MALDI-MS imaging of features smaller than the size of the laser beam
The feasibility of matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging of features smaller than the laser beam size has been demonstrated. The method involves the complete ablation of the MALDI matrix coating the sample at each sample position and moving the sample target a distance less than the diameter of the laser beam before repeating the process. In the limit of complete sample ablation, acquiring signal from adjacent positions spaced by distances smaller than the sample probe enhances image resolution as the measured analyte signal only arises from the overlap of the laser beam size and the non-ablated sample surface. Image acquisition of features smaller than the laser beam size has been demonstrated with peptide standards deposited on electron microscopy calibration grids and with neuropeptides originating from single cells. The presented MS imaging technique enables ∼25 µm imaging spatial resolution using commercial MALDI mass spectrometers having irregular laser beam sizes of several hundred micron diameters. With appropriate sampling, the size of the laser beam is not a strict barrier to the attainable MALDI-MS imaging resolution.
- 5.Spengler, B.; Hubert, M.; Kaufmann, R. MALDI Ion Imaging and Biological Ion Imaging with a New Scanning UV-Laser Microprobe. Proceedings of the 42nd ASMS Conference on Mass Spectrometry and Allied Topics; Chicago, IL, May, 1994.Google Scholar
- 7.Zhang, H.; Stoeckli, M.; Andren, P. E.; Caprioli, R. M. Combining Solid-Phase Preconcentration, Capillary Electrophoresis and Off-Line Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry: Intracerebral Metabolic Processing of Peptide E in Vivo. J. Mass Spectrom. 1999, 34(4), 377–383.CrossRefGoogle Scholar
- 11.Yanagisawa, K.; Shyr, Y.; Xu, B. G. J.; Massion, P. P.; Larsen, P. H.; White, B. C.; Roberts, J. R.; Edgerton, M.; Gonzalez, A.; Nadaf, S.; Moore, J. H.; Caprioli, R. M.; Carbone, D. P. Proteomic Patterns of Tumor Subsets in Non-Small-Cell Lung Cancer. Lancet 2003, 362(9382), 433–439.CrossRefGoogle Scholar
- 22.Dreisewerd, K.; Schurenberg, M.; Karas, M.; Hillenkamp, F. Influence of the Laser Intensity and Spot Size on the Desorption of Molecules and Ions in Matrix-Assisted Laser-Desorption Ionization with a Uniform Beam Profile. Int. J. Mass Spectrom. Ion Processes 1995, 141(2), 127–148.CrossRefGoogle Scholar