MALDI Mass Spectrometry Imaging in Microscope Mode with Infrared Lasers: Bypassing the Diffraction Limits

Jens Soltwisch, Guido Goeritz, Julia H. Jungmann, Andras Kiss, Donald F. Smith, Shane R. Ellis, Ron M. A. Heeren*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Web of Science)


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 ?m, well below the optical limit of diffraction (14 ?m 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.
Original languageEnglish
Pages (from-to)321-325
JournalAnalytical Chemistry
Issue number1
Publication statusPublished - 7 Jan 2014

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