title: MALDI mass spectrometry imaging of proteins exceeding 30,000 daltons.
abstract: BACKGROUND
  Since its introduction 10 years ago by Caprioli and associates, MALDI mass spectrometry imaging has enabled spatial analysis of drugs, lipids, peptides, and polypeptides. In polypeptides, the detectable mass range is limited to small proteins with a mass less than 25 kDa. This is a limitation, as many proteins, including cytokines, growth factors, enzymes, and receptors have molecular weights, exceeding 25 kDa. In the present work, we report the development of a novel strategy to observe higher mass proteins up to 30 kDa.
  
  
  METHODS
  We investigated the development of sample preparation methods based on hexafluoroisopropanol (1,1,1,3,3,3-hexaluoro-2-propanol) and 2,2,2-trifluoroethanol solvents for protein solubilization optimized for high-mass proteins.
  
  
  RESULTS
  We were, for the first time in mass spectrometry imaging, able to detect to proteins up to 70 kDa directly from tissue. These developments indicate future avenues by which the sensitivity of protein mass spectrometry imaging can be further improved. We applied these developments to ovarian cancer and demonstrate that protein are similar to that which can be obtained using 2D gel based analyses.
  
  
  CONCLUSIONS
  Increasing the possibility of detecting proteins and high-mass proteins is key for developing direct tissue proteomics and especially any potential functional investigation. These data will open the door of a novel step in mass spectrometry imaging.
authors.affiliation: Universite Nord de France, CNRS, MALDI Imaging Team, Laboratoire de Neuroimmunologie et Neurochimie Evolutives, Universite Lille 1, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Franck
authors.forename: Rémi
authors.initials: R
authors.lastname: Longuespée
authors.forename: Maxence
authors.initials: M
authors.lastname: Wisztorski
authors.forename: Alexandra
authors.initials: A
authors.lastname: Van Remoortere
authors.forename: René
authors.initials: R
authors.lastname: Van Zeijl
authors.forename: André
authors.initials: A
authors.lastname: Deelder
authors.forename: Michel
authors.initials: M
authors.lastname: Salzet
authors.forename: Liam
authors.initials: L
authors.lastname: McDonnell
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fournier
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001921:Brain / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism; D020005:Propanols; D011506:Proteins / Q000032:analysis* / Q000737:chemistry*; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D014020:Tissue Extracts / Q000378:metabolism; D014270:Trifluoroethanol; D006845:Hydrocarbons, Fluorinated
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020005:Propanols; D011506:Proteins; D014020:Tissue Extracts; D014270:Trifluoroethanol; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated