Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass spectrometry: Instrumentation for sub-micrometer resolved LDI and MALDI surface analysis

Abstract

A new instrument and method is described for laterally resolved mass spectrometric surface analysis. Fields of application are in both the life sciences and the material sciences. The instrument provides for imaging of the distribution of selected sample components from natural and artificial surfaces. Samples are either analyzed by laser desorption ionization (LDI) time-of-flight mass spectrometry or, after preparation with a suitable matrix, by matrixassisted laser desorption ionization (MALDI) mass spectrometry. Areas of 100 ϫ 100 m are scanned with minimal increments of 0.25 m, and between 10,000 and 160,000 mass spectra are acquired per image within 3 to 50 min (scan rate up to 50 pixels per s). The effective lateral resolution is in the range of 0.6 to 1.5 m depending on sample properties, preparation methods and laser wavelength. Optical investigation of the same sample area by UV confocal scanning laser microscopy was found to be very attractive in combination with scanning MALDI mass analysis because pixel-identical images can be created with both techniques providing for a strong increase in analytical information. This article describes the method and instrumentation, including first applicational examples in elemental analysis, imaging of pine tree roots, and investigation of MALDI sample morphology in biomolecular analysis. (J Am Soc Mass Spectrom 2002, 13, 735-748)

Spatial profiling invertebrate ganglia using MALDI MS

“…Commercial MALDI instruments can obtain ϳ25 m resolution. Impressively, Spengler et al recently described a specialized instrument for MALDI MS imaging with resolutions in the micron range [24].…”

Submicron mass spectrometry imaging of single cells by combined use of mega electron volt time-of-flight secondary ion mass spectrometry and scanning transmission ion microscopy

“…Despite the good sensitivity of MALDI, which uses a matrix to enhance the ionization probability, the spatial resolution of the laser beam spot is in the range of 5-10 lm, with 3 lm as the best spatial resolution obtained by analyzing a mouse brain section. 7 Nevertheless, there is another approach called Scanning Microprobe MatrixAssisted Laser Desorption Ionization (SMALDI), 8 with laser focus below 1 lm, but in order to perform high-resolution biological imaging, the limitations in the effective lateral resolution due to matrix application remain to be solved. 9 Contrary to the MALDI technique, the beam spot size with SIMS is well below 1 lm, which provides an excellent spatial resolution; however, the sensitivity of the technique is much worse, thereby limiting the spot area under analysis to $1 lm.…”

Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry

“…The spatial resolution obtained in MALDI microprobe imaging is typically in the 100 to 200 m range, limited by the size of the laser spot used [31,32]. The development of micrometer resolution has been reported [33], however decreasing spot size has been found to lead to decreasing sensitivity for high mass species. An alternative approach for high spatial resolution IMS is the mass microscope.…”