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1. 发明申请

US20140024024A1 METHODS OF DETECTING DNA, RNA AND PROTEIN IN BIOLOGICAL SAMPLES 审中-公开
标题翻译：在生物样品中检测DNA，RNA和蛋白质的方法
公开(公告)号：US20140024024A1
公开(公告)日：2014-01-23
申请号：US13551190
申请日：2012-07-17
申请人： Anup Sood , Michael John Gerdes , Antti Eljas Seppo , Wei Gao , Fiona Mary Ginty , Elizabeth Mary Collins
发明人： Anup Sood , Michael John Gerdes , Antti Eljas Seppo , Wei Gao , Fiona Mary Ginty , Elizabeth Mary Collins
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6841 , C12Q1/6804 , G01N33/53 , C12Q2523/319 , C12Q2543/10 , C12Q2563/107 , C12Q2565/601
摘要： Novel methods of probing multiple targets in a biological sample are provide whereby the targets are DNA, RNA and protein. The method comprises subjecting the sample to an in situ hybridization reaction using a labeled nucleic acid probe that binds an RNA target, observing a signal, and optionally removing the signal. The method further comprises an antigen retrieval protocol, observing a signal, removing the signal, and optionally applying a protease treatment to access the sample's DNA targets by subjecting the sample to an in situ hybridization reaction using a labeled nucleic acid probe, observing a signal from the labeled DNA targets, and optionally removing the signal.
摘要翻译：提供探索生物样品中多个靶标的新方法，其目标是DNA，RNA和蛋白质。该方法包括使用结合RNA靶标的标记的核酸探针对样品进行原位杂交反应，观察信号和任选地除去信号。该方法还包括抗原检索方案，观察信号，去除信号，以及任选应用蛋白酶处理以通过使用标记的核酸探针对样品进行原位杂交反应以观察样品的DNA靶标，观察来自标记的DNA靶标，并任选地去除信号。

2. 发明授权

US08031924B2 Methods and systems for removing autofluorescence from images 有权
标题翻译：从图像中去除自发荧光的方法和系统
公开(公告)号：US08031924B2
公开(公告)日：2011-10-04
申请号：US11948205
申请日：2007-11-30
申请人： Ali Can , Michael John Gerdes , Harvey Ellis Cline
发明人： Ali Can , Michael John Gerdes , Harvey Ellis Cline
IPC分类号： G06K9/00
CPC分类号： G01N21/6458 , G01N21/6428 , G01N2021/6441
摘要： Method and systems for removing any inherent autofluorescence associated with a biological material, comprising: acquiring a first reference image of the biological material; acquiring a first set of one or more images of the biological material using one or more filters corresponding to one or more information dyes; applying the one or more additional dyes to the biological material and then acquiring a second set of one or more images comprising a separate image of the biological material with each of the filters corresponding to the information dyes and a second reference image of the biological material; coregistering the first and second reference images; and then removing any inherent autofluorescence exhibited in the informational images acquired.
摘要翻译：用于去除与生物材料相关联的任何固有自发荧光的方法和系统，包括：获取所述生物材料的第一参考图像; 使用对应于一种或多种信息染料的一个或多个过滤器获取所述生物材料的第一组一个或多个图像; 将一种或多种另外的染料施加到生物材料上，然后获取包含生物材料的单独图像的第二组一个或多个图像，其中每个滤色器对应于信息染料和生物材料的第二参考图像; 整合第一和第二参考图像; 然后去除所获得的信息图像中显示的任何固有自发荧光。

3. 发明授权

US09468894B2 Microfluidic mixing and analytical apparatus 有权
标题翻译：微流控混合分析仪
公开(公告)号：US09468894B2
公开(公告)日：2016-10-18
申请号：US13099187
申请日：2011-05-02
申请人： John Clemmens , C. Frederick Battrell , John Gerdes , Denise Maxine Hoekstra
发明人： John Clemmens , C. Frederick Battrell , John Gerdes , Denise Maxine Hoekstra
IPC分类号： B01F13/00 , B01F11/00 , C12M3/06 , C12M3/00 , C12M1/12 , C12M1/00 , B01L3/00 , G01N35/00
CPC分类号： B01F13/0059 , B01F11/0071 , B01L3/502723 , B01L3/50273 , B01L3/502738 , B01L3/502761 , B01L2300/0816 , B01L2400/0481 , B01L2400/0655 , C12M23/16 , C12M23/42 , C12M25/16 , C12M29/10 , G01N2035/00544 , G01N2035/00564
摘要： Disclosed herein is a device comprising a pair of bellows pumps configured for efficient mixing at a microfluidic scale. By moving a fluid sample and particles in suspension through an aperture between the paired bellows pump mixing chambers, molecular collisions leading to binding between the particles and ligands in the sample are enhanced. Such devices provide an alternative for mixing that does not use a vent and can be used with a variety of particles in suspension such as magnetic beads to capture or purify useful cells and molecules.
摘要翻译：本文公开了一种包括一对波纹管泵的装置，其配置为在微流控尺度上有效地混合。通过将流体样品和悬浮液中的颗粒通过成对的波纹管泵混合室之间的孔移动，导致样品中颗粒和配体之间的结合的分子碰撞得到增强。这样的装置提供了不使用排气口的混合的替代方案，并且可以与诸如磁珠的悬浮液中的各种颗粒一起使用以捕获或净化有用的细胞和分子。

4. 发明授权

US08880351B2 Method and apparatus for analysis of tissue microarrays 有权
标题翻译：用于分析组织微阵列的方法和装置
公开(公告)号：US08880351B2
公开(公告)日：2014-11-04
申请号：US12055121
申请日：2008-03-25
申请人： Ali Can , Michael John Gerdes , Musodiq Olatayo Bello , Xiaodong Tao , Maximilian Seel
发明人： Ali Can , Michael John Gerdes , Musodiq Olatayo Bello , Xiaodong Tao , Maximilian Seel
IPC分类号： G01N33/50 , G06T7/00 , G01N21/64
CPC分类号： G01N21/6452 , G06T7/30 , G06T2207/30072
摘要： The present techniques include methods and systems for finding correspondences between tissue spots in tissue microarray serial sections belonging to the same recipient block. The present techniques may also be used to relate individual tissue cores to clinical information. Using either a whole slide image or the relative x-y coordinates of the tissue spots on the slide, individual tissue spots in different tissue microarrays may be linked to one another and their clinical information.
摘要翻译：本技术包括用于在属于相同受体块的组织微阵列序列区段中发现组织斑点之间的对应关系的方法和系统。本技术还可以用于将个体组织核心与临床信息相关联。使用整个幻灯片图像或幻灯片上组织斑点的相对x-y坐标，不同组织微阵列中的各个组织斑点可以彼此连接并且其临床信息。

5. 发明授权

US08815546B2 Methods for multiplexing amplification reactions 有权
标题翻译：多重扩增反应的方法
公开(公告)号：US08815546B2
公开(公告)日：2014-08-26
申请号：US13619436
申请日：2012-09-14
申请人： John Gerdes , Elaine Best , Jeffrey M. Marmaro
发明人： John Gerdes , Elaine Best , Jeffrey M. Marmaro
IPC分类号： C12P19/34
CPC分类号： C12Q1/686 , C12Q1/6806 , C12Q1/6827 , C12Q1/6844 , C12Q1/689 , C12Q2600/156 , C12Q2600/16 , C12Q2549/113 , C12Q2537/143 , C12Q2531/113 , C12Q2531/101
摘要： A two-step multiplex amplification reaction includes a first step which truncates the standard initial multiplex amplification round to “boost” the sample copy number by only a 100-1000 fold increase in the target. Following the first step the product is divided into optimized secondary single amplification reactions, each containing one of the primer sets that were used previously in the first or multiplexed booster step. The booster step can occur using an aqueous target nucleic acid or using a solid phase archived nucleic acid. In particular, nucleic acid sequences that uniquely identify E. Coli were identified using the multiplex amplification method.
摘要翻译：两步多重扩增反应包括第一步骤，其缩短了标准初始多重扩增循环，以使样本拷贝数“提高”目标只增加100-1000倍。在第一步之后，将产物分成优化的次级单次扩增反应，每个反应都包含先前在第一个或多路增强步骤中使用的引物组之一。增强步骤可以使用水性靶核酸或使用固相归档的核酸进行。特别地，使用多重扩增方法鉴定了唯一鉴定大肠杆菌的核酸序列。

6. 发明申请

US20120271127A1 SANITARY SWAB COLLECTION SYSTEM, MICROFLUIDIC ASSAY DEVICE, AND METHODS FOR DIAGNOSTIC ASSAYS 审中-公开
标题翻译：卫生衣物收集系统，微流感测定装置及诊断方法
公开(公告)号：US20120271127A1
公开(公告)日：2012-10-25
申请号：US13491009
申请日：2012-06-07
申请人： C. Frederick Battrell , Jason Capodanno , John Clemmens , Joan Haab , John Gerdes
发明人： C. Frederick Battrell , Jason Capodanno , John Clemmens , Joan Haab , John Gerdes
IPC分类号： A61B5/00 , A61B5/157 , A61B10/02
CPC分类号： G01N1/02 , A61B10/0045 , A61B10/0096 , B01L3/502715 , B01L3/5029 , B01L7/52 , B01L2200/027 , B01L2200/082 , B01L2200/10 , B01L2300/069 , B01L2300/0854 , B01L2300/087 , B01L2400/0415 , B01L2400/0487 , G01N2001/028
摘要： Biohazard specimen collection containers are provided with an external disposable skin, that is stripped away and discarded after the biohazardous specimen is collected, thus reducing or eliminating objectionable or dangerous residues on the outside surfaces of the container. Further, we teach that the sample collection container with external disposable skin may also serve as an integrated microfluidic biosample processing and analytical device, thereby providing a single entry, disposable assay unit, kit and system for “world-to-result” clinical diagnostic testing. These integrated assay devices are provided with synergic, multiple safe-handling features for protecting healthcare workers who handle them. The modified collection containers and analytical devices find application, for example, in PCR detection of infectious organisms or pathogenic markers collected on a swab.
摘要翻译：生物危害标本收集容器设置有外部一次性皮肤，其在收集生物危险样本之后被剥离并丢弃，从而减少或消除容器外表面上的令人反感或危险的残留物。此外，我们教导，具有外部一次性皮肤的样品收集容器也可用作集成的微流体生物样品处理和分析装置，从而为世界到结果临床诊断测试提供单一入口，一次性测定单元，试剂盒和系统。这些集成测定装置具有协同的多重安全处理功能，用于保护处理它们的医护人员。经修改的收集容器和分析装置可以应用于例如感染生物的PCR检测或在拭子上收集的病原性标记物。

7. 发明授权

US08189884B2 Methods for assessing molecular expression of subcellular molecules 有权
标题翻译：评估亚细胞分子的分子表达方法
公开(公告)号：US08189884B2
公开(公告)日：2012-05-29
申请号：US12056068
申请日：2008-03-26
申请人： Ali Can , Michael John Gerdes , Musodiq Olatayo Bello , Xiaodong Tao
发明人： Ali Can , Michael John Gerdes , Musodiq Olatayo Bello , Xiaodong Tao
IPC分类号： G06K9/00 , G06F19/10
CPC分类号： G06T7/0012 , G06T2207/30072
摘要： The present techniques provide fully automated methods for quantifying the location, strength and percent of expressed target molecules or other biological markers in immunohistochemically stained biological samples. The samples may be automatically segmented, for example into subcellular compartments, from images of compartmental markers. Then, the distribution of a target molecule on each of these compartments is calculated that includes the percentage and strength of expression. This is different than existing intensity or ratio based methods where abundant low expression levels are indistinguishable from scarce high expression levels.
摘要翻译：本技术提供了完全自动化的方法，用于定量免疫组织化学染色的生物样品中表达的靶分子或其他生物标志物的位置，强度和百分比。样品可以从分隔标记的图像中自动分割，例如分成亚细胞室。然后，计算这些隔室中的每一个上的靶分子的分布，其包括表达的百分比和强度。这与现有的强度或基于比例的方法不同，其中丰富的低表达水平与稀缺的高表达水平无法区分。

8. 发明授权

US08135187B2 Method and apparatus for removing tissue autofluorescence 有权
标题翻译：用于去除组织自体荧光的方法和装置
公开(公告)号：US08135187B2
公开(公告)日：2012-03-13
申请号：US12056078
申请日：2008-03-26
申请人： Ali Can , Michael John Gerdes , Musodiq Olatayo Bello , Xiaodong Tao , Francis Edward Pavan-Woolfe , Roshni Bhagalia
发明人： Ali Can , Michael John Gerdes , Musodiq Olatayo Bello , Xiaodong Tao , Francis Edward Pavan-Woolfe , Roshni Bhagalia
IPC分类号： G06K9/00 , A61B1/06
CPC分类号： G06K9/0014 , G01N21/6458
摘要： Techniques for removing image autoflourescence from fluorescently stained biological images are provided herein. The techniques utilize non-negative matrix factorization that may constrain mixing coefficients to be non-negative. The probability of convergence to local minima is reduced by using smoothness constraints. The non-negative matrix factorization algorithm provides the advantage of removing both dark current and autofluorescence.
摘要翻译：本文提供了从荧光染色的生物图像中去除图像自动曝光的技术。这些技术利用可以将混合系数限制为非负的非负矩阵分解。通过使用平滑度约束来减少收敛到局部最小值的概率。非负矩阵分解算法提供了去除暗电流和自发荧光的优点。

9. 发明授权

US07955836B2 Microfluidic mixing and analytical apparatus 有权
标题翻译：微流控混合分析仪
公开(公告)号：US07955836B2
公开(公告)日：2011-06-07
申请号：US12685546
申请日：2010-01-11
申请人： John Clemmens , C. Frederick Battrell , John Gerdes , Denise Maxine Hoekstra
发明人： John Clemmens , C. Frederick Battrell , John Gerdes , Denise Maxine Hoekstra
IPC分类号： C12M1/36
CPC分类号： B01F13/0059 , B01F11/0071 , B01L3/502723 , B01L3/50273 , B01L3/502738 , B01L3/502761 , B01L2300/0816 , B01L2400/0481 , B01L2400/0655 , C12M23/16 , C12M23/42 , C12M25/16 , C12M29/10 , G01N2035/00544 , G01N2035/00564
摘要： Disclosed herein is a device comprising a pair of bellows pumps configured for efficient mixing at a microfluidic scale. By moving a fluid sample and particles in suspension through an aperture between the paired bellows pump mixing chambers, molecular collisions leading to binding between the particles and ligands in the sample are enhanced. Such devices provide an alternative for mixing that does not use a vent and can be used with a variety of particles in suspension such as magnetic beads to capture or purify useful cells and molecules.
摘要翻译：本文公开了一种包括一对波纹管泵的装置，其配置为在微流控尺度上有效地混合。通过将流体样品和悬浮液中的颗粒通过成对的波纹管泵混合室之间的孔移动，导致样品中颗粒和配体之间的结合的分子碰撞得到增强。这样的装置提供了不使用排气口的混合的替代方案，并且可以与诸如磁珠的悬浮液中的各种颗粒一起使用以捕获或净化有用的细胞和分子。

10. 发明申请

US20110092381A1 DETECTION OF PLURALITY OF TARGETS IN BIOLOGICAL SAMPLES 有权
标题翻译：检测目标在生物样本中的多样性
公开(公告)号：US20110092381A1
公开(公告)日：2011-04-21
申请号：US12582745
申请日：2009-10-21
申请人： Anup Sood , John Richard Nelson , Michael John Gerdes
发明人： Anup Sood , John Richard Nelson , Michael John Gerdes
IPC分类号： C40B30/04 , C40B60/12
CPC分类号： C12Q1/6816 , C12Q2600/158 , C12Q2545/101 , C12Q2537/143
摘要： Methods for detecting a plurality of targets in a biological sample are provided. The method comprises contacting the biological sample with a plurality of target-binding probes to form a plurality of target-bound probes, covalently attaching at least one of the target-bound probes to the biological sample, and observing the signals from the target-bound probes sequentially. An associated kit and device for detection of the plurality of targets 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。该方法包括使生物样品与多个靶结合探针接触以形成多个靶结合探针，将至少一个目标结合探针共价连接至生物样品，并观察来自靶标结合的信号顺序探测。还提供了用于检测多个靶的相关联的试剂盒和装置。

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