It is reported that in order to improve mass spectrometry to enhance the study of cytochemical composition, researchers from the University of Münster have developed a method for improving the spatial resolution of matrix-assisted laser desorption ionization (MALDI) mass spectrometry in UK health agencies. Increased by about a thousandth of a millimeter.
The researchers called the technique t-MALDI-2 (‘t’ indicates the transmission mode), which uses two lasers: one for generating a smaller focus on the removed material and the other for another laser It is used to generate the necessary signal enhancement. For many biomolecules, the signal is enhanced by several orders of magnitude, such as fat-soluble vitamins including vitamin D and cholesterol, and drug administration. Their precise distribution in cells and tissues, as well as other information, helps to better understand disease and inflammatory processes and shows new strategies for treating them.
MALDI mass spectrometry defines the nature and composition of a molecule based on their characteristic mass – their “molecular weight”. In this way, it is possible to take samples of the laser-irradiated sample – for example, a thin tissue section obtained from a biopsy, which can define dozens or even hundreds of different biomolecules simultaneously in one measurement. However, to date, mass spectrometry provides much lower resolution than classical optical microscopes. The introduction of the new t-MALDI-2 technology will greatly reduce this gap.
Dr. Marcel Niehaus, one of the two leading authors of the study, explained: “The decisive improvements provided by our approach are based on the combination and extension of the two previously used techniques compared to the established MALDI imaging approach. In the transmission geometry, we have irradiated the sample in the opposite direction. This way, we can place the high-quality microscope lens very close to the sample, thus reducing the size of the laser spot. For geometric reasons This method is different from the standard method of illuminating a sample from the direction of the mass analyzer.”
However, in the tiny regions of the sample removed by the laser, only a very small amount of material is available for subsequent mass spectrometry measurements. Therefore, the second decisive step is to use a method called MALDI-2, which researchers have introduced in Science in 2015. The effect is the so-called post ionization laser, which causes the more uncharged molecules to transfer more to the ionic form. If the molecules have a positive or negative charge, they are visible to the mass analyzer.
In their latest research using the fine structure of the mouse cerebellum and the use of kidney cell culture, the researchers demonstrated the possibilities offered by their technology. Klaus Dreisewerd, a professor of health institutions in the UK and one of the research leaders, said: “Our approach can improve people’s understanding of many in vivo activities from the molecular level. In addition, methods developed by optical microscopy, such as fluorescence microscopy, can be used with Mass spectrometry imaging in ‘multi-mode’ instruments is used in conjunction.”