Tip-Enhanced Laser Ablation Sample Transfer for Biomolecule Mass Spectrometry

  • Suman Ghorai
  • Chinthaka A. Seneviratne
  • Kermit K. Murray
Research Article


Atomic force microscope (AFM) tip-enhanced laser ablation was used to transfer molecules from thin films to a suspended silver wire for off-line mass spectrometry using laser desorption ionization (LDI) and matrix-assisted laser desorption ionization (MALDI). An AFM with a 30 nm radius gold-coated silicon tip was used to image the sample and to hold the tip 15 nm from the surface for material removal using a 355 nm Nd:YAG laser. The ablated material was captured on a silver wire that was held 300 μm vertically and 100 μm horizontally from the tip. For the small molecules anthracene and rhodamine 6G, the wire was cut and affixed to a metal target using double-sided conductive tape and analyzed by LDI using a commercial laser desorption time-of-flight mass spectrometer. Approximately 100 fg of material was ablated from each of the 1 μm ablation spots and transferred with approximately 3% efficiency. For larger polypeptide molecules angiotensin II and bovine insulin, the captured material was dissolved in saturated matrix solution and deposited on a target for MALDI analysis.

Graphical Abstract


Ambient Laser ablation Atomic force microscope Matrix-assisted laser desorption/ionization 



This work was supported by the National Institutes of Health Grant Number R21DA035504. The authors are grateful to R. Shetty and K. Kjoller (Anasys) for helpful discussions.


  1. 1.
    McDonnell, L., Heeren, R.M.: Imaging mass spectrometry. Mass Spectrom. Rev. 26, 606–643 (2007)CrossRefGoogle Scholar
  2. 2.
    Chughtai, K., Heeren, R.M.: Mass spectrometric imaging for biomedical tissue analysis. Chem. Rev. 110, 3237–3277 (2010)CrossRefGoogle Scholar
  3. 3.
    Wu, B., Becker, J.S.: Imaging of elements and molecules in biological tissues and cells in the low-micrometer and nanometer range. Int. J. Mass Spectrom. 307, 112–122 (2011)CrossRefGoogle Scholar
  4. 4.
    Bich, C., Touboul, D., Brunelle, A.: Cluster TOF-SIMS imaging as a tool for micrometric histology of lipids in tissue. Mass Spectrom. Rev. (2013). doi: 10.1002/mas.21399 Google Scholar
  5. 5.
    Norris, J.L., Caprioli, R.M.: Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem. Rev. 113, 2309–2342 (2013)CrossRefGoogle Scholar
  6. 6.
    Becker, J.S.: Imaging of metals in biological tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS): state of the art and future developments. J. Mass Spectrom. 48, 255–268 (2013)CrossRefGoogle Scholar
  7. 7.
    Russo, R.E., Mao, X., Gonzalez, J.J., Zorba, V., Yoo, J.: Laser ablation in analytical chemistry. Anal. Chem. 85, 6162–6177 (2013)CrossRefGoogle Scholar
  8. 8.
    Passarelli, M.K., Ewing, A.G.: Single-cell imaging mass spectrometry. Curr. Opin. Chem. Biol. 17, 854–859 (2013)CrossRefGoogle Scholar
  9. 9.
    Caprioli, R.M., Farmer, T., Gile, J.: Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal. Chem. 69, 4751–4760 (1997)CrossRefGoogle Scholar
  10. 10.
    Masujima, T.: Live single-cell mass spectrometry. Anal. Sci. 25, 953–960 (2009)CrossRefGoogle Scholar
  11. 11.
    Walch, A., Rauser, S., Deininger, S., Höfler, H.: MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology. Histochem. Cell Biol. 130, 421–434 (2008)CrossRefGoogle Scholar
  12. 12.
    Spraggins, J.M., Caprioli, R.M.: High-speed MALDI-TOF imaging mass spectrometry: rapid ion image acquisition and considerations for next generation instrumentation. J. Am. Soc. Mass Spectrom. 22, 1022–1031 (2011)CrossRefGoogle Scholar
  13. 13.
    Spengler, B., Hubert, M.: Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: instrumentation for sub-micrometer resolved LDI and MALDI surface analysis. J. Am. Soc. Mass Spectrom. 13, 735–748 (2002)CrossRefGoogle Scholar
  14. 14.
    Koestler, M., Kirsch, D., Hester, A., Leisner, A., Guenther, S., Spengler, B.: A high-resolution scanning microprobe matrix-assisted laser desorption/ionization ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron resonance mass spectrometer. Rapid Commun. Mass Spectrom. 22, 3275–3285 (2008)CrossRefGoogle Scholar
  15. 15.
    Zavalin, A., Yang, J., Caprioli, R.: Laser Beam filtration for high spatial resolution MALDI imaging mass spectrometry. J. Am. Soc. Mass Spectrom. 24, 1153–1156 (2013)CrossRefGoogle Scholar
  16. 16.
    Zavalin, A., Yang, J., Haase, A., Holle, A., Caprioli, R.: Implementation of a Gaussian beam laser and aspheric optics for high spatial resolution MALDI imaging MS. J. Am. Soc. Mass Spectrom. 25, 1079–1082 (2014)CrossRefGoogle Scholar
  17. 17.
    Rubakhin, S.S., Sweedler, J.V.: A mass spectrometry primer for mass spectrometry imaging. Methods Mol. Biol. 656, 21–49 (2010)CrossRefGoogle Scholar
  18. 18.
    Amstalden van Hove, E.R., Smith, D.F., Heeren, R.M.: A concise review of mass spectrometry imaging. J. Chromatogr. A 1217, 3946–3954 (2010)CrossRefGoogle Scholar
  19. 19.
    Moore, K.L., Lombi, E., Zhao, F.-J., Grovenor, C.R.M.: Elemental imaging at the nanoscale: NanoSIMS and complementary techniques for element localisation in plants. Anal. Bioanal. Chem. 402, 3263–3273 (2012)CrossRefGoogle Scholar
  20. 20.
    Passarelli, M.K., Ewing, A.G., Winograd, N.: Single-cell lipidomics: characterizing and imaging lipids on the surface of individual Aplysia californica neurons with cluster secondary ion mass spectrometry. Anal. Chem. 85, 2231–2238 (2013)CrossRefGoogle Scholar
  21. 21.
    Novotny, L.: The history of near-field optics. Prog. Opt. 50, 137–184 (2007)CrossRefGoogle Scholar
  22. 22.
    Stockle, R., Setz, P., Deckert, V., Lippert, T., Wokaun, A., Zenobi, R.: Nanoscale atmospheric pressure laser ablation-mass spectrometry. Anal. Chem. 73, 1399–1402 (2001)CrossRefGoogle Scholar
  23. 23.
    Zhu, L., Stadler, J., Schmitz, T.A., Krumeich, F., Zenobi, R.: Atmospheric pressure sampling for laser ablation based nanoscale imaging mass spectrometry: ions or neutrals? J. Phys. Chem. C 115, 1006–1013 (2011)CrossRefGoogle Scholar
  24. 24.
    Schmitz, T.A., Gamez, G., Setz, P.D., Zhu, L., Zenobi, R.: Towards nanoscale molecular analysis at atmospheric pressure by a near-field laser ablation ion trap/time-of-flight mass spectrometer. Anal. Chem. 80, 6537–6544 (2008)CrossRefGoogle Scholar
  25. 25.
    Zhu, L., Gamez, G., Schmitz, T., Krumeich, F., Zenobi, R.: Material ejection and redeposition following atmospheric pressure near-field laser ablation on molecular solids. Anal. Bioanal. Chem. 396, 163–172 (2010)CrossRefGoogle Scholar
  26. 26.
    Hwang, D.J., Grigoropoulos, C.P., Yoo, J., Russo, R.E.: Optical near-field ablation-induced plasma characteristics. Appl. Phys. Lett. 89, 254101 (2006)CrossRefGoogle Scholar
  27. 27.
    Novotny, L., Stranick, S.J.: Near-field optical microscopy and spectroscopy with pointed probes. Annu. Rev. Phys. Chem. 57, 303–331 (2006)CrossRefGoogle Scholar
  28. 28.
    Zoriy, M.V., Becker, J.S.: Near-field laser ablation inductively coupled plasma mass spectrometry: a novel elemental analytical technique at the nanometer scale. Rapid Commun. Mass Spectrom. 23, 23–30 (2009)CrossRefGoogle Scholar
  29. 29.
    Bradshaw, J.A., Ovchinnikova, O.S., Meyer, K.A., Goeringer, D.E.: Combined chemical and topographic imaging at atmospheric pressure via microprobe laser desorption/ionization mass spectrometry-atomic force microscopy. Rapid Commun. Mass Spectrom. 23, 3781–3786 (2009)CrossRefGoogle Scholar
  30. 30.
    Shiea, J., Huang, M., Hsu, H., Lee, C., Yuan, C., Beech, I., Sunner, J.: Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids. Rapid Commun. Mass Spectrom. 19, 3701–3704 (2005)CrossRefGoogle Scholar
  31. 31.
    Dill, A.L., Eberlin, L.S., Ifa, D.R., Cooks, R.G.: Perspectives in imaging using mass spectrometry. Chem. Commun. 47, 2741–2746 (2011)CrossRefGoogle Scholar
  32. 32.
    Yao, Z.-P.: Characterization of proteins by ambient mass spectrometry. Mass Spectrom. Rev. 31, 437–447 (2012)Google Scholar
  33. 33.
    Shrestha, B., Vertes, A.: In situ metabolic profiling of single cells by laser ablation electrospray ionization mass spectrometry. Anal. Chem. 81, 8265–8271 (2009)CrossRefGoogle Scholar
  34. 34.
    Huang, M., Jhang, S., Cheng, C., Cheng, S., Shiea, J.: Effects of matrix, electrospray solution, and laser light on the desorption and ionization mechanisms in electrospray-assisted laser desorption ionization mass spectrometry. Analyst 135, 759–766 (2010)CrossRefGoogle Scholar
  35. 35.
    Ovchinnikova, O.S., Kertesz, V., Van Berkel, G.J.: Combining laser ablation/liquid phase collection surface sampling and high-performance liquid chromatography-electrospray ionization-mass spectrometry. Anal. Chem. 83, 1874–1878 (2011)CrossRefGoogle Scholar
  36. 36.
    Park, S.-G., Murray, K.K.: Infrared laser ablation sample transfer for MALDI and electrospray. J. Am. Soc. Mass Spectrom. 22, 1352–1362 (2011)CrossRefGoogle Scholar
  37. 37.
    Park, S.G., Murray, K.K.: Infrared laser ablation sample transfer for MALDI imaging. Anal. Chem. 84, 3240–3245 (2012)CrossRefGoogle Scholar
  38. 38.
    Saito, Y., Hayazawa, N., Kataura, H., Murakami, T., Tsukagoshi, K., Inouye, Y., Kawata, S.: Polarization measurements in tip-enhanced Raman spectroscopy applied to single-walled carbon nanotubes. Chem. Phys. Lett. 410, 136–141 (2005)CrossRefGoogle Scholar
  39. 39.
    Jin, R., Cao, Y.W., Mirkin, C.A., Kelly, K.L., Schatz, G.C.: Photoinduced conversion of silver nanospheres to nanoprisms. Science 294, 1901–1903 (2001)CrossRefGoogle Scholar
  40. 40.
    Sherry, L.J., Jin, R., Mirkin, C.A., Schatz, G.C., Van Duyne, R.P.: Localized surface plasmon resonance spectroscopy of single silver triangular nanoprisms. Nano Lett. 6, 2060–2065 (2006)CrossRefGoogle Scholar
  41. 41.
    Dickreuter, S., Gleixner, J., Kolloch, A., Boneberg, J., Scheer, E., Leiderer, P.: Mapping of plasmonic resonances in nanotriangles. Beilstein J. Nanotechnol. 4, 588–602 (2013)CrossRefGoogle Scholar
  42. 42.
    Grześkiewicz, B., Ptaszyński, K., Kotkowiak, M.: Near- and far-field properties of nanoprisms with rounded edges. Plasmonics 9, 607–614 (2014)CrossRefGoogle Scholar
  43. 43.
    Perdian, D.C., Cha, S., Oh, J., Sakaguchi, D.S., Yeung, E.S., Lee, Y.J.: In-situ probing of cholesterol in astrocytes at the single-cell level using laser desorption ionization mass spectrometric imaging with colloidal silver. Rapid Commun. Mass Spectrom. 24, 1147–1154 (2010)CrossRefGoogle Scholar
  44. 44.
    Cha, S.W., Song, Z.H., Nikolau, B.J., Yeung, E.S.: Direct profiling and imaging of epicuticular waxes on Arabidopsis thaliana by laser desorption/ionization mass spectrometry using silver colloid as a matrix. Anal. Chem. 81, 2991–3000 (2009)CrossRefGoogle Scholar
  45. 45.
    Sun, Z., Findsen, E.W., Isailovic, D.: Atmospheric pressure visible-wavelength MALDI-MS. Int. J. Mass Spectrom. 315, 66–73 (2012)CrossRefGoogle Scholar
  46. 46.
    Cheng, S.C., Huang, M.Z., Wu, L.C., Chou, C.C., Cheng, C.N., Jhang, S.S., Shiea, J.: Building blocks for the development of an interface for high-throughput thin layer chromatography/ambient mass spectrometric analysis: a green methodology. Anal. Chem. 84, 5864–5868 (2012)CrossRefGoogle Scholar
  47. 47.
    Park, S.-G., Murray, K.K.: Infrared laser ablation sample transfer for on-line liquid chromatography electrospray ionization mass spectrometry. J. Mass Spectrom. 47, 1322–1326 (2012)CrossRefGoogle Scholar
  48. 48.
    Cleveland, D., Michel, R.G.: A review of near‐field laser ablation for high‐resolution nanoscale surface analysis. Appl. Spectrosc. Rev. 43, 93–110 (2008)CrossRefGoogle Scholar
  49. 49.
    Little, M.W., Laboy, J., Murray, K.K.: Wavelength dependence of soft infrared laser desorption and ionization. J. Phys. Chem. C 111, 1412–1416 (2007)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2014

Authors and Affiliations

  • Suman Ghorai
    • 1
  • Chinthaka A. Seneviratne
    • 1
  • Kermit K. Murray
    • 1
  1. 1.Department of ChemistryLouisiana State UniversityBaton RougeUSA

Personalised recommendations