Abstract
Common organic matrix-assisted laser desorption/ionization (MALDI) matrices, 2,5-dihydroxybenzoic acid, 3,5-dimethoxy-4-hydroxycinnamic acid, and α-cyano-4-hydroxycinnamic acid, were found to undergo sublimation without decomposition under conditions of reduced pressure and elevated temperature. This solid to vapor-phase transition was exploited to apply MALDI matrix onto tissue samples over a broad surface in a solvent-free application for mass spectrometric imaging. Sublimation of matrix produced an even layer of small crystals across the sample plate. The deposition was readily controlled with time, temperature, and pressure settings and was highly reproducible from one sample to the next. Mass spectrometric images acquired from phospholipid standards robotically spotted onto a MALDI plate yielded a more intense, even signal with fewer sodium adducts when matrix was applied by sublimation relative to samples where matrix was deposited by an electrospray technique. MALDI matrix could be readily applied to tissue sections on glass slides and stainless steel MALDI plate inserts as long as good thermal contact was made with the condenser of the sublimation device. Sections of mouse brain were coated with matrix applied by sublimation and were imaged using a Q-q-TOF mass spectrometer to yield mass spectral images of very high quality. Image quality is likely enhanced by several features of this technique including the microcrystalline morphology of the deposited matrix, increased purity of deposited matrix, and evenness of deposition. This inexpensive method was reproducible and eliminated the potential for spreading of analytes arising from solvent deposition during matrix application.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Schwartz, S. A.; Weil, R. J.; Johnson, M. D.; Toms, S. A.; Caprioli, R. M. Protein Profiling in Brain Tumors Using Mass Spectrometry: Feasibility of a New Technique for the Analysis of Protein Expression. Clin. Cancer Res. 2004, 10, 981–987.
Khatib-Shahidi, S.; Andersson, M.; Herman, J. L.; Gillespie, T. A.; Caprioli, R. M. Direct Molecular Analysis of Whole-Body Animal Tissue Sections by Imaging MALDI Mass Spectrometry. Anal. Chem. 2006, 78, 6448–6456.
Garrett, T. J.; Prieto-Conaway, M. C.; Kovtoun, V.; Bui, H.; Izgarian, N.; Stafford, G.; Yost, R. A. Imaging of Small Molecules in Tissue Sections with a New Intermediate-Pressure MALDI Linear Ion Trap Mass Spectrometer. Int. J. Mass Spectrom. 2007, 260, 166–176.
Aerni, H. R.; Cornett, D. S.; Caprioli, R. M. Automated Acoustic Matrix Deposition for MALDI Sample Preparation. Anal. Chem. 2006, 78, 827–834.
Jurchen, J. C.; Rubakhin, S. S.; Sweedler, J. V. MALDI-MS Imaging of Features Smaller Than the Size of the Laser Beam. J. Am. Soc. Mass Spectrom. 2005, 16, 1654–1659.
Chaurand, P.; Norris, J. L.; Cornett, D. S.; Mobley, J. A.; Caprioli, R. M. New Developments in Profiling and Imaging of Proteins From Tissue Sections by MALDI Mass Spectrometry. J. Proteome Res. 2006, 5, 2889–2900.
Touboul, D.; Kollmer, F.; Niehuis, E.; Brunelle, A.; Laprevote, O. Improvement of Biological Time-of-Flight-Secondary Ion Mass Spectrometry Imaging with a Bismuth Cluster Ion Source. J. Am. Soc. Mass Spectrom. 2005, 16, 1608–1618.
Winograd, N. The Magic of Cluster SIMS. Anal. Chem. 2005, 77, 143A-149A.
Lechene, C.; Hillion, F.; McMahon, G.; Benson, D.; Kleinfeld, A. M.; Kampf, J. P.; Distel, D.; Luyten, Y.; Bonventre, J.; Hentschel, D.; Park, K. M.; Ito, S.; Schwartz, M.; Benichou, G.; Slodzian, G. High-Resolution Quantitative Imaging of Mammalian and Bacterial Cells Using Stable Isotope Mass Spectrometry. J. Biol. 2006, 5, 20.1–20.30.
Altelaar, A. F.; van Minnen, J.; Jimenez, C. R.; Heeren, R. M.; Piersma, S. R. Direct Molecular Imaging of Lymnaea Stagnalis Nervous Tissue at Subcellular Spatial Resolution by Mass Spectrometry. Anal. Chem. 2005, 77, 735–741.
Milne, S.; Ivanova, P.; Forrester, J.; Brown, A. H. Lipidomics: An Analysis of Cellular Lipids by ESI-MS. Methods 2006, 39, 92–103.
Pavia, D. L.; Lampman, G. M.; Kriz, G. S., Jr. Introduction to Organic Laboratory Techniques: A Contemporary Approach 2nd ed.; Saunders College Publishing: New York, 1982.
French, J. The Art of Distillation or a Treatise of the Choicest Spagyrical Preparations, Experiments, and Curiosities, Performed by Way of Distillation. In Art of Distillation, Cotes for E. T. Williams: London, 1667; pp 1616–1657.
Kim, S. H.; Shin, C. M.; Yoo, J. S. First Application of Thermal Vapor Deposition Method to Matrix-Assisted Laser Desorption Ionization Mass Spectrometry: Determination of Molecular Mass of Bis(p-Methyl Benzylidiene) Sorbitol. Rapid Commun. Mass Spectrom. 1998, 12, 701–704.
Jackson, S. N.; Wang, H. Y.; Woods, A. S. In Situ Structural Characterization of Glycerophospholipids and Sulfatides in Brain Tissue Using MALDI-MS/MS. J. Am. Soc. Mass Spectrom. 2007, 18, 17–26.
Jackson, S. N.; Wang, H. Y.; Woods, A. S. In Situ Structural Characterization of Phosphatidylcholines in Brain Tissue Using MALDI-MS/MS. J. Am. Soc. Mass Spectrom. 2005, 16, 2052–2056.
Sjovall, P.; Lausmaa, J.; Johansson, B. Mass Spectrometric Imaging of Lipids in Brain Tissue. Anal. Chem. 2004, 76, 4271–4278.
Paxinos, G.; Franklin, K. B. J. The Mouse Brain in Stereotaxic Coordinates, 2nd ed.; Academic Press: San Diego, CA, 2001.
Author information
Authors and Affiliations
Corresponding author
Additional information
Published online June 30, 2007
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1016/j.jasms.2007.06.010
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.jasms.2007.06.010