Advertisement

MALDI MS Imaging at Acquisition Rates Exceeding 100 Pixels per Second

  • Antonín Bednařík
  • Markéta Machálková
  • Eugene Moskovets
  • Kateřina Coufalíková
  • Pavel Krásenský
  • Pavel Houška
  • Jiří Kroupa
  • Jarmila Navrátilová
  • Jan Šmarda
  • Jan PreislerEmail author
Research Article

Abstract

The practicality of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) applied to molecular imaging of biological tissues is limited by the analysis speed. Typically, a relatively low speed of stop-and-go micromotion of XY stages is considered as a factor substantially reducing the rate with which fresh sample material can be supplied to the laser spot. The sample scan rate in our laboratory-built high-throughput imaging TOF mass spectrometer was significantly improved through the use of a galvanometer-based optical scanner performing fast laser spot repositioning on a target plate. The optical system incorporated into the ion source of our MALDI TOF mass spectrometer allowed focusing the laser beam via a modified grid into a 10-μm round spot. This permitted the acquisition of high-resolution MS images with a well-defined pixel size at acquisition rates exceeding 100 pixel/s. The influence of selected parameters on the total MS imaging time is discussed. The new scanning technique was employed to display the distribution of an antitumor agent in 3D colorectal adenocarcinoma cell aggregates; a single MS image comprising 100 × 100 pixels with 10-μm lateral resolution was recorded in approximately 70 s.

Graphical Abstract

Keywords

Mass spectrometry imaging Laser beam scanning MALDI TOF MSI High throughput Grid ion source 3D cell aggregates Spheroids Colorectal adenocarcinoma 

Notes

Acknowledgments

We gratefully acknowledge the financial support of the Grant Agency of the Masaryk University (MUNI/G/0974/2016), the Czech Science Foundation (GA 15-05387S) and the Ministry of Education, Youth and Sports of the Czech Republic under the projects CEITEC 2020 (LQ1601), Translational Medicine (LQ1605) and NETME CENTRE PLUS (LO1202).

Supplementary material

13361_2018_2078_MOESM1_ESM.pdf (1.1 mb)
ESM 1 (PDF 1.12 MB)

References

  1. 1.
    Yang, J.H., Caprioli, R.M.: Matrix pre-coated targets for high throughput MALDI imaging of proteins. J. Mass Spectrom. 49, 417–422 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Stoeckli, M., Staab, D.: Reproducible matrix deposition for MALDI MSI based on open-source software and hardware. J. Am. Soc. Mass Spectrom. 26, 911–914 (2015)CrossRefPubMedGoogle Scholar
  3. 3.
    Hankin, J.A., Barkley, R.M., Murphy, R.C.: Sublimation as a method of matrix application for mass spectrometric imaging. J. Am. Soc. Mass Spectrom. 18, 1646–1652 (2007)CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Thomas, A., Charbonneau, J.L., Fournaise, E., Chaurand, P.: Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1,5-Diaminonapthalene deposition. Anal. Chem. 84, 2048–2054 (2012)CrossRefPubMedGoogle Scholar
  5. 5.
    Schuerenberg, M., Luebbert, C., Deininger, S.O., Ketterlinus, R., Suckau, D.: MALDI tissue imaging: mass spectrometric localization of biomarkers in tissue slices. Nat. Methods. 4, iii–iiv (2007)CrossRefGoogle Scholar
  6. 6.
    Bouschen, W., Schulz, O., Eikel, D., Spengler, B.: Matrix vapor deposition/recrystallization and dedicated spray preparation for high-resolution scanning microprobe matrix-assisted laser desorption/ionization imaging mass spectrometry (SMALDI-MS) of tissue and single cells. Rapid Commun. Mass Spectrom. 24, 355–364 (2010)CrossRefPubMedGoogle Scholar
  7. 7.
    Rompp, A., Spengler, B.: Mass spectrometry imaging with high resolution in mass and space. Histochem. Cell Biol. 139, 759–783 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kompauer, M., Heiles, S., Spengler, B.: Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-mu m lateral resolution. Nat. Methods. 14, 90–96 (2017)CrossRefPubMedGoogle Scholar
  9. 9.
    Spraggins, J.M., Caprioli, R.: 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)CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Andersson, M., Groseclose, M.R., Deutch, A.Y., Caprioli, R.M.: Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction. Nat. Methods. 5, 101–108 (2008)CrossRefPubMedGoogle Scholar
  11. 11.
    Prentice, B.M., Chumbley, C.W., Caprioli, R.M.: High-speed MALDI MS/MS imaging mass spectrometry using continuous raster sampling. J. Mass Spectrom. 50, 703–710 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Potocnik, N.O., Porta, T., Becker, M., Heeren, R.M.A., Ellis, S.R.: Use of advantageous, volatile matrices enabled by next-generation high-speed matrix-assisted laser desorption/ionization time-of-flight imaging employing a scanning laser beam. Rapid Commun. Mass Spectrom. 29, 2195–2203 (2015)CrossRefGoogle Scholar
  13. 13.
    Cornett, D.S., Frappier, S.L., Caprioli, R.M.: MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal. Chem. 80, 5648–5653 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Schober, Y., Guenther, S., Spengler, B., Rompp, A.: High-resolution matrix-assisted laser desorption/ionization imaging of tryptic peptides from tissue. Rapid Commun. Mass Spectrom. 26, 1141–1146 (2012)CrossRefPubMedGoogle Scholar
  15. 15.
    Belov, M.E., Ellis, S.R., Dilillo, M., Paine, M.R.L., Danielson, W.F., Anderson, G.A., de Graaf, E.L., Eijkel, G.B., Heeren, R.M.A., McDonnell, L.A.: Design and performance of a novel Interface for combined matrix-assisted laser desorption ionization at elevated pressure and electrospray ionization with Orbitrap mass spectrometry. Anal. Chem. 89, 7493–7501 (2017)CrossRefPubMedGoogle Scholar
  16. 16.
    Moskovets, E., Misharin, A., Laiko, V., Doroshenko, V.: A comparative study on the analytical utility of atmospheric and low-pressure MALDI sources for the mass spectrometric characterization of peptides. Methods. 104, 21–32 (2016)CrossRefPubMedGoogle Scholar
  17. 17.
    Soltwisch, J., Kettling, H., Vens-Cappell, S., Wiegelmann, M., Muthing, J., Dreisewerd, K.: Mass spectrometry imaging with laser-induced postionization. Science. 348, 211–215 (2015)CrossRefPubMedGoogle Scholar
  18. 18.
    Ellis, S.R., Soltwisch, J., Paine, M.R.L., Dreisewerd, K., Heeren, R.M.A.: Laser post-ionisation combined with a high resolving power orbitrap mass spectrometer for enhanced MALDI-MS imaging of lipids. Chem. Commun. 53, 7246–7249 (2017)CrossRefGoogle Scholar
  19. 19.
    Schwartz, M., Meyer, B., Wirnitzer, B., Hopf, C.: Standardized processing of MALDI imaging raw data for enhancement of weak analyte signals in mouse models of gastric cancer and Alzheimer's disease. Anal. Bioanal. Chem. 407, 2255–2264 (2015)CrossRefPubMedGoogle Scholar
  20. 20.
    Schramm, T., Hester, A., Klinkert, I., Both, J.P., Heeren, R.M.A., Brunelle, A., Laprevote, O., Desbenoit, N., Robbe, M.F., Stoeckli, M., Spengler, B., Rompp, A.: imzML - a common data format for the flexible exchange and processing of mass spectrometry imaging data. J. Proteome. 75, 5106–5110 (2012)CrossRefGoogle Scholar
  21. 21.
    Robbe, M.F., Both, J.P., Prideaux, B., Klinkert, I., Picaud, V., Schramm, T., Hester, A., Guevara, V., Stoeckli, M., Roempp, A., Heeren, R.M.A., Spengler, B., Gal, O., Haan, S.: Software tools of the Computis European project to process mass spectrometry images. Eur. J. Mass Spectrom. 20, 351–360 (2014)CrossRefGoogle Scholar
  22. 22.
    Caprioli, R.M.: Imaging mass spectrometry: enabling a new age of discovery in biology and medicine through molecular microscopy. J. Am. Soc. Mass Spectrom. 26, 850–852 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Preisler, J., Hu, P., Rejtar, T., Moskovets, E., Karger, B.L.: Capillary array electrophoresis-MALDI mass spectrometry using a vacuum deposition interface. Anal. Chem. 74, 17–25 (2002)CrossRefPubMedGoogle Scholar
  24. 24.
    Moskovets, E., Preisler, J., Chen, H.S., Rejtar, T., Andreev, V., Karger, B.L.: High-throughput axial MALDI-TOF MS using a 2-kHz repetition rate laser. Anal. Chem. 78, 912–919 (2006)CrossRefPubMedGoogle Scholar
  25. 25.
    Jungmann, J.H., Smith, D.F., MacAleese, L., Klinkert, I., Visser, J., Heeren, R.M.A.: Biological tissue imaging with a position and time sensitive pixelated detector. J. Am. Soc. Mass Spectrom. 23, 1679–1688 (2012)CrossRefPubMedGoogle Scholar
  26. 26.
    Soltwisch, J., Goritz, G., Jungmann, J.H., Kiss, A., Smith, D.F., Ellis, S.R., Heeren, R.M.A.: MALDI mass spectrometry imaging in microscope mode with infrared lasers: bypassing the diffraction limits. Anal. Chem. 86, 321–325 (2014)CrossRefPubMedGoogle Scholar
  27. 27.
    Halford, E., Winter, B., Mills, M.D., Thompson, S.P., Parr, V., John, J.J., Nomerotski, A., Vallance, C., Turchetta, R., Brouard, M.: Modifications to a commercially available linear mass spectrometer for mass-resolved microscopy with the pixel imaging mass spectrometry (PImMS) camera. Rapid Commun. Mass Spectrom. 28, 1649–1657 (2014)CrossRefPubMedGoogle Scholar
  28. 28.
    Hazama, H., Aoki, J., Nagao, H., Suzuki, R., Tashima, T., Fujii, K., Masuda, K., Awazu, K., Toyoda, M., Naito, Y.: Construction of a novel stigmatic MALDI imaging mass spectrometer. Appl. Surf. Sci. 255, 1257–1263 (2008)CrossRefGoogle Scholar
  29. 29.
    Bednařík, A., Preisler, J., Kuba, P., Ertl, L., Tomalová, I., Rážová, I., Moskovets, E.: High throughput MS imaging using a fast scanning mirror. Poster TP 430 in 60th ASMS Conference on Mass Spectrometry and Allied Topics, Vancouver, Canada (2012)Google Scholar
  30. 30.
    Bednarik, A., Kuba, P., Moskovets, E., Tomalova, I., Krasensky, P., Houska, P., Preisler, J.: Rapid matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging with scanning desorption laser beam. Anal. Chem. 86, 982–986 (2014)CrossRefPubMedGoogle Scholar
  31. 31.
    Spraggins, J.M., Rizzo, D.G., Moore, J.L., Noto, M.J., Skaar, E.P., Caprioli, R.M.: Next-generation technologies for spatial proteomics: integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis. Proteomics. 16, 1678–1689 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Moskovets, E.V.: Optimization of the reflecting system parameters in the mass-reflectron. Appl. Phys. B Lasers Opt. 53, 253–259 (1991)CrossRefGoogle Scholar
  33. 33.
    Imaging MS controlled vocabulary. https://ms-imaging.org/wp/imzml/controlled-vocabulary/. (Visited July 2018)
  34. 34.
    Straus, R.N., Carew, A., Sandkuijl, D., Closson, T., Baranov, V.I., Loboda, A.: Analytical figures of merit for a novel tissue imaging system. J. Anal. At. Spectrom. 32, 1044–1051 (2017)CrossRefGoogle Scholar
  35. 35.
    Fennema, E., Rivron, N., Rouwkema, J., van Blitterswijk, C., de Boer, J.: Spheroid culture as a tool for creating 3D complex tissues. Trends Biotechnol. 31, 108–115 (2013)CrossRefPubMedGoogle Scholar
  36. 36.
    Hamilton, G.: Multicellular spheroids as an in vitro tumor model. Cancer Lett. 131, 29–34 (1998)CrossRefPubMedGoogle Scholar
  37. 37.
    Sutherland, R.M.: Cell and environment interactions tumor model. Science. 240, 177–184 (1988)CrossRefPubMedGoogle Scholar
  38. 38.
    Sutherland, R.M., McCredie, J.A., Inch, W.R.: Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J. Natl. Cancer Inst. 46, 113–120 (1971)PubMedGoogle Scholar
  39. 39.
    LaBonia, G.J., Lockwood, S.Y., Heller, A.A., Spence, D.M., Hummon, A.B.: Drug penetration and metabolism in 3D cell cultures treated in a 3D printed fluidic device: assessment of irinotecan via MALDI imaging mass spectrometry. Proteomics. 16, 1814–1821 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Lukowski, J.K., Weaver, E.M., Hummon, A.B.: Analyzing liposomal drug delivery Systems in Three-Dimensional Cell Culture Models Using MALDI imaging mass spectrometry. Anal. Chem. 89, 8453–8458 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bakker, B., Eijkel, G.B., Heeren, R.M.A., Karperien, M., Post, J.N., Cillero-Pastor, B.: Oxygen-dependent lipid profiles of three-dimensional cultured human chondrocytes revealed by MALDI-MSI. Anal. Chem. 89, 9438–9444 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Theiner, S., Van Malderen, S.J.M., Van Acker, T., Legin, A., Keppler, B.K., Vanhaecke, F., Koellensperger, G.: Fast high-resolution laser ablation-inductively coupled plasma mass spectrometry imaging of the distribution of platinum-based anticancer compounds in multicellular tumor spheroids. Anal. Chem. 89, 12641–12645 (2017)CrossRefPubMedGoogle Scholar
  43. 43.
    Feenstra, A.D., Duenas, M.E., Lee, Y.J.: Five Micron high resolution MALDI mass spectrometry imaging with simple, interchangeable, multi-resolution optical system. J. Am. Soc. Mass Spectrom. 28, 434–442 (2017)CrossRefPubMedGoogle Scholar
  44. 44.
    Wiley, W.C., McLaren, I.H.: Tme-of-flight mass spectrometer with improved resolution. Rev. Sci. Instrum. 26, 1150–1157 (1955)CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2018

Authors and Affiliations

  • Antonín Bednařík
    • 1
    • 2
  • Markéta Machálková
    • 1
  • Eugene Moskovets
    • 3
  • Kateřina Coufalíková
    • 1
  • Pavel Krásenský
    • 1
  • Pavel Houška
    • 4
  • Jiří Kroupa
    • 4
  • Jarmila Navrátilová
    • 5
    • 6
  • Jan Šmarda
    • 5
  • Jan Preisler
    • 1
    • 2
    Email author
  1. 1.Department of Chemistry, Faculty of ScienceMasaryk UniversityBrnoCzech Republic
  2. 2.Central European Institute of Technology (CEITEC)Masaryk UniversityBrnoCzech Republic
  3. 3.MassTech Inc.ColumbiaUSA
  4. 4.Faculty of Mechanical EngineeringBrno University of TechnologyBrnoCzech Republic
  5. 5.Department of Experimental Biology, Faculty of ScienceMasaryk UniversityBrnoCzech Republic
  6. 6.Center for Biological and Cellular Engineering, International Clinical Research CenterSt. Anne’s University HospitalBrnoCzech Republic

Personalised recommendations