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公开(公告)号：US08900529B2
公开(公告)日：2014-12-02
申请号：US13458092
申请日：2012-04-27
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。
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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。
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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
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。
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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
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。
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5.发明申请公开(公告)号：US20110075914A1
公开(公告)日：2011-03-31
申请号：US12571158
申请日：2009-09-30
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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公开(公告)号：US20100301230A1
公开(公告)日：2010-12-02
申请号：US12474306
申请日：2009-05-29
IPC分类号： G01N21/64
CPC分类号： G01N21/6452 , G01N21/6458 , G01N21/6486 , G02B21/16 , G02B2207/113
摘要： The invention provides method for locating one or more substantially circular-shaped tissue sample positioned on a solid support. The method involves the steps of transmitting light of a preselected wavelength onto a tissue sample, wherein the light induces the tissue sample to autofluoresce, identifying the center location of the tissue sample using the autofluoresced light, correlating the coordinates of the center location of the tissue sample on the solid support using an x, y-coordinate system, and mapping the coordinates of the tissue sample on the solid support to differentiate tissue sample containing regions from blank regions on the solid support. In a second aspect, the invention provides an apparatus for locating one or more substantially circular-shaped tissue sample positioned on a solid support.
摘要翻译： 本发明提供了一种用于定位位于固体支持体上的一个或多个基本圆形的组织样本的方法。 该方法包括以下步骤：将预选波长的光透射到组织样本上，其中光诱导组织样本自发荧光，使用自发荧光识别组织样本的中心位置，将组织的中心位置的坐标相关联 使用x，y坐标系统在固体支持物上进行样品测绘，并将组织样本的坐标映射到固体支持物上，以将含有区域的组织样本与固体支持物上的空白区域区分开。 在第二方面，本发明提供了一种用于定位位于固体支撑体上的一个或多个基本圆形的组织样本的装置。
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公开(公告)号：US06710912B1
公开(公告)日：2004-03-23
申请号：US10326124
申请日：2002-12-23
IPC分类号： G02F1355
CPC分类号： G02F1/3775 , G02F2001/3548 , G02F2202/32
摘要： A technique for achieving quasi phase matching in a photonic band gap structure comprising a first material and a second material is disclosed. In one particular exemplary embodiment, the technique may be realized by calculating a coherence length of an optical interaction of interest involving at least a first frequency and a second frequency; calculating a first lattice constant of the first material to achieve a predetermined first group velocity for a fundamental optical frequency; calculating a second lattice constant of the second material so that a second group velocity of a second optical frequency is substantially the same as the first group velocity associated with the fundamental optical frequency of the first material; determining a photonic band gap arrangement for achieving quasi phase matching in the photonic band gap structure; and implementing the first lattice constant of the first material and the second lattice constant of the second material in accordance with the photonic band gap arrangement to achieve quasi phase matching in the photonic band gap structure.
摘要翻译： 公开了一种在包括第一材料和第二材料的光子带隙结构中实现准相位匹配的技术。 在一个特定示例性实施例中，可以通过计算涉及至少第一频率和第二频率的感兴趣的光学相互作用的相干长度来实现该技术; 计算第一材料的第一晶格常数以实现基本光频率的预定的第一组速度; 计算第二材料的第二晶格常数，使得第二光频率的第二组速度与与第一材料的基本光频率相关联的第一组速度基本相同; 确定用于实现光子带隙结构中的准相位匹配的光子带隙布置; 并且根据光子带隙布置实现第一材料的第一晶格常数和第二材料的第二晶格常数，以实现光子带隙结构中的准相位匹配。
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公开(公告)号：US09164015B2
公开(公告)日：2015-10-20
申请号：US13538898
申请日：2012-06-29
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。
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公开(公告)号：US08964183B2
公开(公告)日：2015-02-24
申请号：US13485026
申请日：2012-05-31
CPC分类号： G01N21/59 , G01N21/4738 , G01N21/6408 , G01N21/6458
摘要： A screening module configured to screen at least a portion of a biological sample disposed on an analysis surface is provided. The screening module comprises a laser source a scanning unit comprising one or more scanning devices, wherein the scanning devices are configured to rotate in an oscillatory scanning motion about an axis of rotation to scan the analysis surface in at least one direction, wherein the scanning unit is physically coupled to the laser source, and a detection unit comprising one or more detection devices.
摘要翻译： 提供了一种被配置为筛选设置在分析表面上的生物样品的至少一部分的筛选模块。 筛选模块包括激光源，扫描单元包括一个或多个扫描装置，其中扫描装置被配置为以围绕旋转轴的振荡扫描运动旋转，以在至少一个方向上扫描分析表面，其中扫描单元 物理耦合到激光源，以及检测单元，其包括一个或多个检测装置。
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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
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。
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