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公开(公告)号：US20220025442A1
公开(公告)日：2022-01-27
申请号：US17374000
申请日：2021-07-13
IPC分类号： C12Q1/6816 , C12Q1/6876 , C12Q1/6811
摘要： The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.
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公开(公告)号：US20190242823A1
公开(公告)日：2019-08-08
申请号：US16058525
申请日：2018-08-08
CPC分类号： G01N21/6428 , C09K11/06 , C09K2211/1018 , C09K2211/1044 , C09K2211/1475 , G01N15/1429 , G01N15/1475 , G01N21/6408 , G01N21/6458 , G01N33/582 , G01N2015/0065 , G01N2021/6421 , G01N2021/6439 , G01N2021/6441 , G01N2201/06113 , G01N2201/12 , G02B21/0076 , G02B21/16 , G02B21/367 , G02B27/58
摘要： The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. For example, the entities may be separated by a distance of less than about 1000 nm, or less than about 300 nm for visible light. In one set of embodiments, the entities may be selectively activatable, i.e., one entity can be activated to produce light, without activating other entities. A first entity may be activated and determined (e.g., by determining light emitted by the entity), then a second entity may be activated and determined. The entities may be immobilized relative to each other and/or to a common entity. The emitted light may be used to determine the positions of the first and second entities, for example, using Gaussian fitting or other mathematical techniques, and in some cases, with sub-diffraction limit resolution. The methods may thus be used, for example, to determine the locations of two or more entities immobilized relative to a common entity, for example, a surface, or a biological entity such as DNA, a protein, a cell, a tissue, etc. The entities may also be determined with respect to time, for example, to determine a time-varying reaction. Other aspects of the invention relate to systems for sub-diffraction limit image resolution, computer programs and techniques for sub-diffraction limit image resolution, methods for promoting sub-diffraction limit image resolution, methods for producing photoswitchable entities, and the like.
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公开(公告)号：US10073035B2
公开(公告)日：2018-09-11
申请号：US15252307
申请日：2016-08-31
IPC分类号： G01N21/64 , C09K11/06 , G01N15/14 , G01N33/58 , G02B21/16 , G02B27/58 , G02B21/00 , G02B21/36 , G01N15/00
CPC分类号： G01N21/6428 , C09K11/06 , C09K2211/1018 , C09K2211/1044 , C09K2211/1475 , G01N15/1429 , G01N15/1475 , G01N21/6408 , G01N21/6458 , G01N33/582 , G01N2015/0065 , G01N2021/6421 , G01N2021/6439 , G01N2021/6441 , G01N2201/06113 , G01N2201/12 , G02B21/0076 , G02B21/16 , G02B21/367 , G02B27/58
摘要： The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. For example, the entities may be separated by a distance of less than about 1000 nm, or less than about 300 nm for visible light. In one set of embodiments, the entities may be selectively activatable, i.e., one entity can be activated to produce light, without activating other entities. A first entity may be activated and determined (e.g., by determining light emitted by the entity), then a second entity may be activated and determined. The entities may be immobilized relative to each other and/or to a common entity. The emitted light may be used to determine the positions of the first and second entities, for example, using Gaussian fitting or other mathematical techniques, and in some cases, with sub-diffraction limit resolution. The methods may thus be used, for example, to determine the locations of two or more entities immobilized relative to a common entity, for example, a surface, or a biological entity such as DNA, a protein, a cell, a tissue, etc. The entities may also be determined with respect to time, for example, to determine a time-varying reaction. Other aspects of the invention relate to systems for sub-diffraction limit image resolution, computer programs and techniques for sub-diffraction limit image resolution, methods for promoting sub-diffraction limit image resolution, methods for producing photoswitchable entities, and the like.
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4.发明申请THREE-DIMENSIONAL SUPER-RESOLUTION FLUORESCENCE IMAGING USING AIRY BEAMS AND OTHER TECHNIQUES 审中-公开三维超分辨率荧光成像使用空气和其他技术公开(公告)号：US20170038574A1
公开(公告)日：2017-02-09
申请号：US15116062
申请日：2015-02-03
发明人： Xiaowei Zhuang , Shu Jia
CPC分类号： G02B21/0076 , G01N21/6458 , G02B21/0068 , G02B21/0088 , G02B21/0092 , G02B21/367 , G02B27/0068 , G02B27/283 , G02B27/58
摘要： The present invention generally relates to super-resolution imaging and other imaging techniques, including imaging in three dimensions. In one aspect, light from emissive entities in a sample may be used to produce polarized beams of light, which can be altered to produce Airy beams. Airy beams can maintain their intensity profiles over large distances without substantial diffraction, according to certain embodiments of the invention. For example, such beams can be used to determine the position of an emissive entity within a sample, and in some embodiments, in 3 dimensions; in some cases, the position may be determined at relatively high resolutions in all 3 dimensions.
摘要翻译： 本发明一般涉及超分辨率成像和其它成像技术，包括三维成像。 在一个方面，来自样品中的发射实体的光可以用于产生偏振光束，其可被改变以产生艾里波束。 根据本发明的某些实施例，通风光束可以在很大的距离上保持其强度分布，而没有实质的衍射。 例如，这样的光束可以用于确定样品内的发射实体的位置，并且在一些实施例中，在三维中; 在某些情况下，可以在所有三维中以相对高的分辨率确定该位置。
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公开(公告)号：US20160202185A1
公开(公告)日：2016-07-14
申请号：US14821569
申请日：2015-08-07
发明人： Xiaowei Zhuang , Bo Huang , Wilfred M. Bates , Wenqin Wang
IPC分类号： G01N21/64
CPC分类号： H04N13/204 , G01N21/64 , G01N21/6428 , G01N21/6458 , G01N2021/6419 , G01N2021/6421 , G01N2021/6439 , G01N2021/6441 , G02B21/16 , G02B21/361 , G02B21/367 , G02B27/58 , H04N7/18
摘要： The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques, including imaging in three dimensions. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. For example, the entities may be separated by a distance of less than about 1000 nm, or less than about 300 nm for visible light. In some cases, the position of the entities can be determined in all three spatial dimensions (i.e., in the x, y, and z directions), and in certain cases, the positions in all three dimensions can be determined to an accuracy of less than about 1000 nm. In one set of embodiments, the entities may be selectively activatable, i.e., one entity can be activated to produce light, without activating other entities. A first entity may be activated and determined (e.g., by determining light emitted by the entity), then a second entity may be activated and determined. The emitted light may be used to determine the x and y positions of the first and second entities, for example, by determining the positions of the images of these entities, and in some cases, with sub-diffraction limit resolution. In some cases, the z positions may be determined using one of a variety of techniques that uses intensity information or focal information (e.g., a lack of focus) to determine the z position. Non-limiting examples of such techniques include astigmatism imaging, off-focus imaging, or multi-focal-plane imaging. Other aspects of the invention relate to systems for sub-diffraction limit image resolution, computer programs and techniques for sub-diffraction limit image resolution, methods for promoting sub-diffraction limit image resolution, and the like.
摘要翻译： 本发明一般涉及副衍射极限图像分辨率和其它成像技术，包括三维成像。 在一个方面，本发明涉及确定和/或成像来自两个或多个实体的光，所述物体被隔开的距离小于入射光的衍射极限。 例如，对于可见光，实体可以分开小于约1000nm或小于约300nm的距离。 在某些情况下，实体的位置可以在所有三个空间维度（即，x，y和z方向）中确定，在某些情况下，可以将所有三维中的位置确定为更小的精度 大约1000nm。 在一组实施例中，实体可以是可选择性地激活的，即，一个实体可以被激活以产生光，而不激活其他实体。 可以激活和确定第一实体（例如，通过确定由实体发射的光），则可以激活和确定第二实体。 发射的光可以用于确定第一和第二实体的x和y位置，例如通过确定这些实体的图像的位置，并且在一些情况下，具有次衍射极限分辨率。 在一些情况下，可以使用使用强度信息或焦点信息（例如，缺乏焦点）的各种技术之一来确定z位置来确定z位置来确定z位置。 这种技术的非限制性实例包括像散成像，离焦成像或多焦平面成像。 本发明的其他方面涉及用于副衍射极限图像分辨率的系统，用于副衍射极限图像分辨率的计算机程序和技术，用于促进副衍射极限图像分辨率的方法等。
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公开(公告)号：US20230348958A1
公开(公告)日：2023-11-02
申请号：US17770943
申请日：2020-12-18
发明人： Xiaowei Zhuang , Bogdan Bintu , Seon S. Kinrot , Pu Zheng , Jun-Han Su
IPC分类号： C12Q1/6841 , G16B40/10 , G16B15/10
CPC分类号： C12Q1/6841 , G16B40/10 , G16B15/10 , C12Q2600/16
摘要： The present invention generally relates to genomics. Some embodiments are directed to imaging the 3D organization of the genome, or part of the genome, with high throughput in the sequence space. Some embodiments are directed to imaging the 3D organization of the genome, or part of the genome, in the context of transcriptional activity and nuclear structures. In addition, certain embodiments are directed to chromatin structures, 3D chromatin organizations, trans-chromosomal interactions and chromatin-nuclear-structure interactions as well as their relationship with transcription, etc. In addition, various embodiments are directed to imaging methods that allow mapping of the 3D organization of the genome, or part of the genome, in the context of nuclear structures and transcriptional activity. Some embodiments are directed to massively multiplexed fluorescence in situ hybridization methods for imaging chromatin loci and/or nascent RNA transcripts at the chromosome or genome scale.
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公开(公告)号：US20230279387A1
公开(公告)日：2023-09-07
申请号：US18297378
申请日：2023-04-07
IPC分类号： C12N15/10 , C07H21/02 , C07H21/04 , G16B25/00 , C12Q1/6806 , G16B25/20 , G16B40/10 , C12Q1/6837
CPC分类号： C12N15/1065 , C12N15/10 , C07H21/02 , C07H21/04 , G16B25/00 , C12Q1/6806 , C12N15/1093 , G16B25/20 , G16B40/10 , C12Q1/6837 , G16B30/00
摘要： The present invention generally relates to systems and methods for imaging or determining nucleic acids, for instance, within cells. In some embodiments, the transcriptome of a cell may be determined. Certain embodiments are directed to determining nucleic acids, such as mRNA, within cells at relatively high resolutions. In some embodiments, a plurality of nucleic acid probes may be applied to a sample, and their binding within the sample determined, e.g., using fluorescence, to determine locations of the nucleic acid probes within the sample. In some embodiments, codewords may be based on the binding of the plurality of nucleic acid probes, and in some cases, the codewords may define an error-correcting code to reduce or prevent misidentification of the nucleic acids. In certain cases, a relatively large number of different targets may be identified using a relatively small number of labels, e.g., by using various combinatorial approaches.
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公开(公告)号：US10412366B2
公开(公告)日：2019-09-10
申请号：US15623658
申请日：2017-06-15
发明人： Xiaowei Zhuang , Bo Huang , Wilfred M. Bates , Wenqin Wang
摘要： The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques, including imaging in three dimensions. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. For example, the entities may be separated by a distance of less than about 1000 nm, or less than about 300 nm for visible light. In some cases, the position of the entities can be determined in all three spatial dimensions (i.e., in the x, y, and z directions), and in certain cases, the positions in all three dimensions can be determined to an accuracy of less than about 1000 nm. In one set of embodiments, the entities may be selectively activatable, i.e., one entity can be activated to produce light, without activating other entities. A first entity may be activated and determined (e.g., by determining light emitted by the entity), then a second entity may be activated and determined. The emitted light may be used to determine the x and y positions of the first and second entities, for example, by determining the positions of the images of these entities, and in some cases, with sub-diffraction limit resolution. In some cases, the z positions may be determined using one of a variety of techniques that uses intensity information or focal information (e.g., a lack of focus) to determine the z position. Non-limiting examples of such techniques include astigmatism imaging, off-focus imaging, or multi-focal-plane imaging. Other aspects of the invention relate to systems for sub-diffraction limit image resolution, computer programs and techniques for sub-diffraction limit image resolution, methods for promoting sub-diffraction limit image resolution, and the like.
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公开(公告)号：US20160370295A1
公开(公告)日：2016-12-22
申请号：US15252307
申请日：2016-08-31
CPC分类号： G01N21/6428 , C09K11/06 , C09K2211/1018 , C09K2211/1044 , C09K2211/1475 , G01N15/1429 , G01N15/1475 , G01N21/6408 , G01N21/6458 , G01N33/582 , G01N2015/0065 , G01N2021/6421 , G01N2021/6439 , G01N2021/6441 , G01N2201/06113 , G01N2201/12 , G02B21/0076 , G02B21/16 , G02B21/367 , G02B27/58
摘要： The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. For example, the entities may be separated by a distance of less than about 1000 nm, or less than about 300 nm for visible light. In one set of embodiments, the entities may be selectively activatable, i.e., one entity can be activated to produce light, without activating other entities. A first entity may be activated and determined (e.g., by determining light emitted by the entity), then a second entity may be activated and determined. The entities may be immobilized relative to each other and/or to a common entity. The emitted light may be used to determine the positions of the first and second entities, for example, using Gaussian fitting or other mathematical techniques, and in some cases, with sub-diffraction limit resolution. The methods may thus be used, for example, to determine the locations of two or more entities immobilized relative to a common entity, for example, a surface, or a biological entity such as DNA, a protein, a cell, a tissue, etc. The entities may also be determined with respect to time, for example, to determine a time-varying reaction. Other aspects of the invention relate to systems for sub-diffraction limit image resolution, computer programs and techniques for sub-diffraction limit image resolution, methods for promoting sub-diffraction limit image resolution, methods for producing photoswitchable entities, and the like.
摘要翻译： 本发明一般涉及副衍射极限图像分辨率和其它成像技术。 在一个方面，本发明涉及确定和/或成像来自两个或多个实体的光，所述物体被隔开的距离小于入射光的衍射极限。 例如，对于可见光，实体可以分开小于约1000nm或小于约300nm的距离。 在一组实施例中，实体可以是可选择性地激活的，即，一个实体可以被激活以产生光，而不激活其他实体。 可以激活和确定第一实体（例如，通过确定由实体发射的光），则可以激活和确定第二实体。 实体可以相对于彼此和/或共同实体被固定。 发射的光可以用于确定第一和第二实体的位置，例如，使用高斯拟合或其他数学技术，并且在一些情况下，具有次衍射极限分辨率。 因此，可以使用这些方法，例如确定相对于共同实体（例如表面）或生物实体（例如DNA，蛋白质，细胞，组织等）固定的两个或多个实体的位置。 实体也可以相对于时间来确定，例如确定时变反应。 本发明的其他方面涉及用于副衍射极限图像分辨率的系统，用于副衍射极限图像分辨率的计算机程序和技术，用于促进副衍射极限图像分辨率的方法，用于产生可照片开关实体的方法等。
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公开(公告)号：US20140063194A1
公开(公告)日：2014-03-06
申请号：US14022168
申请日：2013-09-09
发明人： Xiaowei Zhuang , Bo Huang , Wilfred M. Bates , Wenqin Wang
CPC分类号： H04N13/204 , G01N21/64 , G01N21/6428 , G01N21/6458 , G01N2021/6419 , G01N2021/6421 , G01N2021/6439 , G01N2021/6441 , G02B21/16 , G02B21/361 , G02B21/367 , G02B27/58 , H04N7/18
摘要： The present invention generally relates to sub-diffraction limit image resolution and other imaging techniques, including imaging in three dimensions. In one aspect, the invention is directed to determining and/or imaging light from two or more entities separated by a distance less than the diffraction limit of the incident light. In some cases, the position of the entities can be determined in all three spatial dimensions (i.e., in the x, y, and z directions), and in certain cases, the positions in all three dimensions can be determined to an accuracy of less than about 1000 nm. In some cases, the z positions may be determined using one of a variety of techniques that uses intensity information or focal information (e.g., a lack of focus) to determine the z position. Non-limiting examples of such techniques include astigmatism imaging, off-focus imaging, or multi-focal-plane imaging.
摘要翻译： 本发明一般涉及副衍射极限图像分辨率和其它成像技术，包括三维成像。 在一个方面，本发明涉及确定和/或成像来自两个或多个实体的光，所述物体被隔开的距离小于入射光的衍射极限。 在某些情况下，实体的位置可以在所有三个空间维度（即x，y和z方向）上确定，在某些情况下，可以将所有三维中的位置确定为更小的精度 大约1000nm。 在一些情况下，可以使用使用强度信息或焦点信息（例如，缺乏焦点）的各种技术之一来确定z位置来确定z位置来确定z位置。 这种技术的非限制性实例包括像散成像，离焦成像或多焦平面成像。
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