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1. 发明申请

WO2012003478A2 DETECTING TARGETS USING MASS TAGS AND MASS SPECTROMETRY 审中-公开
标题翻译：用质量标签和质谱法检测目标
公开(公告)号：WO2012003478A2
公开(公告)日：2012-01-05
申请号：PCT/US2011/042853
申请日：2011-07-01
申请人： VENTANA MEDICAL SYSTEMS, INC. , HONG, Rui , WANG, Hong , LEFEVER, Mark , FROEHLICH, Jan , BIENIARZ, Christopher , KELLY, Brian , MILLER, Phillip
发明人： HONG, Rui , WANG, Hong , LEFEVER, Mark , FROEHLICH, Jan , BIENIARZ, Christopher , KELLY, Brian , MILLER, Phillip
IPC分类号： A61K49/00
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不同的质量标签，其可以通过直接或间接的酶促催化转化特异性地沉积在靶标上，以提供用于鉴定组织样品中的靶标的方法。质量标签可以用稳定的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。通过电离质量标签产生的质量代码使用质谱法检测和/或量化。该方法可用于特定样本中多个目标的多路复用检测。在一些实施例中，可以制备分成代表组织样本的部分的区段的地图，其中地图区段包括对应于定量数据的数据，其中确定质量峰的大小并将其与相应组织的目标的量相关联样本部分。

2. 发明申请

WO2011046807A2 MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 审中-公开
标题翻译：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：WO2011046807A2
公开(公告)日：2011-04-21
申请号：PCT/US2010/051857
申请日：2010-10-07
申请人： VENTANA MEDICAL SYSTEMS, INC. , GARSHA, Karl , PESTANO, Gary , OTTER, Michael , NAGY, Alexandra, Dea , NAGLE, Ray, B. , MILLER, Phillip , FROEHLICH, Jan , DAY, William
发明人： GARSHA, Karl , PESTANO, Gary , OTTER, Michael , NAGY, Alexandra, Dea , NAGLE, Ray, B. , MILLER, Phillip , FROEHLICH, Jan , DAY, William
IPC分类号： G01N33/483
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：可以使用多重形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的相关性。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类似于用于病理解释的常规H＆E染色获得的图像。这种多模态图像数据可以流式传输用于组织学样本的实时导航，并且可以与基因DNA探针（FISH），mRNA表达位点（mRNA-ISH）和局部在该位点上的免疫组织化学（IHC）探针的分子定位相结合相同的组织切片，用于评估和绘制准备用于成像质谱的组织切片。

3. 发明公开

EP2588144A2 DETECTING TARGETS USING MASS TAGS AND MASS SPECTROMETRY 有权
标题翻译： NACHWEIS VONZIELMOLEKÜLENMIT MASSENMARKIERUNGEN UND MASSENSPEKTROMETRIE
公开(公告)号：EP2588144A2
公开(公告)日：2013-05-08
申请号：EP11731604.2
申请日：2011-07-01
申请人： Ventana Medical Systems, Inc.
发明人： HONG, Rui , WANG, Hong , LEFEVER, Mark , FROEHLICH, Jan , BIENIARZ, Christopher , KELLY, Brian , MILLER, Phillip
IPC分类号： A61K49/00 , G01N33/543 , G01N33/68 , G01N33/58 , C12Q1/28 , G01N33/532
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：本文公开的特定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。使用质谱法检测和/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的部分的部分的图，其中所述图部分包括与量化数据相对应的数据，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。

4. 发明公开

EP2488860A2 MULTI-MODALITY CONTRAST AND BRIGHTFIELD CONTEXT RENDERING FOR ENHANCED PATHOLOGY DETERMINATION AND MULTI-ANALYTE DETECTION IN TISSUE 审中-公开
标题翻译： MULTIMODALITÄTSKONTRAST和增强的病理学测定的BREITFELD背景和MEHRANALYTERKENNUNG组织
公开(公告)号：EP2488860A2
公开(公告)日：2012-08-22
申请号：EP10823858.5
申请日：2010-10-07
申请人： Ventana Medical Systems, Inc.
发明人： GARSHA, Karl , PESTANO, Gary , OTTER, Michael , NAGY, Alexandra, Dea , NAGLE, Ray, B. , MILLER, Phillip , FROEHLICH, Jan , DAY, William
IPC分类号： G01N33/483
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.

5. 发明授权

EP2588144B1 DETECTING TARGETS USING MASS TAGS AND MASS SPECTROMETRY 有权
标题翻译：用质量标签和质谱法检测目标
公开(公告)号：EP2588144B1
公开(公告)日：2018-05-09
申请号：EP11731604.2
申请日：2011-07-01
申请人： Ventana Medical Systems, Inc.
发明人： HONG, Rui , WANG, Hong , LEFEVER, Mark , FROEHLICH, Jan , BIENIARZ, Christopher , KELLY, Brian Daniel , MILLER, Phillip
IPC分类号： A61K49/00 , G01N33/543 , G01N33/68 , G01N33/58 , C12Q1/28 , G01N33/532
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.

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