The core of this 'Resource' is a novel type of secondary ion mass spectrometer, the Multi-Isotope Imaging Mass Spectrometer (MIMS). Secondary ion mass spectrometry is based upon the sputtering of a few atomic layers from the surface of a sample. During the ejection process, some atoms and clusters are spontaneously ionized. These 'secondary ions' are a characteristic of the composition of the analyzed surface. In a secondary ion mass spectrometer, the secondary ions are separated according to their mass, and a quantitative image of the distribution of the selected mass is formed. MIMS provides high mass separation (M/deltaM > 10,000), high spatial resolution (< 50 nm) and has the unique capability of simultaneously recording several atomic mass images. Of the utmost importance, MINIS makes it possible for the first time (and at the intracellular level) to simultaneously image the distribution and measure the accumulation of molecules labeled with any isotopes, in particular with stable isotopes, for example with 15N. Thus, MIMS allows one to study the localization, the accumulation and the turnover of proteins, fats, sugars and foreign molecules in cellular microdomains. The Resource collaborates with researchers to use the unique advantages of MIMS to bring original information in cell biology, physiology, physiopathology, biochemistry, immunology, transplantation, toxicology, stem cell and gene transfer research. MINIS offers a powerful and quantitative new method for studying intra and transcellular metabolic pathways, signal transduction, RNA and DNA expression and distribution, fatty acid transport, donor-receiver cellular trafficking, stem cell nesting and localization of drugs. Finally, the use of stable isotopes offers a world of labeling possibilities that were impossible with auto-radiography. It will revive and expand the use of tracers in humans. Instrumental development (brighter cesium primary ion source, iodine negative primary ion source, bipolar Cs+/Isource, preanalysis covering of the sample surface with cesium) will increase the resolution to 20nm, will allow sensitive measurements of calcium, alkali metals (Na, K), metals (metalloenzymes) and will allow analysis of the very first atomic layers at the cell surface. Study of secondary ion formation, development of automation and powerful data reduction software, development of standards, and development of methods for long term labeling of cells will increase the breadth of the Resource and will benefit the community of users. A workshop has been and will be organized every year. A Resource website displays a wealth of information to the budding community of users. A secure server allows exchanges of large reams of data between the Resource and users. A webserver for the community of users is being built and will be maintained by the Resource.
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