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1. 发明申请

WO2013134442A1 DUPLEX CHROMOGENIC ASSAY FOR IN SITU DETECTION OF NUCLEIC ACIDS 审中-公开
标题翻译：用于检测核酸的双重色谱测定
公开(公告)号：WO2013134442A1
公开(公告)日：2013-09-12
申请号：PCT/US2013/029467
申请日：2013-03-06
申请人： ADVANCED CELL DIAGNOSTICS, INC.
发明人： WANG, Li-chong , SU, Nan , MA, Xiao-jun , LUO, Yuling
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6841 , C12Q2600/16 , C12Q2537/143 , C12Q2563/103 , C12Q2563/125
摘要： The disclosure provides methods of detecting two or more target nucleic acids. The methods can include the steps of contacting a sample with two or more label probes having distinct enzyme labels and targeting distinct nucleic acid targets, binding the two or more label probes to the target nucleic acids by hybridization; contacting the sample with a first substrate for the first enzyme of the first label probe; reacting the first substrate with the first enzyme, thereby producing a first detectable signal; contacting the sample with a second substrate for the second enzyme of the second label probe; reacting the second substrate with the second enzyme, thereby producing a second detectable signal; and detecting the first detectable signal and the second detectable signal, thereby detecting the first and second target nucleic acids in the sample.
摘要翻译：本公开提供了检测两种或更多种靶核酸的方法。所述方法可以包括以下步骤：将样品与具有不同酶标记的两个或更多个标记探针接触并靶向不同的核酸靶标，通过杂交将两个或多个标记探针结合到靶核酸; 使样品与第一标记探针的第一酶的第一底物接触; 使第一底物与第一酶反应，从而产生第一可检测信号; 使所述样品与所述第二标记探针的第二酶的第二底物接触; 使第二底物与第二酶反应，从而产生第二可检测信号; 并检测第一可检测信号和第二可检测信号，从而检测样品中的第一和第二靶核酸。

2. 发明申请

WO2012054795A1 AN ULTRA SENSITIVE METHOD FOR IN SITU DETECTION OF NUCLEIC ACIDS 审中-公开
标题翻译：用于检测核酸的超敏感方法
公开(公告)号：WO2012054795A1
公开(公告)日：2012-04-26
申请号：PCT/US2011/057202
申请日：2011-10-21
申请人： ADVANCED CELL DIAGNOSTICS, INC. , WU, Xingyong , WANG, Huei-Yu Fay , SU, Nan , WANG, Li-Chong , LUO, Yuling
发明人： WU, Xingyong , WANG, Huei-Yu Fay , SU, Nan , WANG, Li-Chong , LUO, Yuling
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6841 , C12Q1/6818 , C12Q1/682 , C12Q2563/131 , C12Q2537/143 , C12Q2537/125
摘要： Disclosed is a method for in situ detection of one or more target nucleic acids based on a combination of RNAscope® method and a general ISH signal amplification method. This new method produces high signal intensity and while keeps low background noise of signal amplification. The result can be consistently reproduced and the method can be easily adopted for routine clinic diagnostic use. Further, the invention relates to a kit, comprising the components of RNAscope® assay and a general ISH signal amplification assay, for sensitive detection of one or more target nucleic acids.
摘要翻译：公开了一种基于RNA检测方法和一般ISH信号扩增方法的组合来原位检测一种或多种靶核酸的方法。这种新方法产生高信号强度，同时保持低信号放大的背景噪声。结果可以一贯重现，该方法可以方便地用于常规诊所诊断。此外，本发明涉及一种试剂盒，其包含用于灵敏检测一种或多种靶核酸的RNA检测和一般ISH信号扩增测定的组分。

3. 发明申请

WO2017066211A1 IN SITU DETECTION OF NUCLEOTIDE VARIANTS IN HIGH NOISE SAMPLES, AND COMPOSITIONS AND METHODS RELATED THERETO 审中-公开
标题翻译：原位检测高噪声样品中的核苷酸变体，以及与其相关的组合物和方法
公开(公告)号：WO2017066211A1
公开(公告)日：2017-04-20
申请号：PCT/US2016/056479
申请日：2016-10-11
申请人： ADVANCED CELL DIAGNOSTICS, INC.
发明人： LUO, Yuling , WU, Xingyong , PAN, Liuliu , WANG, Xiaoming , MA, Xiao-Jun , SU, Nan , CHEN, Steve
IPC分类号： C07H21/04 , C12M1/34 , C12Q1/68 , G01N33/53
CPC分类号： C12Q1/6841 , C12Q1/682 , C12Q1/6827 , C12Q2565/102
摘要： The invention relates to methods of in situ detection of a nucleic acid variation of a target nucleic acid in a sample, including single nucleotide variations, multi-nucleotide variations or splice sites. The method can comprise the steps of contacting the sample with a probe that detects the nucleic acid variation or splice site and a neighbor probe; contacting the sample with pre-amplifiers that bind to the nucleic acid variation probe or splice site probe and neighbor probe, respectively; contacting the sample with a collaboration amplifier that binds to the pre-amplifiers; and contacting the sample with a label probe system, wherein hybridization of the components forms a signal generating complex (SGC) comprising a target nucleic acid with the nucleic acid variation or splice site, the probes and amplifiers; and detecting in situ signal from the SGC on the sample.
摘要翻译：本发明涉及原位检测样品中靶核酸的核酸变异的方法，包括单核苷酸变异，多核苷酸变异或剪接位点。该方法可以包括以下步骤：使样品与检测核酸变异或剪接位点的探针和邻近探针接触; 使样品与分别结合核酸变异探针或剪接位点探针和相邻探针的前置放大器接触; 使样品与结合前置放大器的协作放大器接触; 并使样品与标记探针系统接触，其中组分的杂交形成包含靶核酸的信号产生复合物（SGC）与核酸变异或剪接位点，探针和放大器; 并检测来自样品上SGC的原位信号。

4. 发明申请

WO2013152295A1 DETECTION OF IMMUNOGLOBULIN LIGHT CHAIN RESTRICATION BY RNA IN SITU HYBRIDIZATION 审中-公开
标题翻译：通过RNA在原位杂交中检测免疫球蛋白轻链限制
公开(公告)号：WO2013152295A1
公开(公告)日：2013-10-10
申请号：PCT/US2013/035460
申请日：2013-04-05
申请人： ADVANCED CELL DIAGNOSTICS, INC. , THE CLEVELAND CLINIC FOUNDATION
发明人： MA, Xiao-Jun , LUO, Yuling , WANG, Hongwei , SU, Nan , TUBBS, Raymond , WANG, Zhen
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C07K16/00 , C07K2317/515 , C12Q1/6886 , C12Q2600/158
摘要： The invention provides a method for detecting immunoglobulin light chain restriction and clonality in B cells by obtaining a sample of B cells from a subject; conducting a duplex in situ hybridization assay on the sample using (i) at least one probe set which is designed to specifically hybridize to immunoglobulin kappa chain constant region (IGKCR) RNA; and (ii) at least one probe set which is designed to specifically hybridize to immunoglobulin lambda chain constant region (IGLCR) RNA; detecting signal associated with hybridized IGKCR probe and signal associated with hybridized IGLCR probe in a population of B cells in the sample; and determining a pattern of signal associated with hybridized IGKCR probe and hybridized IGLCR probe within individual cells in the B cell population, wherein the pattern of signal within individual cells indicates the presence or absence of light chain restriction and clonality of the B cells.
摘要翻译：本发明提供一种通过从受试者获得B细胞样品来检测B细胞中免疫球蛋白轻链限制和克隆性的方法; 使用（i）设计为与免疫球蛋白κ恒定区（IGKCR）RNA特异性杂交的至少一个探针组进行样品上的双链原位杂交测定; 和（ii）设计成与免疫球蛋白λ链恒定区（IGLCR）RNA特异性杂交的至少一个探针组; 检测与杂交的IGKCR探针相关的信号和与样品中B细胞群中的杂交IGLCR探针相关的信号; 以及确定在B细胞群体中的各个细胞内与杂交的IGKCR探针和杂交的IGLCR探针相关联的信号模式，其中各个细胞内的信号模式指示存在或不存在B细胞的轻链限制和克隆。

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