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1. 发明申请

WO2005006960A3 DETECTION OF CELL MEMBRANE-ASSOCIATED PROTEINS USING MEMBRANE FRAGMENTS DISPLAYED ON ENCODED MICROPARTICLE ARRAYS 审中-公开
标题翻译：使用在编码的微阵列上显示的膜片段检测细胞膜相关蛋白
公开(公告)号：WO2005006960A3
公开(公告)日：2005-06-30
申请号：PCT/US2004022782
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： A61B20060101 , C12M1/34 , C12Q1/68 , G01N33/53 , G01N33/543 , G01N33/564 , G01N33/567 , G01N33/569 , G01N33/68
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：公开了与微珠相关的细胞膜片段相关的方法，从而可以确定片段起源的细胞的特征。片段可以被定向为细胞膜的外表面面向外，使得与膜相关的抗原可与配体（包括抗体）接触，这些抗体可以在体内可被抗体接近。该系统尤其用于检测供者血清中的抗体反应性抗体，以及其他细胞膜抗原的检测; 或定量的特定细胞膜抗原。

2. 发明申请

WO2005029705A3 NUMBER CODING FOR IDENTIFICATION OF SUBTYPES OF CODED TYPES OF SOLID PHASE CARRIERS 审中-公开
标题翻译：编号固定相载波编码类型的编号编号
公开(公告)号：WO2005029705A3
公开(公告)日：2005-09-01
申请号：PCT/US2004030499
申请日：2004-09-17
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , CHAU CHIU , TAN ENQING
发明人： SEUL MICHAEL , CHAU CHIU , TAN ENQING
IPC分类号： C12Q1/68 , G01N33/48 , G01N33/50 , G01N33/543 , G01N33/68 , H03M20060101
CPC分类号： G01N33/6845 , G01N33/543 , G01N33/54313 , G01N33/564
摘要： Disclosed is number coding of pairs ("doublets") or small sets ("multiplets") of solid phase carriers provides distinguishable subtypes of a given type of such carriers, where each carrier type is distinguishable on the basis of a C-code. Such number coding is useful for augmenting a coding system, such as a color code, and thereby effectively multiplying the number of "colors" (distinguishable sub-types). It can be applied, for example, in multiplexed nucleic acid or protein analysis.
摘要翻译：公开了固相载波的对（“双”）或小集（“多重”）的数字编码提供给定类型的这种载波的可区分的子类型，其中每个载波类型可以基于C码进行区分。这种数字编码对于增加诸如颜色代码的编码系统是有用的，从而有效地乘以“颜色”的数量（可区分的子类型）。它可以应用于例如多重核酸或蛋白质分析中。

3. 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。

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

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。

6. 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

7. 发明申请

WO2006047471A3 A METHOD OF NUCLEIC ACID TYPING FOR SELECTING REGISTERED DONORS FOR CROSS-MATCHING TO TRANSFUSION RECIPIENTS 审中-公开
标题翻译：一种用于选择用于与输送接收器进行交叉匹配的注册仪表的核酸类型的方法
公开(公告)号：WO2006047471A3
公开(公告)日：2006-12-07
申请号：PCT/US2005038296
申请日：2005-10-24
申请人： BIOARRAY SOLUTIONS LTD , REID MARION E , SEUL MICHAEL , HASHMI GHAZALA , PIERCE MICHAEL
发明人： REID MARION E , SEUL MICHAEL , HASHMI GHAZALA , PIERCE MICHAEL
IPC分类号： C12Q1/68 , C12N15/12
CPC分类号： C12Q1/6881 , C12Q2600/156 , C12Q2600/16
摘要： Disclosed are a method and an algorithm for genetic cross-matching based on the comparison of recipient and donor genotypes - and the underlying combinations of alleles and haplotypes. The method of the invention, rather than focusing on phenotype prediction, instead relies on a comparison of genetic variants identified in the recipient and available donors, whose information preferably will be compiled in a widely available donor registry, to maximize molecular compatibility. The genotypes can be matched based on the weighted clinical significance of a genotypic difference between donor and recipient, such that certain mismatches are more acceptable than others.
摘要翻译：公开了基于受体和供体基因型的比较以及等位基因和单元型的潜在组合的遗传交叉匹配的方法和算法。本发明的方法而不是侧重于表型预测，而是依赖于在接受者和可用供体中鉴定的遗传变异体的比较，其信息优选地将在广泛可用的供体登记册中编译，以最大化分子相容性。可以基于供体和受体之间的基因型差异的加权临床意义来匹配基因型，使得某些错配比其他错配更可接受。

8. 发明申请

WO2006017473A3 AUTOMATED ANALYSIS OF MULTIPLEXED PROBE-TRAGET INTERACTION PATTERNS: PATTERN MATCHING AND ALLELE IDENTIFICATION 审中-公开
标题翻译：多路复用探测器相互作用模式的自动分析：图形匹配和可识别
公开(公告)号：WO2006017473A3
公开(公告)日：2007-04-12
申请号：PCT/US2005027359
申请日：2005-08-02
申请人： BIOARRAY SOLUTIONS LTD , XIONGWU XIA , SEUL MICHAEL
发明人： XIONGWU XIA , SEUL MICHAEL
IPC分类号： C12Q1/68 , G01N33/48
CPC分类号： C12Q1/6827 , G06F19/18 , G06F19/22
摘要： Disclosed are methods and algorithms (and their implementation) supporting the automated analysis and interactive review and refinement ("redaction") of the analysis within an integrated software environment, for automated allele assignments. The implementation, preferably with a software system and a program referred to as the Automated Allele Assignment ("AAA") program, provides a multiplicity of functionalities including: data management by way of an integrated interface to a portal a database to permit visualizing, importing, exporting and creating customizable summery reports; system configuration ("Set-up") including user authorization, training set analysis and probe masking; Pattern Analysis including string matching and probe flipping; and Interactive Redaction combining real-time database computations and "cut-andpaste" editing, generating "warning" statements and supporting annotation. It also includes a thresholding function, a method of setting thresholds, a method of refining thresholds by matching an experimental binary string ("reaction pattern") setting for that probe, probe masking of signals produced by probes which do not contribute significantly to discriminating among alleles.
摘要翻译：公开的方法和算法（及其实现）支持在集成软件环境中进行自动化等位基因分配的自动化分析和交互式审查和细化（“编辑”）分析。该实施方案优选地使用称为自动等位基因分配（“AAA”）程序的软件系统和程序提供了多种功能，包括：通过与门户的集成接口进行数据管理数据库以允许可视化，导入出口创造可定制的夏季报告; 系统配置（“设置”），包括用户授权，训练集分析和探测屏蔽; 模式分析包括字符串匹配和探针翻转; 和Interactive Redaction结合实时数据库计算和“剪切和粘贴”编辑，生成“警告”语句和支持注释。它还包括阈值功能，设置阈值的方法，通过匹配用于该探针的实验二进制串（“反应模式”）设置来精确化阈值的方法，探针对由探针产生的信号进行探针掩蔽，所述探针不对显着区别于等位基因。

9. 发明申请

WO2005045059A3 ALLELE ASSIGNMENT AND PROBE SELECTION IN MULTIPLEXED ASSAYS OF POLYMORPHIC TARGETS 审中-公开
标题翻译：多态目标综合分析中的全局指派和探针选择
公开(公告)号：WO2005045059A3
公开(公告)日：2005-09-09
申请号：PCT/US2004035427
申请日：2004-10-26
申请人： BIOARRAY SOLUTIONS LTD , XIA XIONGWU , SEUL MICHAEL
发明人： XIA XIONGWU , SEUL MICHAEL
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6832 , G06F19/18 , G06F19/20 , G06F19/22 , C12Q2537/143 , C12Q2535/131 , C12Q2537/165
摘要： A method to select a set of probes for multiplexed hybridization analysis of genes with multiple polymorphic regions, which minimizes ambiguities (where the assay results can correspond with more than one allele combination) by one or more of several methods, including: eliminating probes which generate ambiguities; setting a threshold such that only probe-target interactions above the threshold are considered as positive; selectively adding probes until ambiguities are eliminated.
摘要翻译：选择一组探针用于多重多态性区域基因的多重杂交分析的方法，其通过几种方法中的一种或多种方法使歧义性最小化（其中化验结果可以对应于多于一种等位基因组合），所述方法包括：消除产生探针模糊性; 设置阈值，使得只有阈值以上的探针 - 目标相互作用被认为是正面的; 有选择地添加探针直到消除歧义。

10. 发明申请

WO2005010200A3 CONCURRENT OPTIMIZATION IN SELECTION OF PRIMER AND CAPTURE PROBE SETS FOR NUCLEIC ACID ANALYSIS 审中-公开
标题翻译：选择核酸分析初始化和捕获探针组的同时优化
公开(公告)号：WO2005010200A3
公开(公告)日：2005-08-25
申请号：PCT/US2004022781
申请日：2004-07-15
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , VENER TATIANA , XIA XIONGWU
发明人： SEUL MICHAEL , VENER TATIANA , XIA XIONGWU
IPC分类号： C12Q20060101 , C12Q1/68 , G01N33/48
CPC分类号： C12Q1/6876 , C12Q2600/16 , G06F19/20 , G06F19/22
摘要： Disclosed is a method of iteratively optimizing two (or more) interrelated sets of probes for the multi-step analysis of sets of designated sequences, each such sequence requiring, for conversion, at least one conversion probe ("primer"), and each converted sequence requiring, for detection, at least one capture probe. The iterative method disclosed herein for the concurrent optimization of primer and probe selection invokes fast logical string matching functions to perform a complete cross-correlation of probe sequences and target sequences. The score function assigns to each probe-target alignment a "degree of matching" score on the basis of position weighted Hamming distance functions introduced herein. Pairs of probes in the final selection may differ in several positions, while other pairs of probes may differ in only a single position. Not all such positions are of equal importance, and a score function is introduced, reflecting the position of the mismatch within the probe sequence.
摘要翻译：公开了一种迭代优化两个（或多个）相互关联的探针组的方法，用于多步分析指定序列组，每个这样的序列需要用于转化的至少一个转化探针（“引物”），并且每个转化用于检测至少一个捕获探针的序列。本文公开的用于并行优化引物和探针选择的迭代方法调用快速逻辑串匹配函数以执行探针序列和靶序列的完全互相关。得分函数根据本文介绍的位置加权汉明距离函数将每个探针 - 目标对齐分配给“匹配度”。最终选择中的一对探针在几个位置可能有所不同，而其他探针对只能在一个位置上不同。并不是所有这样的位置都是同等重要的，并且引入了分数函数，反映了探针序列内不匹配的位置。

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