Mass Spectrometry-Based Tissue Imaging
In MALDI (matrix-assisted laser desorption/ionization) mass spectrometry, the sample consists of a thin film of proteins or peptides that has been cocrystallized with a matrix selected to “match” the frequency of a UV laser. The laser vaporizes and ionizes the sample, which is then mass-analyzed, typically in a time-of-flight (TOF) mass analyzer. Since the footprint of the laser is small, and the sample is a solid rather than a solution, it is easy to see how this led to the idea of “rastering” the laser across the sample to form a molecular image.
After about ten years of development, MALDI imaging has finally come of age. This is partly due to newer MALDI-MS instrumentation that is capable of higher mass accuracy and resolution, as well as the development of MALDI-MS/MS for gas-phase sequencing. Several commercially-available sprayer/spotters have recently been developed which can produce a uniform coating of matrix on the sample. These sprayer/spotters can also be used to deposit enzyme solutions on targeted areas so that differentially-localized proteins can be identified.
This chapter describes some of the recent work in MALDI imaging, as well as some of the clinical applications of this technique. Finally, a new technique is described (MRM MALDI) which allows the quantitation of differentially-localized proteins on the basis of their peptide MS/MS spectra.
KeywordsImaging Mass Spectrometry Sinapinic Acid High Mass Accuracy MALDI Matrix Laser Desorption Ionization Mass Spectrometry
Unable to display preview. Download preview PDF.
- Caldwell RL, Caprioli RM (2005) Tissue profiling and imaging by matrix-assisted laser desorption ionization mass spectrometry. Proteomics Cancer Res :107–116Google Scholar
- Caldwell RL, Gonzalez A, Oppenheimer SR, Schwartz HS, Caprioli RM (2006) Molecular assessment of the tumor protein microenvironment using imaging mass spectrometry. Cancer Genomics Proteomics 3(4):279–288Google Scholar
- Caprioli RM (2004a) Imaging of proteins in tissue sections using mass spectrometry as a discovery tool. Zhipu Xuebao 25(Suppl):119–120Google Scholar
- Caprioli RM (2004b) Direct imaging and profiling of proteins in tissues using mass spectrometry to aid diagnosis and treatment of disease and to identify therapeutic targets. Abstracts from the 56th Southeast Regional Meeting of the American Chemical Society, Research Triangle Park, NC, 10–13 Nov. 2004, GEN-211Google Scholar
- Caprioli RM (2005) Direct imaging and profiling of proteins in tissues using mass spectrometry to aid diagnosis and treatment of disease and to identify therapeutic targets. Abstracts of Papers from the 229th ACS National Meeting, San Diego, CA, 13–17 March 2005, ANYL-385Google Scholar
- Caprioli RM (2006) In situ molecular imaging of proteins in tissues using mass spectrometry: A new tool for biological and clinical research. Abstracts of Papers from the 231st ACS National Meeting, Atlanta, GA, 26–30 March 2006, ANYL-276Google Scholar
- Caprioli RM, Chaurand P (2001) Profiling and imaging of peptides and proteins in biological tissues using MALDI MS. Adv Mass Spectrom 15:3–18Google Scholar
- Caprioli RM, Farmer TB, Zhang H, Stoeckli M (1997a) Molecular imaging of biological samples by MALDI MS. Book of Abstracts from the 214th ACS National Meeting, Las Vegas, NV, 7–11 Sept. 1997, ANYL-113Google Scholar
- Chaurand P, Caprioli RM (2001) Direct tissue analysis for profiling and imaging of proteins. Abstracts of Papers from the 222nd ACS National Meeting, Chicago, IL, 26–30 Aug. 2001, TOXI-003Google Scholar
- Chaurand P, Sanders ME, Jensen RA, Caprioli RM (2004a) Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. Am J Pathol 165(4):1057–1068Google Scholar
- Chaurand P, Hayn G, Matter U, Caprioli RM (2004e) Exploring the potential of cryodetectors for the detection of matrix-assisted laser desorption/ionization produced ions: application to profiling and imaging mass spectrometry. Zhipu Xuebao 25(suppl):205–206,216Google Scholar
- Deininger S-O, Krieg R, Rauser S, Walch A (2008) Advances in molecular histology with the MALDI molecular imager. Bruker Appl Note MT-89:1–6Google Scholar
- Fuchs B, Schiller J, Suess R, Zscharnack M, Bader A, Mueller P, Schuerenberg M, Becker M, Suckau D (2008) Analysis of stem cell lipids by offline HPTLC-MALDI-TOF MS. Anal Bioanal Chem. Aug 5, Epub ahead of printGoogle Scholar
- Groseclose MR, Chaurand P, Wirth PS, Massion PP, Caprioli RM (2005) Investigating formalin fixed paraffin embedded tissue specimens by imaging MALDI mass spectrometry: application to lung cancer tissue microarrays. Presented at HUPO 4, 29 Aug.—1 Sept. 2005, Munich, GermanyGoogle Scholar
- Holland RD, Wilkes JG, Rafii F, Sutherland JB, Persons CC, Voorhees KJ, Lay JOJ (1996) Rapid identification of intact whole bacteria based on spectral patterns using matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 10:1227–1232PubMedCrossRefGoogle Scholar
- Lange V, Malmström JA, Didion J, King NL, Johansson, BP, Schäfer J, Rameseder J, Wong CH, Deutsch EW, Brusniak MY, Bühlmann P, Björck L, Domon B, Aebersold R (2008) Targeted quantitative analysis of Streptococcus pyogenes virulence factors by multiple reaction monitoring. Mol Cell Proteomics 7(8):1489–1500PubMedCrossRefGoogle Scholar
- Lemaire R, Stauber J, Wisztorski M, Van Camp C, Desmons A, Deschamps M, Proess G, Rudlof I, Woods AS, Day R, Salzet M, Fournier I (2007a) Tag-mass: specific molecular imaging of transcriptome and proteome by mass spectrometry based on photocleavable tag. J Proteome Res 6(6):2057–2067CrossRefGoogle Scholar
- Meistermann H, Norris JL, Aerni H-R, Cornett DS, Friedlein A, Erskine AR, Augustin A, De Vera Mudry MC, Ruepp S, Suter L, Langen H, Caprioli RM, Ducret A (2006) Biomarker discovery by imaging mass spectrometry: transthyretin is a biomarker for gentamicin-induced nephrotoxicity in rat. Mol Cell Proteomics 5(10):1876–1886PubMedCrossRefGoogle Scholar
- Parker CE, Warren MR, Loiselle DR, Dicheva NN, Scarlett CO, Borchers CH (2005) Identification of components of protein complexes, vol. 301. Humana, Patterson, NJ, pp 117–151Google Scholar
- Perkins JR, Smith B, Gallagher RT, Jones DS, Davis SC, Hoffman AD, Tomer KB (1993) Application of electrospray mass spectrometry and matrix-assisted laser desorption ionization time-of-flight mass spectrometry for molecular weight assignment of peptides in complex mixtures. J Am Soc Mass Spectrom 4(8):670–84CrossRefGoogle Scholar
- Reyzer ML, Caprioli RM (2005) MS imaging: new technology provides new opportunities. In: Korfmacher WA (ed) Using mass spectrometry for drug metabolism studies. CRC, Boca Raton, FL, pp 305–328Google Scholar
- Schuerenberg M, Luebbert C, Deininger S, Mueller R, Suckau D (2007) A new preparation technique for MALDI tissue imaging. Presented at the ASMS Workshop on Imaging Mass Spectrometry, Sanibel, FL, 19–22 Jan. 2007Google Scholar