SCANNING TRANSMISSION ELECTRON MICROSCOPE +XRAY ANALYZER

克利夫兰临床基金会的研究所是一个迅速 不断扩大的研究中心，越来越多的核心NIH资助的研究人员。 为了满足研究所迫切的仪器需求，我们 正在申请分析扫描透射电子显微镜， Philips CM 12/STEM，与X射线微量分析系统LINK连接 AN10000。 选择飞利浦显微镜是因为其出色的真空度 系统，能够与20 o水平X射线探测器连接 起飞角度，易于在TEM和STEM模式下使用， 操作控制台。 选择LINK系统的主要原因 是X射线探测器的超高分辨率， 在线元素定量分析程序的适用性 生物样本。 八分之三的主要用户是 研究Ca 2+和其他元素的亚细胞分布： 仓鼠体内心脏的心动周期（Bond博士），轴突中 坐骨神经对甲状旁腺激素反应的制剂 刺激（Dr Breuer）和暴露于氧化低密度 培养的人细胞周期S期的脂蛋白 成纤维细胞（Chisolm博士）。 每个调查员都需要使用 X射线微量分析系统，以及扩展的能力， STEM将提供进行X射线绘图的机会， 除了在TEM中使用固定探针进行光谱收集之外。 博士 Harasaki是第四个使用X射线微分析的人， 生物人工心脏瓣膜表面上的元素定位。 Drs 霍夫和科尔正在研究受体介导的低水平的内吞作用。 密度脂蛋白，使用胶体金标记的标本，在一些 对比度低的标本上的实例。 这些调查人员，连同 Shainoff博士正在研究纤维蛋白原在血小板中的作用， 聚合，将大大受益于增强的图像对比度 在STEM中可用。 布洛克博士使用胶体金标记的标记物， 检查下丘脑血管紧张素II的亚细胞定位 Jacobsen博士研究了钴胺素结合蛋白的作用 在肝肠循环中，使用胶体金标记的抗体， 卡巴氨结合蛋白。 这两名调查员将主要负责 显微镜在传统的传输模式，但也可以受益于 STEM和LINK提供的颗粒计数软件。 的 霍夫博士和科尔博士以及原崎博士的项目还需要 在次级和反向散射图像中提供的增加的分辨率 这可以在STEM中获得（与SEM相比）。 在这种模式下， 操作，他们将利用图像混合能力的 显微镜 总而言之，一种多功能、最先进的分析扫描 透射电子显微镜将大大有利于大量的 研究所的用户，并将履行一个急需的作用， 研究所范围内的设施。

The Research Institute of the Cleveland Clinic Foundation is a rapidly expanding research center with a growing core of NIH-funded investigators. In order to fulfill the urgent instrumentation needs of the Institute, we are requesting an analytical scanning transmission electron microscope, the Philips CM12/STEM, interfaced with an X-ray microanalysis system, the LINK AN10000. The Philips microscope was chosen based on its excellent vacuum system, ability to interface with a horizontal X-ray detector with a 20o take-off angle, ease of use in both TEM and STEM modes and simplified operating consoles. The principle reason that the LINK system was chosen was the exceptionally high resolution of the X-ray detector as well as the suitability of the analytical programs for on-line elemental quantitation of biological samples. Three out of eight of the primary users are investigating subcellular distribution of Ca2+ and other elements: during the cardiac cycle in hamster heart in vivo (Dr Bond), in axonal preparations from sciatic nerve in response to parathyroid hormone stimulation (Dr Breuer) and following exposure to oxidized low density lipoprotein during the S phase of the cell cycle in cultured human fibroblasts (Dr Chisolm). Each of these investigators requires the use of the X-ray microanalysis system, as well as the extended capabilities of the STEM, which will provide the opportunity to carry out X-ray mapping, in addition to spectral collection with a stationary probe in TEM. Dr Harasaki is a fourth user of X-ray microanalysis who will investigate elemental localization on the surfaces of bioprosthetic heart valves. Drs Hoff and Cole are investigating receptor-mediated endocytosis of low density lipoproteins, using colloidal gold labelled specimens, in some instances on specimens of low contrast. These investigators, together with Dr Shainoff, who is studying the role of fibrinogen in platelet aggregation, will greatly benefit from the enhanced image contrast available in STEM. Dr Block uses colloidal-gold labelled markers to examine the subcellular localization of the hypothalamic Angiotensin II system and Dr Jacobsen investigates the role of cobalamin-binding proteins in the enterohepatic circulation, using colloidal gold tagged antibodies to cabalamin-binding proteins. These two investigators will primarily operate the microscope in conventional transmission mode, but may also benefit from the STEM and from the particle counting software provided by LINK. The projects of Drs Hoff and cole, as well as Dr Harasaki, will also require the increased resolution provided in secondary and backscattered images that can be obtained in STEM (compared with SEM). In this mode of operation, they will utilize the image mixing capabilities of the microscope. In summary, a versatile, state-of-the-art analytical scanning transmission electron microscope will greatly benefit a large number of users in the Research Institute and will fulfill a much needed role as an Institute-wide facility.