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    Multi-modality contrast and brightfield context rendering for enhanced pathology determination and multi-analyte detection in tissue
    1.
    发明授权
    Multi-modality contrast and brightfield context rendering for enhanced pathology determination and multi-analyte detection in tissue 有权
    多模态对比和明场上下文渲染，用于增强组织中的病理学确定和多分析物检测

    公开(公告)号：US09310302B2

    公开(公告)日：2016-04-12

    申请号：US13499959

    申请日：2010-10-07

    申请人： Karl Garsha ,  Gary Pestano ,  Michael Otter ,  Alexandra Dea Nagy ,  Ray B. Nagle ,  Phillip Miller ,  Jan Froehlich ,  William Day

    发明人： Karl Garsha ,  Gary Pestano ,  Michael Otter ,  Alexandra Dea Nagy ,  Ray B. Nagle ,  Phillip Miller ,  Jan Froehlich ,  William Day

    IPC分类号： G06K9/36 ,  G01N21/64

    CPC分类号： G01N21/6456

    摘要： Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.

    摘要翻译： 可以使用多重模态对比来产生可以组合和渲染的图像，以产生类似于在透射白光照明下观察到的波长吸收染色产生的图像的图像。 使用其他补充对比模式获得的图像可以使用基于用于显示相同解剖结构和组织化学的经典对比度方法的工程配色方案来呈现，从而提供与医学培训和经验相关的图像。 将衍生自折射率和荧光DAPI复染图像的暗视野对比图像组合以产生与用于病理解释的常规H＆E染色获得的图像相似的图像。 这种多模式图像数据可以流式传输用于组织学样本的实时导航，并且可以与遗传DNA探针（FISH），mRNA表达位点（mRNA-ISH）和定位于其上的免疫组织化学（IHC）探针的分子定位相结合 相同的组织切片，用于评估和绘制用于成像质谱法制备的组织切片。

    MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE
    2.
    发明申请
    MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 有权
    多模式对比度和亮度对比度增强，用于增强组织病理学确定和组织中的多分析检测

    公开(公告)号：US20120200694A1

    公开(公告)日：2012-08-09

    申请号：US13499959

    申请日：2010-10-07

    申请人： Karl Garsha ,  Gary Pestano ,  Michael Otter ,  Alexandra Dea Nagy ,  Ray B. Nagle ,  Phillip Miller ,  Jan Froehlich ,  William Day

    发明人： Karl Garsha ,  Gary Pestano ,  Michael Otter ,  Alexandra Dea Nagy ,  Ray B. Nagle ,  Phillip Miller ,  Jan Froehlich ,  William Day

    IPC分类号： G06K9/36 ,  H04N7/18

    CPC分类号： G01N21/6456

    摘要： Multiple modality contrast can be used to produce images that can be combined and rendered to produce images similar to those produced with wavelength absorbing stains viewed under transmitted white light illumination. Images obtained with other complementary contrast modalities can be presented using engineered color schemes based on classical contrast methods used to reveal the same anatomical structures and histochemistry, thereby providing relevance to medical training and experience. Dark-field contrast images derived from refractive index and fluorescent DAPI counterstain images are combined to produce images similar to those obtained with conventional H&E staining for pathology interpretation. Such multi-modal image data can be streamed for live navigation of histological samples, and can be combined with molecular localizations of genetic DNA probes (FISH), sites of mRNA expression (mRNA-ISH), and immunohistochemical (IHC) probes localized on the same tissue sections, used to evaluate and map tissue sections prepared for imaging mass spectrometry.

    摘要翻译： 可以使用多重模态对比来产生可以组合和渲染的图像，以产生类似于在透射白光照明下观察到的波长吸收染色产生的图像的图像。 使用其他补充对比模式获得的图像可以使用基于用于显示相同解剖结构和组织化学的经典对比度方法的工程配色方案来呈现，从而提供与医学培训和经验相关的图像。 将衍生自折射率和荧光DAPI复染图像的暗视野对比图像组合以产生与用于病理解释的常规H＆E染色获得的图像相似的图像。 这种多模式图像数据可以流式传输用于组织学样本的实时导航，并且可以与遗传DNA探针（FISH），mRNA表达位点（mRNA-ISH）和定位于其上的免疫组织化学（IHC）探针的分子定位相结合 相同的组织切片，用于评估和绘制用于成像质谱法制备的组织切片。

    DETECTING TARGETS USING MASS TAGS AND MASS SPECTROMETRY
    3.
    发明申请
    DETECTING TARGETS USING MASS TAGS AND MASS SPECTROMETRY 有权
    使用大标签和大量光谱检测目标

    公开(公告)号：US20130122516A1

    公开(公告)日：2013-05-16

    申请号：US13805983

    申请日：2011-07-01

    申请人： Rui Hong ,  Hong Wang ,  Mark Lefever ,  Jan Froehlich ,  Christopher Bieniarz ,  Brian Kelly ,  Phillip Miller

    发明人： Rui Hong ,  Hong Wang ,  Mark Lefever ,  Jan Froehlich ,  Christopher Bieniarz ,  Brian Kelly ,  Phillip Miller

    IPC分类号： G01N27/62

    CPC分类号： G01N33/6848 ,  G01N27/62

    摘要： Particular disclosed embodiments disclosed herein concern using a one or more various mass tags, which can be specifically deposited at targets through direct or indirect enzymatic-catalyzed transformation, to provide a method for identifying targets in tissue samples. The mass tags may be labeled with stable isotopes to produce mass tags having the same chemical structure but different masses. Mass codes produced by ionizing the mass tags are detected and/or quantified using mass spectrometry. The method can be used for multiplexed detection of multiple targets in a particular sample. In some embodiments, a map divided into sections representing sections of the tissue sample may be prepared, with the map sections including data corresponding to quantification data wherein the size of a mass peak is determined and correlated with the amount of a target for the corresponding tissue sample section.

    摘要翻译： 本文公开的具体公开的实施方案涉及使用一种或多种各种质量标签，其可以通过直接或间接的酶催化转化特异性沉积在靶上，以提供用于鉴定组织样品中靶标的方法。 质量标签可以用稳定同位素标记，以产生具有相同化学结构但质量不同的质量标签。 使用质谱检测和/或定量通过电离质量标签产生的质量代码。 该方法可用于特定样品中多个目标的多路检测。 在一些实施例中，可以制备分成表示组织样本部分的部分的图，其中，图表部分包括对应于量化数据的数据，其中质量峰的大小被确定并与相应组织的靶的量相关联 样品部分。

    Detecting targets using mass tags and mass spectrometry
    4.
    发明授权
    Detecting targets using mass tags and mass spectrometry 有权
    使用质量标签和质谱检测目标

    公开(公告)号：US09291597B2

    公开(公告)日：2016-03-22

    申请号：US13805983

    申请日：2011-07-01

    申请人： Rui Hong ,  Hong Wang ,  Mark Lefever ,  Jan Froehlich ,  Christopher Bieniarz ,  Brian Kelly ,  Phillip Miller

    发明人： Rui Hong ,  Hong Wang ,  Mark Lefever ,  Jan Froehlich ,  Christopher Bieniarz ,  Brian Kelly ,  Phillip Miller

    IPC分类号： G01N27/62 ,  G01N33/68

    CPC分类号： G01N33/6848 ,  G01N27/62

    摘要： Particular disclosed embodiments disclosed herein concern using a one or more various mass tags, which can be specifically deposited at targets through direct or indirect enzymatic-catalyzed transformation, to provide a method for identifying targets in tissue samples. The mass tags may be labeled with stable isotopes to produce mass tags having the same chemical structure but different masses. Mass codes produced by ionizing the mass tags are detected and/or quantified using mass spectrometry. The method can be used for multiplexed detection of multiple targets in a particular sample. In some embodiments, a map divided into sections representing sections of the tissue sample may be prepared, with the map sections including data corresponding to quantification data wherein the size of a mass peak is determined and correlated with the amount of a target for the corresponding tissue sample section.

    摘要翻译： 本文公开的具体公开的实施方案涉及使用一种或多种各种质量标签，其可以通过直接或间接的酶催化转化特异性沉积在靶上，以提供用于鉴定组织样品中靶标的方法。 质量标签可以用稳定同位素标记，以产生具有相同化学结构但质量不同的质量标签。 使用质谱检测和/或定量通过电离质量标签产生的质量代码。 该方法可用于特定样品中多个目标的多路检测。 在一些实施例中，可以制备分成表示组织样本部分的部分的图，其中，图表部分包括对应于量化数据的数据，其中质量峰的大小被确定并与相应组织的靶的量相关联 样品部分。

    HAPTEN CONJUGATES FOR TARGET DETECTION
    5.
    发明申请
    HAPTEN CONJUGATES FOR TARGET DETECTION 审中-公开
    寻找目标检测

    公开(公告)号：US20130109019A1

    公开(公告)日：2013-05-02

    申请号：US13805978

    申请日：2011-07-01

    申请人： Adrian E. Murillo ,  Jerome W. Kosmeder ,  Eric May ,  William Day ,  Mark Lefever ,  Anne M. Pedata ,  Christopher Bieniarz ,  Phillip Miller

    发明人： Adrian E. Murillo ,  Jerome W. Kosmeder ,  Eric May ,  William Day ,  Mark Lefever ,  Anne M. Pedata ,  Christopher Bieniarz ,  Phillip Miller

    IPC分类号： C07D277/54 ,  C07C237/20 ,  C07D271/12 ,  C07D233/90 ,  C07D243/00 ,  C07D241/52

    CPC分类号： C07D277/54 ,  A61K47/51 ,  C07C235/34 ,  C07C237/20 ,  C07C311/37 ,  C07D233/90 ,  C07D241/52 ,  C07D243/00 ,  C07D271/12 ,  G01N33/581 ,  G01N2333/908

    摘要： Embodiments of hapten conjugates including a hapten, an optional linker, and a peroxidase-activatable aryl moiety are disclosed. In some embodiments, the peroxidase-activatable aryl moiety is tyramine or a tyramine derivative. Embodiments of methods for making and using the hapten conjugates also are disclosed. In particular embodiments, the hapten conjugates are used in a signal amplification assay. In certain embodiments, the hapten is an oxazole, a pyrazole, a thiazole, a benzofurazan, a triterpene, a urea, a thiourea other than a rhodamine thiourea, a nitroaryl other than dinitrophenyl or trinitrophenyl, a rotenoid, a cyclolignan, a heterobiaryl, an azoaryl, a benzodiazepine, or 7-diethylamino-3-carboxycoumarin. The hapten is coupled to the peroxidase-activatable aryl moiety directly or indirectly via a linker. In certain embodiments, the hapten conjugates are used in multiplexed assays.

    摘要翻译： 公开了包含半抗原，任选接头和过氧化物酶活化的芳基部分的半抗原共轭物的实施方案。 在一些实施方案中，过氧化物酶可活化的芳基部分是酪胺或酪胺衍生物。 还公开了制备和使用半抗原共轭物的方法的实施方案。 在具体实施方案中，半抗原共轭物用于信号放大测定。 在某些实施方案中，半抗原是恶唑，吡唑，噻唑，苯并呋咱，三萜，脲，除罗丹明硫脲以外的硫脲，除二硝基苯基或三硝基苯基以外的硝基芳基，旋环体，环链烷基，异二芳基， 偶氮二芳基，苯并二氮杂或7-二乙基氨基-3-羧基香豆素。 半抗原通过接头直接或间接地与过氧化物酶活化的芳基部分偶联。 在某些实施方案中，半抗原共轭物用于多重测定。

    MULTI-LEVEL HIERARCHICAL RADIO-FREQUENCY COMMUNICATION SYSTEM
    8.
    发明申请
    MULTI-LEVEL HIERARCHICAL RADIO-FREQUENCY COMMUNICATION SYSTEM 有权
    多级分层无线电频率通信系统

    公开(公告)号：US20090175318A1

    公开(公告)日：2009-07-09

    申请号：US12330362

    申请日：2008-12-08

    申请人： Steven E. Koenck ,  Alan G. Bunte ,  Keith K. Cargin, JR. ,  George E. Hanson ,  Ronald L. Mahany ,  Phillip Miller ,  Steven H. Salvay ,  Arvin D. Danielson ,  Guy J. West

    发明人： Steven E. Koenck ,  Alan G. Bunte ,  Keith K. Cargin, JR. ,  George E. Hanson ,  Ronald L. Mahany ,  Phillip Miller ,  Steven H. Salvay ,  Arvin D. Danielson ,  Guy J. West

    IPC分类号： H04B1/713 ,  H04B1/69 ,  G06K7/10

    CPC分类号： H04W88/06 ,  H04W24/00 ,  Y02D70/142

    摘要： Portable measuring devices which communicate by low power transceivers through a communication controller with a printer device collect weight and size data on articles to be shipped. The collected weight and size data are combined with origin and destination data, and labels are printed bearing pertinent shipping and routing information in machine readable format. The labels are attached to the articles to be shipped and accompany the articles to their respective destinations. At transfer points the labels are read by scanner devices which also communicate by low power transceiver links with the communication controller. The wireless linking of the scanner devices promotes human safety by the absence of cords which could cause entanglement of an operator in mechanized conveying equipment. The communication controllers at each stage of the shipping process have the capability of transferring received and updated status information on the shipped articles to a central data station.

    摘要翻译： 低功率收发器通过通信控制器与打印机设备进行通信的便携式测量设备可收集待运输物品的重量和尺寸数据。 收集的重量和尺寸数据与原始数据和目的地数据相结合，标签以机器可读格式印刷有关的运输和路由信息。 标签附在要发运的物品上，并将物品随附到各自的目的地。 在转移点，标签由扫描仪设备读取，扫描仪设备也通过低功率收发器链路与通信控制器进行通信。 扫描仪设备的无线连接通过不存在可能导致操作员在机械化输送设备中的缠结的绳索而促进人的安全。 在运送过程的每个阶段的通信控制器具有将已发送的物品上接收和更新的状态信息传送到中央数据站的能力。

    Na+, K+-Atpase Expression in Cervical Dysplasia and Cancer
    9.
    发明申请
    Na+, K+-Atpase Expression in Cervical Dysplasia and Cancer 有权
    Na +，K + -Atpase在子宫颈发育不良和癌症中的表达

    公开(公告)号：US20080286386A1

    公开(公告)日：2008-11-20

    申请号：US12096075

    申请日：2006-12-27

    申请人： Hiroaki Nitta ,  Thomas M. Grogan ,  Phillip Miller

    发明人： Hiroaki Nitta ,  Thomas M. Grogan ,  Phillip Miller

    IPC分类号： A61K36/00 ,  C12Q1/00 ,  G01N33/573 ,  A61P15/02 ,  A61K31/70 ,  C12Q1/68

    CPC分类号： G01N33/57411

    摘要： The present disclosure provides methods of diagnosing cervical dysplasia and cervical cancer by detecting Na+, K+-ATPase expression. For example, it is demonstrated herein that expression of the Na+, K+-ATPase β1-subunit increases in cervical dysplasia and cervical cancer, relative to normal cervical tissue. Also provided are methods of treating cervical dysplasia and cervical cancer by decreasing the biological activity of the Na+, K+-ATPase. For example, therapeutically effective amounts of one or more Na+, K+-ATPase inhibitors can be applied to the cervix to treat cervical dysplasia and cervical cancer.

    摘要翻译： 本公开提供了通过检测Na +，N +， - ATP酶表达来诊断子宫颈发育不良和宫颈癌的方法。 例如，本文证明，相对于正常的宫颈组织，Na +，N +，β-ATP酶β1亚基的表达在宫颈发育不良和宫颈癌中增加。 还提供了通过降低Na +，N + + - ATP酶的生物活性来治疗宫颈发育不良和宫颈癌的方法。 例如，可以将治疗有效量的一种或多种Na + +，K + + - ATP酶抑制剂施用于子宫颈以治疗子宫颈发育不良和宫颈癌。