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Cellular-level mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) by oversampling

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Abstract

Mass spectrometry imaging (MSI) allows for the direct and simultaneous analysis of the spatial distribution of molecular species from sample surfaces such as tissue sections. One of the goals of MSI is monitoring the distribution of compounds at the cellular resolution in order to gain insights about the biology that occurs at this spatial level. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging of cervical tissue sections was performed using a spot-to-spot distance of 10 μm by utilizing the method of oversampling, where the target plate is moved by a distance that is less than the desorption radius of the laser. In addition to high spatial resolution, high mass accuracy (±1 ppm) and high mass resolving power (140,000 at m/z = 200) were achieved by coupling the IR-MALDESI imaging source to a hybrid quadrupole Orbitrap mass spectrometer. Ion maps of cholesterol in tissues were generated from voxels containing <1 cell, on average. Additionally, the challenges of imaging at the cellular level in terms of loss of sensitivity and longer analysis time are discussed.

Cellular-level mass spectrometry imaging using IR-MALDESI and oversampling

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References

  1. Tanaka K, Waki H, Ido Y et al (1988) Protein and polymer analyses up to m/z 100,000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 2:151–153

    Article  CAS  Google Scholar 

  2. Karas M, Hillenkamp F (1988) Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. Anal Chem 60:2299–2301

    Article  CAS  Google Scholar 

  3. Fenn JB, Mann M, Meng CK et al (1989) Electrospray ionization for mass spectrometry of large biomolecules. Science 246:64–71

    Article  CAS  Google Scholar 

  4. Aebersold R, Mann M (2003) Mass spectrometry-based proteomics. Nature 422:198–207. doi:10.1038/nature01511

    Article  CAS  Google Scholar 

  5. Gupta MN, Roy I (2004) Enzymes in organic media. Forms, functions and applications. Eur J Biochem 271:2575–2583. doi:10.1111/j.1432-1033.2004.04163.x

    Article  CAS  Google Scholar 

  6. Caprioli RM, Farmer TB, Gile J (1997) Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem 69:4751–4760

    Article  CAS  Google Scholar 

  7. Nittler L, Delcorte A, Bertrand P, Migeon H-N (2011) Investigating the relation between the secondary yield enhancement and the structure of the metallic overlayer in metal-assisted SIMS. Surf Interface Anal 43:103–106. doi:10.1002/sia.3425

    Article  CAS  Google Scholar 

  8. Lebec V, Boujday S, Poleunis C et al (2014) Time-of-flight secondary ion mass spectrometry investigation of the orientation of adsorbed antibodies on SAMs correlated to biorecognition tests. J Phys Chem C 118:2085–2092. doi:10.1021/jp410845g

    Article  CAS  Google Scholar 

  9. Norris JL, Caprioli RM (2013) Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem Rev 113:2309–2342. doi:10.1021/cr3004295

    Article  CAS  Google Scholar 

  10. Laiko VV, Baldwin MA, Burlingame AL (2000) Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 72:652–657

    Article  CAS  Google Scholar 

  11. Goodwin RJ (2012) Sample preparation for mass spectrometry imaging: small mistakes can lead to big consequences. J Proteome 75:4893–4911. doi:10.1016/j.jprot.2012.04.012

    Article  CAS  Google Scholar 

  12. Takáts Z, Wiseman JM, Gologan B, Cooks RG (2004) Mass spectrometry sampling under ambient conditions with desorption electrospray ionization. Science 306:471–473. doi:10.1126/science.1104404

    Article  Google Scholar 

  13. Cody RB, Laramée J, Durst HD (2005) Versatile new ion source for the analysis of materials in open air under ambient conditions. Anal Chem 77:2297–2302. doi:10.1021/ac050162j

    Article  CAS  Google Scholar 

  14. McEwen CN, McKay RG, Larsen BS (2005) Analysis of solids, liquids, and biological tissues using solids probe introduction at atmospheric pressure on commercial LC/MS instruments. Anal Chem 77:7826–7831. doi:10.1021/ac051470k

    Article  CAS  Google Scholar 

  15. Sampson JS, Hawkridge AM, Muddiman DC (2006) Generation and detection of multiply-charged peptides and proteins by matrix-assisted laser desorption electrospray ionization (MALDESI) Fourier transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom 17:1712–1716. doi:10.1016/j.jasms.2006.08.003

    Article  CAS  Google Scholar 

  16. Eikel D, Vavrek M, Smith S et al (2011) Liquid extraction surface analysis mass spectrometry (LESA-MS) as a novel profiling tool for drug distribution and metabolism analysis: the terfenadine example. Rapid Commun Mass Spectrom 25:3587–3596. doi:10.1002/rcm.5274

    Article  CAS  Google Scholar 

  17. 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. doi:10.1007/s13361-012-0505-9

    Article  CAS  Google Scholar 

  18. Robichaud G, Barry JA, Muddiman DC (2014) IR-MALDESI Mass Spectrometry Imaging of Biological Tissue Sections Using Ice as a Matrix. J Am Soc Mass Spectrom 25:319–328. doi:10.1007/s13361-013-0787-6

    Article  CAS  Google Scholar 

  19. Berkenkamp S, Karas M, Hillenkamp F (1996) Ice as a matrix for IR-matrix-assisted laser desorption/ionization: mass spectra from a protein single crystal. Proc Natl Acad Sci U S A 93:7003–7007

    Article  CAS  Google Scholar 

  20. 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. doi:10.1021/ac300840b

    Article  CAS  Google Scholar 

  21. Nemes P, Vertes A (2007) Laser ablation electrospray ionization for atmospheric pressure, in vivo, and imaging mass spectrometry. Anal Chem 79:8098–8106. doi:10.1021/ac071181r

    Article  CAS  Google Scholar 

  22. Garden RW, Sweedler JV (2000) Heterogeneity within MALDI samples as revealed by mass spectrometric imaging. Anal Chem 72:30–36

    Article  CAS  Google Scholar 

  23. 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 13:735–748

    Article  CAS  Google Scholar 

  24. Koestler M, Kirsch D, Hester A et al (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. doi:10.1002/rcm

    Article  CAS  Google Scholar 

  25. Soltwisch J, Goritz G, Jungmann JH et al (2014) MALDI mass spectrometry imaging in microscope mode with infrared lasers: bypassing the diffraction limits. Anal Chem 86:321–325

    Article  CAS  Google Scholar 

  26. Heeren RM (2014) Getting the picture: the coming of age of imaging MS. Int J Mass Spectrom. doi:10.1016/j.ijms.2014.04.021

    Google Scholar 

  27. Jurchen JC, Rubakhin 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. doi:10.1016/j.jasms.2005.06.006

    Article  CAS  Google Scholar 

  28. Kampmeier J, Dreisewerd K, Schurenberg M, Strupat K (1997) Investigations of 2, 5-DHB and succinic acid as matrices for IR and UV MALDI. Part : I UV and IR laser ablation in the MALDI process. Int J Mass Spectrom Ion Process 176:31–41

    Article  Google Scholar 

  29. Olsen JV, de Godoy LMF, Li G et al (2005) Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol Cell Proteomics 4:2010–2021. doi:10.1074/mcp. T500030-MCP200

    Article  CAS  Google Scholar 

  30. Kessner D, Chambers M, Burke R et al (2008) ProteoWizard: open source software for rapid proteomics tools development. Bioinformatics 24:2534–2536. doi:10.1093/bioinformatics/btn323

    Article  CAS  Google Scholar 

  31. Robichaud G, Garrard KP, Barry JA, Muddiman DC (2013) MSiReader: an open-source interface to view and analyze high resolving power MS imaging files on Matlab platform. J Am Soc Mass Spectrom 24:718–721. doi:10.1007/s13361-013-0607-z

    Article  CAS  Google Scholar 

  32. Rogowitz BE, Treinish LA (1998) Data visualization: the end of the rainbow. IEEE Spectr 35:52–59

    Article  Google Scholar 

  33. Light A, Bartlein PJ (2004) The end of the rainbow? Color schemes for improved data graphics. EOS Trans Am Geophys Union 85:385–391. doi:10.1029/2004EO400002

    Article  Google Scholar 

  34. Borland D, Taylor MR (2007) Rainbow color map (still) considered harmful. IEEE Comput Graph Appl 27:14–17

    Article  Google Scholar 

  35. Barry J, Robichaud G, Bokhart MT et al (2014) Mapping antiretroviral drugs in tissue by IR-MALDESI MSI coupled to the Q Exactive and comparison with LC-MS/MS SRM assay. J Am Soc Mass Spectrom 25:2038–2047. doi:10.1007/s13361-014-0884-1

    Article  CAS  Google Scholar 

  36. Brunzel NA (2004) Fundamentals of urine & body fluid analysis, 2nd edn. Saunders, Philadelphia, PA

    Google Scholar 

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Acknowledgments

The authors thank Professor Angela D. M. Kashuba and her group from UNC Eshelman School of Pharmacy for providing the cervical tissues samples. The authors also gratefully acknowledge the financial assistance received from the National Institutes of Health (R01GM087964), the W.M. Keck foundation, and North Carolina State University.

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Authors and Affiliations

  1. W.M. Keck Fourier Transform Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC, 27695, USA

    Milad Nazari & David C. Muddiman

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  1. Milad Nazari
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  2. David C. Muddiman
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Correspondence to David C. Muddiman.

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Published in the topical collection Mass Spectrometry Imaging with guest editors Andreas Römpp and Uwe Karst.

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Nazari, M., Muddiman, D.C. Cellular-level mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) by oversampling. Anal Bioanal Chem 407, 2265–2271 (2015). https://doi.org/10.1007/s00216-014-8376-5

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  • DOI: https://doi.org/10.1007/s00216-014-8376-5

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