Multi-Isotope Imaging Mass Spectrometry (MIMS)

Here’s a new method to visualize intracellular molecules, as reported in the open access Journal of Biology

Echoing the journey through the human body in Fantastic Voyage, doctors might soon be able to track individual donor cells after a transplant, or to find where and how much of a cancer treatment drug there is within a cell. New technology described in a study published today in the open access journal Journal of Biology makes it possible to image and quantify molecules within individual mammalian or bacterial cells. Claude Lechene and colleagues describe the development of multi-isotope imaging mass spectrometry (MIMS), which has applications in all fields of biology and biomedical research…
Lechene, of Harvard Medical School and Brigham and Women’s Hospital in the US, worked with colleagues from around the world to develop and test the new methodology.
A beam of ions is used to bombard the surface atoms of the biological sample, and a fraction of the atoms are emitted and ionized. These “secondary ions” can then be manipulated with ion optics – in the way lenses and prisms manipulate visible light – to create an atomic mass image of the sample. Lechene et al. developed MIMS by combining the use of a novel secondary-ion mass spectrometer developed by Georges Slodzian, from the Universite Paris-Sud in France, labeling with stable isotopes and building quantitative image-analysis software.
MIMS can generate quantitative, three-dimensional images of proteins, DNA, RNA, sugar and fatty acids at a subcellular level in tissue sections or cells. “Using MIMS, we can image and quantify the fate of these molecules when they go into cells, where they go, and how quickly they are replaced,” says Lechene.
The method does not need staining or use of radioactive labelling. Instead, it is possible to use stable isotopes to track molecules. For example, researchers could track stem cells by labelling DNA with 15N. “These stable isotopes do not alter the DNA and are not toxic to people; with MIMS and stable isotope labelling we could track these cells, where they are and how they have changed several years later,” says Lechene.
“The most significant feature of this technique is that it opens up a whole new world of imaging; we haven’t yet imagined all that we can do with it,” says Peter Gillespie from the Oregon Health and Science University in Portland, USA in an accompanying news article, also published today in Journal of Biology.

Picture caption: The primary Cs+ beam hits the sample and sputters the surface. Atoms and molecular fragments are ejected from the sample surface; during this process a fraction of the secondary particles are ionized. The identity of the secondary particles, determined by mass spectrometry, indicates the atoms or atomic clusters from the molecules in the sample that have been hit by the primary Cs+ beam. The figure shows only the types of atoms and ions that are relevant to this article; other particles formed by sputtering are not represented. Cs, cesium.
The article…
The press release…