Analytical and Bioanalytical Chemistry

, Volume 408, Issue 14, pp 3769–3781 | Cite as

Multigrid MALDI mass spectrometry imaging (mMALDI MSI)

  • Annett Urbanek
  • Stefan Hölzer
  • Katrin Knop
  • Ulrich S. Schubert
  • Ferdinand von Eggeling
Research Paper

Abstract

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an important technique for the spatially resolved molecular analysis of tissue sections. The selection of matrices influences the resulting mass spectra to a high degree. For extensive and simultaneous analysis, the application of different matrices to one tissue sample is desirable. To date, only a single matrix could be applied to a tissue section per experiment. However, repetitive removal of the matrix makes this approach time-consuming and damaging to tissue samples. To overcome these drawbacks, we developed a multigrid MALDI MSI technique (mMALDI MSI) that relies on automated inkjet printing to place differing matrices onto predefined dot grids. We used a cooled printhead to prevent cavitation of low viscosity solvents in the printhead nozzle. Improved spatial resolution of the dot grids was achieved by using a triple-pulse procedure that reduced droplet volume. The matrices can either be applied directly to the thaw-mounted tissue sample or by precoating the slide followed by mounting of the tissue sample. During the MALDI imaging process, we were able to precisely target different matrix point grids with the laser to simultaneously produce distinct mass spectra. Unlike the standard method, the prespotting approach optimizes the spectra quality, avoids analyte delocalization, and enables subsequent hematoxylin and eosin (H&E) staining.

Graphical Abstract

Scheme of the pre-spotted multigrid MALDI MSI workflow

Keywords

Mass spectrometry imaging Inkjet printing Simultaneous analysis Sub-pixel Multiplex Multigrid 

Supplementary material

216_2016_9465_MOESM1_ESM.pdf (1.7 mb)
ESM 1(PDF 1788 kb)

References

  1. 1.
    Balluff B, Schöne C, Höfler H, Walch A. MALDI imaging mass spectrometry for direct tissue analysis: technological advancements and recent applications. Histochem Cell Biol. 2011;136:227–44.CrossRefGoogle Scholar
  2. 2.
    Bocklitz T, Bräutigam K, Urbanek A, Hoffmann F, von Eggeling F, Ernst G, et al. Novel workflow for combining Raman spectroscopy and MALDI-MSI for tissue based studies. Anal Bioanal Chem. 2015;407:7865–73.CrossRefGoogle Scholar
  3. 3.
    Ogrinc Potočnik NPT, Becker M, Heeren RM, Ellis SR. 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. 2015;29:2195–203.CrossRefGoogle Scholar
  4. 4.
    Kaletas BK, van der Wiel IM, Stauber J, Dekker LJ, Güzel C, Kros JM, et al. Sample preparation issues for tissue imaging by imaging MS. Proteomics. 2009;9:2622–33.CrossRefGoogle Scholar
  5. 5.
    Mirza SP, Raju NP, Vairamani M. Estimation of the proton affinity values of fifteen matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions using the kinetic method. J Am Soc Mass Spectrom. 2004;15:431–5.CrossRefGoogle Scholar
  6. 6.
    Crecelius AC, Schubert US, von Eggeling F. MALDI mass spectrometric imaging meets “omics”: recent advances in the fruitful marriage. Analyst. 2015;140:5806–20.CrossRefGoogle Scholar
  7. 7.
    Goodwin RJA. Sample preparation for mass spectrometry imaging: small mistakes can lead to big consequences. J ProteomE. 2012;75:4893–911.CrossRefGoogle Scholar
  8. 8.
    Caprioli JYRM. Matrix sublimation/recrystallization for imaging proteins by mass spectrometry at high spatial resolution. Anal Chem. 2011;83:5728–34.CrossRefGoogle Scholar
  9. 9.
    Schwamborn K, Caprioli RM. Molecular imaging by mass spectrometry—looking beyond classical histology. Nat Rev Cancer. 2010;10:639–46.CrossRefGoogle Scholar
  10. 10.
    Chughtai K, Heeren RMA. Mass spectrometric imaging for biomedical tissue analysis. Chem Rev. 2010;110:3237–77.CrossRefGoogle Scholar
  11. 11.
    Griffiths RL, Bunch J. A survey of useful salt additives in matrix-assisted laser desorption/ionization mass spectrometry and tandem mass spectrometry of lipids: introducing nitrates for improved analysis. Rapid Commun Mass Spectrom. 2012;26:1557–66.CrossRefGoogle Scholar
  12. 12.
    Cerruti CD, Touboul D, Guérineau V, Petit VW, Laprévote O, Brunelle A. MALDI imaging mass spectrometry of lipids by adding lithium salts to the matrix solution. Anal Bioanal Chem. 2011;401:75–87.CrossRefGoogle Scholar
  13. 13.
    Laugesen S, Roepstorff P. Combination of two matrices results in improved performance of MALDI MS for peptide mass mapping and protein analysis. J Am Soc Mass Spectrom. 2003;14:992–1002.CrossRefGoogle Scholar
  14. 14.
    Steven RT, Bunch J. Repeat MALDI MS imaging of a single tissue section using multiple matrices and tissue washes. Anal Bioanal Chem. 2013;405:4719–28.CrossRefGoogle Scholar
  15. 15.
    Baluya DL, Garrett TJ, Yost RA. Automated MALDI matrix deposition method with inkjet printing for imaging mass spectrometry. Anal Chem. 2007;79:6862–7.CrossRefGoogle Scholar
  16. 16.
    Delaney JT, Urbanek A, Wehder L, Perelaer J, Crecelius AC, Eggeling F, et al. Combinatorial optimization of multiple MALDI matrices on a single tissue sample using inkjet printing. ACS Comb Sci. 2011;13:218–22.CrossRefGoogle Scholar
  17. 17.
    Gan HY, Shan X, Eriksson T, Lok BK, Lam YC. Reduction of droplet volume by controlling actuating waveforms in inkjet printing for micro-pattern formation. J Micromech Microeng. 2009;19:055010 (055018pp).CrossRefGoogle Scholar
  18. 18.
    Shigeta K, Traub H, Panne U, Okino A, Rottmannc L, Jakubowskia N. Application of a micro-droplet generator for an ICP-sector field mass spectrometer – optimization and analytical characterization. J Anal At Spectrom. 2013;28:646–56.CrossRefGoogle Scholar
  19. 19.
    Grove KJ, Frappier SL, Caprioli RM. Matrix pre-coated MALDI MS targets for small molecule imaging in tissues. J Am Soc Mass Spectrom. 2011;22:192–5.CrossRefGoogle Scholar
  20. 20.
    Yang J, Caprioli RM. Matrix pre-coated targets for high throughput MALDI imaging of proteins. J Mass Spectrom. 2014;49(5):417–22.CrossRefGoogle Scholar
  21. 21.
    Gemoll TRU, Habermann JK. MALDI mass spectrometry imaging in oncology. Mol Med Rep. 2011;4:1045–51.Google Scholar
  22. 22.
    Rauser S, Marquardt C, Balluff B, Deininger SO, Albers C, Belau E, et al. Classification of HER2 receptor status in breast cancer tissues by MALDI imaging mass spectrometry. J Proteome Res. 2010;9:1854–63.CrossRefGoogle Scholar
  23. 23.
    Meding S, Nitsche U, Balluff B, Elsner M, Rauser S, Schöne C, et al. Tumor classification of six common cancer types based on proteomic profiling by MALDI imaging. J Proteome Res. 2012;11:1996–2003.CrossRefGoogle Scholar
  24. 24.
    Ernst G, Guntinas-Lichius O, Hauberg-Lotte L, Trede D, Becker M, Alexandrov T, et al. Histomolecular interpretation of pleomorphic adenomas of the salivary gland by matrix-assisted laser desorption ionization imaging and spatial segmentation. Head Neck. 2015;37:1014–21.CrossRefGoogle Scholar
  25. 25.
    Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.CrossRefGoogle Scholar
  26. 26.
    Otsu N. A threshold selection method from gray-level histograms. IEEE Trans Syst Man Cybern. 1979;9:62–6.CrossRefGoogle Scholar
  27. 27.
    Meyer W, Döring M. Liquid handling in the pico- and nanoliter range. In: Ehrfeld W, editor. Proceedings IMRET 3. Microreaction technology: industrial prospects. Berlin: springer; 1999. p. 312–9.Google Scholar
  28. 28.
    Urbanek A, Schubert US. Verfahren zur MALDI-MSI Analytik von Objekten, insbesondere biologischen Gewebeproben, und Target zur Analytik sowie dessen Herstellung. Germany Patent AZ 102015003440.5. 2015.Google Scholar
  29. 29.
    Ko SH, Grigoropoulos CP. Unconventional, laser based OLED material direct patterning and transfer methods. Organic light emitting diode - material, process and devices. 2011. doi:10.5772/18967.
  30. 30.
    Tsujimura T. Next-generation OLED technologies. In: Lowe AC, editor. OLED displays. Weinheim: Wiley; 2012. p. 143–85. doi:10.1002/9781118173053.ch6.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Annett Urbanek
    • 1
    • 2
  • Stefan Hölzer
    • 1
    • 2
  • Katrin Knop
    • 1
    • 2
  • Ulrich S. Schubert
    • 1
    • 2
  • Ferdinand von Eggeling
    • 2
    • 3
    • 4
    • 5
  1. 1.Laboratory of Organic and Macromolecular Chemistry (IOMC)Friedrich Schiller University JenaJenaGermany
  2. 2.Jena Center for Soft Matter (JCSM)Friedrich Schiller University JenaJenaGermany
  3. 3.Institute of Physical ChemistryFriedrich Schiller University JenaJenaGermany
  4. 4.ENT DepartmentJena University HospitalJenaGermany
  5. 5.Leibniz Institute of Photonic Technology (IPHT)JenaGermany

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