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1. 发明授权

US06867038B2 Isolation of cellular material under microscopic visualization 失效
标题翻译：在微观可视化下分离细胞材料
公开(公告)号：US06867038B2
公开(公告)日：2005-03-15
申请号：US09780234
申请日：2001-02-09
申请人： Lance A. Liotta , Michael Emmert-Buck , David B. Krizman , Rodrigo Chuaqui , W. Marston Linehan , Jeffry M. Trent , Robert F. Bonner , Seth R. Goldstein , Paul D. Smith , John I. Peterson
发明人： Lance A. Liotta , Michael Emmert-Buck , David B. Krizman , Rodrigo Chuaqui , W. Marston Linehan , Jeffry M. Trent , Robert F. Bonner , Seth R. Goldstein , Paul D. Smith , John I. Peterson
IPC分类号： C12M1/26 , C12M1/34 , G01N1/02 , G01N1/04 , G01N1/08 , G01N1/28 , G01N1/31 , G01N15/14 , G01N33/50 , G01N35/00 , G02B21/32 , C12N5/00
CPC分类号： G01N1/2813 , G01N1/04 , G01N1/08 , G01N1/2806 , G01N1/286 , G01N1/31 , G01N15/1468 , G01N33/50 , G01N2001/028 , G01N2001/2833 , G01N2001/284 , G01N2035/00237 , G02B21/32 , Y10T428/2813 , Y10T436/10
摘要： A method of microdissection which involves forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes a selectively activatable adhesive layer which provides, for example, chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated, the transfer surface and tissue sample are separated. During separation, the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample, the zone of cells of interest may then be molecularly analyzed.
摘要翻译：一种显微解剖的方法，其包括使用显微镜形成组织样本的细胞的图像场，从细胞的图像区鉴定至少一个感兴趣区域的至少一个感兴趣区域，所述细胞的至少一个区域包括不同类型的细胞，并且从所述组织样品中提取所述感兴趣的细胞的至少一个区域。通过使组织样品与可以选择性活化的转移表面接触使得其区域粘附到待提取的感兴趣的细胞区域来实现提取。转移表面包括可选择性活化的粘合剂层，其提供例如化学或静电附着到组织样品的选定区域。在转印表面被激活之后，转印表面和组织样品被分离。在分离期间，感兴趣的细胞区保持粘附到转移表面，并因此与组织样品分离，然后可以分析分析感兴趣的细胞区域。

2. 发明授权

US06251516B1 Isolation of cellular material under microscopic visualization 失效
标题翻译：在微观可视化下分离细胞材料
公开(公告)号：US06251516B1
公开(公告)日：2001-06-26
申请号：US09018596
申请日：1998-02-04
申请人： Robert F. Bonner , Lance A. Liotta , Michael Emmert-Buck , David B. Krizman , Rodrigo Chuaqui , W. Marston Linehan , Jeffry M. Trent , Seth R. Goldstein , Paul D. Smith , John I. Peterson
发明人： Robert F. Bonner , Lance A. Liotta , Michael Emmert-Buck , David B. Krizman , Rodrigo Chuaqui , W. Marston Linehan , Jeffry M. Trent , Seth R. Goldstein , Paul D. Smith , John I. Peterson
IPC分类号： B32B712
CPC分类号： G01N1/2813 , G01N1/04 , G01N1/08 , G01N1/2806 , G01N1/286 , G01N1/31 , G01N15/1468 , G01N33/50 , G01N2001/028 , G01N2001/2833 , G01N2001/284 , G01N2035/00237 , G02B21/32 , Y10T428/2813 , Y10T428/2839
摘要： A method of microdissection which involves forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes a selectively activatable adhesive layer which provides, for example, chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated, the transfer surface and tissue sample are separated. During separation, the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample, the zone of cells of interest may then be molecularly analyzed.
摘要翻译：一种显微解剖的方法，其包括使用显微镜形成组织样本的细胞的图像场，从细胞的图像区鉴定至少一个感兴趣区域的至少一个感兴趣区域，所述细胞的至少一个区域包括不同类型的细胞，并且从所述组织样品中提取所述感兴趣的细胞的至少一个区域。通过使组织样品与可以选择性活化的转移表面接触使得其区域粘附到待提取的感兴趣的细胞区域来实现提取。转移表面包括可选择性活化的粘合剂层，其提供例如化学或静电附着到组织样品的选定区域。在转印表面被激活之后，转印表面和组织样品被分离。在分离期间，感兴趣的细胞区保持粘附到转移表面，并因此与组织样品分离，然后可以分析分析感兴趣的细胞区域。

3. 发明授权

US08597715B2 Target activated microtransfer 有权
标题翻译：靶活化微转移
公开(公告)号：US08597715B2
公开(公告)日：2013-12-03
申请号：US12753566
申请日：2010-04-02
申请人： Michael R. Emmert-Buck , Michael Anthony Tangrea , Robert F. Bonner , Rodrigo Chuaqui , Thomas J. Pohida
发明人： Michael R. Emmert-Buck , Michael Anthony Tangrea , Robert F. Bonner , Rodrigo Chuaqui , Thomas J. Pohida
IPC分类号： B05D1/00
CPC分类号： G01N33/56966 , G01N33/543 , Y10T428/2813 , Y10T428/2839
摘要： A method of removing a target from a biological sample which involves placing a transfer surface in contact with the biological sample, and then focally altering the transfer surface to allow selective separation of the target from the biological sample. In disclosed embodiments, the target is a cell or cellular component of a tissue section and the transfer surface is a film that can be focally altered to adhere the target to the transfer surface. Subsequent separation of the film from the tissue section selectively removes the adhered target from the tissue section. The transfer surface is activated from within the target to adhere the target to the transfer surface, for example by heating the target to adhere it to a thermoplastic transfer surface. Such in situ activation can be achieved by exposing the biological sample to an immunoreagent that specifically binds to the target (or a component of the target). The immunoreagent can alter the transfer surface directly (for example with a heat generating enzyme carried by the immunoreagent), or indirectly (for example by changing a characteristic of the target). In some embodiments, the immunoreagent deposits a precipitate in the target that increases its light absorption relative to surrounding tissue, such that the biological specimen can be exposed to light to selectively heat the target. Alternatively, the immunoreagent is an immunofluorescent agent that carries a fluorophore that absorbs light and emits heat.
摘要翻译：一种从生物样品中除去靶的方法，其包括将转移表面与生物样品接触，然后焦点改变转移表面以允许靶与生物样品的选择性分离。在所公开的实施方案中，靶是组织切片的细胞或细胞组分，并且转移表面是可以被焦点改变以将靶附着到转移表面的膜。随后从组织切片分离膜，从组织切片选择性地去除粘附的靶。转移表面从靶内活化，以将靶附着到转印表面，例如通过加热靶以将其粘附到热塑性转印表面。可以通过将生物样品暴露于特异性结合靶（或靶的成分）的免疫反应物来实现这种原位激活。免疫反应物可以直接（例如用免疫反应物携带的发热酶）或间接地（例如通过改变靶的特征）来改变转移表面。在一些实施方案中，免疫反应物在靶中沉积沉淀物，其相对于周围组织增加其光吸收，使得生物样品可暴露于光以选择性加热靶标。或者，免疫反应剂是携带吸收光并发出热量的荧光团的免疫荧光剂。

4. 发明申请

US20100190177A1 TARGET ACTIVATED MICROTRANSFER 有权
标题翻译：目标活化微量RNA
公开(公告)号：US20100190177A1
公开(公告)日：2010-07-29
申请号：US12753566
申请日：2010-04-02
申请人： Michael R. Emmert-Buck , Michael Anthony Tangrea , Robert F. Bonner , Rodrigo Chuaqui , Thomas J. Pohida
发明人： Michael R. Emmert-Buck , Michael Anthony Tangrea , Robert F. Bonner , Rodrigo Chuaqui , Thomas J. Pohida
IPC分类号： C12Q1/68 , B01L3/00 , G01N33/53 , G01N1/28 , G01N33/566
CPC分类号： G01N33/56966 , G01N33/543 , Y10T428/2813 , Y10T428/2839
摘要： A method of removing a target from a biological sample which involves placing a transfer surface in contact with the biological sample, and then focally altering the transfer surface to allow selective separation of the target from the biological sample. In disclosed embodiments, the target is a cell or cellular component of a tissue section and the transfer surface is a film that can be focally altered to adhere the target to the transfer surface. Subsequent separation of the film from the tissue section selectively removes the adhered target from the tissue section. The transfer surface is activated from within the target to adhere the target to the transfer surface, for example by heating the target to adhere it to a thermoplastic transfer surface. Such in situ activation can be achieved by exposing the biological sample to an immunoreagent that specifically binds to the target (or a component of the target). The immunoreagent can alter the transfer surface directly (for example with a heat generating enzyme carried by the immunoreagent), or indirectly (for example by changing a characteristic of the target). In some embodiments, the immunoreagent deposits a precipitate in the target that increases its light absorption relative to surrounding tissue, such that the biological specimen can be exposed to light to selectively heat the target. Alternatively, the immunoreagent is an immunofluorescent agent that carries a fluorophore that absorbs light and emits heat.
摘要翻译：一种从生物样品中除去靶的方法，其包括将转移表面与生物样品接触，然后焦点改变转移表面以允许靶与生物样品的选择性分离。在所公开的实施方案中，靶是组织切片的细胞或细胞组分，并且转移表面是可以被焦点改变以将靶附着到转移表面的膜。随后从组织切片分离膜，从组织切片选择性地去除粘附的靶。转移表面从靶内活化，以将靶附着到转印表面，例如通过加热靶以将其粘附到热塑性转印表面。可以通过将生物样品暴露于特异性结合靶（或靶的成分）的免疫反应物来实现这种原位激活。免疫反应物可以直接（例如用免疫反应物携带的发热酶）或间接地（例如通过改变靶的特征）来改变转移表面。在一些实施方案中，免疫反应物在靶中沉积沉淀物，其相对于周围组织增加其光吸收，使得生物样品可暴露于光以选择性加热靶标。或者，免疫反应剂是携带吸收光并发出热量的荧光团的免疫荧光剂。

5. 发明申请

US20060134692A1 Target activated microtransfer 有权
公开(公告)号：US20060134692A1
公开(公告)日：2006-06-22
申请号：US10543218
申请日：2003-07-23
申请人： Michael Emmert-Buck , Michael Tangrea , Robert Bonner , Rodrigo Chuaqui
发明人： Michael Emmert-Buck , Michael Tangrea , Robert Bonner , Rodrigo Chuaqui
IPC分类号： G01N33/53 , G01N33/537 , G01N33/543
CPC分类号： G01N33/56966 , G01N33/543 , Y10T428/2813 , Y10T428/2839
摘要： A method of removing a target from a biological sample which involves placing a transfer surface in contact with the biological sample, and then focally altering the transfer surface to allow selective separation of the target from the biological sample. In disclosed embodiments, the target is a cell or cellular component of a tissue section and the transfer surface is a film that can be focally altered to adhere the target to the transfer surface. Subsequent separation of the film from the tissue section selectively removes the adhered target from the tissue section. The transfer surface is activated from within the target to adhere the target to the transfer surface, for example by heating the target to adhere it to a thermoplastic transfer surface. Such in situ activation can be achieved by exposing the biological sample to an immunoreagent that specifically binds to the target (or a component of the target). The immunoreagent can alter the transfer surface directly (for example with a heat generating enzyme carried by the immunoreagent), or indirectly (for example by changing a characteristic of the target). In some embodiments, the immunoreagent deposits a precipitate in the target that increases its light absorption relative to surrounding tissue, such that the biological specimen can be exposed to light to selectively heat the target. Alternatively, the immunoreagent is an immunofluorescent agent that carries a fluorophore that absorbs light and emits heat.

6. 发明授权

US07709047B2 Target activated microtransfer 有权
标题翻译：靶活化微转移
公开(公告)号：US07709047B2
公开(公告)日：2010-05-04
申请号：US10543218
申请日：2003-07-23
申请人： Michael R. Emmert-Buck , Michael Anthony Tangrea , Robert F. Bonner , Rodrigo Chuaqui , Thomas J. Pohida
发明人： Michael R. Emmert-Buck , Michael Anthony Tangrea , Robert F. Bonner , Rodrigo Chuaqui , Thomas J. Pohida
IPC分类号： B05D1/00
CPC分类号： G01N33/56966 , G01N33/543 , Y10T428/2813 , Y10T428/2839
摘要： A method of removing a target from a biological sample which involves placing a transfer surface in contact with the biological sample, and then focally altering the transfer surface to allow selective separation of the target from the biological sample. In disclosed embodiments, the target is a cell or cellular component of a tissue section and the transfer surface is a film that can be focally altered to adhere the target to the transfer surface. Subsequent separation of the film from the tissue section selectively removes the adhered target from the tissue section. The transfer surface is activated from within the target to adhere the target to the transfer surface, for example by heating the target to adhere it to a thermoplastic transfer surface. Such in situ activation can be achieved by exposing the biological sample to an immunoreagent that specifically binds to the target (or a component of the target). The immunoreagent can alter the transfer surface directly (for example with a heat generating enzyme carried by the immunoreagent), or indirectly (for example by changing a characteristic of the target). In some embodiments, the immunoreagent deposits a precipitate in the target that increases its light absorption relative to surrounding tissue, such that the biological specimen can be exposed to light to selectively heat the target. Alternatively, the immunoreagent is an immunofluorescent agent that carries a fluorophore that absorbs light and emits heat.
摘要翻译：一种从生物样品中除去靶的方法，其包括将转移表面与生物样品接触，然后焦点改变转移表面以允许靶与生物样品的选择性分离。在所公开的实施方案中，靶是组织切片的细胞或细胞组分，并且转移表面是可以被焦点改变以将靶附着到转移表面的膜。随后从组织切片分离膜，从组织切片选择性地去除粘附的靶。转移表面从靶内活化，以将靶附着到转印表面，例如通过加热靶以将其粘附到热塑性转印表面。可以通过将生物样品暴露于特异性结合靶（或靶的成分）的免疫反应物来实现这种原位激活。免疫反应物可以直接（例如用免疫反应物携带的发热酶）或间接地（例如通过改变靶的特征）来改变转移表面。在一些实施方案中，免疫反应物在靶中沉积沉淀物，其相对于周围组织增加其光吸收，使得生物样品可暴露于光以选择性加热靶标。或者，免疫反应剂是携带吸收光并发出热量的荧光团的免疫荧光剂。

7. 发明申请

US20060172278A1 Target activated microtransfer 有权
公开(公告)号：US20060172278A1
公开(公告)日：2006-08-03
申请号：US11202848
申请日：2005-08-12
申请人： Robert Bonner , Thomas Pohida , Michael Emmert-Buck , Michael Tangrea , Rodrigo Chuaqui
发明人： Robert Bonner , Thomas Pohida , Michael Emmert-Buck , Michael Tangrea , Rodrigo Chuaqui
IPC分类号： C12Q1/00 , G01N1/30 , C12M1/34
CPC分类号： G01N33/543 , G01N33/56966 , G01N2001/284 , Y10T428/2813
摘要： A device for performing target activated transfer that includes a mounting surface for mounting a tissue sample; and a light source positioned to substantially uniformly irradiate both stained and unstained regions of the tissue sample with light energy that activates the reagent to selectively adhere the stained regions to a transfer surface. Also described is an automated system for transferring tissue from a tissue sample to a transfer substrate. The system includes means for holding a tissue section that includes targets specifically stained with an absorptive stain thereby resulting in a stained tissue surface, and a flexible transfer film that includes a lower thermoplastic layer in sufficient thermal contact with the stained tissue surface; an irradiating assembly configured to provide a predetermined uniform light dose to the entire tissue section; and means for applying a constant pressure to the transfer film during irradiation.

8. 发明申请

US20110287951A1 METHODS AND SYSTEMS FOR PURIFYING, TRANSFERRING, AND/OR MANIPULATING NUCLEIC ACIDS 审中-公开
标题翻译：净化，转运和/或操作核酸的方法和系统
公开(公告)号：US20110287951A1
公开(公告)日：2011-11-24
申请号：US13147167
申请日：2010-01-29
申请人： Michael R. Emmert-Buck , Michael Armani , Elisabeth Smela , Benjamin Shapiro , Michael A. Tangrea , Jaime Rodriguez-Canales , Rodrigo Chuaqui , John Gillespie
发明人： Michael R. Emmert-Buck , Michael Armani , Elisabeth Smela , Benjamin Shapiro , Michael A. Tangrea , Jaime Rodriguez-Canales , Rodrigo Chuaqui , John Gillespie
IPC分类号： C40B30/00 , C12S3/20 , C07H1/06 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6806 , B01L3/5025 , B01L3/50853 , B01L3/50857 , B01L7/52 , B01L2300/0819 , B01L2400/0415 , B01L2400/0487 , C12N15/1006 , C12Q2565/631 , C12Q2565/513 , C12Q2547/101 , C12Q2523/125
摘要： The disclosure provides methods, systems, and devices for purifying, transferring or manipulating nucleic acids while maintaining the 2D spatial relationship of the nucleic acids as they were present in the original sample having 2D spatial information.
摘要翻译：本公开提供了用于纯化，转移或操纵核酸的方法，系统和装置，同时保持核酸的2D空间关系，因为它们存在于具有2D空间信息的原始样品中。

9. 发明申请

US20060292627A1 PB39, a gene dysregulated in prostate cancer, and uses thereof 审中-公开
标题翻译： PB39，前列腺癌失调的基因及其用途
公开(公告)号：US20060292627A1
公开(公告)日：2006-12-28
申请号：US11511259
申请日：2006-08-29
申请人： Rodrigo Chuaqui , Kristina Cole , Lance Liotta , Michael Emmert-Buck
发明人： Rodrigo Chuaqui , Kristina Cole , Lance Liotta , Michael Emmert-Buck
IPC分类号： C12Q1/68 , G01N33/574 , C07H21/04 , C12P21/06 , C07K16/30 , C07K14/82
CPC分类号： C07K14/47 , C12Q1/6886 , C12Q2600/112
摘要： A novel gene, PB39, that is up-regulated, or over-expressed, in prostate cancer has been identified. The gene has been identified by means of its cDNA obtained by reverse transcription of the corresponding mRNA. Microdissection of prostate glands that had been surgically removed from prostate cancer patients revealed a novel up-regulated transcript in an aggressive prostate carcinoma. Differential analysis for the presence of this gene was carried out from the same glands by comparing tanscription in microdissected normal prostatic epithelium versus that in microdissected invasive tumor. The transcript was over-expressed in 5 of 10 prostate carcinomas examined. A variant transcript was over-expressed in 4 of 4 prostate carcinomas, and was found in 1 of 4 normal samples. The invention provides a purified and isolated nucleic acid that includes the sequence of PB39 or its complement, the sequence of a variant of PB39 or its complement, and a primer or probe, that includes a sequence that is a fragment of these sequences. Additionally, the polypeptide encoded by these genes, an antibody to the polypeptide, and methods of detection of PB39 or its gene product are provided.
摘要翻译：已经鉴定出在前列腺癌中上调或过度表达的新基因PB39。该基因已通过其相应mRNA的逆转录获得的cDNA鉴定。从前列腺癌患者手术切除的前列腺的显微解剖显示在侵袭性前列腺癌中有一种新的上调的转录物。通过比较显微解剖正常前列腺上皮与显微解剖浸润性肿瘤中的变体，从同一腺体进行该基因存在的差异分析。在检查的10个前列腺癌中的5个中，转录物过表达。在4个前列腺癌中的4个中，变体转录物过表达，并且在4个正常样品中的1个中发现。本发明提供了纯化和分离的核酸，其包括PB39或其互补序列，PB39或其互补序列变体的序列，以及引物或探针，其包括作为这些序列的片段的序列。另外，提供了由这些基因编码的多肽，多肽的抗体，以及检测PB39或其基因产物的方法。

10. 发明申请

US20060147926A1 Method and apparatus for performing multiple simultaneous manipulations of biomolecules in a two-dimensional array 审中-公开
标题翻译：用于在二维阵列中进行多次同时操作生物分子的方法和装置
公开(公告)号：US20060147926A1
公开(公告)日：2006-07-06
申请号：US10535521
申请日：2003-11-20
申请人： Michael Emmert-Buck , Rodrigo Chuaqui , Michael Tangrea
发明人： Michael Emmert-Buck , Rodrigo Chuaqui , Michael Tangrea
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6837 , B01J2219/00641 , B01J2219/00722 , B01J2219/00725 , C12Q1/6806
摘要： This invention relates to methods and apparati for performing multiple simultaneous manipulations of biomolecules in a two-dimensional array, such as a gel, membrane, tissue biopsy, etc. Such manipulations particularly include assays and nucleic acid amplification protocols.
摘要翻译：本发明涉及在二维阵列（例如凝胶，膜，组织活组织检查等）中进行多重同时操作生物分子的方法和装置。这种操作特别包括测定和核酸扩增方案。

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