The mass spectrometry imaging lab – University of Copenhagen

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Department of Pharmacy > Research > Section of Analytical Biosciences > Drug Metabolism Lab > The mass spectrometry

The mass spectrometry imaging lab

  

With a number of recently developed techniques it is possible to use mass spectrometry (MS) to create images, which show the distribution of low-molecular weight compounds on a surface. With MS imaging, we are not only visualizing biological structures, but also obtaining chemical information about which compounds they are built of. The techniques, which are these years gradually being introduced also in the pharmaceutical industry, can be applied e.g. in studies of drugs in laboratory animals or in studies of tumors or other modifications in tissue, thus contributing to the understanding of the symptoms, the progress and the cure of various diseases. In our research group we are using MS imaging techniques in a number of different fields, with a particular focus on studies within pharmacology and plant science. We are currently using MS imaging in studies of:

  • Brain ischemia in rats and mice. The technique is applied to investigate changes on the molecular level related to brain ischemia and recovery from brain ischemia, focusing on the biosynthesis and degradation of lipids in the cellular membranes.
  • Penetration of drugs through skin, using pig skin as a model. Imaging analyses, showing the distribution and metabolism of drugs through the skin compartments.
  • Penetration of anti-cancer drugs through skin after laser treatment
  • Distribution and metabolism of drugs in animal tissue (mice)
  • Distribution and metabolism of drugs in insect models (locust grasshopper)
  • Enzymatic reactions in plant material

Besides imaging, we are also working with development and application of new ionization techniques for direct and rapid analysis with mass spectrometry, e.g. for direct mass spectrometry analysis of tablets or TLC-plates.

 

 

Mass spectrometry imaging

Mass spectrometry is one of the most widely used analytical techniques and extensively used within fields such as pharmaceutical and environmental analysis, showing obvious advantages with regards to sensitivity, selectivity and identification capabilities.

Most mass spectrometric analyses today are performed on samples in solution. This implies that if a non-liquid sample is to be analyzed, e.g. a piece of animal or plant tissue, a liquid extraction must be performed prior to the mass spectrometric analysis. Such an approach may very well be used to show that a particular compound was present in the sample, but all information about where in the sample the compounds was present is lost in the extraction process.

The spatial information in the mass spectrometric analysis can be retained if the extraction process is avoided or performed very locally in the sample. This is possible with many of the new ambient ionization techniques such as Desorption Electrospray Ionization (DESI).

DESI and other techniques are particular in the way that they are capable of ionizing and desorbing analytes directly from a surface, such that traditional liquid extractions can be avoided. One can thus move the sample below the ionization spot while looking at the mass spectra being recorded and thereby see exactly where in the sample a given compound was detected. By automatizing the movement of the sample below the ionization spot such that the entire sample is scanned spot by spot, pixel by pixel, while the mass spectrometer is recording spectra, images can be generated showing the spatial distributions of all the detected compounds.

The advantage of mass spectrometry images, compared to most other images, is that they are specific to chemical compound being imaged. When a drug is images in a laboratory animal, one can thus distinguish the original drug from the metabolites which may have formed in the body.