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1. 发明申请

WO2005113826A1 GENOTYPING OF MULTIPLE LOCI WITH PCR FOR DIFFERENT LOCI AMPLIFICATION AT DIFFERENT TEMPERATURES 审中-公开
标题翻译：用不同温度下不同位置放大PCR的多位点基因
公开(公告)号：WO2005113826A1
公开(公告)日：2005-12-01
申请号：PCT/US2005/017419
申请日：2005-05-17
申请人： BIOARRAY SOLUTIONS LTD. , YANG, Jiacheng
发明人： YANG, Jiacheng
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6881 , C07H21/04 , C12Q1/686 , C12Q2600/16 , C12Q2527/15 , C12Q2537/143 , C12Q2527/101
摘要： Disclosed is a method of performing simulltaneous PCR amplification of several designated different loci in a sample each including a different target subsequence, using a set of pairs of forward and reverse primers, wherein the pairs are complementary to target subsequences, where different primer pairs are in different reaction chambers and the sample is also present in the reaction chambers, and wherein different primer pairs have different sequences. Different reaction chambers are provided different annealing temperatures, preferably at the same time, such that the annealing temperatures selected enhance annealing conditions for the primer pairs and the target subsequences within the reaction chambers. The method allows PCR to proceed more quickly, which is important to increase throughput in a multiplexed assay, and can be particularly important for HLA-typing in a transplantation setting.
摘要翻译：公开了一种使用一组正向和反向引物对样品中的几个指定的不同基因座进行单因素PCR扩增的方法，每个含有不同的靶序列，其中该对与目标子序列互补，其中不同的引物对位于不同的反应室和样品也存在于反应室中，并且其中不同的引物对具有不同的序列。不同的反应室提供不同的退火温度，优选同时，使得所选择的退火温度增强了反应室内引物对和靶子序列的退火条件。该方法允许PCR更快地进行，这对于在多重测定中增加产量是重要的，并且对于在移植设置中的HLA分型可能是特别重要的。

2. 发明申请

WO2005006960A2 DETECTION OF CELL MEMBRANE-ASSOCIATED PROTEINS USING MEMBRANE FRAGMENTS DISPLAYED ON ENCODED MICROPARTICLE ARRAYS 审中-公开
标题翻译：用编码的微粒阵列显示膜片段检测细胞膜相关蛋白
公开(公告)号：WO2005006960A2
公开(公告)日：2005-01-27
申请号：PCT/US2004/022782
申请日：2004-07-15
申请人： BIOARRAY SOLUTIONS LTD. , SEUL, Michael , YANG, Jiacheng , TAN, Enqing
发明人： SEUL, Michael , YANG, Jiacheng , TAN, Enqing
IPC分类号： A61B
CPC分类号： G01N33/5432 , G01N33/564 , G01N33/56972 , G01N33/6854 , Y10S435/971 , Y10T436/110833
摘要： Disclosed are methods relating to cell membrane fragments associated with microbeads, so that the characteristics of the cells the fragments originated from can be determined. The fragments can be oriented with what was the outer surface of the cell membrane facing outwardly, so that the antigens associated with the membrane can be contact with ligands (including antibodies) to antigens in the membranes which would be accessible to antibodies in vivo. The system is useful, inter alia, for detection of panel reactive antibodies in donor serum, as well as detection of other cell membrane antigens; or quantitation of particular cell membrane antigens.
摘要翻译：公开了涉及与微珠相关的细胞膜片段的方法，从而可以确定片段起源于细胞的特征。片段可以用细胞膜的外表面朝外定向，使得与膜相关的抗原可以与配体（包括抗体）接触抗体在体内可接近的膜中的抗原。该系统尤其可用于检测供体血清中的组反应性抗体，以及检测其他细胞膜抗原; 或定量特定的细胞膜抗原。

3. 发明申请

WO2005045060A2 MULTIPLEXED NUCLEIC ACID ANALYSIS BY FRAGMENTATION OF DOUBLE-STRANDED DNA 审中-公开
标题翻译：通过双链DNA分解的多重核酸分析
公开(公告)号：WO2005045060A2
公开(公告)日：2005-05-19
申请号：PCT/US2004/035428
申请日：2004-10-26
申请人： BIOARRAY SOLUTIONS, LTD. , YANG, Jiacheng
发明人： YANG, Jiacheng
IPC分类号： C12Q
CPC分类号： C12Q1/6827 , C12Q2565/519 , C12Q2523/107
摘要： A method of fragmentation of double stranded DNA is disclosed for use in nucleic acid analysis, notably in the multiplexed analysis of polymorphisms and mutations. The method produces a multiplicity of labeled sense and anti-sense fragments which are not complementary, and thus do not significantly re-anneal under conditions suitable for hybridization analysis (or capture-mediated elongation analysis) of the polymorphisms and/or mutations. The fragments display a desired or predicted length distribution. Cleavage sites can be selected such that the fragments are short, yet long enough to allow discrimination among fragments in an assay, and as a matter of statistical probability, such that the majority of fragments contain at least one labeled nucleotide to facilitate detection.
摘要翻译：公开了用于核酸分析的双链DNA的断裂方法，特别是在多态性和突变的多重分析中。该方法产生多个标记的有义和反义片段，其不互补，因此在适合于多态性和/或突变的杂交分析（或捕获介导的延伸分析）的条件下不显着再退火。片段显示所需或预测的长度分布。可以选择切割位点使得片段短，但足够长以允许在测定中的片段之间的区别，并且作为统计概率，使得大多数片段含有至少一个标记的核苷酸以便于检测。

4. 发明申请

WO2005042763A2 OPTIMIZATION OF GENE EXPRESSION ANALYSIS USING IMMOBILIZED CAPTURE PROBES 审中-公开
标题翻译：使用固定捕获探针优化基因表达分析
公开(公告)号：WO2005042763A2
公开(公告)日：2005-05-12
申请号：PCT/US2004035426
申请日：2004-10-26
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , BANERJEE SUKANTA , YANG JIACHENG , VENER TATIANA
发明人： SEUL MICHAEL , BANERJEE SUKANTA , YANG JIACHENG , VENER TATIANA
IPC分类号： C12Q20060101 , C12Q1/68 , C12Q
CPC分类号： C12Q1/6832 , B01J2219/00459 , B01J2219/00576 , B01J2219/00608 , B01J2219/00648 , B01J2219/00722 , C12Q1/6809 , C12Q1/6834 , C12Q1/6837 , C12Q2537/143 , C12Q2565/501 , C12Q2565/507 , C12Q2533/101 , C12Q2565/514 , C12Q2565/519
摘要： Disclosed are methods of multiplexed analysis of oligonucleotides in a sample, including: methods of probe and target "engineering", as well as methods of assay signal analysis relating to the modulation of the probe-target affinity constant, K by a variety of factors including the elastic properties of target strands and layers of immobilized ("grafted") probes; and assay methodologies relating to: the tuning of assay signal intensities including dynamic range compression and on-chip signal amplification; the combination of hybridization-mediated and elongation-mediated detection for the quantitative determination of abundance of messages displaying a high degree of sequence similarity, including, for example, the simultaneous determination of the relative expression levels, and identification of the specific class of, untranslated AU-rich subsequences located near the 3' terminus of mRNA; and a new method of subtractive differential gene expression analysis which requires only a single color label.
摘要翻译：公开了样品中寡核苷酸多重分析的方法，包括：探针和靶标“工程”的方法，以及通过多种因素与探针 - 靶亲和常数K的调节相关的信号分析方法，包括目标链和固定（“接枝”）探针层的弹性性质; 以及与以下方法相关的测定方法：调整测定信号强度，包括动态范围压缩和片上信号放大; 杂交介导和延长介导检测的组合用于定量测定显示高度序列相似性的消息丰度，包括例如同时确定相对表达水平，以及鉴定特异性类别，未翻译位于mRNA的3'末端附近的富含子序列; 以及仅需要单一颜色标签的减法差分基因表达分析的新方法。

5. 发明申请

WO2007121018A2 PROBE DENSITY CONSIDERATIONS AND ELONGATION OF SELF-COMPLEMENTARY LOOPED PROBES WHERE PROBES ARE ATTACHED TO A SOLID PHASE 审中-公开
标题翻译：探索密集度考察和自我补充循环探测器的延伸，探头附着在固体相位
公开(公告)号：WO2007121018A2
公开(公告)日：2007-10-25
申请号：PCT/US2007/064118
申请日：2007-03-16
申请人： BIOARRAY SOLUTIONS LTD. , SEUL, Michael , ZHANG, Yi , BANARJEE, Sukanta , YANG, Jiacheng , CHAU, Chiu
发明人： SEUL, Michael , ZHANG, Yi , BANARJEE, Sukanta , YANG, Jiacheng , CHAU, Chiu
IPC分类号： C12Q1/68 , C12M3/00
CPC分类号： C12Q1/6837 , C12Q1/6818 , C12Q1/6827 , C12Q2565/1015 , C12Q2537/143 , C12Q2533/101 , C12Q2535/125 , C12Q2525/301
摘要： in a multiplexed assay method earned out in solution, wherein the solution contains nucleic acid targets and., wherein several different types of oligonucleotide probes, each type having a different sequence in a region designated as a target binding domain, are used to detect the nucleic acid targets, said assay method including a method for increasing the effective concentration of the nucleic acid targets at the surface of a bead to which the oligonucleotide probes are bound, by one or more of the following steps: adjusting assay conditions so as to increase the effective concentration of the targets available for binding to the probes, by one or more of the following: (i) selecting a particular probe density on the surface of the bead; (ii) selecting a solution having an ionic strength greater than a threshold; (ii) selecting a target domain of a size less than a threshold; or (iii) selecting target domains within a specified proximity to a terminal end of the targets.
摘要翻译：在溶液中获得的多重测定方法中，其中溶液含有核酸靶标，其中使用几个不同类型的寡核苷酸探针，每种类型在被称为靶结合结构域的区域中具有不同序列，以检测核酸所述测定方法包括通过一个或多个以下步骤增加寡核苷酸探针结合珠粒表面上的核酸靶的有效浓度的方法：调节测定条件以增加通过一种或多种以下方法有效浓度可用于结合探针的靶标：（i）在珠粒表面上选择特定的探针密度; （ii）选择具有大于阈值的离子强度的溶液; （ii）选择小于阈值的大小的目标域; 或（iii）在目标的终端的指定接近范围内选择目标域。

6. 发明申请

WO2006028987A2 NUCLEIC ACID AMPLIFICATION WITH INTEGRATED MULTIPLEX DETECTION 审中-公开
标题翻译：具有集成多重检测的核酸扩增
公开(公告)号：WO2006028987A2
公开(公告)日：2006-03-16
申请号：PCT/US2005031357
申请日：2005-09-02
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , KORZHEVA NATALIYA , YANG JIACHENG , ZHANG YI
发明人： SEUL MICHAEL , KORZHEVA NATALIYA , YANG JIACHENG , ZHANG YI
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6865 , C12Q2563/149 , C12Q2563/107 , C12Q2537/143
摘要： A method mediated with in-vitro transcription ("IVT") which permits miniaturization of multiplexed DNA and RN analysis, and in which elongation-mediated multiplexed analysis of polymorphisms (eMAP®) is used as the analysis step, is described. Also described is a method mediated with IVT is for selecting a designated strand from T7-tagged double a stranded DNA: wherein, the selected strand forms the template for RNA synthesis. In one embodiment, double stranded DNA incorporating the T7 (or other) promoter sequence at the 3' end or the 5'end is produced, for example, by amplification of genomic DNA using the Polymerase Chain Reaction (PCR). Also disclosed are nested PCR designs permitting allele analysis in combination with strand selection by IVT. Further, in one embodiment of a homogeneous format for transcription-mediated amplification and multiplexed detection (which may be particularly suited for viral or pathogen detection), encoded microparticles display "looped" capture probe configurations permitting the generation of a signal upon capture of RNA product and real-time assay monitoring.
摘要翻译：描述了使用多体DNA和RN分析进行小型化的体外转录（“IVT”）介导的方法，其中使用延长介导的多态性复合分析（eMAP）作为分析步骤。还描述了用IVT介导的用于从T7标记的双链DNA选择指定链的方法：其中所选择的链形成用于RNA合成的模板。在一个实施方案中，例如通过使用聚合酶链反应（PCR）扩增基因组DNA来产生在3'末端或5'端掺入T7（或其它）启动子序列的双链DNA。还公开了允许等位基因分析与IVT的链选择组合的巢式PCR设计。此外，在用于转录介导的扩增和多重检测（其可能特别适用于病毒或病原体检测）的均匀形式的一个实施方案中，编码的微粒显示“循环”捕获探针构型，其允许在捕获RNA产物时产生信号和实时测定监测。

7. 发明申请

WO2006130347A3 CREATION OF FUNCTIONALIZED MICROPARTICLE LIBRARIES BY OLIGONUCLEOTIDE LIGATION OR ELONGATION 审中-公开
标题翻译：通过寡核苷酸结合或延伸产生功能化的微生物图谱
公开(公告)号：WO2006130347A3
公开(公告)日：2007-11-22
申请号：PCT/US2006019203
申请日：2006-05-17
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , YANG JIACHENG , BANERJEE SUKANTA
发明人： SEUL MICHAEL , YANG JIACHENG , BANERJEE SUKANTA
IPC分类号： C12Q1/68
CPC分类号： B01J19/0046 , B01J2219/005 , B01J2219/00545 , B01J2219/00576 , B01J2219/00648 , B01J2219/00722 , B01J2219/00725 , C12N15/1093 , C40B20/04 , C40B50/14
摘要： Disclosed are methods of for constructing a bead-displayed library of oligonucleotide probes (or sequence-modified capture moieties such as protein-nucleic acid conjugates) by ligation of a capture probe, having an analyte-specific sequence, to an anchor probe that is attached, at its 5 '-end, (or possibly at the 3' end) to an encoded carrier such as a color-coded microparticle ("bead"). Such a library can also be constructed by elongation of an anchor probe, using a second probe as the elongation template, wherein the second probe has an anchor-specific subsequence and an analyte-specific subsequence.
摘要翻译：公开了通过将具有分析物特异性序列的捕获探针连接到所连接的锚定探针上来构建寡核苷酸探针（或序列修饰的捕获部分，例如蛋白质 - 核酸缀合物）的珠显示文库的方法在5'端，（或可能在3'端）与经编码的载体（如着色微粒（“珠”））相连。也可以使用第二探针作为延伸模板，通过锚定探针的伸长来构建这种文库，其中第二探针具有锚特异性亚序列和分析物特异性亚序列。

8. 发明申请

WO2005045060A3 MULTIPLEXED NUCLEIC ACID ANALYSIS BY FRAGMENTATION OF DOUBLE-STRANDED DNA 审中-公开
标题翻译：双链DNA片段复合核酸分析
公开(公告)号：WO2005045060A3
公开(公告)日：2005-07-21
申请号：PCT/US2004035428
申请日：2004-10-26
申请人： BIOARRAY SOLUTIONS LTD , YANG JIACHENG
发明人： YANG JIACHENG
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q2565/519 , C12Q2523/107
摘要： A method of fragmentation of double stranded DNA is disclosed for use in nucleic acid analysis, notably in the multiplexed analysis of polymorphisms and mutations. The method produces a multiplicity of labeled sense and anti-sense fragments which are not complementary, and thus do not significantly re-anneal under conditions suitable for hybridization analysis (or capture-mediated elongation analysis) of the polymorphisms and/or mutations. The fragments display a desired or predicted length distribution. Cleavage sites can be selected such that the fragments are short, yet long enough to allow discrimination among fragments in an assay, and as a matter of statistical probability, such that the majority of fragments contain at least one labeled nucleotide to facilitate detection.
摘要翻译：公开了用于核酸分析的双链DNA片段化方法，特别是在多态性和突变的多重分析中。该方法产生多个标记的有义和反义片段，它们不互补，因此在适合于多态性和/或突变的杂交分析（或捕获介导的延伸分析）的条件下不显着再退火。该片段显示期望的或预测的长度分布。可以选择切割位点，使得片段短而足够长以允许在测定中片段之间的区分，并且作为统计概率的问题，使得大多数片段含有至少一个标记的核苷酸以便于检测。

9. 发明申请

WO2007121018A3 PROBE DENSITY CONSIDERATIONS AND ELONGATION OF SELF-COMPLEMENTARY LOOPED PROBES 审中-公开
标题翻译：探索密度考虑和自组织循环探测的延伸
公开(公告)号：WO2007121018A3
公开(公告)日：2008-12-04
申请号：PCT/US2007064118
申请日：2007-03-16
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , ZHANG YI , BANARJEE SUKANTA , YANG JIACHENG , CHAU CHIU
发明人： SEUL MICHAEL , ZHANG YI , BANARJEE SUKANTA , YANG JIACHENG , CHAU CHIU
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6837 , C12Q1/6818 , C12Q1/6827 , C12Q2565/1015 , C12Q2537/143 , C12Q2533/101 , C12Q2535/125 , C12Q2525/301
摘要： This invention relates to a multiplexed assay method earned out in solution, wherein the solution contains nucleic aad targets and, wherein several different types of oligonucleotide probes are used to detect the nucleic acid targets The assay method includes a method for increasing the effective concentration of the nucleic acid targets at the surface of a bead to which the oligonucleotide probes are bound, by one or more of the following steps adjusting assay conditions so as to increase the effective concentration of the targets available for binding to the probes, including (?) selecting a particular probe density on the surface of the bead, (??) selecting a solution having an ionic strength greater than a threshold, (??) selecting a target domain of a size less than a threshold, or (in) selecting target domains within a specified proximity to a terminal end of the targets
摘要翻译：本发明涉及在溶液中获得的多重测定方法，其中所述溶液含有核酸靶，并且其中使用几种不同类型的寡核苷酸探针来检测所述核酸靶。所述测定方法包括增加所述核酸靶的有效浓度的方法通过一个或多个以下步骤调节测定条件以增加可用于结合探针的靶标的有效浓度，包括（？）选择的寡核苷酸探针结合的珠粒表面上的核酸靶标选择具有大于阈值的离子强度的溶液，选择小于阈值的目标区域的（Δε）选择靶区域，在目标的终端的指定接近度内

10. 发明申请

WO2006130347A2 CREATION OF FUNCTIONALIZED MICROPARTICLE LIBRARIES BY OLIGONUCLEOTIDE LIGATION OR ELONGATION 审中-公开
标题翻译：通过寡核苷酸结合或延伸产生功能化的微生物图谱
公开(公告)号：WO2006130347A2
公开(公告)日：2006-12-07
申请号：PCT/US2006/019203
申请日：2006-05-17
申请人： BIOARRAY SOLUTIONS, LTD. , SEUL, Michael , YANG, Jiacheng , BANERJEE, Sukanta
发明人： SEUL, Michael , YANG, Jiacheng , BANERJEE, Sukanta
CPC分类号： B01J19/0046 , B01J2219/005 , B01J2219/00545 , B01J2219/00576 , B01J2219/00648 , B01J2219/00722 , B01J2219/00725 , C12N15/1093 , C40B20/04 , C40B50/14
摘要： Disclosed are methods of for constructing a bead-displayed library of oligonucleotide probes (or sequence-modified capture moieties such as protein-nucleic acid conjugates) by ligation of a capture probe, having an analyte-specific sequence, to an anchor probe that is attached, at its 5 '-end, (or possibly at the 3' end) to an encoded carrier such as a color-coded microparticle ("bead"). Such a library can also be constructed by elongation of an anchor probe, using a second probe as the elongation template, wherein the second probe has an anchor-specific subsequence and an analyte-specific subsequence.
摘要翻译：公开了通过将具有分析物特异性序列的捕获探针连接到所连接的锚定探针上来构建寡核苷酸探针（或序列修饰的捕获部分，例如蛋白质 - 核酸缀合物）的珠显示文库的方法在5'端，（或可能在3'端）与经编码的载体（如着色微粒（“珠”））相连。也可以使用第二探针作为延伸模板，通过锚定探针的伸长来构建这种文库，其中第二探针具有锚特异性亚序列和分析物特异性亚序列。

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