Abstract
An atmospheric pressure laser desorption/ionization mass spectrometry imaging ion source has been developed that combines high spatial resolution and high mass resolution for the in situ analysis of biological tissue. The system is based on an infrared laser system working at 2.94 to 3.10 μm wavelength, employing a Nd:YAG laser-pumped optical parametrical oscillator. A Raman-shifted Nd:YAG laser system was also tested as an alternative irradiation source. A dedicated optical setup was used to focus the laser beam, coaxially with the ion optical axis and normal to the sample surface, to a spot size of 30 μm in diameter. No additional matrix was needed for laser desorption/ionization. A cooling stage was developed to reduce evaporation of physiological cell water. Ions were formed under atmospheric pressure and transferred by an extended heated capillary into the atmospheric pressure inlet of an orbital trapping mass spectrometer. Various phospholipid compounds were detected, identified, and imaged at a pixel resolution of up to 25 μm from mouse brain tissue sections. Mass accuracies of better than 2 ppm and a mass resolution of 30,000 at m/z = 400 were achieved for these measurements.
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References
Chughtai K, Heeren RMA (2010) Mass spectrometric imaging for biomedical tissue analysis. Chem Rev 110(5):3237–3277
McDonnell LA, Heeren RMA (2007) Imaging mass spectrometry. Mass Spectrom Rev 26(4):606–643
Spengler B, Hubert M (2002) 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(6):735–748
Spengler B, Hubert M, Kaufmann R (1994) MALDI ion imaging and biological ion imaging with a new scanning UV-laser microprobe. In: Proceedings of the 42nd Annual Conference on Mass Spectrometry and Allied Topics, Chicago, IL, May 29–June 3, 1994. p 1041
Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM (2001) Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat Med 7(4):493–496
Römpp 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(22):3834–3838
Guenther S, Römpp A, Kummer W, Spengler B (2011) AP-MALDI imaging of neuropeptides in mouse pituitary gland with 5 μm spatial resolution and high mass accuracy. Int J Mass Spectrom 305:228–237
Römpp A, Guenther S, Takats Z, Spengler B (2011) Mass spectrometry imaging with high resolution in mass and space (HR2 MSI) for reliable investigation of drug compound distributions on the cellular level. Anal Bioanal Chem 401:65–73
Schober Y, Guenther S, Spengler B, Römpp A (2012) High resolution MALDI imaging of tryptic peptides directly from tissue. Rapid Commun Mass Spectrom 26:1141–1146
Schober Y, Schramm T, Spengler B, Römpp A (2011) Protein identification by accurate mass MALDI imaging of tryptic peptides. Rapid Commun Mass Spectrom 25:2475–2483
Acquadro E, Cabella C, Ghiani S, Miragoli L, Bucci EM, Corpillo D (2009) Matrix-assisted laser desorption ionization imaging mass spectrometry detection of a magnetic resonance imaging contrast agent in mouse liver. Anal Chem 81(7):2779–2784
Solon EG, Schweitzer A, Stoeckli M, Prideaux B (2010) Autoradiography, MALDI-MS, and SIMS-MS imaging in pharmaceutical discovery and development. AAPS J 12(1):11–26
Dreisewerd K, Draude F, Kruppe S, Rohlfing A, Berkenkamp S, Pohlentz G (2007) Molecular analysis of native tissue and whole oils by infrared laser mass spectrometry. Anal Chem 79:4514–4520
Wieliczka DM, Weng S, Querry MR (1989) Wedge shaped cell for highly absorbent liquids: infrared optical constants of water. Appl Opt 28:1714–1719
Dreisewerd K, Berkenkamp S, Leisner A, Rohlfing A, Menzel C (2003) Fundamentals of matrix-assisted laser desorption/ionization mass spectrometry with pulsed infrared lasers. Int J Mass Spectrom 226:189–209
Berkenkamp S, Kirpekar F, Hillenkamp F (1998) Infrared MALDI mass spectrometry of large nucleic acids. Science 281:260–262
Leisner A, Rohlfing A, Berkenkamp S, Hillenkamp F, Dreisewerd K (2004) Infrared laser post-ionization of large biomolecules from an IR-MALD(I) plume. J Am Soc Mass Spectrom 15:934–941
Nemes P, Vertes A (2007) Laser ablation electrosray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal Chem 79:8098–8106
Barry JA, Muddiman DC (2011) Global optimization of the infrared matrix-assisted laser desorption electrospray ionization (IR MALDESI) source for mass spectrometry using statistical design of experiments. Rapid Commun Mass Spectrom 25:3527–3536
Rezenom YH, Dong J, Murray K (2008) Infrared laser-assisted desorption electrospray ionization mass spectrometry. Analyst 133:226–232
Peng IX, Loo RRO, Margalith E, Little MW, Loo JA (2010) Electrospray-assisted laser desorption ionization mass spectrometry (ELDI-MS) with an infrared laser for characterizing peptides and proteins. Analyst 135:767–772
Shiea J, Huang MZ, Hsu HJ, Lee CY, Yuan CH, Beech I, Sunner J (2005) Electrospray-assisted laser desorption/ionization mass spectrometry for direct ambient analysis of solids. Rapid Commun Mass Spectrom 19:3701–3704
Shrestha B, Patt JM, Vertes A (2011) In situ cell-by-cell imaging and analysis of small cell populations by mass spectrometry. Anal Chem 83:2947–2955
Pirkl A, Soltwisch J, Draude F, Dreisewerd K (2012) Infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry employing a cooling stage and water ice as a matrix. Anal Chem 84:5669–5676
Jurchen JC, Rubakin SS, Sweedler JV (2005) MALDI-MS imaging of features smaller than the size of the laser beam. J Am Soc Mass Spectrom 16:1654–1659
Li Y, Shrestha B, Vertes A (2007) Atmospheric pressure molecular imaging by infrared MALDI mass spectrometry. Anal Chem 79:523–532
Robichaud G, Barry JA, Garrard KP, Muddiman DC (2013) Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging source coupled to a FT-ICR mass spectrometer. J Am Soc Mass Spectrom 24:92–100
Koestler M, Kirsch D, Hester A, Leisner A, Guenther S, Spengler B (2008) 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
Bouschen W, Spengler B (2007) Artifacts of MALDI sample preparation investigated by high-resolution scanning microprobe matrix-assisted laser desorption/ionization (SMALDI) imaging mass spectrometry. Int J Mass Spectrom 266:129–137
Bouschen W, Schulz O, Eikel D, Spengler B (2010) 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(3):355–364
Paschke C, Leisner A, Hester A, Maass K, Guenther S, Bouschen W, Spengler B (2013) Mirion—a software package for automatic processing of mass spectrometric images. J Am Soc Mass Spectrom. doi:10.1007/s13361-013-0667-0
Guenther S, Koestler M, Schulz O, Spengler B (2010) Laser spot size and laser power dependence of ion formation in high resolution MALDI imaging. Int J Mass Spectrom 294(1):7–15
Sud M, Fahy E, Cotter D, Dennis EA, Subramaniam S (2011) LIPID MAPS-Nature Lipidomics Gateway: an online resource for students and educators interested in lipids. J Chem Educ 89:291–292
Römpp A, Spengler B (2013) Mass spectrometry imaging with high resolution in mass and space. J Histochem Cell Biol 139:759–783. doi:10.1007/s00418-013-1097-6
Acknowledgments
Financial support by the Bundesministerium fuer Bildung und Forschung, BMBF (project 0313442), by the State of Hesse (LOEWE Research Focus “Ambiprobe”) and by the Deutsche Forschungsgemeinschaft (Sp 314/12-1, Sp 314/13-1) is gratefully acknowledged. We thank Wolfgang Kummer for providing the mouse samples, Lilli Walz for H&E staining of mouse tissue sections, and Zoltan Takats for providing access to the LTQ Orbitrap system (ERC starting grant 210356-DESI_JeDI-Imaging).
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Published in the topical collection Photo Ionisation in Mass Spectrometry with guest editor Ralf Zimmermann.
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Römpp, A., Schäfer, K.C., Guenther, S. et al. High-resolution atmospheric pressure infrared laser desorption/ionization mass spectrometry imaging of biological tissue. Anal Bioanal Chem 405, 6959–6968 (2013). https://doi.org/10.1007/s00216-013-7180-y
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DOI: https://doi.org/10.1007/s00216-013-7180-y