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1. 发明申请

WO2020092796A1 METHODS FOR DIGITAL MULTIPLEXING OF NUCLEIC ACIDS IN SITU 审中-公开
公开(公告)号：WO2020092796A1
公开(公告)日：2020-05-07
申请号：PCT/US2019/059204
申请日：2019-10-31
申请人： ADVANCED CELL DIAGNOSTICS, INC.
发明人： MA, Xiao-Jun , PARK, Emily , CHEN, Shiping
IPC分类号： C12Q1/68
摘要： The invention relates to methods of multiplex detection of a plurality of target nucleic acids using combinations of labels by contacting a sample comprising a cell comprising a plurality of target nucleic acids with a set of probes, wherein the set of probes comprises subsets of probes comprising a plurality detectable labels that provide unique labeling of each target nucleic acid, wherein each probe subset comprises one or more distinct labels, wherein the number and/or combination of distinct labels is unique for each target nucleic acid; and detecting the detectable labels bound to the respective target nucleic acids. The invention also relates to samples, slides and kits for multiplex detection of target nucleic acids.

2. 发明申请

WO2014160949A1 DIFFERENTIATION BETWEEN TRANSIENT AND PERSISTENT HIGH RISK HPV INFECTION BY IN SITU HYBRIDIZATION 审中-公开
标题翻译：瞬态和高危HPV感染之间的差异在原位杂交
公开(公告)号：WO2014160949A1
公开(公告)日：2014-10-02
申请号：PCT/US2014/032195
申请日：2014-03-28
申请人： ADVANCED CELL DIAGNOSTICS, INC.
发明人： MA, Xiao-Jun , WANG, Hongwei , WU, Xingyong , LUO, Yuling
IPC分类号： C12Q1/70 , G01N33/53
CPC分类号： C12Q1/708 , C12Q2600/112 , C12Q2600/118 , G01N2333/025
摘要： The invention relates to methods of categorizing a cervical tissue or cytology sample by performing an in situ hybridization assay using an antisense E6 or E7 probe on a cervical tissue sample, wherein the antisense E6 or E7 probe can simultaneously detect HPV DNA and HPV RNA; detecting the presence of HPV nucleic acid; and categorizing the cervical tissue sample based on HPV nucleic acid expression.
摘要翻译：本发明涉及通过使用宫颈组织样品上的反义E6或E7探针进行原位杂交测定来对宫颈组织或细胞学样品进行分类的方法，其中反义E6或E7探针可以同时检测HPV DNA和HPV RNA; 检测HPV核酸的存在; 并根据HPV核酸表达对宫颈组织样品进行分类。

3. 发明申请

WO2011094669A1 METHODS OF IN SITU DETECTION OF NUCLEIC ACIDS 审中-公开
标题翻译：现场检测核酸的方法
公开(公告)号：WO2011094669A1
公开(公告)日：2011-08-04
申请号：PCT/US2011/023126
申请日：2011-01-31
申请人： ADVANCED CELL DIAGNOSTICS, INC. , LUO, Yuling , FLANAGAN, John, James , CHEN, Shiping , WANG, Huei-yu, Fay
发明人： LUO, Yuling , FLANAGAN, John, James , CHEN, Shiping , WANG, Huei-yu, Fay
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C12Q1/6841 , C12Q2600/158 , C12Q2565/626 , C12Q2545/114
摘要： Methods of detecting the presence or absence of a class of nucleic acid targets in single cells through direct or indirect capture of labels to the nucleic acids are provided, where such labels to the class of nucleic acid targets are indistinguishable from each other. Also described are methods of detecting individual cells, particularly a cell of a specific type from large heterogeneous cell populations, through detection of one or more of nucleic acid targets, where the labels to the one or more of nucleic acid targets are indistinguishable from each other. Related kits are also described.
摘要翻译：提供了通过对核酸直接或间接捕获标记来检测单细胞中一类核酸靶的存在或不存在的方法，其中与核酸靶标类别的这种标记彼此不可区分。还描述了通过检测一个或多个核酸靶标来检测单个细胞，特别是来自大异质细胞群体的特定类型的细胞的方法，其中一个或多个核酸靶标的标记彼此不可区分。还介绍了相关工具包。

4. 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。

5. 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。

6. 发明申请

WO2012040168A3 BIOMARKERS FOR DIFFERENTIATING MELANOMA FROM BENIGN NEVUS IN THE SKIN 审中-公开
标题翻译：生物标志物用于鉴别皮肤良性黑色素瘤中的黑色素瘤
公开(公告)号：WO2012040168A3
公开(公告)日：2012-07-12
申请号：PCT/US2011052305
申请日：2011-09-20
申请人： ADVANCED CELL DIAGNOSTICS INC , MA XIAO-JUN , WU XINGYONG , LUO YULING
发明人： MA XIAO-JUN , WU XINGYONG , LUO YULING
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/158 , C12Q2600/16
摘要： Disclosed is a method for diagnosing melanoma in a human subject, as well as a method for providing a prognosis to a human subject who is at risk of developing melanoma recurrence, and a method for determining the stage of melanoma in a human subject, comprising the step of determining the level of expression of phosphatase and actin regulator 1 (PHACTR1) gene, or fragments thereof, either alone or in combination with the level of expression of secreted integrin-binding phosphoprotein (SPP1), preferentially expressed antigen in melanoma (PRAME), growth differentiation factor 15 (GDF15), and chemokine C-X-C motif ligand 10 (CXCL10) genes. Further, the invention relates to a diagnostic kit, comprising at least one substance for detection of the expression of PHACTR1, or fragments thereof, either alone or in combination with the detection of SPP1, PRAME, GDF15, and CXCL10, for the diagnosis or prognosis of melanoma.
摘要翻译：本发明公开了一种用于诊断人类受试者中黑素瘤的方法，以及一种用于对处于发展中的黑素瘤复发风险的人类受试者提供预后的方法以及一种用于确定受试者中黑素瘤阶段的方法，该方法包括步骤：单独测定磷酸酶和肌动蛋白调节因子1（PHACTR1）基因或其片段的表达水平，或者与分泌的整联蛋白结合磷蛋白（SPP1）的表达水平组合，优先在黑素瘤中表达的抗原（PRAME），生长分化因子15（GDF15）和趋化因子CXC基序配体10（CXCL10）基因。此外，本发明涉及诊断试剂盒，其包含至少一种用于检测PHACTR1或其片段的表达的至少一种物质，其单独或与检测SPP1，PRAME，GDF15和CXCL10组合用于诊断或预后黑色素瘤。

7. 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。

8. 发明申请

WO2012103414A3 RNASCOPE® HPV ASSAY FOR DETERMINING HPV STATUS IN HEAD AND NECK CANCERS AND CERVICAL LESIONS 审中-公开
标题翻译：用于确定头颈部和颈部癌症和宫颈癌HPV状态的RNASCOPE®HPV测定
公开(公告)号：WO2012103414A3
公开(公告)日：2012-10-11
申请号：PCT/US2012022856
申请日：2012-01-27
申请人： ADVANCED CELL DIAGNOSTICS INC , MA XIAO-JUN , FLANAGAN JOHN , LUO YULING
发明人： MA XIAO-JUN , FLANAGAN JOHN , LUO YULING
IPC分类号： C12Q1/68 , C12Q1/70
CPC分类号： C12Q1/708 , C12Q1/6841 , C12Q1/6886 , C12Q2600/112 , C12Q2600/118
摘要： The present invention provides a method and a kit for determining whether a head and neck cancer is HPV-related. In one embodiment, an RNAscope® HPV assay was designed to detect the presence of E6/E7 mRNA of certain high-risk HPV subtypes related to head and neck cancer. The present invention also provides a method and a kit for determining whether a cervical lesion is a benign lesion or a cervical intraepithethial neoplasm lesion. In one embodiment, an RNAscope® HPV assay was designed to detect the presence of E6/E7 mRNA of certain high-risk HPV subtypes related to cervical cancer. The present invention further provides a method for determining the progression of cervical intraepithethial neoplasm based on the spatial pattern and levels of the E6/E7 mRNA of certain high-risk HPV subtypes. The present invention also provides a method for determining the risk of developing cervical cancer in a human diagnosed with cervical intraepithethial neoplasm based on presence and absence of the certain subgroups of high-risk HPV subtypes.
摘要翻译：本发明提供了一种用于确定头颈癌是否与HPV相关的方法和试剂盒。在一个实施方案中，设计了RNA检测HPV检测来检测某些与头颈癌相关的高危HPV亚型的E6 / E7 mRNA的存在。本发明还提供了一种用于确定子宫颈病变是否是良性病变或子宫颈上皮内肿瘤病变的方法和试剂盒。在一个实施方案中，设计了RNA检测HPV检测来检测与子宫颈癌相关的某些高危HPV亚型的E6 / E7 mRNA的存在。本发明还提供了一种基于某些高风险HPV亚型的E6 / E7 mRNA的空间格局和水平来确定子宫颈上皮内肿瘤进展的方法。本发明还提供了一种基于存在和不存在某些亚型的高风险HPV亚型的方法来确定诊断为宫颈上皮内瘤的人的宫颈癌发生风险的方法。

9. 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。

10. 发明申请

WO2012040168A2 BIOMARKERS FOR DIFFERENTIATING MELANOMA FROM BENIGN NEVUS IN THE SKIN 审中-公开
标题翻译：用于从皮肤中的新陈代谢来分化MELANOMA的生物标记物
公开(公告)号：WO2012040168A2
公开(公告)日：2012-03-29
申请号：PCT/US2011/052305
申请日：2011-09-20
申请人： ADVANCED CELL DIAGNOSTICS, INC. , MA, Xiao-Jun , WU, Xingyong , LUO, Yuling
发明人： MA, Xiao-Jun , WU, Xingyong , LUO, Yuling
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/158 , C12Q2600/16
摘要： Disclosed is a method for diagnosing melanoma in a human subject, as well as a method for providing a prognosis to a human subject who is at risk of developing melanoma recurrence, and a method for determining the stage of melanoma in a human subject, comprising the step of determining the level of expression of phosphatase and actin regulator 1 (PHACTR1) gene, or fragments thereof, either alone or in combination with the level of expression of secreted integrin-binding phosphoprotein (SPP1), preferentially expressed antigen in melanoma (PRAME), growth differentiation factor 15 (GDF15), and chemokine C-X-C motif ligand 10 (CXCL10) genes. Further, the invention relates to a diagnostic kit, comprising at least one substance for detection of the expression of PHACTR1, or fragments thereof, either alone or in combination with the detection of SPP1, PRAME, GDF15, and CXCL10, for the diagnosis or prognosis of melanoma.
摘要翻译：公开了一种用于诊断人类受试者中的黑素瘤的方法，以及用于对患有黑色素瘤复发风险的人类受试者提供预后的方法，以及用于确定人类受试者的黑色素瘤阶段的方法，包括单独或与分泌的整联蛋白结合磷蛋白（SPP1）的表达水平相结合的磷酸酶和肌动蛋白调节剂1（PHACTR1）基因或其片段的表达水平的测定步骤，优先表达黑素瘤抗原（PRAME），生长分化因子15（GDF15）和趋化因子CXC基序配体10（CXCL10）基因。此外，本发明涉及一种诊断试剂盒，其包含至少一种用于检测PHACTR1或其片段的表达的物质，或者与检测SPP1，PRAME，GDF15和CXCL10一起或与SPP1，PRAME，GDF15和CXCL10的检测结合用于诊断或预后的黑色素瘤。

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