title: MALDI mass spectrometry imaging in microscope mode with infrared lasers: bypassing the diffraction limits.
abstract: This letter demonstrates the use of infrared matrix-assisted laser desorption/ionization coupled with microscope mode mass spectrometry imaging. It is aimed to explore the use of intrinsic water in tissue as a matrix for imaging at spatial resolutions below the diffraction limit of the employed IR optics. Stigmatic ion optics with a magnification factor of ~70 were used to project the spatial distribution of produced ions onto a detector while separating ions with different mass-to-charge ratios using a time-of-flight mass spectrometer. A pixelated detector was used to simultaneously record arrival time and impact position. A previously described dried-droplet sample system of 2,5-dihydroxybenzoic acid (DHB) and 5 peptides covered by a copper grid for defined surface structure was used to benchmark the light- and ion-optical setup for spatial resolution and mass spectrometric performance. A spatial resolving power of 9.8 μm, well below the optical limit of diffraction (14 μm for the given setup), was established. After, frozen cryo-sections from a biological model system were measured by exploiting the endogenous water content as a matrix. Principal component analysis enabled a clear distinction between distinct tissue regions identified by both light microscopy and MS imaging.
authors.affiliation: FOM Institute AMOLF , Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: Jens
authors.initials: J
authors.lastname: Soltwisch
authors.forename: Guido
authors.initials: G
authors.lastname: Göritz
authors.forename: Julia H
authors.initials: JH
authors.lastname: Jungmann
authors.forename: András
authors.initials: A
authors.lastname: Kiss
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smith
authors.forename: Shane R
authors.initials: SR
authors.lastname: Ellis
authors.forename: Ron M A
authors.initials: RM
authors.lastname: Heeren
mesh_terms: D000818:Animals; D007259:Infrared Rays; D007834:Lasers / Q000706:statistics & numerical data; D008099:Liver / Q000737:chemistry / Q000166:cytology; D036441:Osmeriformes; D011897:Random Allocation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*