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1. 发明申请

US20120134603A1 METHODS FOR SCALING IMAGES TO DIFFERING EXPOSURE TIMES 有权
标题翻译：将图像缩放到不同的曝光时间的方法
公开(公告)号：US20120134603A1
公开(公告)日：2012-05-31
申请号：US12956909
申请日：2010-11-30
申请人： Zhengyu Pang , Robert John Filkins
发明人： Zhengyu Pang , Robert John Filkins
IPC分类号： G06K9/32
CPC分类号： G06T5/009 , G06T2207/10064 , G06T2207/30024
摘要： Methods for scaling an image taken an optimal exposure time to a selected exposure time, generally comprising, determining a dark pixel intensity of an imaging device; acquiring a first image at an optimal exposure time; and adjusting a pixel intensity of one or more pixels in the first image, based at least in part on the dark pixel intensity, for a second exposure time that is different from the optimal exposure time.
摘要翻译：用于将拍摄了最佳曝光时间的图像缩放到所选择的曝光时间的方法，通常包括：确定成像装置的暗像素强度; 以最佳曝光时间获取第一图像; 以及至少部分地基于所述暗像素强度来调整与所述最佳曝光时间不同的第二曝光时间的所述第一图像中的一个或多个像素的像素强度。

2. 发明授权

US07741045B2 Sequential analysis of biological samples 有权
标题翻译：生物样品的顺序分析
公开(公告)号：US07741045B2
公开(公告)日：2010-06-22
申请号：US11864085
申请日：2007-09-28
申请人： Michael J. Gerdes , Anup Sood , Michael Christopher Montalto , Ali Can , Fiona Ginty , Maureen Ann Bresnahan , Robert John Filkins , Zhengyu Pang
发明人： Michael J. Gerdes , Anup Sood , Michael Christopher Montalto , Ali Can , Fiona Ginty , Maureen Ann Bresnahan , Robert John Filkins , Zhengyu Pang
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G01N33/582 , C12Q1/6816 , G01N33/542 , C12Q2545/101 , C12Q2527/125
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets, binding at least one fluorescent probe to one or more target present in the sample, and binding at least at least one control probe to one or more target present in the sample. The methods include the steps of observing a signal from the fluorescent probe and a control signal from the control probe and applying to the sample a basic solution containing an oxidizing agent that selectively inactivates the fluorescent probe and not the control probe. The methods further include the steps of binding at least one fluorescent probe to one or more target present in the sample and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供含有多个靶标的生物样品，将至少一种荧光探针结合至样品中存在的一种或多种靶标，以及将至少一种对照探针结合至样品中存在的一种或多种靶标。所述方法包括以下步骤：观察来自荧光探针的信号和来自对照探针的控制信号，并向样品施加含有选择性灭活荧光探针而不是对照探针的氧化剂的碱性溶液。所述方法还包括将至少一种荧光探针结合到样品中存在的一种或多种目标物并观察来自荧光探针的信号的步骤。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

3. 发明申请

US20080118934A1 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES 有权
标题翻译：生物样品的序列分析
公开(公告)号：US20080118934A1
公开(公告)日：2008-05-22
申请号：US11864085
申请日：2007-09-28
申请人： Michael J. Gerdes , Anup Sood , Michael Christopher Montalto , Ali Can , Fiona Ginty , Maureen Ann Bresnahan , Robert John Filkins , Zhengyu Pang
发明人： Michael J. Gerdes , Anup Sood , Michael Christopher Montalto , Ali Can , Fiona Ginty , Maureen Ann Bresnahan , Robert John Filkins , Zhengyu Pang
IPC分类号： G01N33/53 , G01N33/566 , G01N33/567
CPC分类号： G01N33/582 , C12Q1/6816 , G01N33/542 , C12Q2545/101 , C12Q2527/125
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets, binding at least one fluorescent probe to one or more target present in the sample, and binding at least at least one control probe to one or more target present in the sample. The methods include the steps of observing a signal from the fluorescent probe and a control signal from the control probe and applying to the sample a basic solution containing an oxidizing agent that selectively inactivates the fluorescent probe and not the control probe. The methods further include the steps of binding at least one fluorescent probe to one or more target present in the sample and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供含有多个靶标的生物样品，将至少一种荧光探针结合至样品中存在的一种或多种靶标，以及将至少一种对照探针结合至样品中存在的一种或多种靶标。所述方法包括以下步骤：观察来自荧光探针的信号和来自对照探针的控制信号，并向样品施加含有选择性灭活荧光探针而不是对照探针的氧化剂的碱性溶液。所述方法还包括将至少一种荧光探针结合到样品中存在的一种或多种目标物并观察来自荧光探针的信号的步骤。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

4. 发明授权

US08818069B2 Methods for scaling images to differing exposure times 有权
标题翻译：将图像缩放到不同曝光时间的方法
公开(公告)号：US08818069B2
公开(公告)日：2014-08-26
申请号：US12956909
申请日：2010-11-30
申请人： Zhengyu Pang , Robert John Filkins
发明人： Zhengyu Pang , Robert John Filkins
IPC分类号： G06K9/00 , G06T5/00
CPC分类号： G06T5/009 , G06T2207/10064 , G06T2207/30024
摘要： A method is provided for scaling an image taken at a given exposure time to a selected exposure time. The method generally comprises: determining a dark pixel intensity of an imaging device; acquiring a first image at a given exposure time; and adjusting a pixel intensity of one or more pixels in the first image, based at least in part on the dark pixel intensity, for a second exposure time that is different from the given exposure time.
摘要翻译：提供了一种用于将在给定曝光时间拍摄的图像缩放到所选择的曝光时间的方法。该方法通常包括：确定成像装置的暗像素强度; 在给定的曝光时间获取第一图像; 以及至少部分地基于所述暗像素强度来调整与所述给定曝光时间不同的第二曝光时间的所述第一图像中的一个或多个像素的像素强度。

5. 发明申请

US20120252685A1 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES 有权
标题翻译：生物样品的序列分析
公开(公告)号：US20120252685A1
公开(公告)日：2012-10-04
申请号：US11864098
申请日：2007-09-28
申请人： Thomas Pirrie Treynor , Anup Sood , Michael J. Gerdes , Zhengyu Pang
发明人： Thomas Pirrie Treynor , Anup Sood , Michael J. Gerdes , Zhengyu Pang
IPC分类号： C40B30/04 , C40B40/10 , C40B40/06 , G01N21/64
CPC分类号： G01N33/581 , G01N33/6803
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a sample containing multiple targets, binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample, and reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator. The methods include the steps of observing a signal from the fluorescent signal generator and applying to the sample a solution containing an oxidizing agent that substantially inactivates both the fluorescent signal generator and the enzyme. The methods further include the steps of binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample of step, reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator; and observing a signal from the fluorescent signal generator. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供含有多个靶标的样品，将至少一种具有与酶偶联的结合剂的探针结合至样品中存在的一种或多种靶标，以及使结合的探针与偶联于荧光信号发生器。所述方法包括以下步骤：观察来自荧光信号发生器的信号，并向样品施加含有基本上灭活荧光信号发生器和酶的氧化剂的溶液。所述方法还包括以下步骤：将具有与酶偶联的粘合剂的至少一种探针与步骤样品中存在的一种或多种靶结合，使结合的探针与偶联于荧光信号发生器的酶底物反应; 并观察来自荧光信号发生器的信号。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

6. 发明申请

US20080118944A1 SEQUENTIAL ANALYSIS OF BIOLOGICAL SAMPLES 有权
标题翻译：生物样品的序列分析
公开(公告)号：US20080118944A1
公开(公告)日：2008-05-22
申请号：US11864093
申请日：2007-09-28
申请人： Melinda Larsen , Anup Sood , Michael J. Gerdes , Michael Christopher Montalto , Zhengyu Pang , Fiona Ginty
发明人： Melinda Larsen , Anup Sood , Michael J. Gerdes , Michael Christopher Montalto , Zhengyu Pang , Fiona Ginty
IPC分类号： C12Q1/02 , G01N21/76 , G01N33/00 , G01N33/68
CPC分类号： G01N33/53 , C12Q1/68 , G01N33/542 , G01N33/582 , Y10T436/143333
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets adhered to a solid support, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The method further includes the steps of oxidizing the bound fluorescent probe with a solution containing an oxidizing agent that substantially inactivates the fluorescent probe, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供包含粘附到固体支持物上的多个靶的生物样品，将至少一种荧光探针结合到样品中存在的一种或多种靶，并观察来自荧光探针的信号。所述方法还包括以下步骤：用含有基本上灭活荧光探针的氧化剂的溶液氧化结合的荧光探针，将至少一种荧光探针结合到样品中存在的一种或多种靶，并观察来自荧光探针的信号。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

7. 发明授权

US08305579B2 Sequential analysis of biological samples 有权
标题翻译：生物样品的顺序分析
公开(公告)号：US08305579B2
公开(公告)日：2012-11-06
申请号：US11864098
申请日：2007-09-28
申请人： Thomas Pirrie Treynor , Anup Sood , Michael J. Gerdes , Zhengyu Pang
发明人： Thomas Pirrie Treynor , Anup Sood , Michael J. Gerdes , Zhengyu Pang
IPC分类号： G01N21/85
CPC分类号： G01N33/581 , G01N33/6803
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a sample containing multiple targets, binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample, and reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator. The methods include the steps of observing a signal from the fluorescent signal generator and applying to the sample a solution containing an oxidizing agent that substantially inactivates both the fluorescent signal generator and the enzyme. The methods further include the steps of binding at least one probe having a binder coupled to an enzyme to one or more target present in the sample of step, reacting the bound probe with an enzyme substrate coupled to a fluorescent signal generator; and observing a signal from the fluorescent signal generator. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供含有多个靶标的样品，将至少一种具有与酶偶联的结合剂的探针结合至样品中存在的一种或多种靶标，以及使结合的探针与偶联于荧光信号发生器。所述方法包括以下步骤：观察来自荧光信号发生器的信号，并向样品施加含有基本上灭活荧光信号发生器和酶的氧化剂的溶液。所述方法还包括以下步骤：将具有与酶偶联的粘合剂的至少一种探针与步骤样品中存在的一种或多种靶结合，使结合的探针与偶联于荧光信号发生器的酶底物反应; 并观察来自荧光信号发生器的信号。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

8. 发明申请

US20130286043A1 SYSTEMS AND METHODS FOR ANALYZING BIOMARKER CO-LOCALIZATION IN A BIOLOGICAL TISSUE 审中-公开
标题翻译：用于分析生物组织中的生物标记物定位的系统和方法
公开(公告)号：US20130286043A1
公开(公告)日：2013-10-31
申请号：US13460018
申请日：2012-04-30
申请人： Vidya Pundalik Kamath , Zhengyu Pang , Brion Daryl Sarachan
发明人： Vidya Pundalik Kamath , Zhengyu Pang , Brion Daryl Sarachan
IPC分类号： G06F3/048 , G09G5/00
CPC分类号： G09G5/026 , G06F3/1423 , G09G2340/12 , G09G2370/022 , G09G2380/08 , G16B20/00 , G16B45/00
摘要： Systems and methods are disclosed for selecting a field of view for a biological sample, selecting first and second biomarkers, each having a corresponding image in a multiplexed biomarker image of the selected field of view, automatically analyzing expression level criterion for each of the first and second biomarkers, rendering the corresponding images of the selected field-of-view in an overlaid manner on the graphical user interface and highlighting a first set of biological units in the biological tissue that meets both the biomarker expression level criterion for both the first and second biomarkers.
摘要翻译：公开了用于选择生物样品的视野的系统和方法，选择第一和第二生物标志物，每个生物标志物在所选视场的复用生物标志物图像中具有相应的图像，自动分析第一和第第二生物标志物，以覆盖的方式将所选择的视野的相应图像呈现在图形用户界面上，并突出显示生物组织中的第一组生物标志物表达水平标准，用于第一和第二生物标志物。

9. 发明申请

US20110091081A1 METHOD AND SYSTEM FOR ANALYZING THE EXPRESSION OF BIOMARKERS IN CELLS IN SITU IN THEIR TISSUE OF ORIGIN 审中-公开
标题翻译：用于分析生物标志物在其原始组织中的表达的方法和系统
公开(公告)号：US20110091081A1
公开(公告)日：2011-04-21
申请号：US12580651
申请日：2009-10-16
申请人： Brion Daryl Sarachan , Thomas Paul Repoff , Colin Craig McCulloch , Fiona Mary Ginty , Megan Pearl Rothney , Zhengyu Pang
发明人： Brion Daryl Sarachan , Thomas Paul Repoff , Colin Craig McCulloch , Fiona Mary Ginty , Megan Pearl Rothney , Zhengyu Pang
IPC分类号： G06K9/00 , C12Q1/02 , C12Q1/68 , G06F19/00
CPC分类号： C12Q1/6881 , G01N33/5023 , G01N33/5082 , G06T7/11 , G06T7/174 , G06T2207/10056 , G06T2207/20221 , G06T2207/30024
摘要： The present application discloses a technique for obtaining and storing data on expression of multiple biomarkers in individual cells or the compartments of individual cells in a tissue specimen and methods of utilizing that data to create groups, the members of which share some degree of similarity greater than the general population from which the data is drawn, by an analysis of digital images of a portion of the tissue specimen which has been iteratively stained to generate optical signals, typically fluorescent, reflective of the amount of each of the biomarkers examined. The analysis of the images involves a segmentation routine whereby each pixel of the examined images is assigned to an individual cell or a compartment of an individual cell, the intensity of the signal representative of each biomarker is measured for each pixel, a dataset is created in which each cell or compartments of each cell is associated with a signal intensity for each biomarker examined, and the dataset is interrogated with appropriate numerical tools to create groups. It also discloses the display of such groups on images of the tissue examined such that the individual cells belonging to a particular group are marked or indicated on one of the images examined. It further discloses examining the biomarker data for each group for possible association with a biological condition or process in cases in which tissue specimens drawn from different subjects or different portions of the tissue of a subject have been examined. It also discloses using this examination in the diagnoses, prognoses or assessment of the response to therapy of a condition or disease.
摘要翻译：本申请公开了一种用于获得和存储组织样本中个体细胞或个体细胞的多个生物标志物表达的数据的技术，以及利用该数据创建组的方法，其成员具有一定程度的相似性，大于通过对经过迭代染色以产生光信号的组织标本的一部分的数字图像的分析，通常是荧光的，反映了所检查的每个生物标志物的量，绘制数据的一般群体。图像的分析涉及分割程序，其中检查的图像的每个像素被分配给单个单元的单个单元或隔室，针对每个像素测量代表每个生物标志物的信号的强度，数据集被创建在每个细胞的每个细胞或隔室与所检测的每个生物标志物的信号强度相关联，并且用适当的数值工具询问数据集以产生组。它还公开了在所检查的组织的图像上显示这样的组，使得属于特定组的各个细胞在所检查的图像之一上被标记或指示。它还公开了在从受试者的不同受试者或组织的不同部分抽取的组织标本已经被检查的情况下，检查每组的生物标志物数据与生物学条件或过程的可能关联。它还公开了在对病症或疾病的治疗反应的诊断，预后或评估中使用该检查。

10. 发明授权

US07741046B2 Sequential analysis of biological samples 有权
标题翻译：生物样品的顺序分析
公开(公告)号：US07741046B2
公开(公告)日：2010-06-22
申请号：US11864093
申请日：2007-09-28
申请人： Melinda Larsen , Anup Sood , Michael J. Gerdes , Michael Christopher Montalto , Zhengyu Pang , Fiona Ginty
发明人： Melinda Larsen , Anup Sood , Michael J. Gerdes , Michael Christopher Montalto , Zhengyu Pang , Fiona Ginty
IPC分类号： C12Q1/68 , G01N33/53
CPC分类号： G01N33/53 , C12Q1/68 , G01N33/542 , G01N33/582 , Y10T436/143333
摘要： Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets adhered to a solid support, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The method further includes the steps of oxidizing the bound fluorescent probe with a solution containing an oxidizing agent that substantially inactivates the fluorescent probe, binding at least one fluorescent probe to one or more target present in the sample, and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.
摘要翻译：提供了探测生物样品中多个靶标的方法。所述方法包括以下步骤：提供包含粘附到固体支持物上的多个靶的生物样品，将至少一种荧光探针结合到样品中存在的一种或多种靶，并观察来自荧光探针的信号。所述方法还包括以下步骤：用含有基本上灭活荧光探针的氧化剂的溶液氧化结合的荧光探针，将至少一种荧光探针结合到样品中存在的一种或多种靶，并观察来自荧光探针的信号。本文公开的方法还提供结合，观察和氧化的多次迭代，用于导出关于单个样本中的多个目标的信息。还提供了相关的套件。

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