公开(公告)号：US06987266B2

公开(公告)日：2006-01-17

申请号：US10475821

申请日：2002-04-22

Applicant: Sriram Subramaniam

Inventor： Sriram Subramaniam

IPC: G01N1/42 ,  H01J37/26

CPC classification number: G01N23/2251 ,  G01N23/04 ,  H01J37/22 ,  H01J2237/28

Abstract: The invention includes methods for automating acquisition of electron microscopic images. Methods use in the invention include development of search algorithms, including spiral search algorithms for the automated determination of areas suitable for imaging in vitrified specimens at liquid nitrogen temperatures, development of criteria to image areas that meet user-specific needs for the thickness of vitreous ice in which the proteins are embedded, automated setting of key imaging parameters such as extent of defocus and magnification required for recording images, automated assessment of most suitable conditions such as thermal and mechanical stability of specimen stage immediately before recording of the image, recording a “low-dose” image of radiation sensitive biological specimens by carrying out all of the setting and assessment steps on an area immediately adjacent to the area of interest, thereby avoiding pre-exposure of the final imaged area to electrons, creation of a seamless interface to transfer the images recorded on a CCD camera directly to computers capable of processing the recorded images, and carrying out the entire process of data collection from a remote computer either within the network, or connected to the network through a telephone modem from any remote location.

Abstract translation: 本发明包括用于自动采集电子显微镜图像的方法。 本发明中使用的方法包括开发搜索算法，包括用于自动确定在液氮温度下在玻璃化样品中成像的区域的螺旋搜索算法，满足用户对玻璃冰厚度需求的图像区域的标准的制定 其中嵌入蛋白质，自动设置关键成像参数，例如记录图像所需的散焦程度和放大倍数，在记录图像之前自动评估最合适的条件，例如样品台的热和机械稳定性，记录“ 低剂量“的辐射敏感生物标本的图像，通过在紧邻感兴趣区域的一个区域上进行所有设置和评估步骤，从而避免最终成像区域预先暴露于电子，创建无缝界面 将记录在CCD相机上的图像直接传输到能够支持的电脑上 f处理记录的图像，以及从网络内的远程计算机执行数据收集的整个过程，或者通过来自任何远程位置的电话调制解调器连接到网络。

公开(公告)号：US08941057B2

公开(公告)日：2015-01-27

申请号：US12676861

申请日：2008-09-04

Applicant: Sriram Subramaniam

Inventor： Sriram Subramaniam

IPC: G01D21/00 ,  H01J49/00 ,  G01N33/68 ,  G01N33/50 ,  H01J37/28 ,  H01J37/305 ,  B82Y35/00

CPC classification number: G01N33/6848 ,  B82Y35/00 ,  G01N33/5082 ,  H01J37/28 ,  H01J37/3053 ,  H01J49/0004 ,  H01J2237/26 ,  H01J2237/28 ,  H01J2237/31745 ,  H01J2237/31749

Abstract: The invention provides a probe and a method of obtaining a three-dimensional compositional map of one or more targets in a biological sample, or a portion thereof, comprising: (a) milling a surface layer of a biological sample with a focused ion beam, thereby creating a newly exposed surface layer of the biological sample; (b) imaging the newly exposed surface layer of the biological sample; (c) identifying the chemical composition of the newly exposed surface layer of the biological sample, or a portion thereof, with a mass spectrometer; and (d) repeating (a) to (c) until a three-dimensional compositional map of one or more targets in the biological sample, or portion thereof, is obtained. Uses of the three-dimensional map obtained from the inventive method are further provided.

Abstract translation: 本发明提供一种探针和一种获得生物样品或其一部分中的一种或多种靶的三维组成图的方法，其包括：（a）用聚焦离子束研磨生物样品的表面层， 从而产生生物样品的新暴露的表面层; （b）对生物样品的新暴露的表面层进行成像; （c）用质谱仪鉴定生物样品的新暴露表面层或其一部分的化学成分; 和（d）重复（a）至（c），直到得到生物样品中的一种或多种目标或其部分的三维组成图。 还提供了从本发明方法获得的三维图的使用。

公开(公告)号：US20110011190A1

公开(公告)日：2011-01-20

申请号：US12676861

申请日：2008-09-04

Applicant: Sriram Subramaniam

Inventor： Sriram Subramaniam

IPC: G01D21/00 ,  H01J49/00

CPC classification number: G01N33/6848 ,  B82Y35/00 ,  G01N33/5082 ,  H01J37/28 ,  H01J37/3053 ,  H01J49/0004 ,  H01J2237/26 ,  H01J2237/28 ,  H01J2237/31745 ,  H01J2237/31749

Abstract: The invention provides a probe and a method of obtaining a three-dimensional compositional map of one or more targets in a biological sample, or a portion thereof, comprising: (a) milling a surface layer of a biological sample with a focused ion beam, thereby creating a newly exposed surface layer of the biological sample; (b) imaging the newly exposed surface layer of the biological sample; (c) identifying the chemical composition of the newly exposed surface layer of the biological sample, or a portion thereof, with a mass spectrometer; and (d) repeating (a) to (c) until a three-dimensional compositional map of one or more targets in the biological sample, or portion thereof, is obtained. Uses of the three-dimensional map obtained from the inventive method are further provided.

Abstract translation: 本发明提供一种探针和一种获得生物样品或其一部分中的一种或多种靶的三维组成图的方法，其包括：（a）用聚焦离子束研磨生物样品的表面层， 从而产生生物样品的新暴露的表面层; （b）对生物样品的新暴露的表面层进行成像; （c）用质谱仪鉴定生物样品的新暴露表面层或其一部分的化学成分; 和（d）重复（a）至（c），直到得到生物样品中的一种或多种目标或其部分的三维组成图。 还提供了从本发明方法获得的三维图的使用。

公开(公告)号：US20050056784A1

公开(公告)日：2005-03-17

申请号：US10475821

申请日：2002-04-22

Applicant: Sriram Subramaniam

Inventor： Sriram Subramaniam

IPC: G01N23/04 ,  G01N23/225 ,  G21K7/00 ,  H01J37/22

CPC classification number: G01N23/2251 ,  G01N23/04 ,  H01J37/22 ,  H01J2237/28

Abstract: The invention includes methods for automating acquisition of electron microscopic images. Methods use in the invention include development of search algorithms, including spiral search algorithms for the automated determination of areas suitable for imaging in vitrified specimens at liquid nitrogen temperatures, development of criteria to image areas that meet user-specific needs for the thickness of vitreous ice in which the proteins are embedded, automated setting of key imaging parameters such as extent of defocus and magnification required for recording images, automated assessment of most suitable conditions such as thermal and mechanical stability of specimen stage immediately before recording of the image, recording a “low-dose” image of radiation sensitive biological specimens by carrying out all of the setting and assessment steps on an area immediately adjacent to the area of interest, thereby avoiding pre-exposure of the final imaged area to electrons, creation of a seamless interface to transfer the images recorded on a camera directly to computers capable of processing the recorded images, and carrying Automated out the entire process of data collection from a remote computer either within the network, or connected to the network through a telephone modem from any remote location.

Abstract translation: 本发明包括用于自动采集电子显微镜图像的方法。 本发明中使用的方法包括开发搜索算法，包括用于自动确定在液氮温度下在玻璃化样品中成像的区域的螺旋搜索算法，满足用户对玻璃冰厚度需求的图像区域的标准的制定 其中嵌入蛋白质，自动设置关键成像参数，例如记录图像所需的散焦程度和放大倍数，在记录图像之前自动评估最合适的条件，例如样品台的热和机械稳定性，记录“ 低剂量“的辐射敏感生物标本的图像，通过在紧邻感兴趣区域的一个区域上进行所有设置和评估步骤，从而避免最终成像区域预先暴露于电子，创建无缝界面 将摄像机上记录的图像直接传输到能够播放的计算机 加载记录的图像，并且携带从网络中的远程计算机自动完成数据收集的整个过程，或者通过来自任何远程位置的电话调制解调器连接到网络。

公开(公告)号：US20080168342A1

公开(公告)日：2008-07-10

申请号：US12053392

申请日：2008-03-21

Applicant: Andrey Shur ,  Daniel F. Emerson ,  David Ornstein ,  Joe King ,  Oliver H. Foehr ,  Wei Zhu ,  Jerry Dunietz ,  Sriram Subramaniam

Inventor： Andrey Shur ,  Daniel F. Emerson ,  David Ornstein ,  Joe King ,  Oliver H. Foehr ,  Wei Zhu ,  Jerry Dunietz ,  Sriram Subramaniam

IPC: G06F17/00

CPC classification number: G06F17/2288 ,  G06F17/217 ,  G06F17/2205 ,  G06F17/2229 ,  G06F17/2247 ,  G06F17/30011

Abstract: Modular content framework and document format methods and systems are described. The described framework and format define a set of building blocks for composing, packaging, distributing, and rendering document-centered content. These building blocks define a platform-independent framework for document formats that enable software and hardware systems to generate, exchange, and display documents reliably and consistently. The framework and format have been designed in a flexible and extensible fashion. In addition to this general framework and format, a particular format, known as the reach package format, is defined using the general framework. The reach package format is a format for storing paginated documents. The contents of a reach package can be displayed or printed with full fidelity among devices and applications in a wide range of environments and across a wide range of scenarios.

Abstract translation: 描述了模块化内容框架和文档格式方法和系统。 描述的框架和格式定义了一组构建块，用于组合，打包，分发和呈现以文档为中心的内容。 这些构建模块定义了一个独立于平台的文档格式框架，可以使软件和硬件系统可靠，可靠地生成，交换和显示文档。 框架和格式的设计灵活可扩展。 除了这个一般框架和格式之外，使用通用框架定义了一种称为覆盖包格式的特定格式。 覆盖包格式是用于存储分页文档的格式。 可以在广泛的环境和广泛的场景下，在设备和应用程序之间以完全保真的方式显示或打印覆盖包的内容。