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1. 发明授权

US08900529B2 Microfluidic chamber device and fabrication 有权
标题翻译：微流体室装置和制造
公开(公告)号：US08900529B2
公开(公告)日：2014-12-02
申请号：US13458092
申请日：2012-04-27
申请人： Kashan Ali Shaikh , Jessica Marie Godin , Alex David Corwin , Robert John Filkins
发明人： Kashan Ali Shaikh , Jessica Marie Godin , Alex David Corwin , Robert John Filkins
IPC分类号： B01L99/00
CPC分类号： B32B37/0076 , B01L3/5027 , B01L3/502707 , B01L9/527 , B01L2200/027 , B01L2200/0689 , B01L2300/0816 , B01L2300/0822 , B01L2300/0867 , B01L2300/0877 , B01L2300/0887 , B01L2400/0655 , B32B37/182 , B32B38/0008 , B32B2535/00 , Y10T156/10 , Y10T156/1056 , Y10T156/108
摘要： A microfluidic flow cell subassembly, which may be assembled into a flow cell having fluidic connections outside of the main substrate, is described for encapsulating a sample to allow for subsequent controlled delivery of reagents to the sample, such as multiplexed in situ biomarker staining and analysis. Methods for fabricating the subassembly and assembled flow cell are also provided. The method includes the steps of adhering a gasket layer to a substrate layer, wherein the gasket layer may contain enclosed features and adhering an adherent layer to the gasket layer. The subassembly may be sealed against a solid support to form a flow cell.
摘要翻译：描述了可以组装成具有在主底物外部的流体连接的流动池的微流体流动池子组件，用于封装样品以允许随后控制的试剂递送到样品中，例如原位复合生物标记染色和分析。还提供了用于制造子组件和组装流动池的方法。该方法包括以下步骤：将衬垫层粘附到衬底层，其中衬垫层可以包含封闭特征并将粘附层粘附到衬垫层。子组件可以密封在固体支撑件上以形成流动池。

2. 发明申请

US20130287645A1 MICROFLUIDIC CHAMBER DEVICE AND FABRICATION 有权
标题翻译：微流化器件和制造
公开(公告)号：US20130287645A1
公开(公告)日：2013-10-31
申请号：US13458092
申请日：2012-04-27
申请人： Kashan Ali Shaikh , Jessica Marie Godin , Alex David Corwin , Robert John Filkins
发明人： Kashan Ali Shaikh , Jessica Marie Godin , Alex David Corwin , Robert John Filkins
IPC分类号： B01L3/00 , B32B38/10 , B32B38/04 , B32B37/00
CPC分类号： B32B37/0076 , B01L3/5027 , B01L3/502707 , B01L9/527 , B01L2200/027 , B01L2200/0689 , B01L2300/0816 , B01L2300/0822 , B01L2300/0867 , B01L2300/0877 , B01L2300/0887 , B01L2400/0655 , B32B37/182 , B32B38/0008 , B32B2535/00 , Y10T156/10 , Y10T156/1056 , Y10T156/108
摘要： A microfluidic flow cell subassembly, which may be assembled into a flow cell having fluidic connections outside of the main substrate, is described for encapsulating a sample to allow for subsequent controlled delivery of reagents to the sample, such as multiplexed in situ biomarker staining and analysis. Methods for fabricating the subassembly and assembled flow cell are also provided. The method includes the steps of adhering a gasket layer to a substrate layer, wherein the gasket layer may contain enclosed features and adhering an adherent layer to the gasket layer. The subassembly may be sealed against a solid support to form a flow cell.
摘要翻译：描述了可以组装成具有在主底物外部的流体连接的流动池的微流体流动池子组件，用于封装样品以允许随后控制的试剂递送到样品中，例如原位复合生物标记染色和分析。还提供了用于制造子组件和组装流动池的方法。该方法包括以下步骤：将衬垫层粘附到衬底层，其中衬垫层可以包含封闭特征并将粘附层粘附到衬垫层。子组件可以密封在固体支撑件上以形成流动池。

3. 发明申请

US20140001337A1 SYSTEMS AND METHODS FOR PROCESSING AND IMAGING OF BIOLOGICAL SAMPLES 有权
标题翻译：用于处理和成像生物样品的系统和方法
公开(公告)号：US20140001337A1
公开(公告)日：2014-01-02
申请号：US13538898
申请日：2012-06-29
申请人： Alex David Corwin , Robert John Filkins , Jun Xie , Nannan Chen , Kashan Ali Shaikh
发明人： Alex David Corwin , Robert John Filkins , Jun Xie , Nannan Chen , Kashan Ali Shaikh
IPC分类号： H01L27/146
CPC分类号： G01N1/312
摘要： A method for processing and imaging a first and second plurality of samples, comprising processing at least one sample from the first plurality of samples, imaging the at least one sample from the first plurality of samples, while being capable of simultaneously processing at least one sample from the second plurality of samples; and imaging the at least one processed sample from the second plurality of samples.
摘要翻译：一种用于处理和成像第一和第二多个样品的方法，包括处理来自所述第一多个样品的至少一个样品，对来自所述第一多个样品的所述至少一个样品进行成像，同时能够同时处理至少一个样品从第二多个样本; 以及对来自所述第二多个样本的所述至少一个处理的样品进行成像。

4. 发明申请

US20120135458A1 CLOSED LOOP MONITORING OF AUTOMATED MOLECULAR PATHOLOGY SYSTEM 有权
标题翻译：自动分子病理学系统闭环监测
公开(公告)号：US20120135458A1
公开(公告)日：2012-05-31
申请号：US12957203
申请日：2010-11-30
申请人： Alex David Corwin , Robert John Filkins , Jun Xie , Christopher James Sevinsky , Kashan Ali Shaikh
发明人： Alex David Corwin , Robert John Filkins , Jun Xie , Christopher James Sevinsky , Kashan Ali Shaikh
IPC分类号： G01N1/30 , C12M1/36
CPC分类号： G01N1/312 , G01N2001/368
摘要： A closed loop automated method for staining of a biological sample is provided. The method comprises providing a biological sample, staining at least a portion of the biological sample by flowing in a reagent, monitoring one or more optical characteristics of the biological sample, and calculating a figure of merit based on at least one of the optical characteristics. An automated device for iterative staining of a biological sample is also provided.
摘要翻译：提供了一种用于染色生物样品的闭环自动化方法。该方法包括提供生物样品，通过在试剂中流动来染色生物样品的至少一部分，监测生物样品的一种或多种光学特性，以及基于至少一种光学特性来计算品质因数。还提供了用于生物样品的迭代染色的自动化装置。

5. 发明申请

US20140055853A1 OPEN TOP MICROFLUIDIC DEVICE FOR MULTIPLEXING 审中-公开
标题翻译：用于多路复用的开顶微型器件
公开(公告)号：US20140055853A1
公开(公告)日：2014-02-27
申请号：US13595175
申请日：2012-08-27
申请人： Alex David Corwin , Robert John Filkins , Kashan Ali Shaikh , Adriana Ines Larriera Moreno
发明人： Alex David Corwin , Robert John Filkins , Kashan Ali Shaikh , Adriana Ines Larriera Moreno
IPC分类号： B01L3/00 , G02B21/26 , G01N21/13
CPC分类号： G01N1/31 , B01L3/502715 , B01L3/508 , B01L9/52 , B01L9/527 , B01L2300/041 , B01L2300/046 , B01L2300/0822 , B01L2300/0877 , G01N1/312 , G01N2001/317
摘要： An open top microfluidic device comprising a microfluidic slide carrier and one or more multiplexing stations is provided which allows sequential staining and imaging without the need for using or removing a coverslip on a mounted biological sample.
摘要翻译：提供了包括微流体载玻片载体和一个或多个多路复用站的开口顶部微流体装置，其允许顺序染色和成像，而不需要在安装的生物样品上使用或去除盖玻片。

6. 发明授权

US09164015B2 Systems and methods for processing and imaging of biological samples 有权
标题翻译：用于生物样品处理和成像的系统和方法
公开(公告)号：US09164015B2
公开(公告)日：2015-10-20
申请号：US13538898
申请日：2012-06-29
申请人： Alex David Corwin , Robert John Filkins , Jun Xie , Nannan Chen , Kashan Ali Shaikh
发明人： Alex David Corwin , Robert John Filkins , Jun Xie , Nannan Chen , Kashan Ali Shaikh
IPC分类号： H01L27/146 , G01N1/31
CPC分类号： G01N1/312
摘要： A method for processing and imaging a first and second plurality of samples, comprising processing at least one sample from the first plurality of samples, imaging the at least one sample from the first plurality of samples, while being capable of simultaneously processing at least one sample from the second plurality of samples; and imaging the at least one processed sample from the second plurality of samples.
摘要翻译：一种用于处理和成像第一和第二多个样品的方法，包括处理来自所述第一多个样品的至少一个样品，对来自所述第一多个样品的所述至少一个样品进行成像，同时能够同时处理至少一个样品从第二多个样本; 以及对来自所述第二多个样本的所述至少一个处理的样品进行成像。

7. 发明授权

US08673643B2 Closed loop monitoring of automated molecular pathology system 有权
标题翻译：自动分子病理系统闭环监测
公开(公告)号：US08673643B2
公开(公告)日：2014-03-18
申请号：US12957203
申请日：2010-11-30
申请人： Alex David Corwin , Robert John Filkins , Jun Xie , Christopher James Sevinsky , Kashan Ali Shaikh
发明人： Alex David Corwin , Robert John Filkins , Jun Xie , Christopher James Sevinsky , Kashan Ali Shaikh
IPC分类号： G01N35/02 , G01N33/53 , B05D3/00 , G01N1/31 , G01N1/30 , G01N33/48
CPC分类号： G01N1/312 , G01N2001/368
摘要： A closed loop automated method for staining of a biological sample is provided. The method comprises providing a biological sample, staining at least a portion of the biological sample by flowing in a reagent, monitoring one or more optical characteristics of the biological sample, and calculating a figure of merit based on at least one of the optical characteristics. An automated device for iterative staining of a biological sample is also provided.
摘要翻译：提供了一种用于染色生物样品的闭环自动化方法。该方法包括提供生物样品，通过在试剂中流动来染色生物样品的至少一部分，监测生物样品的一种或多种光学特性，以及基于至少一种光学特性来计算品质因数。还提供了用于生物样品的迭代染色的自动装置。

8. 发明申请

US20120231967A1 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：US20120231967A1
公开(公告)日：2012-09-13
申请号：US13457531
申请日：2012-04-27
申请人： Anup Sood , Michael Christopher Montalto , Michael Gerdes , Maximilian Lewis Seel , Robert John Filkins
发明人： Anup Sood , Michael Christopher Montalto , Michael Gerdes , Maximilian Lewis Seel , Robert John Filkins
IPC分类号： C40B30/04
CPC分类号： G01N33/53 , C12Q1/68 , G01N33/542 , G01N33/582 , Y10T436/143333
摘要： Methods for detecting multiple targets in a biological sample are provided. The methods includes contacting the sample with a first probe; physically binding the first probe to a first target; observing a first signal from the first probe; applying a chemical agent to modify the first signal; contacting the sample with a second probe; physically binding the second probe to a second target; and observing a second signal from the second probe. The methods disclosed herein also provide for multiple iterations of binding, observing, signal modification for deriving information about multiple targets in a single sample. An associated kit and device are also provided.
摘要翻译：提供了用于检测生物样品中多个靶的方法。所述方法包括使样品与第一探针接触; 将第一探针物理地绑定到第一靶; 观察来自第一探针的第一信号; 施用化学试剂来修饰第一信号; 使样品与第二探针接触; 将第二探针物理地绑定到第二靶上; 并观察来自第二探测器的第二信号。本文公开的方法还提供绑定，观察，信号修改的多次迭代，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和设备。

9. 发明申请

US20120135449A1 ITERATIVE STAINING OF BIOLOGICAL SAMPLES 审中-公开
标题翻译：生物样本的迭代染色
公开(公告)号：US20120135449A1
公开(公告)日：2012-05-31
申请号：US13365525
申请日：2012-02-03
申请人： Jun Xie , Robert John Filkins , Fiona Mary Ginty , Michael Christopher Montalto , Anup Sood , Jeffrey Bernard Fortin , Wei-Cheng Tian , Michael John Gerdes
发明人： Jun Xie , Robert John Filkins , Fiona Mary Ginty , Michael Christopher Montalto , Anup Sood , Jeffrey Bernard Fortin , Wei-Cheng Tian , Michael John Gerdes
IPC分类号： G01N21/75 , C12M1/34
CPC分类号： G01N1/312
摘要： Automated methods and devices that facilitate iterative staining of biological samples from imaging applications are provided. The methods include the steps of providing a small volume flow cell containing a biological sample, applying a stain to the biological sample, combining at least two precursor reagents to form an activated destaining agent and wherein the activated destaining agent decomposition rate is greater than or similar to the destaining reaction rate, flowing the destaining agent over the biological sample at a flow rate that is greater than the decomposition rate of the activated destaining agent, and releasing the sample from the flow cell wherein the integrity of the sample is intact. The process of staining, combining and flowing may be iteratively repeated. Also disclosed herein are devices for iterative staining of biological samples comprising a flow cell, in fluid communication with a premixer, wherein the volume capacity of the premixer is smaller than about five times the volume capacity of the flow cell.
摘要翻译：提供了促进成像应用中生物样品的迭代染色的自动化方法和装置。所述方法包括以下步骤：提供含有生物样品的小体积流动池，向生物样品施加染色，将至少两种前体试剂结合以形成活化的脱色剂，并且其中所述活化脱色剂分解速率大于或等于以脱色反应速率使脱色剂以大于活化脱色剂的分解速率的流速流过生物样品，并将样品从流动池中释放出来，其中样品的完整性是完整的。染色，组合和流动的过程可以迭代地重复。本文还公开了用于重复染色生物样品的装置，其包括与预混合器流体连通的流动池，其中预混合器的体积容量小于流动池的体积容量的约五倍。

10. 发明申请

US20110075914A1 SYSTEM AND METHOD FOR THE QUANTITATIVE ASSESSMENT OF DIGITAL HISTOLOGY IMAGES 审中-公开
标题翻译：数字化学图像定量评估系统与方法
公开(公告)号：US20110075914A1
公开(公告)日：2011-03-31
申请号：US12571158
申请日：2009-09-30
申请人： Robert John Filkins , Kevin Kenny , David Henderson , Jens Rittscher
发明人： Robert John Filkins , Kevin Kenny , David Henderson , Jens Rittscher
IPC分类号： G06K9/00
CPC分类号： G06K9/00127 , G06K9/036 , G06T7/0002 , G06T7/41 , G06T2200/32 , G06T2207/10056 , G06T2207/30024
摘要： The present disclosure concerns a method and system for assessing image quality of sub-images used to form a composite image using an algorithm developed by applying statistical correlation techniques to historical data on features of sub-images which were manually evaluated by experts and using those assessment to make decisions about the further processing of the sub-images which are being assessed. The method and system find particular value in the processing of sub-images generated while there is relative motion between the specimen under examination and the objective lens of a microscope such as when the microscope stage follows a planned traverse in the focal plane and a digital image is created at intervals correlated to the motion of the stage so that a region of interest in the specimen under examination is covered by the sub-images. The further processing decisions include manually examining the sub-images assessed to have unacceptable image quality, reimaging the entire region of interest and recreating specific sub-images. The method and system may also involve overlaying portions of a composite image with an indication that they were drawn from sub-images of unacceptable image quality.
摘要翻译：本公开涉及一种用于评估用于形成合成图像的子图像的图像质量的方法和系统，该方法和系统使用通过将统计相关技术应用于由专家手动评估的子图像的特征的历史数据而开发的算法，并使用这些评估做出关于正在评估的子图像的进一步处理的决定。该方法和系统在检查中的样本与显微镜的物镜之间产生的子图像的处理中发现特定的值，例如当显微镜载物台在焦平面上进行计划的横越时，以及数字图像以与舞台的运动相关的间隔创建，使得被检查的样本中的感兴趣区域被子图像覆盖。进一步的处理决定包括手动检查评估为具有不可接受的图像质量的子图像，重新映像整个感兴趣区域并重新创建特定子图像。该方法和系统还可以包括将合成图像的部分重叠，并显示它们是从不可接受的图像质量的子图像中提取的。

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