NanoSIMS 50L Ion Micro-Analyzer

描述（由申请人提供）：我们正在申请新一代二次离子质谱仪NanoSIMS 50L离子微分析仪的资助。该仪器是多同位素成像质谱（MIMS）的核心，这是我们国家成像质谱资源（NRIMS, NIBIB/NIH）首创的革命性技术（Lechene et al. 2006， J. Biol: 5:20; Lechene et al. 2007, Science, 317:1563）。MIMS允许在亚细胞水平上比较分布和测量几个分子，这些分子在完全相同的位置标记有不同的稳定同位素。有了MIMS，人们第一次可以看到（高分辨率）和测量（高精度）单个细胞的亚细胞区室，这些成分和过程以前没有被看到或测量过。细胞内同位素定量成像适用于大量分子，这些分子可以用任何稳定（或放射性）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、肾脏病学、免疫学、移植学、干细胞学、肿瘤学、传染病学、微生物学和病毒学等领域的研究人员合作，开拓MIMS。我们的目标是研究蛋白质、脂肪酸、糖、外源分子和药物在细胞微域的定位和周转；固氮与微生物代谢；病毒渗透;DNA在对称和非对称分裂中的复制；细胞谱系，供体细胞向受体龛的迁移，干细胞的嵌套。MIMS生物医学应用将继续扩大。稳定同位素对人类研究是无价的。MIMS可以检测任何同位素标记，从而在放射性标记不能使用的许多情况下，为跟踪标记的代谢前体或药物的细胞结合提供了一种技术。用稳定的同位素标记细胞DNA，可以长期无风险地跟踪细胞。这为研究细胞迁移、细胞在宿主和供体之间的交换、干细胞鉴定和细胞肿瘤转移提供了最有力的方法。最后，引用J. Weitzman Research News的文章（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；我们还没有想象过我们能用它做什么。这项技术的新颖性意味着它需要一些时间来吸收细节，[但它]为空间分辨率和检测细胞中的稳定和放射性化合物设定了一个惊人的新标准。被J. Weitzman （2006， J. Biol. 5:16）称为“成像革命”的MIMS将有助于解决所有生物医学研究领域的棘手问题。

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.