公开(公告)号：US10078037B2

公开(公告)日：2018-09-18

申请号：US14085653

申请日：2013-11-20

Applicant: FEI Company

Inventor： Frank Lison ,  Jens Greiser ,  Matthias Langhorst

IPC: G01N1/30 ,  G01N1/31 ,  G01N21/64 ,  G01N35/00

CPC classification number: G01N1/30 ,  G01N1/312 ,  G01N21/6458 ,  G01N35/00594 ,  G01N35/0092

Abstract: Described is a system and method for detecting whether a biological event has occurred in a cellular sample, and then activating a fluidics system to fix the cell at the point in time with the event occurred. In one example, a sample preparation system includes a camera linked to a confocal microscope that is interrogating a cellular sample. Once a detectable event, such as a binding event, has occurred, the sample preparation system releases a fixative to fix the cell at the point in time when the event was detected.

公开(公告)号：US11735404B2

公开(公告)日：2023-08-22

申请号：US17017580

申请日：2020-09-10

Applicant: FEI Company

Inventor： Alex De Marco ,  Sergey Gorelick ,  Chad Rue ,  Joseph Christian ,  Kenny Mani ,  Steven Randolph ,  Matthias Langhorst

IPC: H01J37/32 ,  H01J49/00 ,  G01N1/32

CPC classification number: H01J49/0027 ,  G01N1/32 ,  H01J37/32009 ,  H01J2237/0807 ,  H01J2237/31745 ,  H01J2237/31749

Abstract: The invention relates to a method, a device and a system for the treatment of biological frozen samples using plasma focused ion beams (FIB). The samples can then be used for mass spectrometry (MS), genomics, such as gene sequencing analysis or next generation sequencing (NGS) analysis, and proteomics. The present invention particularly relates to a method of treatment of at least one biological sample. This method is particularly used for high performance microscopy, proteomics analytics, sequencing, such as NGS etc. According to the present invention the method comprises the steps of providing at least one biological sample in frozen form. The milling treats at least one part of the sample by a plasma ion beam comprising at least one of an O+ and/or a Xe+ plasma.

公开(公告)号：US20140147832A1

公开(公告)日：2014-05-29

申请号：US14085653

申请日：2013-11-20

Applicant: FEI COMPANY

Inventor： Frank Lison ,  Jens Greiser ,  Matthias Langhorst

IPC: G01N1/30 ,  G01N1/31

CPC classification number: G01N1/30 ,  G01N1/312 ,  G01N21/6458 ,  G01N35/00594 ,  G01N35/0092

Abstract: Described is a system and method for detecting whether a biological event has occurred in a cellular sample, and then activating a fluidics system to fix the cell at the point in time with the event occurred. In one example, a sample preparation system includes a camera linked to a confocal microscope that is interrogating a cellular sample. Once a detectable event, such as a binding event, has occurred, the sample preparation system releases a fixative to fix the cell at the point in time when the event was detected.

Abstract translation: 描述了用于检测细胞样品中是否已经发生生物学事件，然后激活流体系统以在发生事件的时间点固定细胞的系统和方法。 在一个示例中，样品制备系统包括连接到询问细胞样品的共焦显微镜的照相机。 一旦发生了可检测的事件，例如结合事件，样品制备系统释放固定剂，以在检测到事件的时间点固定细胞。

公开(公告)号：US09478393B2

公开(公告)日：2016-10-25

申请号：US14752570

申请日：2015-06-26

Applicant: FEI Company

Inventor： Pavel Potocek ,  Faysal Boughorbel ,  Berend Helmerus Lich ,  Matthias Langhorst

IPC: G01Q10/06 ,  H01J37/244 ,  G02B21/00 ,  H01J37/285 ,  H01J37/28

CPC classification number: H01J37/244 ,  G02B21/002 ,  G02B21/008 ,  H01J37/222 ,  H01J37/28 ,  H01J37/285 ,  H01J2237/226

Abstract: A method of imaging a specimen comprises directing a beam to irradiate a specimen; detecting radiation emanating from the specimen; scanning the beam along a path; for each sample point in said path, recording a measurement set M={(Dn, Pn)}, where Dn is the detector output as a function of value Pn of measurement parameter P; deconvolving M and spatially resolving it into a set representing depth-resolved imagery of the specimen, whereby, at point pi within the specimen, in a first probing session, irradiating, in a first beam configuration, pi with Point Spread Function F1, whereby said beam configuration is different to P; in at least a second probing session, irradiating, in a second beam configuration, pi with Point Spread Function F2 which overlaps partially with F1 in a zone Oi in which pi is located; sing an Independent Component Analysis algorithm to perform spatial resolution in Oi.

公开(公告)号：US20160013015A1

公开(公告)日：2016-01-14

申请号：US14752570

申请日：2015-06-26

Applicant: FEI Company

Inventor： Pavel Potocek ,  Faysal Boughorbel ,  Berend Helmerus Lich ,  Matthias Langhorst

IPC: H01J37/244 ,  H01J37/285 ,  H01J37/28 ,  G02B21/00

CPC classification number: H01J37/244 ,  G02B21/002 ,  G02B21/008 ,  H01J37/222 ,  H01J37/28 ,  H01J37/285 ,  H01J2237/226

Abstract: A method of accumulating an image of a specimen using a scanning-type microscope, comprising the following steps: Directing a beam of radiation from a source through an illuminator so as to irradiate a surface S of the specimen; Using a detector to detect a flux of radiation emanating from the specimen in response to said irradiation; Causing said beam to follow a scan path relative to said surface; For each of a set of sample points in said scan path, recording an output Dn of the detector as a function of a value Pn of a selected measurement parameter P, thus compiling a measurement set M={(Dn, Pn)}, where n is a member of an integer sequence; Using computer processing apparatus to automatically deconvolve the measurement set M and spatially resolve it so as to produce reconstructed imagery of the specimen, wherein, considered at a given point pi within the specimen, the method comprises the following steps: In a first probing session, employing a first beam configuration B1 to irradiate the point pi with an associated first Point Spread Function F1, whereby said beam configuration is different to said measurement parameter; In at least a second probing session, employing a second beam configuration B2 to irradiate the point pi with an associated second Point Spread Function F2, whereby: F2 overlaps partially with F1 in a common overlap zone Oi in which point pi is located; F1 and F2 have respective non-overlapping zones F1′ and F2′ outside of Oi, Using a Source Separation algorithm in said computer processing apparatus to perform image reconstruction in said overlap zone Oi considered separately from said non-overlapping zones F1′ and F2′.

Abstract translation: 使用扫描型显微镜对试样的图像进行累积的方法，包括以下步骤：使来自源的辐射束通过照射器引导，以照射样本的表面S; 使用检测器来响应于所述照射来检测从样品发出的辐射通量; 使所述光束相对于所述表面跟随扫描路径; 对于所述扫描路径中的一组采样点中的每一个，记录检测器的输出Dn作为所选择的测量参数P的值Pn的函数，从而编译测量集M = {（Dn，Pn）}，其中 n是整数序列的成员; 使用计算机处理装置对测量集M进行自动解卷积并对其进行空间解析以产生样本的重建图像，其中，在样本内的给定点pi处考虑，该方法包括以下步骤：在第一探测会话中， 采用第一光束配置B1以相关联的第一点扩展函数F1照射点pi，由此所述光束配置与所述测量参数不同; 在至少第二探测会话中，采用第二光束配置B2以相关联的第二点扩展函数F2照射点pi，由此：F2在与其相对应的位置的公共重叠区域Oi中部分地与F1重叠; F1和F2在Oi外部具有各自的非重叠区域F1'和F2'，在所述计算机处理设备中使用源分离算法，在与所述非重叠区域F1'和F2'分开考虑的所述重叠区域Oi中执行图像重建， 。