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1. 发明授权

US5784162A Spectral bio-imaging methods for biological research, medical diagnostics and therapy 失效
标题翻译：用于生物研究，医学诊断和治疗的光谱生物成像方法
公开(公告)号：US5784162A
公开(公告)日：1998-07-21
申请号：US571047
申请日：1995-12-12
申请人： Dario Cabib , Robert A. Buckwald , Zvi Malik , Yuval Garini , Nir Katzir , Dirk G. Soeknsen
发明人： Dario Cabib , Robert A. Buckwald , Zvi Malik , Yuval Garini , Nir Katzir , Dirk G. Soeknsen
IPC分类号： G01B11/00 , A61B3/00 , A61B3/12 , A61B5/00 , A61B10/00 , C12Q1/68 , G01J3/02 , G01J3/12 , G01J3/26 , G01J3/28 , G01J3/44 , G01J3/443 , G01J3/45 , G01J3/453 , G01N21/27 , G01N21/64 , G01N33/48 , G01N33/483 , G01N33/50 , G01N33/569 , G01N33/58 , G02B21/36 , G06K9/00 , G06K9/76 , G01B9/02
CPC分类号： G01N21/6458 , C12Q1/6841 , C12Q1/6883 , G01J3/12 , G01J3/1256 , G01J3/26 , G01J3/2823 , G01J3/4406 , G01J3/453 , G01N21/6428 , G01N21/6486 , G01N33/5005 , G01N33/56966 , G01N33/582 , G06K9/00127 , G06K9/76 , G01J2003/2866 , G01J3/02 , G01N2021/6417 , G01N2021/6423
摘要： According to the present invention there are provided spectral imaging methods for biological research, medical diagnostics and therapy comprising the steps of (a) preparing a sample to be spectrally imaged; (b) viewing the sample through an optical device, the optical device being optically connected to an imaging spectrometer, the optical device and the imaging spectrometer obtaining a spectrum of each pixel of the sample by: (i) collecting incident light simultaneously from all pixels of the sample using collimating optics; (ii) passing the incident collimated light through an interferometer system having a number of elements, to form an exiting light beam; (iii) passing the exiting light beam through a focusing optical system which focuses the exiting light beam on a detector having a two-dimensional array of detector elements, so that at each instant each of the detector elements is the image of one pixel of the sample, so that the real image of the sample is stationary on the plane of the detector array, and so that each of the detector elements produces a signal which is a particular linear combination of light intensity emitted by the pixel at different wavelengths, wherein the linear combination is a function of the instantaneous optical path difference; (iv) rotating one or more of the elements of the interferometer system, so that the optical path difference between the two coherent beams generated by the interferometer system is scanned simultaneously for all the pixels of the sample; and (v) recording signals of each of the detector elements as function of time using a recording device to form a first spectral cube of data; and (c) interpreting the first spectral cube of data using a mathematical algorithm.
摘要翻译：根据本发明，提供了用于生物学研究，医学诊断和治疗的光谱成像方法，其包括以下步骤：（a）制备待成像的样品; （b）通过光学装置观察样品，光学装置光学连接到成像光谱仪，光学装置和成像光谱仪通过以下步骤获得样品的每个像素的光谱：（i）从所有像素同时收集入射光的样品使用准直光学; （ii）使入射的准直光通过具有多个元件的干涉仪系统，以形成出射的光束; （iii）使出射的光束通过聚焦光学系统，该聚焦光学系统将出射的光束聚焦在具有检测器元件的二维阵列的检测器上，使得在每个瞬间，每个检测器元件是样本，使得样本的真实图像在检测器阵列的平面上是静止的，并且使得每个检测器元件产生信号，其是由不同波长的像素发射的光强度的特定线性组合，其中线性组合是瞬时光程差的函数; （iv）旋转干涉仪系统的一个或多个元件，使得由干涉仪系统产生的两个相干光束之间的光程差同时扫描样品的所有像素; 以及（v）使用记录装置记录每个检测器元件的信号作为时间的函数，以形成数据的第一光谱立方体; 和（c）使用数学算法解释数据的第一个频谱立方体。

2. 发明授权

US5936731A Method for simultaneous detection of multiple fluorophores for in situ hybridization and chromosome painting 失效
标题翻译：同时检测多种荧光团用于原位杂交和染色体绘画的方法
公开(公告)号：US5936731A
公开(公告)日：1999-08-10
申请号：US575191
申请日：1995-12-20
申请人： Dario Cabib , Robert A. Buckwald , David Wine , Yuval Garini , Nir Katzir , Dirk G. Soeknsen , Moshe Lavi
发明人： Dario Cabib , Robert A. Buckwald , David Wine , Yuval Garini , Nir Katzir , Dirk G. Soeknsen , Moshe Lavi
IPC分类号： G01B9/02 , A61B3/12 , A61B5/00 , C12Q1/68 , G01B11/06 , G01J3/02 , G01J3/12 , G01J3/26 , G01J3/28 , G01J3/44 , G01J3/453 , G01N21/27 , G01N21/64 , G01N33/48 , G01N33/50 , G01N33/569 , G01N33/58 , G06K9/00 , G06K9/76
CPC分类号： G01N21/6458 , A61B3/12 , C12Q1/6816 , C12Q1/6841 , C12Q1/6883 , G01B11/0675 , G01J3/12 , G01J3/1256 , G01J3/26 , G01J3/2823 , G01J3/4406 , G01J3/453 , G01J3/4535 , G01N21/6428 , G01N33/5005 , G01N33/56966 , G01N33/582 , G06K9/00127 , G06K9/76 , A61B3/1241 , C12Q2600/156 , G01J2003/2866 , G01J3/02 , G01N2021/6417 , G01N2021/6441
摘要： A fluorescent in situ hybridization method comprising the steps of (a) providing a cell nuclei having chromosomes hybridized with at least one nucleic acid probe including at least one nucleic acid molecule labeled with at least one fluorophore; (b) viewing the cell nuclei through a fluorescence microscope optically connected to an imaging spectrometer for obtaining a spectrum of each pixel of the cell nuclei by (i) collecting incident collimated light simultaneously from all pixels of the cell nuclei; (ii) passing the incident collimated light through an interferometer system so that the light is first split into two coherent beams and then recombine to interfere and form an exiting light beam; (iii) focusing the exiting light beam on a detector having an array of detector elements, so that at each instant each of the elements is the image of one and always the same pixel for the entire duration of the measurement and so that each of the elements produces a signal which is a particular linear combination of light intensity emitted by the pixel at different wavelengths; (iv) rotating or translating one or more of the elements of the interferometer, so that the optical path difference is scanned simultaneously for all the pixels of the cell nuclei; and (v) recording signals of each of the detector elements as function of time using a recording device to form a first spectral cube of data; and (c) interpreting the first spectral cube of data using a mathematical algorithm.
摘要翻译：荧光原位杂交方法包括以下步骤：（a）提供具有染色体的细胞核，所述染色体与至少一种核酸探针杂交，所述核酸探针包括至少一个用至少一个荧光团标记的核酸分子; （b）通过光学连接到成像光谱仪的荧光显微镜观察细胞核，通过（i）从细胞核的所有像素同时收集入射准直光，以获得细胞核的每个像素的光谱; （ii）使入射的准直光通过干涉仪系统，使得光首先分裂成两个相干光束，然后重组以干涉并形成出射的光束; （iii）将出射的光束聚焦在具有检测器元件阵列的检测器上，使得在每个时刻，在整个测量持续时间内，每个元件是一个并且总是相同像素的图像，并且使得每个元件产生信号，其是由不同波长的像素发射的光强度的特定线性组合; （iv）旋转或平移干涉仪的一个或多个元件，使得对于细胞核的所有像素同时扫描光程差; 以及（v）使用记录装置记录每个检测器元件的信号作为时间的函数，以形成数据的第一光谱立方体; 和（c）使用数学算法解释数据的第一个频谱立方体。

3. 发明授权

US6055325A Color display of chromosomes or portions of chromosomes 失效
标题翻译：染色体或染色体部分的彩色显示
公开(公告)号：US6055325A
公开(公告)日：2000-04-25
申请号：US942327
申请日：1997-10-01
申请人： Yuval Garini , Dario Cabib , Robert A. Buckwald , Dirk G. Soenksen , Nir Katzir , David Wine , Moshe Lavi
发明人： Yuval Garini , Dario Cabib , Robert A. Buckwald , Dirk G. Soenksen , Nir Katzir , David Wine , Moshe Lavi
IPC分类号： G01B9/02 , A61B3/12 , A61B5/00 , C12Q1/68 , G01B11/06 , G01J3/02 , G01J3/12 , G01J3/26 , G01J3/28 , G01J3/44 , G01J3/453 , G01N21/27 , G01N21/64 , G01N33/48 , G01N33/50 , G01N33/569 , G01N33/58 , G06K9/00 , G06K9/76
CPC分类号： G01N21/6458 , A61B3/12 , C12Q1/6816 , C12Q1/6841 , C12Q1/6883 , G01B11/0675 , G01J3/12 , G01J3/1256 , G01J3/26 , G01J3/2823 , G01J3/4406 , G01J3/453 , G01J3/4535 , G01N21/6428 , G01N33/5005 , G01N33/56966 , G01N33/582 , G06K9/00127 , G06K9/76 , A61B3/1241 , C12Q2600/156 , G01J2003/2866 , G01J3/02 , G01N2021/6417 , G01N2021/6441
摘要： A color display comprising an image of all chromosomes or portions of chromosomes of a cell, each of the chromosomes or portions of chromosomes being painted with a different fluorophore or a combination of fluorophores, the image presenting the chromosomes or portions of chromosomes in different distinctive colors, wherein each of the chromosomes or portions of chromosomes is associated with one of the different distinctive colors.
摘要翻译：一种彩色显示器，其包括所有染色体或细胞染色体部分的图像，每个染色体或染色体部分用不同的荧光团或荧光团的组合进行染色，所述染色体或染色体的部分以不同的特征呈现其中每个染色体或染色体的部分与不同的独特颜色之一相关联。

4. 发明授权

US5798262A Method for chromosomes classification 失效
公开(公告)号：US5798262A
公开(公告)日：1998-08-25
申请号：US844516
申请日：1997-04-18
申请人： Yuval Garini , Nir Katzir , David Wine , Dario Cabib
发明人： Yuval Garini , Nir Katzir , David Wine , Dario Cabib
IPC分类号： G01N33/48 , C12M1/00 , C12M3/00 , C12N15/09 , C12N15/11 , C12Q1/68 , G01J3/02 , G01J3/12 , G01J3/26 , G01J3/28 , G01J3/44 , G01J3/453 , G01N1/28 , G01N21/64 , G01N21/75 , G01N33/483 , G01N33/50 , G01N33/52 , G01N33/569 , G01N33/58 , G01N37/00 , G02B21/00 , G02B21/16 , G06K9/00 , G06K9/76 , C12M1/34 , G06F15/00
CPC分类号： G01J3/12 , C12Q1/6816 , G01J3/1256 , G01J3/26 , G01J3/2823 , G01J3/4406 , G01J3/453 , G01N21/6428 , G01N21/6456 , G01N33/5005 , G01N33/56966 , G01N33/582 , G06K9/00127 , G06K9/0014 , G06K9/76 , G01J2003/2866 , G01J3/02 , G01N2021/6423 , G01N2021/6441
摘要： A method for finding L internal reference vectors for classification of L chromosomes or portions of chromosomes of a cell, the L chromosomes or portions of chromosomes being painted with K different fluorophores or combinations thereof, wherein K basic chromosomes or portions of chromosomes of the L chromosomes or portions of chromosomes are each painted with only one of the K different fluorophores, whereas the other L-K of the L chromosomes or portions of chromosomes are each painted with a different combination of the K different fluorophores, the method comprising the steps of (a) using a multi-band collection device for measuring a first vector for each pixel of each of the L chromosomes or portions of chromosomes; (b) identifying pixels belonging to each of the K basic chromosomes or portions of chromosomes and defining the pixels as basic pixels, so as to obtain K basic classes of basic pixels; (c) using at least one basic pixel from each of the K basic classes for obtaining K basic vectors, the K basic vectors being K internal reference vectors; (d) using the K basic vectors for identifying pixels belonging to the other L-K chromosomes or portions of chromosomes; and (e) using the pixels belonging to the other L-K chromosomes or portions of chromosomes for calculating the other L-K internal reference vectors, thereby finding all of the L internal reference vectors. A method for classification of L chromosomes or portions of chromosomes of a cell similarly painted using the above method for finding L internal reference vectors, and using the L reference vectors for classification of each of the pixels into one of L classification classes. And, images presenting color chromosomes.

5. 发明授权

US5834203A Method for classification of pixels into groups according to their spectra using a plurality of wide band filters and hardwire therefore 失效
标题翻译：因此，使用多个宽带滤波器和硬件根据其频谱将像素分类为组的方法
公开(公告)号：US5834203A
公开(公告)日：1998-11-10
申请号：US917213
申请日：1997-08-25
申请人： Nir Katzir , David Wine , Yuval Garini , Dario Cabib
发明人： Nir Katzir , David Wine , Yuval Garini , Dario Cabib
IPC分类号： G01N21/64 , G01N15/14 , G01N21/78 , G01N33/533 , G01N33/566 , G01N33/58 , G02B21/06 , C12Q1/68 , F21V9/08 , G02B21/16
CPC分类号： G01N21/6428 , G01N21/6458 , G02B21/06 , G01N15/1475 , G01N2021/6441
摘要： A method of classification of pixels into groups of pixels according to their association with a single fluorophore or a combination of fluorophores selected from a plurality of fluorophores, each of the fluorophores having characterizing excitation and emission spectra and specifying excitation and emission peaks, the method comprising the steps of (a) providing a plurality of pairs of wide-band excitation filters and wide-band emission filters; (b) exciting fluorophores of each of the pixels with light filtered through one of the wide-band excitation filters, and recording emitted light intensity as retrieved after passing through its paired emission filter; (c) repeating step (b) for all of the plurality of pairs of filters, such that each of the pixels is representable by a vector of a plurality of dimensions, the number of dimensions being equal to the number of the plurality of pairs of filters; (c) using an algorithm for evaluating the presence of each of the plurality of fluorophores in each of the pixels, thereby classifying each of the pixels into a group of pixels according to its association with a single fluorophore or combination of fluorophores.
摘要翻译：根据其与单个荧光团或选自多个荧光团的荧光团的组合的关联或每个荧光团具有表征激发和发射光谱以及指定激发和发射峰值的方式，将像素分类为像素组的方法，所述方法包括：（a）提供多对宽带激励滤波器和宽带发射滤波器的步骤; （b）每个像素的激发荧光团，其中通过一个宽带激发滤光器之一滤光，并且记录经过其成对发射滤光片之后检索的发射光强度; （c）对于所有多对滤波器重复步骤（b），使得每个像素可以由多个维度的向量表示，维数等于多对滤波器的数量过滤器（c）使用用于评估每个像素中的每个多个荧光团的存在的算法，从而根据其与单个荧光团或荧光团的组合的关联将每个像素分类为一组像素。

6. 发明授权

US5906919A Method for chromosomes classification 失效
标题翻译：染色体分类方法
公开(公告)号：US5906919A
公开(公告)日：1999-05-25
申请号：US962845
申请日：1997-11-03
申请人： Yuval Garini , Nir Katzir , David Wine , Dario Cabib
发明人： Yuval Garini , Nir Katzir , David Wine , Dario Cabib
IPC分类号： G01N33/48 , C12M1/00 , C12M3/00 , C12N15/09 , C12N15/11 , C12Q1/68 , G01J3/02 , G01J3/12 , G01J3/26 , G01J3/28 , G01J3/44 , G01J3/453 , G01N1/28 , G01N21/64 , G01N21/75 , G01N33/483 , G01N33/50 , G01N33/52 , G01N33/569 , G01N33/58 , G01N37/00 , G02B21/00 , G02B21/16 , G06K9/00 , G06K9/76
CPC分类号： G01J3/12 , C12Q1/6816 , G01J3/1256 , G01J3/26 , G01J3/2823 , G01J3/4406 , G01J3/453 , G01N21/6428 , G01N21/6456 , G01N33/5005 , G01N33/56966 , G01N33/582 , G06K9/00127 , G06K9/0014 , G06K9/76 , G01J2003/2866 , G01J3/02 , G01N2021/6423 , G01N2021/6441
摘要： A method for finding L internal reference vectors for classification of L chromosomes or portions of chromosomes of a cell, the L chromosomes or portions of chromosomes being painted with K different fluorophores or combinations thereof, wherein K basic chromosomes or portions of chromosomes of the L chromosomes or portions of chromosomes are each painted with only one of the K different fluorophores, whereas the other L-K of the L chromosomes or portions of chromosomes are each painted with a different combination of the K different fluorophores, the method comprising the steps of (a) using a multi-band collection device for measuring a first vector for each pixel of each of the L chromosomes or portions of chromosomes; (b) identifying pixels belonging to each of the K basic chromosomes or portions of chromosomes and defining the pixels as basic pixels, so as to obtain K basic classes of basic pixels; (c) using at least one basic pixel from each of the K basic classes for obtaining K basic vectors, the K basic vectors being K internal reference vectors; (d) using the K basic vectors for identifying pixels belonging to the other L-K chromosomes or portions of chromosomes; and (e) using the pixels belonging to the other L-K chromosomes or portions of chromosomes for calculating the other L-K internal reference vectors, thereby finding all of the L internal reference vectors. A method for classification of L chromosomes or portions of chromosomes of a cell similarly painted using the above method for finding L internal reference vectors, and using the L reference vectors for classification of each of the pixels into one of L classification classes. And, images presenting color chromosomes.
摘要翻译：一种用于分析L染色体或细胞染色体部分的L个内部参照载体的方法，L染色体或染色体部分用K个不同的荧光团或其组合进行染色，其中K个基本染色体或L个染色体的染色体部分或染色体的部分各自仅涂覆有K个不同荧光团中的一个，而L个染色体的其他LK或染色体部分各自用不同的K个不同荧光团的组合进行涂布，该方法包括以下步骤：（a）使用多频带收集装置测量每个L染色体或染色体部分的每个像素的第一个载体; （b）识别属于K个基本染色体或染色体部分的像素，并将该像素定义为基本像素，以获得基本像素的K个基本类别; （c）使用来自K个基本类别的至少一个基本像素来获得K个基本向量，所述K个基本向量是K个内部参考向量; （d）使用K个基本载体来识别属于其他L-K染色体或染色体部分的像素; 和（e）使用属于其他L-K染色体或染色体部分的像素来计算其他L-K内部参考矢量，从而找到所有L个内部参考矢量。使用上述用于寻找L个内部参考向量的方法，并且使用L个参考向量将每个像素分类为L个分类等级之一来分类L染色体或染色体部分的方法。而且，呈现彩色染色体的图像。

7. 发明授权

US5995645A Method of cancer cell detection 失效
标题翻译：癌细胞检测方法
公开(公告)号：US5995645A
公开(公告)日：1999-11-30
申请号：US984990
申请日：1997-12-04
申请人： Dirk C. Soenksen , George McNamara , Yuval Garini , Nir Katzir
发明人： Dirk C. Soenksen , George McNamara , Yuval Garini , Nir Katzir
IPC分类号： G01J3/46 , C12Q1/68 , G01B11/06 , G01J3/02 , G01J3/12 , G01J3/26 , G01J3/28 , G01J3/44 , G01J3/453 , G01J5/10 , G01N1/30 , G01N21/27 , G01N21/64 , G01N21/78 , G01N33/483 , G01N33/50 , G01N33/569 , G01N33/58 , G06K9/00 , G06K9/76 , G06T1/00 , G01N33/48 , G01N33/574
CPC分类号： G01N21/6458 , G01B11/0675 , G01J3/12 , G01J3/1256 , G01J3/26 , G01J3/2823 , G01J3/4406 , G01J3/453 , G01J5/10 , G01N21/6428 , G01N33/5005 , G01N33/56966 , G01N33/582 , G06K9/00127 , G06K9/76 , G01J2003/2866 , G01J3/02 , G01N2021/6417 , G01N2021/6423 , G01N2021/6441
摘要： A method for cancer cell detection including the steps of (a) staining an analyzed sample with at least first and second dyes, the dyes being selected such that the first dye better adheres to normal cells whereas the second dye better adheres to cancer cells; (b) spectrally imaging the sample through an optical device being optically connected to an imaging spectrometer thereby obtaining a spectrum of each pixel of the sample; (c) based on the spectra, evaluating concentrations of the first and second dyes for each of the pixels; and (d) based on the concentrations detecting the presence of cancer cells in the sample.
摘要翻译：一种用于癌细胞检测的方法，包括以下步骤：（a）用至少第一和第二染料对分析的样品进行染色，所述染料选择为使得第一染料更好地附着于正常细胞，而第二染料更好地附着于癌细胞; （b）通过光学连接到成像光谱仪的光学装置对样品进行光谱成像，从而获得样品的每个像素的光谱; （c）基于光谱，评估每个像素的第一和第二染料的浓度; 和（d）基于检测样品中癌细胞存在的浓度。

8. 发明授权

US09133506B2 Methods and systems for analyzing biological samples 有权
标题翻译：分析生物样品的方法和系统
公开(公告)号：US09133506B2
公开(公告)日：2015-09-15
申请号：US12087543
申请日：2007-01-09
申请人： Nir Katzir , Tsafrir Kolatt , Irit Bar-Am
发明人： Nir Katzir , Tsafrir Kolatt , Irit Bar-Am
IPC分类号： G06F19/20 , C12Q1/06 , C12Q1/68 , G06K9/00
CPC分类号： C12Q1/6841 , G06K9/00134
摘要： Methods, computer readable storage media and systems which can be used for analyzing labeled biological samples, identifying chromosomal aberrations, identifying genetically abnormal cells and/or computationally scanning the samples using randomly or randomized scanning methods are provided. Specifically, the present invention can be used to analyze FISH-stained samples and automatically identify chromosomal aberrations associated with abnormal intensity ratio of stained occurrences in the sample.
摘要翻译：提供了可用于分析标记的生物样品，识别染色体畸变，识别遗传异常细胞和/或使用随机或随机扫描方法计算扫描样品的方法，计算机可读存储介质和系统。具体地，本发明可用于分析FISH染色的样品，并自动识别与样品中染色事件的异常强度比相关的染色体畸变。

9. 发明申请

US20090048785A1 Methods And Systems For Analyzing Biological Samples 有权
标题翻译：用于分析生物样品的方法和系统
公开(公告)号：US20090048785A1
公开(公告)日：2009-02-19
申请号：US12087543
申请日：2007-01-09
申请人： Nir Katzir , Tsafrir Kolatt , Irit Bar-Am
发明人： Nir Katzir , Tsafrir Kolatt , Irit Bar-Am
IPC分类号： G06F19/00 , G01N33/48
CPC分类号： C12Q1/6841 , G06K9/00134
摘要： Methods, computer readable storage media and systems which can be used for analyzing labeled biological samples, identifying chromosomal aberrations, identifying genetically abnormal cells and/or computationally scanning the samples using randomly or randomized scanning methods are provided. Specifically, the present invention can be used to analyze FISH-stained samples and automatically identify chromosomal aberrations associated with abnormal intensity ratio of stained occurrences in the sample.
摘要翻译：提供了可用于分析标记的生物样品，识别染色体畸变，识别遗传异常细胞和/或使用随机或随机扫描方法计算扫描样品的方法，计算机可读存储介质和系统。具体地，本发明可用于分析FISH染色的样品，并自动识别与样品中染色事件的异常强度比相关的染色体畸变。

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