NanoSIMS 50L Ion Micro-Analyzer

描述(由申请者提供)：我们正在为新一代二次离子质谱仪--NanoSIMS 50L离子显微分析仪申请资金。该仪器是多同位素成像质谱仪(MIMS)的核心，这是我国国家成像质谱库(NRIMS，NIBIB/NIH)开创的一项革命性技术(Lechene等人)。2006年，J.Biol：5：20；Lechene等人。2007，科学，317：1563)。MIMS允许在亚细胞水平上比较几个标记了不同稳定同位素的分子在完全相同的位置的分布和测量。利用MIMS，人们第一次可以在亚细胞室中看到(高分辨率)和测量(高精度)以前从未见过或测量过的单个细胞成分和过程。细胞内同位素定量成像适用于大量的分子，这些分子可以用任何稳定的(或放射性的)同位素标记，并将有助于生物医学研究的所有领域的研究。我们将继续与细胞生物学、生物化学、心脏病学、肾病学、免疫学、移植、干细胞、癌症、传染病、微生物学和病毒学的研究人员合作，开创MIMS的先河。我们的目标是研究蛋白质、脂肪酸、糖、外源分子的定位和周转，以及药物在细胞微区的定位；固氮和微生物代谢；病毒穿透；对称和不对称分裂中的DNA复制；细胞谱系，供体细胞向受体壁龛的迁移，干细胞的嵌套。MIMS的生物医学应用将继续扩大。稳定的同位素对人类研究来说是无价的。MIMS可以检测任何同位素标记，从而提供了一种在许多不能使用放射性标记的情况下跟踪标记的代谢前体或药物的细胞掺入的技术。用稳定的同位素标记细胞DNA允许对细胞进行非常长期和无风险的跟踪。这为研究细胞迁移、宿主和供体之间的细胞交换、干细胞的鉴定和细胞肿瘤转移提供了最有力的方法。最后，正如J.Weitzman Research News文章(2006，J.Biol.(5：16)：这项技术最重要的特点是它开辟了一个全新的成像世界；我们还没有想象到我们可以用它做什么。这项技术的新颖性意味着需要一段时间才能吸收细节，[但它]为细胞中稳定和放射性化合物的空间分辨率和检测设定了一个壮观的新标准。J·魏茨曼(J.Weitzman，2006，J.Biol)所引用的公共卫生相关性被称为“成像革命”。5：16)，MIMS将帮助解决生物医学研究所有领域的难题。

DESCRIPTION (provided by applicant): We are requesting funding for a NanoSIMS 50L Ion Micro-Analyzer, a new generation of secondary ion mass spectrometer. This instrument is at the core of Multi-Isotope Imaging Mass Spectrometry (MIMS), a revolutionary technology pioneered in our National Resource for Imaging Mass Spectrometry (NRIMS, NIBIB/NIH) (Lechene et al. 2006, J. Biol: 5:20; Lechene et al. 2007, Science, 317:1563). MIMS allows comparison at a subcellular level of the distribution and measurement of several molecules labeled with different stable isotopes at exactly the same location. With MIMS, for the first time, one can both see (at high resolution) and measure (with high precision) in subcellular compartments of individual cells components and processes that have not before been seen or measured. Intracellular isotope quantitative imaging is applicable to an immense array of molecules, which may be labeled with any stable (or radioactive) isotope and will contribute to studies in all domains of biomedical research. We will continue to pioneer MIMS in collaboration with researchers in cell biology, biochemistry, cardiology, nephrology, immunology, transplantation,stem cell, cancerology, infectious disease, microbiology and virology. Our aims are to study the localization and the turnover of proteins, fatty acids, sugars, foreign molecules, and the localization of drugs in cellular micro domains; nitrogen fixation and microbe metabolism; virus penetration; DNA replication in symmetric and asymmetric division; cell lineage , the migration of donor cells to receiver niches, the nesting of stem cell. MIMS biomedical applications will continue to expand. Stable isotopes are invaluable for human studies. MIMS can detect any isotope label, thus providing a technique for following the cellular incorporation of labeled metabolic precursors or drugs in the numerous situations where radiolabels cannot be used. Tagging cellular DNA with stable isotopes allows one very long-term and risk-free tracking of cells. This provide a most powerful method for the study of cell migration, cell exchange between a host and a donor, identification of stem cells and cell tumor metastasis. Finally, as quoted in J. Weitzman Research News article (2006, J. Biol. 5:16): 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. The novelty of the technique means it will take some time for the details to be absorbed, [but it] sets a spectacular new standard for spatial resolution and detection of stable and radioactive compounds in cells. PUBLIC HEALTH RELEVANCE Called 'an imaging revolution' as quoted by J. Weitzman (2006, J. Biol. 5:16), MIMS will help solve intractable problems in all fields of biomedical research.