes P, Woods AS, Vertes A (2010) Simultaneous imaging of small metabolites and lipids in rat brain tissues at atmospheric pressure by laser ablation electrospray ionization mass spectrometry. Anal Chem 82:982–988CrossRefGoogle Scholar
  7. 7.
    Lalli PM, Sanvido GB, Garcia JS, Haddad R, Cosso GR, Maia DRJ, Zacca JJ, Maldanerc AO, Eberlin MN (2010) Fingerprinting and aging of ink by easy ambient sonic-spray ionization mass spectrometry. Analyst 135:745–750CrossRefGoogle Scholar
  8. 8.
    Laskin J, Heath BS, Roach PJ, Cazares L, Semmes OJ (2012) Tissue imaging using nanospray desorption electrospray ionization mass spectrometry. Anal Chem 84:141–148CrossRefGoogle Scholar
  9. 9.
    Huang M, Cheng S, Cho Y, Shiea J (2011) Ambient ionization mass spectrometry: a tutorial. Anal Chim Acta 702:1–15CrossRefGoogle Scholar
  10. 10.
    Weston DJ (2010) Ambient ionization mass spectrometry: current understanding of mechanistic theory; analytical performance and application areas. Analyst 1359:661–668CrossRefGoogle Scholar
  11. 11.
    Chen H, Hu B, Zhang X (2010) Principle and application of ambient mass spectrometry for direct analysis of complex samples. Chin J Anal Chem 38:1069–1088CrossRefGoogle Scholar
  12. 12.
    Ifa DR, Wu C, Ouyang Z, Cooks RG (2010) Desorption electrospray ionization and other ambient ionization methods: current progress and preview. Analyst 135:669–681CrossRefGoogle Scholar
  13. 13.
    Alberici RM, Simas RC, Sanvido GB, Romao W, Lalli PM, Benassi M, Cunha IBS, Eberlin MN (2010) Ambient mass spectrometry: bringing MS into the “real world”. Anal Bioanal Chem 398:265–294CrossRefGoogle Scholar
  14. 14.
    Huang M, Yuan C, Cheng S, Cho Y, Shiea J (2010) Ambient ionization mass spectrometry. Annu Rev Anal Chem 3:43–65CrossRefGoogle Scholar
  15. 15.
    Harris GA, Nyadong L, Fernandez FM (2008) Recent developments in ambient ionization techniques for analytical mass spectrometry. Analyst 133:1297–130CrossRefGoogle Scholar
  16. 16.
    Van Berkel GJ, Pasilis SP, Ovchinnikova O (2008) Established and emerging atmospheric pressure surface sampling/ionization techniques for mass spectrometry. J Mass Spectrom 43:1161–1180CrossRefGoogle Scholar
  17. 17.
    Cooks RG, Ouyang Z, Takats Z, Wiseman JM (2006) Ambient mass spectrometry. Science 311:1566–1570CrossRefGoogle Scholar
  18. 18.
    Takats Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473CrossRefGoogle Scholar
  19. 19.
    Ifa DR, Wiseman JM, Song Q, Cooks RG (2007) Development of capabilities for imaging mass spectrometry under ambient conditions with desorption electrospray ionization (DESI). Int J Mass Spectrom 259:8–15CrossRefGoogle Scholar
  20. 20.
    Takats Z, Wiseman JM, Cooks RG (2005) Ambient mass spectrometry using desorption electrospray ionization (DESI): instrumentation, mechanisms and applications in forensics, chemistry, and biology. J Mass Spectrom 40:1261–1275CrossRefGoogle Scholar
  21. 21.
    Chen H, Talaty NN, Takats Z, Cooks RG (2005) Desorption electrospray ionization mass spectrometry for high-throughput analysis of pharmaceutical samples in the ambient environment. Anal Chem 77:6915–6927CrossRefGoogle Scholar
  22. 22.
    Williams JP, Scrivens JH (2005) Rapid accurate mass desorption electrospray ionization tandem mass spectrometry of pharmaceutical samples. Rapid Commun Mass Spectrom 19:3643–3650CrossRefGoogle Scholar
  23. 23.
    Rodriguez-Cruz SE (2006) Rapid analysis of controlled substances using desorption electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 20:53–60CrossRefGoogle Scholar
  24. 24.
    Leuthold LA, Mandscheff JF, Fathi M, Giroud C, Augsburger M, Varesio E, Hopfgartner G (2006) Desorption electrospray ionization mass spectrometry: direct toxicological screening and analysis of illicit ecstasy tablets. Rapid Commun Mass Spectrom 20:103–110CrossRefGoogle Scholar
  25. 25.
    Kauppila TJ, Wiseman JM, Ketola RA, Kotiaho T, Cooks RG, Kostiainen R (2006) Desorption electrospray ionization mass spectrometry for the analysis of pharmaceuticals and metabolites. Rapid Commun Mass Spectrom 20:387–392CrossRefGoogle Scholar
  26. 26.
    Weston DJ, Bateman R, Wilson ID, Wood TR, Creaser CS (2005) Direct analysis of pharmaceutical drug formulations using ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry combined with desorption electrospray ionization. Anal Chem 77:7572–7580CrossRefGoogle Scholar
  27. 27.
    Wiseman JM, Puolitaival SM, Takats Z, Cooks RG, Caprioli RM (2005) Mass spectrometric profiling of intact biological tissue by using desorption electrospray ionization. Angew Chem Int Ed 44:7094–7097CrossRefGoogle Scholar
  28. 28.
    Talaty N, Takats Z, Cooks RG (2005) Rapid in situ detection of alkaloids in plant tissue under ambient conditions using desorption electrospray ionization. Analyst 130:1624–1633CrossRefGoogle Scholar
  29. 29.
    Van Berkel GJ, Ford MJ, Deibel MA (2005) Thin-layer chromatography and mass spectrometry coupled using desorption electrospray ionization. Anal Chem 77:1207–1215CrossRefGoogle Scholar
  30. 30.
    Van Berkel GJ, Tomkins BA, Kertesz V (2007) Thin-layer chromatography/desorption electrospray ionization mass spectrometry: investigation of goldenseal alkaloids. Anal Chem 79:2778–2789CrossRefGoogle Scholar
  31. 31.
    Bereman MS, Nyadong L, Fernandez FM, Muddiman DC (2006) Direct high-resolution peptide and protein analysis by desorption electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. Rapid Commun Mass Spectrom 20:3409–3411CrossRefGoogle Scholar
  32. 32.
    Ricci C, Nyadong L, Fernandez FM, Newton PN, Kazarian SG (2007) Combined Fourier-transform infrared imaging and desorption electrospray-ionization linear ion-trap mass spectrometry for analysis of counterfeit antimalarial tablets. Anal Bioanal Chem 387:551–559CrossRefGoogle Scholar
  33. 33.
    Nyadong L, Green MD, De Jesus VR, Newton PN, Fernandez FM (2007) Reactive desorption electrospray ionization linear ion trap mass spectrometry of latest-generation counterfeit antimalarials via noncovalent complex formation. Anal Chem 79:2150–2157CrossRefGoogle Scholar
  34. 34.
    Kertesz V, Van Berkel GJ, Vavrek M, Koeplinger KA, Schneider BB, Covey TR (2008) Comparison of drug distribution images from whole-body thin tissue sections obtained using desorption electrospray ionization tandem mass spectrometry and autoradiography. Anal Chem 80:5168–5177CrossRefGoogle Scholar
  35. 35.
    Girod M, Shi Y, Cheng JX, Cooks RG (2011) Mapping lipid alterations in traumatically injured rat spinal cord by desorption electrospray ionization imaging mass spectrometry. Anal Chem 83:207–215CrossRefGoogle Scholar
  36. 36.
    Muller T, Oradu S, Ifa DR, Cooks RG, Krautler B (2011) Direct plant tissue analysis and imprint imaging by desorption electrospray ionization mass spectrometry. Anal Chem 83:5754–5761CrossRefGoogle Scholar
  37. 37.
    Wu C, Ifa DR, Manicke NE, Cooks RG (2009) Rapid, direct analysis of cholesterol by charge labeling in reactive desorption electrospray Ionization. Anal Chem 81:7618–7624CrossRefGoogle Scholar
  38. 38.
    Kertesz V, Van Berkel GJ (2008) Improved imaging resolution in desorption electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 22:2639–2644CrossRefGoogle Scholar
  39. 39.
    Kertesz V, Van Berkel GJ (2008) Scanning and surface alignment considerations in chemical imaging with desorption electrospray mass spectrometry. Anal Chem 80:1027–1032CrossRefGoogle Scholar
  40. 40.
    Wiseman JM, Ifa DR, Venter A, Cooks RG (2008) Ambient molecular imaging by desorption electrospray ionization mass spectrometry. Nat Protoc 3:517–524CrossRefGoogle Scholar
  41. 41.
    Badu-Tawiah A, Bland C, Campbell DI, Cooks RG (2010) Non-aqueous spray solvents and solubility effects in desorption electrospray ionization. J Am Soc Mass Spectrom 219:572–579CrossRefGoogle Scholar
  42. 42.
    Wiseman JM, Li JB (2010) Elution, partial separation, and identification of lipids directly from tissue slices on planar chromatography media by desorption electrospray ionization mass spectrometry. Anal Chem 82:8866–8874CrossRefGoogle Scholar
  43. 43.
    Eberlin LS, Ferreira CR, Dill AL, Ifa DR, Cheng L, Cooks RG (2011) Nondestructive, histologically compatible tissue imaging by desorption electrospray ionization mass spectrometry. ChemBioChem 12:2129–2132CrossRefGoogle Scholar
  44. 44.
    Eberlin LS, Liu X, Ferreira CR, Santagata S, Agar NYR, Cooks RG (2011) Desorption electrospray ionization then MALDI mass spectrometry imaging of lipid and protein distributions in single tissue sections. Anal Chem 83:8366–8371CrossRefGoogle Scholar
  45. 45.
    Kumar GL, Kiernan JA (2010) Special stains and H&E, 2nd edition. Dako, CaliforniaGoogle Scholar
  46. 46.
    Tuckey RC, Lee G, Costa ND, Stevenson PM (1984) The composition and distribution of lipids in the rat ovary. Mol Cell Endocrinol 38:187–195CrossRefGoogle Scholar
  47. 47.
    Neill JD, Plant TM, Pfaff DW, Challis JRG, Kretser DM, Richards JS, Wassarman PM (2006) Knobil and Neill’s physiology of reproduction, 3rd edn. Elsevier Inc, MissouriGoogle Scholar
  48. 48.
    Carricaburv V, Fournier B (2001) Phosphoinositide fatty acids regulate phosphatidylinositol 5-kinase, phospholipase C and protein kinase C activities. Eur J Biochem 268:238–1249Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Dahlia I. Campbell
    • 1
  • Christina R. Ferreira
    • 1
  • Livia S. Eberlin
    • 1
  • R. Graham Cooks
    • 1
  1. 1.Chemistry DepartmentPurdue UniversityWest LafayetteUSA

Personalised recommendations