Abstract
Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) techniques are continually being assessed with a view to improving the quality of information obtained from a given sample. A single tissue section will typically only be analyzed once by MALDI MSI and is then either used for histological staining or discarded. In this study, we explore the idea of repeat analysis of a single tissue section by MALDI MSI as a route toward improving sensitivity, structural characterization, and diversity of detected analyte classes. Repeat analysis of a single tissue section from a fresh frozen mouse brain is investigated with both α-cyano-4-hydroxycinnamic acid (CHCA) and para-nitroaniline (PNA). Repeat analysis is then applied to the acquisition of MALDI MSI and MALDI tandem mass spectrometry imaging employing collision induced dissociation (MS/MS imaging employing CID) from a formalin-fixed mouse brain section. Finally, both lipid and protein data are acquired from the same tissue section via repeat analysis utilizing CHCA, sinapinic acid (SA), and a tissue wash step. PNA was found to outperform CHCA as a matrix for repeat analysis; multiple lipids were identified using MS/MS imaging; both lipid and protein images were successfully acquired from a single tissue section.

Repeat analysis by MALDI MS imaging of a single tissue section is investigated with multiple matrices and tissue washes to provide increased molecular information from a single tissue section






Similar content being viewed by others
References
Bunch J, Clench MR, Richards DS (2004) Determination of pharmaceutical compounds in skin by imaging matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom 18(24):3051–3060. doi:10.1002/rcm.1725
Cornett DS, Frappier SL, Caprioli RM (2008) MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal Chem 80(14):5648–5653
Crecelius AC, Cornett DS, Caprioli RM, Williams B, Dawant BM, Bodenheimer B (2005) Three-dimensional visualization of protein expression in mouse brain structures using imaging mass spectrometry. J Am Soc Mass Spectrom 16(7):1093–1099
Balluff B, Rauser S, Meding S, Elsner M, Schöne C, Feuchtinger A, Schuhmacher C, Novotny A, Jütting U, Maccarrone G (2011) MALDI imaging identifies prognostic seven-protein signature of novel tissue markers in intestinal-type gastric cancer. Am J Pathol 179:2720–2729
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(2):228–237
Stoeckli M, Staab D, Staufenbiel M, Wiederhold KH, Signor L (2002) Molecular imaging of amyloid β peptides in mouse brain sections using mass spectrometry. Anal Biochem 311(1):33–39
Vidová V, Pól J, Volný M, Novák P, Havlíček V, Wiedmer SK, Holopainen JM (2010) Visualizing spatial lipid distribution in porcine lens by MALDI imaging high-resolution mass spectrometry. J Lipid Res 51(8):2295–2302
Cerruti CD, Benabdellah F, Laprévote O, Touboul D, Brunelle A (2012) MALDI imaging and structural analysis of rat brain lipid negative ions with 9-aminoacridine matrix. Anal Chem 84(5):2164–2171
Palmer AD, Griffiths R, Styles I, Claridge E, Calcagni A, Bunch J (2012) Sucrose cryo-protection facilitates imaging of whole eye sections by MALDI mass spectrometry. J Mass Spectrom 47(2):237–241
Angel PM, Spraggins JM, Baldwin HS, Caprioli R (2012) Enhanced sensitivity for high spatial resolution lipid analysis by negative ion mode matrix assisted laser desorption ionization imaging mass spectrometry. Anal Chem 84(3):1557–1564
Veloso A, Astigarraga E, Barreda-Gómez G, Manuel I, Ferrer I, Teresa Giralt M, Ochoa B, Fresnedo O, Rodríguez-Puertas R, Fernández JA (2011) Anatomical distribution of lipids in human brain cortex by imaging mass spectrometry. J Am Soc Mass Spectrom 22(2):329–338
Lanni EJ, Rubakhin SS, Sweedler JV (2012) Mass spectrometry imaging and profiling of single cells. J Proteomics 75:5036–5051
Stoeckli M, Staab D, Schweitzer A (2007) Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections. Int J Mass Spectrom 260(2):195–202
Soltwisch J, Jaskolla TW, Hillenkamp FH, Karas M, Dreisewerd K (2012) Ion yields in UV-MALDI mass spectrometry as a function of excitation laser wavelength and optical and physico-chemical properties of classical and halogen-substituted MALDI matrixes. Anal Chem 84:6567–6576
Shanta SR, Zhou LH, Park YS, Kim YH, Kim Y, Kim KP (2011) Binary matrix for MALDI imaging mass spectrometry of phospholipids in both ion modes. Anal Chem 83(4):1252–1259
Luo G, Marginean I, Vertes A (2002) Internal energy of ions generated by matrix-assisted laser desorption/ionization. Anal Chem 74(24):6185–6190
Chernushevich IV, Loboda AV, Thomson BA (2001) An introduction to quadrupole–time-of-flight mass spectrometry. J Mass Spectrom 36(8):849–865
Yagnik GB, Korte AR, Lee YJ (2013) Multiplex mass spectrometry imaging for latent fingerprints. J Mass Spectrom 48(1):100–104
Perdian D, Lee YJ (2010) Imaging MS methodology for more chemical information in less data acquisition time utilizing a hybrid linear ion trap–orbitrap mass spectrometer. Anal Chem 82(22):9393–9400
Holle A, Haase A, Kayser M, Hohndorf J (2006) Optimizing UV laser focus profiles for improved MALDI performance. J Mass Spectrom 41(6):705–716. doi:10.1002/jms.1041
Clench MR, Trim PJ, Djidja MC, Atkinson SJ, Oakes K, Cole LM, Anderson DMG, Hart PJ, Francese S (2010) Introduction of a 20 kHz Nd:YVO4 laser into a hybrid quadrupole time-of-flight mass spectrometer for MALDI-MS imaging. Anal Bioanal Chem 397(8):3409–3419. doi:10.1007/s00216-010-3874-6
Wiegelmann M, Soltwisch J, Jaskolla TW, Dreisewerd K (2012) Matching the laser wavelength to the absorption properties of matrices increases the ion yield in UV-MALDI mass spectrometry. Anal Bioanal Chem [Epub ahead of print]
Chughtai S, Chughtai K, Pastor BC, Kiss A, Agrawal P, MacAleese L, Heeren R (2012) A multimodal mass spectrometry imaging approach for the study of musculoskeletal tissues. Int J Mass Spectrom 325–327:150–160
Matusch A, Fenn LS, Depboylu C, Klietz M, Strohmer S, McLean JA, Becker JS (2012) Combined elemental and biomolecular mass spectrometry imaging for probing the inventory of tissue at a micrometer scale. Anal Chem 84(7):3170–3178
Garrett TJ, Prieto-Conaway MC, Kovtoun V, Bui H, Izgarian N, Stafford G, Yost RA (2007) Imaging of small molecules in tissue sections with a new intermediate-pressure MALDI linear ion trap mass spectrometer. Int J Mass Spectrom 260(2):166–176
Eberlin LS, Liu X, Ferreira CR, Santagata S, Agar NYR, Cooks RG (2011) Desorption electrospray ionization then MALDI mass spectrometry imaging of lipid and protein distributions in single tissue sections. Anal Chem 83(22):8366–8371
Seeley EH, Oppenheimer SR, Mi D, Chaurand P, Caprioli RM (2008) Enhancement of protein sensitivity for MALDI imaging mass spectrometry after chemical treatment of tissue sections. J Am Soc Mass Spectrom 19(8):1069–1077
Race AM, Styles IB, Bunch J (2012) Inclusive sharing of mass spectrometry imaging data requires a converter for all. J Proteomics 75(16):5111–5112. doi:10.1016/j.jprot.2012.05.035
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(10):1654–1659. doi:10.1016/j.jasms.2005.06.006
Simmons DA (2008) Improved MALDI-MS imaging performance using continuous laser rastering. Applied Biosystems Technical Note
Steven RT, Race AM, Bunch J (2013) para-Nitroaniline is a promising matrix for MALDI-MS imaging on intermediate pressure MS systems. J Am Soc Mass Spectrom. doi:10.1007/s13361-013-0586-0
Jackson SN, Ugarov M, Post JD, Egan T, Langlais D, Schultz JA, Woods AS (2008) A study of phospholipids by ion mobility TOFMS. J Am Soc Mass Spectrom 19(11):1655–1662
Fournier I, Beavis R, Blais J, Tabet J, Bolbach G (1997) Hysteresis effects observed in MALDI using oriented, protein-doped matrix crystals. Int J Mass Spectrom Ion Process 169:19–29
Fournier I, Tabet JC, Bolbach G (2002) Irradiation effects in MALDI and surface modifications: part I: sinapinic acid monocrystals. Int J Mass Spectrom 219(3):515–523
Fournier I, Marinach C, Tabet JC, Bolbach G (2003) Irradiation effects in MALDI, ablation, ion production, and surface modifications. Part II: 2,5-dihydroxybenzoic acid monocrystals. J Am Soc Mass Spectrom 14(8):893–899. doi:10.1016/S1044-0305(03)00347-7
Tarzi OI, Nonami H, Erra-Balsells R (2009) The effect of temperature on the stability of compounds used as UV-MALDI-MS matrix: 2, 5-dihydroxybenzoic acid, 2, 4, 6-trihydroxyacetophenone, α-cyano-4-hydroxycinnamic acid, 3, 5-dimethoxy-4-hydroxycinnamic acid, nor-harmane and harmane. J Mass Spectrom 44(2):260–277
Wang HYJ, Liu CB, Wu HW, Kuo JS (2010) Direct profiling of phospholipids and lysophospholipids in rat brain sections after ischemic stroke. Rapid Commun Mass Spectrom 24(14):2057–2064
Amstalden van Hove ER, Smith DF, Heeren R (2010) A concise review of mass spectrometry imaging. J Chromatogr A 1217(25):3946–3954
Al-Saad KA, Siems WF, Hill H, Zabrouskov V, Knowles NR (2003) Structural analysis of phosphatidylcholines by post-source decay matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. J Am Soc Mass Spectrom 14(4):373–382
Stübiger G, Belgacem O (2007) Analysis of lipids using 2, 4, 6-trihydroxyacetophenone as a matrix for MALDI mass spectrometry. Anal Chem 79(8):3206–3213
Carter CL, McLeod CW, Bunch J (2011) Imaging of phospholipids in formalin fixed rat brain sections by matrix assisted laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom 22(11):1991–1998
Prideaux B, Dartois V, Staab D, Weiner DM, Goh A, Via LE, Barry CE III, Stoeckli M (2011) High-sensitivity MALDI-MRM-MS imaging of moxifloxacin distribution in tuberculosis-infected rabbit lungs and granulomatous lesions. Anal Chem 83(6):2112–2118
Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM (2006) Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. Anal Chem 78(18):6448–6456
Alzate O (2009) Neuroproteomics. CRC, Boca Raton
Shrivas K, Hayasaka T, Goto-Inoue N, Sugiura Y, Zaima N, Setou M (2010) Ionic matrix for enhanced MALDI imaging mass spectrometry for identification of phospholipids in mouse liver and cerebellum tissue sections. Anal Chem 82(21):8800–8806
Zemski Berry KA, Hankin JA, Barkley RM, Spraggins JM, Caprioli RM, Murphy RC (2011) MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem Rev 111(10):6491–6512. doi:10.1021/cr200280p
Acknowledgments
The authors would like to thank the EPSRC for funding via studentships for R.T.S. through the PSIBS Doctoral Training Centre at the University of Birmingham (EP/F50053X/1).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
ESM 1
(PDF 1.97 mb)
Rights and permissions
About this article
Cite this article
Steven, R.T., Bunch, J. Repeat MALDI MS imaging of a single tissue section using multiple matrices and tissue washes. Anal Bioanal Chem 405, 4719–4728 (2013). https://doi.org/10.1007/s00216-013-6899-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-013-6899-9

