MIMS allows one to image the atomic composition of biological samples in cellular microdomains and therefore to study the localization, the accumulation, and the turnover of proteins, lipids, nucleic acids, carbohydrates and other molecules labeled with any isotope, particularly stable isotopes.
A number of features make this secondary ion mass spectrometer uniquely suited for biological studies:
1. For the first time it is possible to simultaneously image the distribution and measure the accumulation down to the subcellular level of molecules labeled with any isotope or combination of isotopes, such as 2D, 13C, 15N or 18O. The use of stable isotopes offers immense advantages in the study of health related questions, opening a world of labeling possibilities that were impossible with autoradiography, such as a broad expansion of the use of isotopic tracers in humans for diagnostic and clinical research.
2. MIMS allows four analytical images to be simultaneously recorded from the same volume sputtered by a single scan of a sample. Because the quantitative images are produced in parallel from the same sputtered volume, they are in exact registration with each other, allowing us to accurately measure isotope ratio differences of a few percent. In addition, the sensitivity of the instrument is high enough to detect as few as 300 atoms of 15N in the analyzed volume.
3. The present lower limit for the spatial resolution is 35nm x 35nm, allowing one to analyze sub-cellular organelles. As little as a few atomic layers on the surface may be sampled. Thus, one can study cellular surfaces or what would be the equivalent of ultra-thin sections a few nm thick. The upper limit of the field of analysis is large enough for tissue studies. In addition, the same sample may be analyzed at a succession of depths through controlled erosion.
4. By sputtering away layer-after-layer of a sample, we produce thousands of quantitative images containing an immense breadth of information in 3D space. This allows us to perform quantitative MIMS tomography (QMT) on whole cells, from the roof to the ground floor. The stack of analyzed layers can be viewed as a 3D reconstruction as well as played as a movie - MIMS time-lapse autography - to reveal phenomena that are difficult to detect in the absence of retinal persistence.
MIMS offers an extremely powerful method for performing both quantitation and imaging. Potential MIMS biomedical applications include the study of intra- and inter-cellular metabolic pathways, protein turnover, RNA and DNA expression and distribution, fatty acid transport, nucleo-cytoplasmic translocation, donor-recipient cellular trafficking, cell lineage labeling, and drug localization, to name just a few.
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