公开(公告)号：US20130316365A1

公开(公告)日：2013-11-28

申请号：US13825298

申请日：2011-09-21

Applicant: Elly van Donselaar ,  Matthia Karreman ,  Hans Gerritsen ,  Theo Verrips ,  Uwe Luecken

Inventor： Elly van Donselaar ,  Matthia Karreman ,  Hans Gerritsen ,  Theo Verrips ,  Uwe Luecken

IPC: G01N1/30

CPC classification number: G01N1/30 ,  G01N1/06 ,  G01N1/42

Abstract: The invention relates to a method of forming sections for inspection in an electron microscope and a fluorescent light microscope. Conventionally these sections are made by for example the Tokuyama method, which involves freeze substitution and fixing at cryogenic temperatures. A problem is the time that it takes to come from a sample to sections, as the diffusion speed of the chemicals (organic solvents and fixatives) is extremely low. The invention comprises the sectioning of the sample at cryogenic temperature and fixing afterwards. As the sections are much thinner (e.g. 100 nm or less) than the sample (often >1 μm), the total time it takes to come from a sample to a section ready for inspection is less than 8 hours. This makes it possible to achieve results relevant for health care within one workday.

Abstract translation: 本发明涉及一种在电子显微镜和荧光显微镜中形成检查部分的方法。 通常这些部分是通过例如Tokuyama方法制成的，其涉及在低温下的冷冻置换和固定。 问题是从样品到样品的时间，化学品（有机溶剂和固定剂）的扩散速度极低。 本发明包括样品在低温下的切片和固定。 由于切片比样品（通常> 1um）更薄（例如100nm或更小），从样品到准备检查的部分所花费的总时间小于8小时。 这样可以在一个工作日内实现与医疗保健有关的结果。

公开(公告)号：US20090000400A1

公开(公告)日：2009-01-01

申请号：US12163298

申请日：2008-06-27

Applicant: Michael Frederick Hayles ,  Uwe Luecken

Inventor： Michael Frederick Hayles ,  Uwe Luecken

IPC: G01N1/02 ,  G01N23/00

CPC classification number: G01N1/06 ,  G01N1/286 ,  G02B21/32 ,  H01J37/20 ,  H01J2237/2001 ,  H01J2237/208 ,  H01J2237/31745

Abstract: The invention relates to the extraction of a frozen hydrated sample for TEM (Transmission Electron Microscope) inspection, such as a vitrified biological sample, from a substrate and the attaching of said sample to a manipulator. Such a hydrated sample should be held at a cryogenic temperature to avoid ice formation. By melting or sublimating a part of the sample material outside the area to be studied in the TEM and freezing the material to the manipulator (10), a bond is formed between sample (1) and manipulator. This makes it possible to transport the sample from the substrate to e.g. a TEM grid.In a preferred embodiment a part (2) of the manipulator (10) is held at a cryogenic temperature, and the melting or sublimation is caused by heating the tip (3) of the manipulator by electric heating of the tip and then cooling the tip of the manipulator to a cryogenic temperature, thereby freezing the sample (1) to the manipulator.

Abstract translation: 本发明涉及从基材提取用于TEM（透射电子显微镜）检查的冷冻水合样品，例如玻璃化生物样品，并将所述样品附着到机械手。 这样的水合样品应保持在低温温度以避免冰层形成。 通过在TEM中将待研究区域外的一部分样品材料熔化或升华，并将材料冷冻至机械手（10），在样品（1）和机械手之间形成结合体。 这使得可以将样品从衬底输送到例如。 一个TEM网格。 在优选实施例中，操纵器（10）的部分（2）保持在低温温度，并且通过对尖端的电加热来加热操纵器的尖端（3），然后冷却尖端而引起熔化或升华 的操纵器到低温，从而将样品（1）冷冻到机械手。

公开(公告)号：US08338782B2

公开(公告)日：2012-12-25

申请号：US13217088

申请日：2011-08-24

Applicant: Uwe Luecken ,  Remco Schoenmakers ,  Frank Jeroen Pieter Schuurmans

Inventor： Uwe Luecken ,  Remco Schoenmakers ,  Frank Jeroen Pieter Schuurmans

IPC: H01J37/26 ,  G01N23/00 ,  G21K7/00

CPC classification number: H01J37/222 ,  H01J37/26 ,  H01J37/265 ,  H01J2237/2446

Abstract: In a transmission electron microscope detector system, image data is read out from the pixels and analyzed during an image acquisition period. The image acquisition process is modified depending on the results of the analysis. For example, the analyses may indicate the inclusion in the data of an image artifact, such as charging or bubbling, and data including the artifact may be eliminated form the final image. CMOS detectors provide for selective read out of pixels at high data rates, allowing for real-time adaptive imaging.

Abstract translation: 在透射电子显微镜检测器系统中，从像素读出图像数据，并在图像采集期间进行分析。 图像采集过程根据分析结果进行修改。 例如，分析可以指示在图像伪像的数据中包括例如充电或冒泡，并且可以从最终图像中消除包括伪影的数据。 CMOS检测器提供以高数据速率选择性读出像素，允许实时自适应成像。

公开(公告)号：US20120049061A1

公开(公告)日：2012-03-01

申请号：US13217088

申请日：2011-08-24

Applicant: Uwe Luecken ,  Remco Schoenmakers ,  Frank Jeroen Pieter Schuurmans

Inventor： Uwe Luecken ,  Remco Schoenmakers ,  Frank Jeroen Pieter Schuurmans

IPC: H01J37/26

CPC classification number: H01J37/222 ,  H01J37/26 ,  H01J37/265 ,  H01J2237/2446

Abstract: In a transmission electron microscope detector system, image data is read out from the pixels and analyzed during an image acquisition period. The image acquisition process is modified depending on the results of the analysis. For example, the analyses may indicate the inclusion in the data of an image artifact, such as charging or bubbling, and data including the artifact may be eliminated form the final image. CMOS detectors provide for selective read out of pixels at high data rates, allowing for real-time adaptive imaging.

Abstract translation: 在透射电子显微镜检测器系统中，从像素读出图像数据，并在图像采集期间进行分析。 图像采集过程根据分析结果进行修改。 例如，分析可以指示在图像伪像的数据中包括例如充电或冒泡，并且可以从最终图像中消除包括伪影的数据。 CMOS检测器提供以高数据速率选择性读出像素，允许实时自适应成像。

公开(公告)号：US20120049060A1

公开(公告)日：2012-03-01

申请号：US13217013

申请日：2011-08-24

Applicant: Uwe Luecken ,  Cornelis Sander Kooijman ,  Frank Jeroen Pieter Schuurmans

Inventor： Uwe Luecken ,  Cornelis Sander Kooijman ,  Frank Jeroen Pieter Schuurmans

IPC: H01J47/00 ,  G01N23/00

CPC classification number: H01J37/244 ,  H01J37/05 ,  H01J37/26 ,  H01J2237/05 ,  H01J2237/24455 ,  H01J2237/2446 ,  H01J2237/24485 ,  H01J2237/2802 ,  H01J2237/2817

Abstract: A detector system for a transmission electron microscope includes a first detector for recording a pattern and a second detector for recording a position of a feature of the pattern. The second detector is preferably a position sensitive detector that provides accurate, rapid position information that can be used as feedback to stabilize the position of the pattern on the first detector. In one embodiment, the first detector detects an electron energy loss electron spectrum, and the second detector, positioned behind the first detector and detecting electrons that pass through the first detector, detects the position of the zero-loss peak and adjusts the electron path to stabilize the position of the spectrum on the first detector.

Abstract translation: 用于透射电子显微镜的检测器系统包括用于记录图案的第一检测器和用于记录图案的特征位置的第二检测器。 第二检测器优选地是位置敏感检测器，其提供精确，快速的位置信息，其可以用作反馈以稳定图案在第一检测器上的位置。 在一个实施例中，第一检测器检测电子能量损失电子光谱，并且第二检测器位于第一检测器后面并检测通过第一检测器的电子，检测零损耗峰值的位置并调整电子通路 稳定第一检测器上的光谱位置。

公开(公告)号：US08569693B2

公开(公告)日：2013-10-29

申请号：US13446908

申请日：2012-04-13

Applicant: Maarten Bischoff ,  Alexander Henstra ,  Uwe Luecken ,  Peter Christiaan Tiemeijer

Inventor： Maarten Bischoff ,  Alexander Henstra ,  Uwe Luecken ,  Peter Christiaan Tiemeijer

IPC: G21K7/00

CPC classification number: H01J37/26 ,  H01J37/153 ,  H01J2237/1532

Abstract: A charged particle apparatus is equipped with a third stigmator positioned between the objective lens and a detector system, as a result of which a third degree of freedom is created for reducing the linear distortion. Further, a method of using said three stigmators, comprises exciting the first stigmator to reduce astigmatism when imaging the sample, exciting the second stigmator to reduce astigmatism when imaging the diffraction plane, and exciting the third stigmator to reduce the linear distortion.

Abstract translation: 带电粒子装置配备有位于物镜和检测器系统之间的第三标示器，结果为了减少线性失真产生了第三自由度。 此外，使用所述三个标记器的方法包括：激光所述第一标示器以在对所述样品进行成像时减少散光，激励所述第二标示器以在对所述衍射平面进行成像时减少散光，以及激励所述第三施放器以减少所述线性失真。

公开(公告)号：US20120128028A1

公开(公告)日：2012-05-24

申请号：US13304181

申请日：2011-11-23

Applicant: Stephanus Hubertus Leonardus van den Boom ,  Pleun Dona ,  Laurens Franz Taemsz Kwakman ,  Uwe Luecken ,  Hervé-William Rémigy ,  Hendrik Nicolaas Slingerland ,  Martin Verheijen ,  Gerbert Jeroen van der Water

Inventor： Stephanus Hubertus Leonardus van den Boom ,  Pleun Dona ,  Laurens Franz Taemsz Kwakman ,  Uwe Luecken ,  Hervé-William Rémigy ,  Hendrik Nicolaas Slingerland ,  Martin Verheijen ,  Gerbert Jeroen van der Water

IPC: G01K13/00 ,  G01K11/00

CPC classification number: G01K5/68 ,  G01K11/20 ,  H01J37/20 ,  H01J37/26 ,  H01J2237/2001 ,  H01J2237/24585

Abstract: A method of determining the temperature of a sample carrier in a charged particle-optical apparatus, characterized in that the method comprises the observation of the sample carrier with a beam of charged particles, the observation giving information about the temperature of the sample carrier. The invention is based on the insight that a charged particle optical apparatus, such as a TEM, STEM, SEM or FIB, can be used to observe temperature related changes of a sample carrier. The changes may be mechanical changes (e.g. of a bimetal), crystallographic changes (e.g. of a perovskite), and luminescent changes (in intensity or decay time). In a preferred embodiment the sample carrier shows two bimetals, showing metals with different thermal expansion coefficients, bending in opposite directions. The distance between the two bimetals is used as a thermometer.

Abstract translation: 一种确定带电粒子光学装置中的样品载体的温度的方法，其特征在于，所述方法包括用带电粒子束观察样品载体，所述观察给出关于样品载体的温度的信息。 本发明基于如下观点：带电粒子光学装置如TEM，STEM，SEM或FIB可用于观察样品载体的温度相关变化。 这些改变可以是机械变化（例如双金属），晶体学变化（例如钙钛矿）和发光变化（强度或衰变时间）。 在优选实施例中，样品载体显示两个双金属，显示具有不同热膨胀系数的金属，在相反方向上弯曲。 两个双金属片之间的距离用作温度计。

公开(公告)号：US20100072366A1

公开(公告)日：2010-03-25

申请号：US12564617

申请日：2009-09-22

Applicant: Peter Christiaan Tiemeijer ,  Uwe Luecken ,  Alan Frank De Jong ,  Hendrik Nicolaas Slingerland

Inventor： Peter Christiaan Tiemeijer ,  Uwe Luecken ,  Alan Frank De Jong ,  Hendrik Nicolaas Slingerland

IPC: G01N23/04 ,  H01J37/26

CPC classification number: H01J37/153 ,  H01J37/263 ,  H01J2237/1534 ,  H01J2237/2823

Abstract: The invention relates to a method for correcting distortions introduced by the projection system (106) of a TEM. As known to the person skilled in the art distortions may limit the resolution of a TEM, especially when making a 3D reconstruction of a feature using tomography. Also when using strain analysis in a TEM the distortions may limit the detection of strain.To this end the invention discloses a detector equipped with multipoles (152), the multipoles warping the image of the TEM in such a way that distortions introduced by the projection system are counteracted. The detector may further include a CCD or a fluorescent screen (151) for detecting the electrons.

Abstract translation: 本发明涉及一种用于校正由TEM的投影系统（106）引入的失真的方法。 如本领域技术人员所知，失真可能限制TEM的分辨率，特别是当使用层析成像进行特征的3D重建时。 此外，当在TEM中使用应变分析时，失真可能会限制应变的检测。 为此，本发明公开了一种装备有多极（152）的检测器，该多极体使得TEM的图像翘曲，使得由投影系统引入的失真被抵消。 检测器还可以包括用于检测电子的CCD或荧光屏（151）。

公开(公告)号：US08757873B2

公开(公告)日：2014-06-24

申请号：US13304181

申请日：2011-11-23

Applicant: Stephanus Hubertus Leonardus van den Boom ,  Pleun Dona ,  Laurens Franz Taemsz Kwakman ,  Uwe Luecken ,  Hervé-William Rémigy ,  Hendrik Nicolaas Slingerland ,  Martin Verheijen ,  Gerbert Jeroen van de Water

Inventor： Stephanus Hubertus Leonardus van den Boom ,  Pleun Dona ,  Laurens Franz Taemsz Kwakman ,  Uwe Luecken ,  Hervé-William Rémigy ,  Hendrik Nicolaas Slingerland ,  Martin Verheijen ,  Gerbert Jeroen van de Water

IPC: G01K1/00 ,  G01K13/12 ,  G01K11/00 ,  G01K11/20 ,  G01K5/68 ,  H01J37/20 ,  H01J37/26

CPC classification number: G01K5/68 ,  G01K11/20 ,  H01J37/20 ,  H01J37/26 ,  H01J2237/2001 ,  H01J2237/24585

Abstract: A method of determining the temperature of a sample carrier in a charged particle-optical apparatus, characterized in that the method comprises the observation of the sample carrier with a beam of charged particles, the observation giving information about the temperature of the sample carrier. The invention is based on the insight that a charged particle optical apparatus, such as a TEM, STEM, SEM or FIB, can be used to observe temperature related changes of a sample carrier. The changes may be mechanical changes (e.g. of a bimetal), crystallographic changes (e.g. of a perovskite), and luminescent changes (in intensity or decay time). In a preferred embodiment the sample carrier shows two bimetals, showing metals with different thermal expansion coefficients, bending in opposite directions. The distance between the two bimetals is used as a thermometer.

Abstract translation: 一种确定带电粒子光学装置中的样品载体的温度的方法，其特征在于，所述方法包括用带电粒子束观察样品载体，所述观察给出关于样品载体的温度的信息。 本发明基于如下观点：带电粒子光学装置如TEM，STEM，SEM或FIB可用于观察样品载体的温度相关变化。 这些改变可以是机械变化（例如双金属），晶体学变化（例如钙钛矿）和发光变化（强度或衰变时间）。 在优选实施例中，样品载体显示两个双金属，显示具有不同热膨胀系数的金属，在相反方向上弯曲。 两个双金属片之间的距离用作温度计。

公开(公告)号：US08692196B2

公开(公告)日：2014-04-08

申请号：US12564617

申请日：2009-09-22

Applicant: Peter Christiaan Tiemeijer ,  Uwe Luecken ,  Alan Frank de Jong ,  Hendrik Nicolaas Slingerland

Inventor： Peter Christiaan Tiemeijer ,  Uwe Luecken ,  Alan Frank de Jong ,  Hendrik Nicolaas Slingerland

IPC: G01N23/00

CPC classification number: H01J37/153 ,  H01J37/263 ,  H01J2237/1534 ,  H01J2237/2823

Abstract: The invention relates to a method for correcting distortions introduced by the projection system (106) of a TEM. As known to the person skilled in the art distortions may limit the resolution of a TEM, especially when making a 3D reconstruction of a feature using tomography. Also when using strain analysis in a TEM the distortions may limit the detection of strain.To this end the invention discloses a detector equipped with multipoles (152), the multipoles warping the image of the TEM in such a way that distortions introduced by the projection system are counteracted. The detector may further include a CCD or a fluorescent screen (151) for detecting the electrons.

Abstract translation: 本发明涉及一种用于校正由TEM的投影系统（106）引入的失真的方法。 如本领域技术人员所知，失真可能限制TEM的分辨率，特别是当使用层析成像进行特征的3D重建时。 此外，当在TEM中使用应变分析时，失真可能会限制应变的检测。 为此，本发明公开了一种装备有多极（152）的检测器，该多极体使得TEM的图像翘曲，使得由投影系统引入的失真被抵消。 检测器还可以包括用于检测电子的CCD或荧光屏（151）。