Patents by Inventor Xiaowei Zhuang

Xiaowei Zhuang has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 11959075
    Abstract: 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.
    Type: Grant
    Filed: March 16, 2023
    Date of Patent: April 16, 2024
    Assignee: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Publication number: 20240112755
    Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells or tissues. In one aspect, a sample is exposed to a plurality of nucleic acid probes that are determined within the sample. In some cases, however, background fluorescence or off-target binding may make it more difficult to determine properly bound nucleic acid probes. Accordingly, other components of the samples that may be contributing to the background, such as proteins, lipids, and/or other non-targets, may be “cleared” from the sample to improve determination. However, in certain embodiments, nucleic acids or other desired targets may be prevented from also being cleared, e.g., using polymers or gels within the sample. Other aspects are generally directed to compositions or kits involving such systems, methods of using such systems, or the like.
    Type: Application
    Filed: May 1, 2023
    Publication date: April 4, 2024
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Jeffrey R. Moffitt, Junjie George Hao, Tian Lu
  • Publication number: 20230348958
    Abstract: 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.
    Type: Application
    Filed: December 18, 2020
    Publication date: November 2, 2023
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Bogdan Bintu, Seon S. Kinrot, Pu Zheng, Jun-Han Su
  • Patent number: 11788123
    Abstract: The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells. The cells may be exposed to a nucleic acid comprising an identification portion, which may be used to distinguish the cells from each other. In some embodiments, the cells may be exposed to a nucleic acid comprising an expression portion. The identification portion, the expression portion, or both may be introduced into the genome of a host organism or as exogenous materials, e.g. plasmids.
    Type: Grant
    Filed: May 25, 2018
    Date of Patent: October 17, 2023
    Assignee: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, George Alexander Emanuel, Jeffrey R. Moffitt
  • Publication number: 20230323339
    Abstract: 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.
    Type: Application
    Filed: March 16, 2023
    Publication date: October 12, 2023
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Publication number: 20230323338
    Abstract: 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.
    Type: Application
    Filed: March 16, 2023
    Publication date: October 12, 2023
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Publication number: 20230279383
    Abstract: 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.
    Type: Application
    Filed: October 13, 2022
    Publication date: September 7, 2023
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Publication number: 20230279387
    Abstract: 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.
    Type: Application
    Filed: April 7, 2023
    Publication date: September 7, 2023
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Patent number: 11383402
    Abstract: A method for reinforcing and enhancing bamboo/wood materials employs a sulfuric acid hydrolysis method to prepare a nanocellulose dispersion solution; then with the nanocellulose dispersion solution having a certain concentration as a precursor, nano zinc oxide is in-situ produced on the surface of the nanocellulose; and the cellulose dispersion solution is improved by compounding. The obtained treatment solution is impregnated into the pores of bamboo/wood materials in a specific manner to play the role of filling, binding and consolidating the bamboo/wood tissues, so that the treated bamboo/wood materials have enhanced hardness, strength and dimension stability, and significantly-improved mildew- and corrosion-resistance. The method is suitable for the reinforcing and enhancing treatment of wood materials with relatively-loose texture, such as fast-growing wood and wood from a planted forest, and is also suitable for the reinforcement and restoration of slightly-rotten wood materials.
    Type: Grant
    Filed: September 22, 2020
    Date of Patent: July 12, 2022
    Assignees: Zhejiang Academy of Forestry, Zhejiang Jiahe Bamboo Industry Technology Co., Ltd.
    Inventors: Haixia Yu, Manping Xu, Wenfu Zhang, Xiaowei Zhuang, Jin Wang, Xin Pan
  • Publication number: 20220205983
    Abstract: The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells, e.g., to build genotype-phenotype corresponse for high-throughput screening. In some cases, the cells may be manipulated, e.g., using CRISPR or other techniques. In certain embodiments, nucleic acids may be introduced to the cell, e.g., using a lentivirus. The nucleic acids may contain a guide portion comprising a DNA or RNA recognition sequence, a reporter portion, and an identification portion comprising one or more read sequences. The guide portion may be used to alter the phenotype of the cells, e.g., using a sequence, e.g., an sgRNA sequence, that can be targeted using CRISPR or other techniques, and in some cases, the phenotype of the cells may be determined using various imaging approaches. The identification portion may be determined using MERFISH or other suitable techniques.
    Type: Application
    Filed: April 17, 2020
    Publication date: June 30, 2022
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Chong Wang, Tian Lu
  • Publication number: 20220064697
    Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids in cells or other samples. In some cases, the transcriptome of a cell may be determined. Certain embodiments are generally directed to determining nucleic acids and other targets in a sample at relatively high resolutions. For instance, nucleic acid probes may be applied to sample, and binding of the nucleic acid probes to a target may be amplified using primary and secondary amplifier nucleic acids. In some cases, there is a maximum number of amplifier nucleic acids that can be bound to a target, e.g., the binding is saturatable, and cannot grow indefinitely, even in the presence of abundant reagents. This may be advantageous, for example, for controlling the brightness of each binding event, controlling the size of the amplified regions (e.g., during imaging), and/or for limiting the degree of amplification noise (i.e. the final variation in amplified signal from molecule to molecule), etc.
    Type: Application
    Filed: December 12, 2019
    Publication date: March 3, 2022
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Chenglong Xia, Jeffrey R. Moffitt
  • Publication number: 20220025442
    Abstract: 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.
    Type: Application
    Filed: July 13, 2021
    Publication date: January 27, 2022
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Patent number: 11098303
    Abstract: 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.
    Type: Grant
    Filed: July 29, 2015
    Date of Patent: August 24, 2021
    Assignee: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Kok-Hao Chen, Alistair Boettiger, Jeffrey R. Moffitt, Siyuan Wang
  • Publication number: 20210138684
    Abstract: A method for reinforcing and enhancing bamboo/wood materials employs a sulfuric acid hydrolysis method to prepare a nanocellulose dispersion solution; then with the nanocellulose dispersion solution having a certain concentration as a precursor, nano zinc oxide is in-situ produced on the surface of the nanocellulose; and the cellulose dispersion solution is improved by compounding. The obtained treatment solution is impregnated into the pores of bamboo/wood materials in a specific manner to play the role of filling, binding and consolidating the bamboo/wood tissues, so that the treated bamboo/wood materials have enhanced hardness, strength and dimension stability, and significantly-improved mildew- and corrosion-resistance. The method is suitable for the reinforcing and enhancing treatment of wood materials with relatively-loose texture, such as fast-growing wood and wood from a planted forest, and is also suitable for the reinforcement and restoration of slightly-rotten wood materials.
    Type: Application
    Filed: September 22, 2020
    Publication date: May 13, 2021
    Inventors: Haixia Yu, Manping Xu, Wenfu Zhang, Xiaowei Zhuang, Jin Wang, Xin Pan
  • Patent number: 10794828
    Abstract: 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.
    Type: Grant
    Filed: August 8, 2018
    Date of Patent: October 6, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Wilfred M. Bates, Michael J. Rust
  • Publication number: 20200099916
    Abstract: 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.
    Type: Application
    Filed: July 31, 2019
    Publication date: March 26, 2020
    Inventors: Xiaowei Zhuang, Bo Huang, Wilfred M. Bates, Wenqin Wang
  • Publication number: 20200095630
    Abstract: The present invention generally relates to imaging cells, for example, to determine phenotypes and/or genotypes in populations of cells. In some aspects, cells may be analyzed, e.g., imaged, to determine their phenotype, and their genotypes may be determined by exposing the cells to nucleic acid probes, e.g., as in smFISH, MERFISH, FISH, in situ hybridization, or other suitable techniques. In some cases, the cells may be exposed to a nucleic acid comprising an identification portion, which may be used to distinguish the cells from each other. In some embodiments, the cells may be exposed to a nucleic acid comprising an expression portion, e.g. a gene, or coding region for a non-translated RNA, etc., that when expressed, produces a protein, RNA, DNA, or the like that may alter the phenotype of the cell or the variable nucleic acid sequence can consist of promoters, gene regulatory elements, transcription factor binding sites, Cas9 guide RNA coding regions, etc. that otherwise alter the phenotype of the cell.
    Type: Application
    Filed: May 25, 2018
    Publication date: March 26, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, George Alexander Emanuel, Jeffrey R. Moffitt
  • Publication number: 20190276881
    Abstract: The present invention generally relates to microscopy, and to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells. In certain aspects, a sample is contained within an expandable material, which is expanded and imaged in some fashion. Expansion of the material improves the effective resolution of the subsequent image. This may be combined, for example, with other super-resolution techniques, such as STORM, and/or with techniques such as MERFISH for determining nucleic acids such as mRNA within the sample, for example, by binding nucleic acid probes to the sample. Other aspects are generally directed to compositions or devices for use in such methods, kits for use in such methods, or the like.
    Type: Application
    Filed: November 8, 2017
    Publication date: September 12, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Jeffrey R. Moffitt, Guiping Wang
  • Patent number: 10412366
    Abstract: 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.
    Type: Grant
    Filed: June 15, 2017
    Date of Patent: September 10, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Bo Huang, Wilfred M. Bates, Wenqin Wang
  • Publication number: 20190264270
    Abstract: The present invention generally relates to systems and methods for imaging or determining nucleic acids or other desired targets, for instance, within cells or tissues. In one aspect, a sample is exposed to a plurality of nucleic acid probes that are determined within the sample. In some cases, however, background fluorescence or off-target binding may make it more difficult to determine properly bound nucleic acid probes. Accordingly, other components of the samples that may be contributing to the background, such as proteins, lipids, and/or other non-targets, may be “cleared” from the sample to improve determination. However, in certain embodiments, nucleic acids or other desired targets may be prevented from also being cleared, e.g., using polymers or gels within the sample. Other aspects are generally directed to compositions or kits involving such systems, methods of using such systems, or the like.
    Type: Application
    Filed: November 8, 2017
    Publication date: August 29, 2019
    Applicant: President and Fellows of Harvard College
    Inventors: Xiaowei Zhuang, Jeffrey R. Moffitt, Junjie George Hao, Tian Lu