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1. 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。

2. 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

3. 发明申请

WO2007035893A2 MESSAGE ABUNDANCE AND ALLELE COPY NUMBER DETERMINATION USING IVT WITH SINGLE-STRANDED PRIMER-PROMOTER-SELECTOR CONSTRUCTS 审中-公开
标题翻译：消息接收和复制使用IVT与单条的PRIMER-PROMOTER-SELECTOR构造复制数字确定
公开(公告)号：WO2007035893A2
公开(公告)日：2007-03-29
申请号：PCT/US2006036889
申请日：2006-09-21
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , KORZHEVA NATALIYA
发明人： SEUL MICHAEL , KORZHEVA NATALIYA
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6837 , C12N15/1096 , C12Q1/6858 , C12Q1/6865 , C12Q1/6876 , C12Q2521/107 , C12Q2525/143 , C12Q2563/179 , C12Q2565/137 , C12Q2545/114 , C12Q2531/113
摘要： Disclosed is a single stranded primer-pronioter-selector construct comprising (in 3' to 5' orientation) a primer subsequence annealing to the target, a T7 or other promoter subsequence (the template strand), and a selector subsequence. The primer can be extended by template mediated elongation, including reverse transcription, or ligation to another oligonucleotide. The promoter sequence is oriented to direct the in-vitro transcription (IVT) opposite to that of primer extension, where the selector subsequence serves as a template for IVT. The selector is associated with the target subsequence of interest and it, and the amplified product are unique subsequences, dissimilar to other sequence present in the sample. The constructs is useful for determination of the presence and relative abundance of designated subsequences in the sample, multiplex gene expression analysis, multiplex allele counting, determination of polymorphic/mutation site, and loss of heterozygosity.
摘要翻译：公开了一种单链引物 - 发音者选择器构建体，其包含（靶向3'至5'取向）引物亚序列退火，T7或其它启动子亚序列（模板链）和选择子序列。引物可通过模板介导的延伸扩增，包括逆转录或连接至另一寡核苷酸。启动子序列被定向以引导与引物延伸相反的体外转录（IVT），其中选择子序列用作IVT的模板。选择器与感兴趣的目标子序列相关联，并且扩增产物是与样本中存在的其他序列不同的唯一子序列。该构建体可用于确定样品中指定子序列的存在和相对丰度，多重基因表达分析，多重等位基因计数，多态性/突变位点的确定和杂合性的丧失。

4. 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。

5. 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。

6. 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。

7. 发明申请

WO2004074913A2 A DYNAMICALLY CONFIGURABLE ELECTRODE FORMED OF PIXELS 审中-公开
标题翻译：形成像素的动态可配置电极
公开(公告)号：WO2004074913A2
公开(公告)日：2004-09-02
申请号：PCT/US2004005820
申请日：2004-02-14
申请人： BIOARRAY SOLUTIONS LTD , SEUL MICHAEL , ZHANG YI
发明人： SEUL MICHAEL , ZHANG YI
IPC分类号： B01L3/00 , G01N27/414 , G01N27/417 , G01N27/447 , G01N27/453 , G02F20060101 , G02F
CPC分类号： B01L3/502715 , B01J2219/00653 , B01L3/50273 , B01L3/502761 , B01L2200/0647 , B01L2200/0668 , B01L2300/0816 , B01L2300/0819 , B01L2300/089 , B01L2400/0415 , B03C5/005 , B03C5/026
摘要： A dynamically configurable electrode includes a first planar electrode and a planar array of pixels in a different plane, wherein a polarizable liquid medium (including electrolyte solutions) is to reside in the gap between electrodes. The pixels are individually addressable by a time-varying voltage, and adjacent pixels receive, at any instant in time, either the same voltage waveform or a different voltage waveform. Adjacent pixels receiving different voltage waveforms generate corresponding movement of dipolar entities, including dipolar particles, ions, or dipolar molecules in the polarizable liquid medium between the electrodes, which can in turn generate fluid flow and movement of particles suspended in the fluid along the planar array surface.
摘要翻译：动态配置电极包括第一平面电极和不同平面中的平面像素阵列，其中可极化液体介质（包括电解质溶液）驻留在电极之间的间隙中。这些像素可以通过时变电压单独寻址，并且相邻像素在任何时刻接收相同的电压波形或不同的电压波形。接收不同电压波形的相邻像素产生偶极实体的相应运动，包括在电极之间的可极化液体介质中的偶极子，离子或偶极子分子，这反过来又会沿着平面阵列产生悬浮在流体中的流体流动和运动表面。

8. 发明申请

WO2009064280A3 A TRANSFUSION REGISTRY AND EXCHANGE NETWORK 审中-公开
标题翻译：转移注册和交换网络
公开(公告)号：WO2009064280A3
公开(公告)日：2009-07-02
申请号：PCT/US2007072193
申请日：2007-11-14
申请人： BIOARRAY SOLUTIONS LTD , ZHANG YI , SEUL MICHAEL
发明人： ZHANG YI , SEUL MICHAEL
IPC分类号： A61B5/00
CPC分类号： G06Q10/00 , G06Q50/22
摘要： Disclosed is a registry for candidate transfusion donors, which invokes an inventory management policy to create and actively manage lists of candidate donors in order to minimize imbalances between demand and supply across multiple regions and across multiple categories of donors and recipients. Together with a genotyping laboratory, the registry does targeted recruitment of prospective donors who are typed for a set of genetic markers relating to clinically relevant antigens including mutations of Human Erythrocyte Antigens (HEA), genetic variants of Rh, and possibly additional antigens such as HLA and HPA. The registry monitors incoming demand for transfusion antigen genotypes, preferably stratify the demand into a set of categories representing stable subpopulations, and will apply strategies, disclosed herein, to tune the composition of candidate donor lists to match the demand, thereby avoiding excess, and unnecessary, typing of candidate donors,
摘要翻译：公布了候选人输血捐助者的登记册，该登记处援引了库存管理政策，以创建和主动管理候选人捐助者名单，以便最大限度地减少多个地区和多个捐助者和接受者之间的需求与供应之间的不平衡。与基因分型实验室一起，注册管理机构确实针对招募潜在的捐赠者，这些捐赠者是针对一系列与临床相关抗原相关的遗传标记，包括人类红细胞抗原（HEA）的突变，Rh的遗传变异体和可能的其他抗原如HLA 和HPA。注册管理机监测输血抗原基因型的输入需求，最好将需求分为一组代表稳定亚群体的类别，并将应用本文所披露的策略来调整候选捐献者名单的组成以匹配需求，从而避免过多和不必要的，候选人的打字，

9. 发明申请

WO2008051630A3 A TRANSFUSION REGISTRY AND EXCHANGE NETWORK 审中-公开
标题翻译：转移注册和交换网络
公开(公告)号：WO2008051630A3
公开(公告)日：2008-10-30
申请号：PCT/US2007067420
申请日：2007-04-25
申请人： BIOARRAY SOLUTIONS LTD , ZHANG YI , SEUL MICHAEL
发明人： ZHANG YI , SEUL MICHAEL
IPC分类号： G06F19/00 , G06F17/00
CPC分类号： G06F19/327 , G06Q30/02 , G06Q30/0202 , G06Q50/22 , G06Q50/24 , G16H40/20
摘要： Disclosed is a registry for candidate transfusion donors, which invokes an inventory management policy to create and actively manage lists of candidate donors in order to minimize imbalances between demand and supply across multiple regions and across multiple categories of donors and recipients. Together with a genotyping laboratory, the registry does targeted recruitment of prospective donors who are typed for a set of genetic markers relating to clinically relevant antigens including mutations of Human Erythrocyte Antigens (HEA), genetic variants of Rh, and possibly additional antigens such as HLA and HPA. The registry monitors incoming demand for transfusion antigen genotypes, preferably stratify the demand into a set of categories representing stable subpopulations, and will apply strategies, disclosed herein, to tune the composition of candidate donor lists to match the demand, thereby avoiding excess, and unnecessary, typing of candidate donors.
摘要翻译：公布了候选人输血捐助者的登记册，该登记处援引了库存管理政策，以创建和主动管理候选人捐助者名单，以便最大限度地减少多个地区和多个捐助者和接受者之间的需求与供应之间的不平衡。与基因分型实验室一起，注册管理机构确实针对招募潜在的捐赠者，这些捐赠者是针对一系列与临床相关抗原相关的遗传标记，包括人类红细胞抗原（HEA）的突变，Rh的遗传变异体和可能的其他抗原如HLA 和HPA。注册管理机监测输血抗原基因型的输入需求，最好将需求分为一组代表稳定亚群体的类别，并将应用本文所披露的策略来调整候选捐献者名单的组成以匹配需求，从而避免过多和不必要的，候选人捐款人的打字。

10. 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。

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