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1. 发明申请

WO2004080579A3 LIQUID TISSUE PREPARATION FROM HISTOPATOLOGICALLY PROCESSED BIOLOGICAL SAMPLES, TISSUES AND CELLS 审中-公开
标题翻译：来自生物化学生物样品，组织和细胞的液体组织制备
公开(公告)号：WO2004080579A3
公开(公告)日：2005-03-31
申请号：PCT/US2004007142
申请日：2004-03-10
申请人： EXPRESSION PATHOLOGY INC , EMMERT-BUCK MICHAEL R , DARFLER MARLENE M , KRIZMAN DAVID B
发明人： EMMERT-BUCK MICHAEL R , DARFLER MARLENE M , KRIZMAN DAVID B
IPC分类号： B01F20060101 , B01F1/00 , C07K16/00 , C12N15/00 , C12P21/04 , G01N1/30 , G01N1/40 , G01N1/44 , G01N33/53 , G01N33/574
CPC分类号： G01N1/4044 , C12N15/1003 , C12Q1/37 , G01N1/30 , G01N1/44
摘要： The current invention provides a method for directly converting histopathologically processed biological samples, tissues, and cells into a multi-use biomolecule lysate. This method allows for simultaneous extraction, isolation, solublization, and storage of all biomolecules contained within the histopathologically processed biological sample, thereby forming a representative library of said sample. This multi-use biomolecule lysate is dilutable, soluble, capable of being fractionated, and used in any number of subsequent experiments.
摘要翻译：本发明提供了将组织病理学处理的生物样品，组织和细胞直接转化成多用途生物分子裂解物的方法。该方法允许同时提取，分离，溶解和储存包含在组织病理学处理的生物样品中的所有生物分子，从而形成所述样品的代表性文库。这种多用途生物分子裂解物是可稀释的，可溶的，能够分级，并用于任何数量的后续实验。

2. 发明申请

WO2004080579A2 LIQUID TISSUE PREPARATION FROM HISTOPATOLOGICALLY PROCESSED BIOLOGICAL SAMPLES, TISSUES AND CELLS 审中-公开
标题翻译：来自生物化学生物样品，组织和细胞的液体组织制备
公开(公告)号：WO2004080579A2
公开(公告)日：2004-09-23
申请号：PCT/US2004/007142
申请日：2004-03-10
申请人： EXPRESSION PATHOLOGY, INC. , EMMERT-BUCK, Michael, R. , DARFLER, Marlene, M. , KRIZMAN, David, B.
发明人： EMMERT-BUCK, Michael, R. , DARFLER, Marlene, M. , KRIZMAN, David, B.
IPC分类号： B01F
CPC分类号： G01N1/4044 , C12N15/1003 , C12Q1/37 , G01N1/30 , G01N1/44
摘要： The current invention provides a method for directly converting histopathologically processed biological samples, tissues, and cells into a multi-use biomolecule lysate. This method allows for simultaneous extraction, isolation, solublization, and storage of all biomolecules contained within the histopathologically processed biological sample, thereby forming a representative library of said sample. This multi-use biomolecule lysate is dilutable, soluble, capable of being fractionated, and used in any number of subsequent experiments.
摘要翻译：本发明提供了将组织病理学处理的生物样品，组织和细胞直接转化成多用途生物分子裂解物的方法。该方法允许同时提取，分离，溶解和储存包含在组织病理学处理的生物样品中的所有生物分子，从而形成所述样品的代表性文库。这种多用途生物分子裂解物是可稀释的，可溶的，能够分级，并用于任何数量的后续实验。

3. 发明申请

WO2003066878A3 NUCLEIC ACID ANALYSIS USING LAYERED EXPRESSION SCANNING 审中-公开
公开(公告)号：WO2003066878A3
公开(公告)日：2003-08-14
申请号：PCT/US2003/002933
申请日：2003-01-31
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES , 20/20 GENE SYSTEMS, INC. , EMMERT-BUCK, Michael, R. , CHUAQUI, Rodrigo , FLAIG, Michael, J. , KNEZEVIC, Vladmir
发明人： EMMERT-BUCK, Michael, R. , CHUAQUI, Rodrigo , FLAIG, Michael, J. , KNEZEVIC, Vladmir
IPC分类号： C12Q1/68
摘要： Provided herein are methods of producing duplicates of nucleic acid samples, such as Northern blots, Southern blots, and sequencing gels, and methods of analyzing nucleic acids on such duplicates. Also provided are kits for using in producing duplicates of nucleic acid samples, and reagents for use in these kits and methods.

4. 发明申请

WO2010088517A8 METHODS AND SYSTEMS FOR PURIFYING TRANSFERRING AND/OR MANIPULATING NUCLEIC ACIDS 审中-公开
标题翻译：用于净化转运和/或操作核酸的方法和系统
公开(公告)号：WO2010088517A8
公开(公告)日：2011-07-28
申请号：PCT/US2010022586
申请日：2010-01-29
申请人： US HEALTH , UNIV MARYLAND , EMMERT-BUCK MICHAEL R , ARMANI MICHAEL , SMELA ELISABETH , SHAPIRO BENJAMIN , TANGREA MICHAEL A , RODRIGUEZ-CANALES JAIME , CHUAQUI RODRIGO , GILLESPIE JOHN
发明人： EMMERT-BUCK MICHAEL R , ARMANI MICHAEL , SMELA ELISABETH , SHAPIRO BENJAMIN , TANGREA MICHAEL A , RODRIGUEZ-CANALES JAIME , CHUAQUI RODRIGO , GILLESPIE JOHN
IPC分类号： 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。

5. 发明申请

WO2004048928A3 METHOD AND APPARATUS FOR PERFORMING MULTIPLE SIMULTANEOUS MANIPULATIONS OF BIOMOLECULES IN A TWO-DIMENSIONAL ARRAY 审中-公开
标题翻译：用于在二维阵列中执行生物分子的多个同时操纵的方法和设备
公开(公告)号：WO2004048928A3
公开(公告)日：2004-09-16
申请号：PCT/US0337208
申请日：2003-11-20
申请人： US HEALTH , EMMERT-BUCK MICHAEL R , CHUAQUI RODRIGO F , TANGREA MICHAEL A
发明人： EMMERT-BUCK MICHAEL R , CHUAQUI RODRIGO F , TANGREA MICHAEL A
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：本发明涉及用于以二维阵列（诸如凝胶，膜，组织活检等）对生物分子进行多个同时操作的方法和装置，这种操作特别包括测定和核酸扩增方案。

6. 发明申请

WO2004068104A2 TARGET ACTIVATED MICROTRANSFER 审中-公开
标题翻译：靶向活性微转运体
公开(公告)号：WO2004068104A2
公开(公告)日：2004-08-12
申请号：PCT/US0323317
申请日：2003-07-23
申请人： US GOV HEALTH & HUMAN SERV , EMMERT-BUCK MICHAEL R , TANGREA MICHAEL A , BONNER ROBERT F , CHUAQUI RODRIGO F
发明人： EMMERT-BUCK MICHAEL R , TANGREA MICHAEL A , BONNER ROBERT F , CHUAQUI RODRIGO F
IPC分类号： G01N33/543 , G01N33/569 , G01N
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 involved 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 or 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 fluorosphore that absorbs light and emits heat.
摘要翻译：一种从生物样品中去除目标物的方法，其涉及将转印表面与生物样品接触，然后局部地改变转印表面以允许目标物与生物样品的选择性分离。在公开的实施例中，目标是组织切片的细胞或细胞组分，并且转印表面是可以局部改变以将目标粘附到转印表面的膜。随后从组织部分分离膜选择性地从组织部分移除粘附的目标。例如通过加热靶以粘附或热塑性转印表面，转印表面从靶内激活以将靶附着到转印表面。这种原位激活可通过将生物样品暴露于特异性结合靶标（或靶标组分）的免疫试剂来实现。免疫试剂可以直接改变转移表面（例如用免疫试剂携带的生热酶），或间接改变（例如通过改变靶标的特征）。在一些实施方案中，免疫试剂将沉淀物沉积在靶中，相对于周围组织增加其光吸收，使得生物样本可暴露于光以选择性地加热靶。或者，免疫试剂是携带吸收光并发热的荧光磷光体的免疫荧光剂。

7. 发明申请

WO0210751A8 TRANSFER MICRODISSECTION 审中-公开
标题翻译：转移显微镜
公开(公告)号：WO0210751A8
公开(公告)日：2004-03-04
申请号：PCT/US0108095
申请日：2001-03-14
申请人： US GOV HEALTH & HUMAN SERV , EMMERT-BUCK MICHAEL R , HALDEMAN-ENGLERT CHAD R , BONNER ROBERT F , LIOTTA LANCE A
发明人： EMMERT-BUCK MICHAEL R , HALDEMAN-ENGLERT CHAD R , BONNER ROBERT F , LIOTTA LANCE A
IPC分类号： G01N1/28 , G01N33/50 , G01N33/543
CPC分类号： G01N33/5005 , G01N1/2813 , G01N33/54386 , G01N2001/284
摘要： The present disclosure concerns methods, systems, and devices for analyzing a biological material, such as a cellular or other specimen. In one disclosed example, the method selectively transfers biomolecules from a target region of interest in a biological sample (such as a tissue section). The transfer may occur, for example, by selectively focally altering a characteristic of a transfer layer adjacent the target region, such that the biomolecules can move through the altered area of the transfer layer. In particular examples, the transfer layer is altered by focally increasing a permeability of the transfer layer, for example by removing a focal portion of the transfer layer, and transporting the biomolecules through the altered region of the transfer layer, to microdissect the biomolecules of interest from the biological sample. In yet other embodiments, the microdissected biomolecules can be applied to an analysis substrate containing an identification molecule, such as a nucleic acid array, layered expression scan, or wells containing antibodies. Transfer microdissection allows biomolecules from regions of interest in the biological specimen to be selectively analyzed. For example, nests of highly atypical or metastatic cells in a tumor section can be analyzed for differential expression of certain proteins.
摘要翻译：本公开涉及用于分析生物材料（例如细胞或其它样品）的方法，系统和装置。在一个公开的实施例中，该方法选择性地将生物分子从目标感兴趣区域转移到生物样品（例如组织切片）中。转移可以例如通过选择性地改变邻近目标区域的转移层的特性，使得生物分子可以移动通过转移层的改变的区域而发生。在具体实例中，转移层通过聚焦增加转移层的渗透性而被改变，例如通过去除转移层的焦点部分，以及将生物分子传输通过转移层的改变区域，以显微分解感兴趣的生物分子来自生物样品。在其他实施方案中，显微切割的生物分子可以应用于含有鉴定分子，如核酸阵列，分层表达扫描或含有抗体的孔的分析底物。转移显微切割允许选择性分析来自生物样本中感兴趣区域的生物分子。例如，可以分析肿瘤部分中的非典型或转移性细胞的巢，以鉴别某些蛋白质的差异表达。

8. 发明申请

WO0248674A2 METHODS, DEVICES, ARRAYS AND KITS FOR DETECTING AND ANALYZING BIOMOLECULES 审中-公开
标题翻译：用于检测和分析生物分子的方法，装置，阵列和试剂盒
公开(公告)号：WO0248674A2
公开(公告)日：2002-06-20
申请号：PCT/US0144009
申请日：2001-11-20
申请人： 20 20 GENE SYSTEMS INC , US HEALTH , KNEZEVIC VLADIMIR , EMMERT-BUCK MICHAEL R , BAIBAKOVA GALINA , HARTMANN DAN-PAUL , HEWITT STEPHEN , MITCHELL CAPRE , GARDNER KEVIN
发明人： KNEZEVIC VLADIMIR , EMMERT-BUCK MICHAEL R , BAIBAKOVA GALINA , HARTMANN DAN-PAUL , HEWITT STEPHEN , MITCHELL CAPRE , GARDNER KEVIN
IPC分类号： G01N33/53 , C12Q1/68 , C40B30/04 , G01N27/447 , G01N33/566 , G01N33/68 , G01N37/00 , G01N
CPC分类号： C40B30/04 , G01N27/44739 , G01N33/6845
摘要： The present disclosure is directed to devices, arrays, kits and methods for detecting biomolecules in a tissue section (such as a fresh or archival sample, tissue microarray, or cells harvested by an LCM procedure) or other substantially two-dimensional sample (such as an electrophoretic gel or cDNA microarray) by creating "carbon copies" of the biomolecules eluted from the sample and visualizing the biomolecules on the copies using one or more detector molecules (e.g., antibodies or DNA probes) having specific affinity for the biomolecules of interest. Specific methods are provided for identifying the pattern of biomolecules (e.g., proteins and nucleic acids) in the samples. Other specific methods are provided for the identification and analysis of proteins and other biological molecules produced by cells and/or tissue, especially human cells and/or tissue. The disclosure also provides a plurality of differentially prepared and/or processed membranes that can be used in described methods, and which permit the identification and analysis of biomolecules.
摘要翻译：本公开涉及用于检测组织部分（例如新鲜或归档样品，组织微阵列或通过LCM程序收获的细胞）中的生物分子或其他基本上二维样品（例如，通过产生从样品洗脱的生物分子的“碳拷贝”并使用对感兴趣的生物分子具有特异性亲和力的一个或多个检测器分子（例如，抗体或DNA探针）使拷贝上的生物分子可视化，从而形成电泳凝胶或cDNA微阵列。提供了用于鉴定样品中生物分子（例如蛋白质和核酸）的模式的具体方法。提供了其他具体方法用于鉴定和分析由细胞和/或组织，特别是人细胞和/或组织产生的蛋白质和其它生物分子。本公开还提供可以在所述方法中使用并且允许生物分子的鉴定和分析的多种差异制备和/或加工的膜。

9. 发明申请

WO0107915A8 LAYERED DEVICE WITH CAPTURE REGIONS FOR CELLULAR ANALYSIS 审中-公开
标题翻译：具有捕获区域的层状设备用于细胞分析
公开(公告)号：WO0107915A8
公开(公告)日：2002-03-07
申请号：PCT/US0020354
申请日：2000-07-26
申请人： US HEALTH , EMMERT BUCK MICHAEL R
发明人： EMMERT-BUCK MICHAEL R
IPC分类号： G01N33/48 , C12M1/00 , C12M1/34 , C12N15/09 , C12Q1/02 , C12Q1/68 , C40B30/04 , G01N27/447 , G01N33/483 , G01N33/53 , G01N33/543 , G01N33/566 , G01N33/574 , G01N33/68
CPC分类号： G01N33/6803 , C12Q1/6841 , C40B30/04 , G01N33/54386 , G01N33/57434 , G01N33/6845 , G01N2333/4712 , G01N2333/4742 , G01N2333/7051 , G01N2333/96455 , G01N2333/96486
摘要： Disclosed herein are substrates having different capture regions, such as contiguous layers, wherein the different capture regions of the substrate contain different identification molecules. Components of the specimen are transfered through the capture regions under conditions which allow the components to interact with different identification molecules in the different regions of the substrate. Transfer is effected by capillary action of a solution moving through the cellular specimen or by electrophoresis. The transfer may occur in such a way as to maintain a geometric correspondence to the specimen, e.g. a correspondence to the cytoarchitecture of a cellular specimen. Example of cellular specimens include tissue sections such as tumor tissue sections. Cytostat sections cut slightly thicker than usual, i.e. 25 to 50 mu m, allow the detection of molecules of moderate and low level abundance.
摘要翻译：本文公开了具有不同捕获区域（例如连续层）的底物，其中底物的不同捕获区域含有不同的鉴定分子。在允许组分与衬底的不同区域中的不同识别分子相互作用的条件下将样品的组分转移通过捕获区域。转移通过移动通过细胞标本的溶液的毛细管作用或通过电泳来实现。转移可以以保持与样品的几何对应关系的方式发生，例如，对应于细胞样品的细胞结构。细胞标本的实例包括组织切片如肿瘤组织切片。细胞定位切片比通常切割得稍微厚一些，即25至50微米，允许检测中等和低水平丰度的分子。

10. 发明申请

WO2004068104A3 TARGET ACTIVATED MICROTRANSFER 审中-公开
公开(公告)号：WO2004068104A3
公开(公告)日：2004-08-12
申请号：PCT/US2003/023317
申请日：2003-07-23
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH , EMMERT-BUCK, Michael, R. , TANGREA, Michael, A. , BONNER, Robert, F. , CHUAQUI, Rodrigo, F.
发明人： EMMERT-BUCK, Michael, R. , TANGREA, Michael, A. , BONNER, Robert, F. , CHUAQUI, Rodrigo, F.
IPC分类号： G01N33/543
摘要： A method of removing a target from a biological sample which involved 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 or 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 fluorosphore that absorbs light and emits heat.

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