National Resource for Imaging Mass Spectrometry

描述(由申请人提供)：本资源开发和使用多同位素成像质谱仪(MIMS)，将新型二次离子质谱仪与示踪方法和密集的定量图像分析相结合。 MIMS在高二次离子透过率、高空间分辨率(35 Nm)下提供高质量分离(M/AM&GT；10,000)，并具有同时记录多个原子质量图像的独特能力。最重要的是，MIMS首次能够在细胞内水平同时成像和测量标记有任何同位素的分子的分布和累积，特别是标记有稳定同位素的分子，例如15N。因此，MIMS使人们能够研究蛋白质、脂肪酸、糖和外来分子在细胞微区的定位、积累和周转；DNA和RNA的表达和分布；供体细胞向受体壁龛的迁移、干细胞的嵌套和药物的细胞内定位。最后，稳定同位素的使用开启了一个标记可能性的世界，应该会重振和扩大示踪剂在人类中的使用。 该资源与细胞生物学、病理学、生物化学、免疫学、移植、药理学、干细胞研究、微生物学和病毒学的研究人员合作。碘负离子一次离子源的开发将开启二次正离子的亚细胞同位素比成像，特别是利用钙的多种稳定同位素来分析这种基本的和普遍存在的细胞内试剂的功能，以及金属酶的定量成像。对二次离子形成的研究将指导标记方案。自动化的发展将使我们能够全天候进行复杂的分析，从上到下分解一个细胞，在连续的数百个定量原子质量图像中，每个图像都是通过几个原子层的溅射获得的。强大的软件将允许我们从海量数据和3D空间中快速提取和减少定量信息。细胞DNA长期标记方法的发展将直接有利于免疫学、移植、干细胞和癌症研究。我们将通过组织关于管理信息管理系统理论和实践的年度讲习班和关于使用管理信息管理系统数据简化软件的讲习班来培训用户。我们将继续在资源网站上积累跨越我们所有程序、结果和事件的信息。我们将使我们的网站成为我们自己和用户社区的集中存储库。 该资源正在开发多同位素成像质谱仪(MIMS)，这是一项使成像和量化单个哺乳动物或细菌细胞内的分子成为可能的新技术。正如J.Weitzman(2006，J.Biol)引用的那样，被称为“一场成像革命”。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): This Resource develops and uses Multi-isotope Imaging Mass Spectrometry (MIMS), the combination of a novel type of secondary ion mass spectrometer with tracer methods and intensive quantitative image analysis. MIMS provides high mass separation (M/AM > 10,000) at high secondary ion transmission, high spatial resolution (35 nm) and has the unique capability of simultaneously recording several atomic mass images. Of the utmost importance, MIMS makes it possible for the first time, 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 15N. Thus, MIMS allows one to study the localization, the accumulation and the turnover of proteins, fatty acids, sugars and foreign molecules in cellular micro domains; the expression and distribution of DNA and RNA; the migration of donor cells to receiver niches, the nesting of stem cell and the intracellular localization of drugs. Finally, the use of stable isotopes opens a world of labeling possibilities that should revive and expand the use of tracers in humans. The Resource collaborates with researchers in cell biology, pathology, biochemistry, immunology, transplantation, pharmacology, stem cell research, microbiology and virology. Development of an iodine negative primary ion source will open subcellular isotope ratio imaging of secondary positive ions, in particular the experimental use of the multiple stable isotopes of calcium to dissect the function of this essential and ubiquitous intracellular agent, and the quantitative imaging of metallo-enzymes. Study of secondary ion formation will guide labeling schemes. Development of automation will allow us to perform complex analyzes 24/7, decomposing a cell from top to bottom in a succession of hundreds of quantitative atomic mass images, each obtained from the sputtering of a few atomic layers. Powerful software will allow us to rapidly extract and reduce quantitative information from reams of data and in a 3D space. Development of methods for long term labeling of cellular DNA will directly benefit immunology, transplantation, stem cell and cancer research. We will train users by organizing yearly workshop on the theory and practice of MIMS and a workshop on the use of the MIMS data reduction software. We will continue to accumulate on the Resource website information spanning all our procedures, results and happenings. We will make of our Web Site a centralized repository for ourselves and the community of users. This Resource is developing multi-isotope imaging mass spectrometry (MIMS), a new technology that makes it possible to image and quantify molecules within individual mammalian or bacterial cells. Called 'an imaging revolution' as quoted by J. Weitzman (2006, J. Biol. 5:16), MIMS will help solving intractable problems in all fields of biomedical research.