公开(公告)号：US20110284744A1

公开(公告)日：2011-11-24

申请号：US12884001

申请日：2010-09-16

Applicant: Ahmed H. Zewail ,  Oh-Hoon Kwon ,  Omar Farghaly Mohammed Abdelsaboor ,  Ding-Shyue Yang

Inventor： Ahmed H. Zewail ,  Oh-Hoon Kwon ,  Omar Farghaly Mohammed Abdelsaboor ,  Ding-Shyue Yang

IPC: H01J37/28 ,  H01J37/26

CPC classification number: H01J37/28 ,  H01J37/228 ,  H01J37/285 ,  H01J2237/0432 ,  H01J2237/2004 ,  H01J2237/20207 ,  H01J2237/2065 ,  H01J2237/2611 ,  H01J2237/2803

Abstract: A 4D electron tomography system includes a stage having one or more degrees of freedom, an electron source, and electron optics operable to direct electron pulses to impinge on a sample supported on the stage. A pulse of the electron pulses impinges on the sample at a first time. The system also includes a laser system and optics operable to direct optical pulses to impinge on the sample. A pulse of the optical pulses impinges on the sample at a second time. The system further includes a detector operable to receive the electron pulses passing through the sample, a controller operable to independently modify an orientation of the stage and at least one of the first time or the second time, a memory operable to store sets of images, and a processor operable to form a 4D tomgraphic image set from the sets of images.

Abstract translation: 4D电子断层摄影系统包括具有一个或多个自由度的阶段，电子源和可操作以将电子脉冲引导到支撑在舞台上的样本上的电子光学器件。 电子脉冲的脉冲在第一次撞击样品。 该系统还包括激光系统和光学器件，其可操作以引导光脉冲撞击样品。 光脉冲的脉冲在第二次撞击样品。 该系统还包括可操作以接收通过样品的电子脉冲的检测器，可操作以独立地修改载物台的取向和第一时间或第二时间中的至少一个的控制器，可操作地存储图像集合的存储器， 以及处理器，可操作以从所述图像集合形成4D成像图像集。

公开(公告)号：US07906760B2

公开(公告)日：2011-03-15

申请号：US12335143

申请日：2008-12-15

Applicant: Hidetoshi Nishiyama ,  Mitsuo Suga ,  Mitsuru Koizumi

Inventor： Hidetoshi Nishiyama ,  Mitsuo Suga ,  Mitsuru Koizumi

IPC: H01J37/20

CPC classification number: G01N23/2202 ,  H01J37/228 ,  H01J2237/2004 ,  H01J2237/208 ,  H01J2237/2608 ,  H01J2237/2808

Abstract: An electron microscope method for inspecting a liquid specimen and a reagent solution therefor. A culture medium and biological cells are put in the sample holder. A plugging agent is mixed into the liquid sample. The cells can be irradiated with a primary beam via a film. An image of the cells or information about the cells is obtained by detecting a resulting secondary signal. If the film is destroyed, the plugging agent plugs up the damaged portion of the film. Consequently, liquid leakage can be minimized.

Abstract translation: 用于检查液体试样的电子显微镜方法及其试剂溶液。 将培养基和生物细胞放入样品架中。 将堵塞剂混合到液体样品中。 细胞可以通过膜用初级束照射。 通过检测所得到的辅助信号来获得单元的图像或关于单元的信息。 如果胶片被破坏，则堵塞剂堵塞胶片的损坏部分。 因此，可以使液体泄漏最小化。

公开(公告)号：US20100193398A1

公开(公告)日：2010-08-05

申请号：US12365698

申请日：2009-02-04

Applicant: CHARLES P. MARSH ,  ERIC OLSON ,  TODOR I. DONCHEV ,  IVAN PETROV ,  JIANGUO WEN ,  RYAN FRANKS ,  DONGXIANG LIAO

Inventor： CHARLES P. MARSH ,  ERIC OLSON ,  TODOR I. DONCHEV ,  IVAN PETROV ,  JIANGUO WEN ,  RYAN FRANKS ,  DONGXIANG LIAO

IPC: B65D85/00 ,  B23P11/00

CPC classification number: H01J37/26 ,  G02B21/34 ,  H01J37/20 ,  H01J2237/2004 ,  H01J2237/2005 ,  H01J2237/28 ,  Y10T29/49826

Abstract: A reusable sample-holding device for readily loading very small wet samples for observation of the samples by microscopic equipment, in particular in a vacuum environment. Embodiments may be used with a scanning electron microscope (SEM), a transmission electron microscope (TEM), an X-ray microscope, optical microscope, and the like. For observation of the sample, embodiments provide a thin-membrane window etched in the center of each of two silicon wafers abutting to contain the sample in a small uniform gap formed between the windows. This gap may be adjusted by employing spacers. Alternatively, the thickness of a film established by the fluid in which the sample is incorporated determines the gap without need of a spacer. To optimize resolution each window may have a thickness on the order of 50 nm and the gap may be on the order of 50 nm.

Abstract translation: 一种可重复使用的样品保持装置，用于容易地加载非常小的湿样品，以通过显微设备，特别是在真空环境中观察样品。 实施例可以用扫描电子显微镜（SEM），透射电子显微镜（TEM），X射线显微镜，光学显微镜等来使用。 为了观察样品，实施方案提供了在两个硅晶片的每一个的中心蚀刻的薄膜窗口，其邻接以将样品容纳在窗口之间形成的小的均匀间隙中。 该间隙可以通过使用间隔物来调节。 或者，通过其中包含样品的流体建立的膜的厚度确定了间隙而不需要间隔物。 为了优化分辨率，每个窗口可以具有大约50nm的厚度，并且间隙可以在50nm量级。

公开(公告)号：US07745802B2

公开(公告)日：2010-06-29

申请号：US12023443

申请日：2008-01-31

Applicant: Hidetoshi Nishiyama ,  Mitsuru Koizumi

Inventor： Hidetoshi Nishiyama ,  Mitsuru Koizumi

IPC: G01N1/28 ,  G21K5/08 ,  H01J37/20

CPC classification number: H01J37/28 ,  H01J37/20 ,  H01J37/228 ,  H01J2237/0266 ,  H01J2237/2004 ,  H01J2237/206 ,  H01J2237/2608 ,  H01J2237/2808

Abstract: A specimen holder, a specimen inspection apparatus, and a specimen inspection method permitting a specimen consisting of cultured cells to be observed or inspected. Also, a method of fabricating the holder is offered. The holder has an open specimen-holding surface. At least a part of this surface is formed by a film. A specimen cultured on the specimen-holding surface of the film can be irradiated via the film with a primary beam for observation or inspection of the specimen. Consequently, the cultured specimen (e.g., cells) can be observed or inspected in vitro. Especially, if an electron beam is used as the primary beam, the specimen in vitro can be observed or inspected by SEM. Because the specimen-holding surface is open, a manipulator can gain access to the specimen. A stimulus can be given to the specimen using the manipulator. The reaction can be observed or inspected.

Abstract translation: 试样支架，试样检查装置和允许观察或检查由培养细胞组成的试样的试样检查方法。 此外，提供了制造保持器的方法。 支架具有开放的标本保持表面。 该表面的至少一部分由膜形成。 可以在膜的试样保持表面上培养的样品通过膜通过主光束照射，用于观察或检查样品。 因此，可以在体外观察或检查培养的标本（例如细胞）。 特别地，如果使用电子束作为主光束，则可以通过SEM观察或检查体外的样本。 由于样品保持表面是开放的，操纵器可以进入样品。 可以使用机械手对试样给予刺激。 可以观察或检查反应。

公开(公告)号：US20090242795A1

公开(公告)日：2009-10-01

申请号：US12078223

申请日：2008-03-28

Applicant: Chih-Yu Chao

Inventor： Chih-Yu Chao

IPC: H01J37/20 ,  G21K5/10

CPC classification number: H01J37/20 ,  G01N1/42 ,  H01J2237/2001 ,  H01J2237/2002 ,  H01J2237/2003 ,  H01J2237/2004 ,  H01J2237/26

Abstract: The present invention relates to a cryo-charging specimen holder for the electron microscope, particularly to a cryo-charging specimen holder for the electron microscope to hold various biological materials. The major feature of the invention is to charge the biological specimen and freeze the specimen at low temperature. The ice around the biological sample is also doped, so that after charging the doped ice surrounding the sample has a conductivity level comparable to that of conductor. Therefore, the sample can be embedded by the doped and charged ice obtaining the property of conductor, in order to be observed by the electron microscope.

Abstract translation: 本发明涉及一种用于电子显微镜的低温充电试样架，特别涉及用于电子显微镜保持各种生物材料的低温充电试样架。 本发明的主要特征是对生物样品充电并在低温下冷冻试样。 生物样品周围的冰也被掺杂，因此在充电之后，样品周围的掺杂冰具有与导体相当的导电率。 因此，可以通过掺杂和充电的冰来嵌入样品，获得导体的性质，以便通过电子显微镜观察。

公开(公告)号：US20090242762A1

公开(公告)日：2009-10-01

申请号：US12407918

申请日：2009-03-20

Applicant: Hidetoshi Nishiyama ,  Mitsuru Koizumi

Inventor： Hidetoshi Nishiyama ,  Mitsuru Koizumi

IPC: G01N23/00

CPC classification number: G01N23/2251 ,  G01N23/2204 ,  G01N2223/307 ,  G01N2223/612 ,  G01N2223/637 ,  H01J37/20 ,  H01J37/228 ,  H01J37/265 ,  H01J37/28 ,  H01J2237/182 ,  H01J2237/2004 ,  H01J2237/244 ,  H01J2237/2808

Abstract: Method and apparatus have a film including a first surface to hold the liquid sample thereon, a vacuum chamber for reducing the pressure of an ambient in contact with a second surface of the film, primary beam irradiation means connected with the vacuum chamber and irradiating the sample with a primary beam via the film, signal detection means for detecting a secondary signal produced from the sample in response to the beam irradiation, a partitioning plate for partially partitioning off the space between the film and the primary beam irradiation means in the vacuum chamber, and a vacuum gauge for detecting the pressure inside the vacuum chamber.

Abstract translation: 方法和装置具有包括用于将液体样品保持在其上的第一表面的膜，用于降低与膜的第二表面接触的环境压力的真空室，与真空室连接并照射样品的主光束照射装置 通过胶片具有主光束，信号检测装置，用于响应于光束照射检测从样品产生的二次信号;分隔板，用于在真空室中部分地分隔膜和主光束照射装置之间的空间， 以及用于检测真空室内的压力的真空计。

公开(公告)号：US20080308731A1

公开(公告)日：2008-12-18

申请号：US12023443

申请日：2008-01-31

Applicant: Hidetoshi Nishiyama ,  Mitsuru Koizumi

Inventor： Hidetoshi Nishiyama ,  Mitsuru Koizumi

IPC: G01N23/00 ,  G21K5/10

CPC classification number: H01J37/28 ,  H01J37/20 ,  H01J37/228 ,  H01J2237/0266 ,  H01J2237/2004 ,  H01J2237/206 ,  H01J2237/2608 ,  H01J2237/2808

Abstract: A specimen holder, a specimen inspection apparatus, and a specimen inspection method permitting a specimen consisting of cultured cells to be observed or inspected. Also, a method of fabricating the holder is offered. The holder has an open specimen-holding surface. At least a part of this surface is formed by a film. A specimen cultured on the specimen-holding surface of the film can be irradiated via the film with a primary beam for observation or inspection of the specimen. Consequently, the cultured specimen (e.g., cells) can be observed or inspected in vitro. Especially, if an electron beam is used as the primary beam, the specimen in vitro can be observed or inspected by SEM. Because the specimen-holding surface is open, a manipulator can gain access to the specimen. A stimulus can be given to the specimen using the manipulator. The reaction can be observed or inspected.

Abstract translation: 试样支架，试样检查装置和允许观察或检查由培养细胞组成的试样的试样检查方法。 此外，提供了制造保持器的方法。 支架具有开放的标本保持表面。 该表面的至少一部分由膜形成。 可以在膜的试样保持表面上培养的样品通过膜通过主光束照射，用于观察或检查样品。 因此，可以在体外观察或检查培养的标本（例如细胞）。 特别地，如果使用电子束作为主光束，则可以通过SEM观察或检查体外的样本。 由于样品保持表面是开放的，操纵器可以进入样品。 可以使用机械手对试样给予刺激。 可以观察或检查反应。

公开(公告)号：US5406087A

公开(公告)日：1995-04-11

申请号：US183149

申请日：1994-01-18

Applicant: Yoshinori Fujiyoshi ,  Mikio Naruse

Inventor： Yoshinori Fujiyoshi ,  Mikio Naruse

IPC: B01L3/00 ,  G01Q30/02 ,  G01Q30/14 ,  G01Q30/20 ,  H01J37/20 ,  H01J37/26

CPC classification number: H01J37/26 ,  B01L3/508 ,  H01J37/20 ,  H01J2237/2004

Abstract: There is disclosed a simple specimen-holding device for use with an electron microscope. The device comprises a pair of films which transmit the electron beam. The films are reinforced with a network of reinforcing members and placed on a specimen stage. A specimen to be investigated is held in a thin space formed between the films, together with moisture. The fringes of the films are compressed together to hermetically isolate the space between the films from the specimen chamber of the microscope which is evacuated. The electron beam passes through the thin space sandwiched between the films. This permits the specimen to be observed in an almost unmodified state with little damage to the specimen.

Abstract translation: 公开了一种用于电子显微镜的简单的标本保持装置。 该装置包括一对透射电子束的膜。 薄膜用加强件网络加固并放置在样品台上。 要研究的样品保持在薄膜之间形成的薄薄空间以及水分。 膜的条纹被压缩在一起，以将隔离空间的膜与被抽出的显微镜的样品室隔开。 电子束通过夹在膜之间的薄空间。 这允许在几乎未改变的状态下观察样品，对样品几乎没有损伤。

公开(公告)号：WO2016056096A1

公开(公告)日：2016-04-14

申请号：PCT/JP2014/077034

申请日：2014-10-09

Applicant: 株式会社日立ハイテクノロジーズ

Inventor： 砂押　毅志 ,  長久保　康平 ,  二村　和孝

IPC: H01J37/20 ,  H01J37/28

CPC classification number: H01J37/28 ,  H01J37/18 ,  H01J37/20 ,  H01J2237/1825 ,  H01J2237/2001 ,  H01J2237/2004 ,  H01J2237/2802

Abstract: 高精度かつ安定した試料観察が可能な電子顕微鏡を提供する。試料ステージと、試料（１１１）上で電子線を走査する電子光学系と、前記試料ステージおよび前記電子光学系を真空に保持する真空系と、前記試料から放出される二次電子を検出する二次電子検出器（１０９）と、前記試料を透過する透過電子を検出する透過電子検出器（１１３，１１６）と、前記二次電子検出器および前記透過電子検出器により検出した二次電子および透過電子に基づき、二次電子像および透過電子像を取得し、前記二次電子像および前記透過電子像を記憶する制御装置（１１７）と、を有する電子顕微鏡であって、前記試料ステージは、前記試料を冷却する冷却手段（１２２，１２３）を備え、前記真空系は、前記試料近傍の水分を吸着するコールドトラップ（１２０）と、前記真空系の真空度を計測する真空計（１２１）と、を備える。

Abstract translation: 提供了可以稳定且高精度地观察样品的电子显微镜。 电子显微镜包括：样品台; 扫描样品（111）上的电子束的电子光学系统; 真空系统，其将样品台和电子光学系统保持在真空中; 二次电子检测器（109），其检测从样品发射的二次电子; 透射电子检测器（113,116），其检测透射通过样品的透射电子; 以及控制装置（117），其基于二次电子和由二次电子检测器和透射电子检测器检测的透射电子获得二次电子图像和透射电子图像，并存储二次电子图像和透射电子 图片。 样品台设置有用于冷却样品的冷却装置（122,123）。 真空系统设有从样品周围吸湿的冷阱（120）和测量真空系统的真空度的真空计（121）。

公开(公告)号：WO2015134575A1

公开(公告)日：2015-09-11

申请号：PCT/US2015/018686

申请日：2015-03-04

Applicant: UNIVERSITY OF WASHINGTON

Inventor： WANG, Liguo

IPC: H01J37/26 ,  H01J37/244 ,  H01L21/44 ,  H01L33/42

CPC classification number: H01J37/16 ,  C23F1/40 ,  C23F4/00 ,  H01J37/20 ,  H01J37/26 ,  H01J37/261 ,  H01J2237/2001 ,  H01J2237/2002 ,  H01J2237/2003 ,  H01J2237/2004

Abstract: AA grid assembly for cryo-electron microscopy may be fabricated using standard nanofabrication processes. The grid assembly may comprise two support members, each support member comprising a silicon substrate coated with an electron-transparent silicon nitride layer. These two support members are positioned together with the silicon nitride layers facing each other with a rigid spacer layer disposed there between. The rigid spacer layer defines one or more chambers in which a biological sample may be provided and fast frozen with a high degree of control of the ice thickness.

Abstract translation: 用于低温电子显微镜的AA网格组件可以使用标准的纳米制造工艺制造。 栅格组件可以包括两个支撑构件，每个支撑构件包括涂覆有电子透明氮化硅层的硅衬底。 这两个支撑构件与其间设置有刚性间隔层的彼此面对的氮化硅层一起定位。 刚性间隔层限定一个或多个室，其中可以提供生物样品并以高度控制冰厚度快速冷冻。