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    Nucleic acid sequence analysis from combined mixtures of amplified fragments
    71.
    发明授权
    Nucleic acid sequence analysis from combined mixtures of amplified fragments 有权
    来自扩增片段的组合混合物的核酸序列分析

    公开(公告)号：US08765379B2

    公开(公告)日：2014-07-01

    申请号：US13017244

    申请日：2011-01-31

    申请人： Radoje Drmanac

    发明人： Radoje Drmanac

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6874 ,  C07H21/04 ,  C07K1/047 ,  C12Q1/6806 ,  C12Q1/682 ,  C12Q1/6837 ,  C12Q1/6869 ,  C12Q2525/151 ,  C12Q2525/313 ,  C12Q2531/125 ,  C12Q2565/513 ,  G01N15/1404 ,  G01N15/1434 ,  Y10S977/778 ,  Y10S977/789 ,  Y10S977/792 ,  Y10S977/88 ,  Y10S977/882 ,  C12Q2521/307 ,  C12Q2525/161 ,  C12Q2535/122 ,  C12Q2563/179 ,  C12Q2565/514

    摘要： The invention provides methods and kits for ordering sequence information derived from one or more target polynucleotides. In one aspect, one or more tiers or levels of fragmentation and aliquoting are generated, after which sequence information is obtained from fragments in a final level or tier. Each fragment in such final tier is from a particular aliquot, which, in turn, is from a particular aliquot of a prior tier, and so on. For every fragment of an aliquot in the final tier, the aliquots from which it was derived at every prior tier is known, or can be discerned. Thus, identical sequences from overlapping fragments from different aliquots can be distinguished and grouped as being derived from the same or different fragments from prior tiers. When the fragments in the final tier are sequenced, overlapping sequence regions of fragments in different aliquots are used to register the fragments so that non-overlapping regions are ordered. In one aspect, this process is carried out in a hierarchical fashion until the one or more target polynucleotides are characterized, e.g. by their nucleic acid sequences, or by an ordering of sequence segments, or by an ordering of single nucleotide polymorphisms (SNPs), or the like.

    摘要翻译： 本发明提供了用于排序从一个或多个目标多核苷酸衍生的序列信息的方法和试剂盒。 在一个方面，产生一个或多个分层或等级的碎片和等分试样，之后从最终级别或层级的片段获得序列信息。 这样的最后一层中的每个片段都来自特定的等分试样，而这些等分试样又是来自先前层的特定等分试样，等等。 对于最后一层中的等分试样的每个片段，从每个先前的层次派生的等分试样是已知的，或者可以被辨别出来。 因此，来自不同等分试样的重叠片段的相同序列可以被区分并分组为从与先前层相同或不同的片段衍生的。 当最终层中的片段被排序时，使用不同等分试样的片段的重叠序列区域来登记片段，使得非重叠区域被排序。 在一个方面，该方法以分级方式进行，直到一个或多个目标多核苷酸被表征为例如。 通过其核酸序列，或通过序列片段的排序，或通过单核苷酸多态性（SNP）等的排序。

    METHOD FOR NUCLEIC ACID DETECTION USING VOLTAGE ENHANCEMENT
    73.
    发明申请
    METHOD FOR NUCLEIC ACID DETECTION USING VOLTAGE ENHANCEMENT 有权
    使用电压增强的核酸检测方法

    公开(公告)号：US20120122721A1

    公开(公告)日：2012-05-17

    申请号：US13337968

    申请日：2011-12-27

    申请人： Andres Fernandez ,  Bryan Staker ,  Radoje Drmanac

    发明人： Andres Fernandez ,  Bryan Staker ,  Radoje Drmanac

    IPC分类号： C40B30/04

    CPC分类号： C12Q1/6832 ,  C12Q1/6825 ,  C12Q2523/307 ,  C12Q2565/501 ,  C12Q2565/607

    摘要： Methods are provided for carrying out nucleic acid analysis, including sequence identification, employing voltage and/or controlled electric charge to enhance operation. A device comprises substrates for nucleic acid analysis, a first electrically conductive layer, a first electrically insulative layer of dielectric material on the first conductive layer, a second electrically conductive layer disposed upon the first insulative layer in a pattern to define discrete attachment sites for macromolecules on the first insulative layer, the second conductive layer provided with means for resisting affinity for the macromolecules to impede their attachment to sites on the second conductive layer, and terminals for the first and second conductive layers for applying a voltage pattern between the first and the second conductive layers to control affinity between the macromolecules and the discrete attachment sites.

    摘要翻译： 提供用于进行核酸分析的方法，包括序列鉴定，采用电压和/或受控电荷以增强操作。 一种器件包括用于核酸分析的衬底，第一导电层，第一导电层上的介电材料的第一电绝缘层，第二导电层，以图案形式设置在第一绝缘层上，以限定大分子的离散附着位点 在第一绝缘层上，第二导电层设置有用于抵抗大分子阻挡其附着于第二导电层上的部位的亲和力的装置，以及用于在第一和第二绝缘层之间施加电压图案的第一和第二导电层的端子 第二导电层以控制大分子和离散附着位点之间的亲和力。

    Nucleic acid analysis by random mixtures of non-overlapping fragments
    76.
    发明授权
    Nucleic acid analysis by random mixtures of non-overlapping fragments 有权
    通过非重叠片段的随机混合物进行核酸分析

    公开(公告)号：US07709197B2

    公开(公告)日：2010-05-04

    申请号：US11451692

    申请日：2006-06-13

    申请人： Radoje Drmanac

    发明人： Radoje Drmanac

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： C12Q1/6874 ,  C07H21/04 ,  C07K1/047 ,  C12Q1/6806 ,  C12Q1/682 ,  C12Q1/6837 ,  C12Q1/6869 ,  C12Q2525/151 ,  C12Q2525/313 ,  C12Q2531/125 ,  C12Q2565/513 ,  G01N15/1404 ,  G01N15/1434 ,  Y10S977/778 ,  Y10S977/789 ,  Y10S977/792 ,  Y10S977/88 ,  Y10S977/882 ,  C12Q2521/307 ,  C12Q2525/161 ,  C12Q2535/122 ,  C12Q2563/179 ,  C12Q2565/514

    摘要： The invention provides methods and kits for ordering sequence information derived from one or more target polynucleotides. In one aspect, one or more tiers or levels of fragmentation and aliquoting are generated, after which sequence information is obtained from fragments in a final level or tier. Each fragment in such final tier is from a particular aliquot, which, in turn, is from a particular aliquot of a prior tier, and so on. For every fragment of an aliquot in the final tier, the aliquots from which it was derived at every prior tier is known, or can be discerned. Thus, identical sequences from overlapping fragments from different aliquots can be distinguished and grouped as being derived from the same or different fragments from prior tiers. When the fragments in the final tier are sequenced, overlapping sequence regions of fragments in different aliquots are used to register the fragments so that non-overlapping regions are ordered. In one aspect, this process is carried out in a hierarchical fashion until the one or more target polynucleotides are characterized, e.g. by their nucleic acid sequences, or by an ordering of sequence segments, or by an ordering of single nucleotide polymorphisms (SNPs), or the like.

    摘要翻译： 本发明提供了用于排序从一个或多个目标多核苷酸衍生的序列信息的方法和试剂盒。 在一个方面，产生一个或多个分层或等级的碎片和等分试样，之后从最终级别或层级的片段获得序列信息。 这样的最后一层中的每个片段都来自特定的等分试样，而这些等分试样又是来自先前层的特定等分试样，等等。 对于最后一层中的等分试样的每个片段，从每个先前的层次派生的等分试样是已知的，或者可以被辨别出来。 因此，来自不同等分试样的重叠片段的相同序列可以被区分并分组为从与先前层相同或不同的片段衍生的。 当最终层中的片段被排序时，使用不同等分试样的片段的重叠序列区域来登记片段，使得非重叠区域被排序。 在一个方面，该方法以分级方式进行，直到一个或多个目标多核苷酸被表征为例如。 通过其核酸序列，或通过序列片段的排序，或通过单核苷酸多态性（SNP）等的排序。

    Efficient Shotgun Sequencing Methods
    77.
    发明申请
    Efficient Shotgun Sequencing Methods 有权
    高效霰弹枪测序方法

    公开(公告)号：US20090318304A1

    公开(公告)日：2009-12-24

    申请号：US12325922

    申请日：2008-12-01

    申请人： Radoje Drmanac ,  Clifford Reid

    发明人： Radoje Drmanac ,  Clifford Reid

    IPC分类号： C40B30/04

    CPC分类号： C12Q1/6869 ,  C12Q1/6874 ,  C12Q2549/119 ,  C12Q2537/149 ,  C12Q2565/137

    摘要： Methods are provided for efficient shotgun sequencing to allow efficient selection and sequencing of nucleic acids of interest contained in a library. The nucleic acids of interest can be defined any time before or after preparation of the library. One example of nucleic acids of interest is missing or low confidence genome sequences resulting from an initial sequencing procedure. Other nucleic acids of interest include subsets of genomic DNA, RNA or cDNAs (exons, genes, gene sets, transciptomes). By designing an efficient (simple to implement, speedy, high specificity, low cost) selection procedure, a more complete sequence is achieved with less effort than by using highly redundant shotgun sequencing in an initial sequencing procedure

    摘要翻译： 提供了有效的霰弹枪测序的方法，以允许文库中包含的感兴趣的核酸的有效选择和测序。 感兴趣的核酸可以在文库制备之前或之后的任何时间进行定义。 感兴趣的核酸的一个实例是由初始测序程序产生的缺失或低置信基因组序列。 感兴趣的其他核酸包括基因组DNA，RNA或cDNAs（外显子，基因，基因组，转录本）的子集。 通过设计一种高效（简单实施，快速，高特异性，低成本）选择程序，通过在初始测序程序中使用高度冗余的霰弹枪测序，以更少的努力实现更完整的顺序

    Methods and Compositions for Efficient Nucleic Acid Sequencing
    78.
    发明申请
    Methods and Compositions for Efficient Nucleic Acid Sequencing 审中-公开
    高效核酸测序的方法和组合

    公开(公告)号：US20080108074A1

    公开(公告)日：2008-05-08

    申请号：US11929038

    申请日：2007-10-30

    申请人： Radoje Drmanac

    发明人： Radoje Drmanac

    IPC分类号： C12Q1/68 ,  C12M1/34

    CPC分类号： C12Q1/6874

    摘要： Disclosed are novel methods and compositions for rapid and highly efficient nucleic acid sequencing based upon hybridization with two sets of small oligonucleotide probes of known sequences. Extremely large nucleic acid molecules, including chromosomes and non-amplified RNA, may be sequenced without prior cloning or subcloning steps. The methods of the invention also solve various current problems associated with sequencing technology such as, for example, high noise to signal ratios and difficult discrimination, attaching many nucleic acid fragments to a surface, preparing many, longer or more complex probes and labelling more species.

    摘要翻译： 公开了基于与已知序列的两组小寡核苷酸探针杂交的用于快速和高效核酸测序的新颖方法和组合物。 非常大的核酸分子，包括染色体和非扩增的RNA，可以在没有先前的克隆或亚克隆步骤的情况下进行测序。 本发明的方法还解决了与排序技术相关的各种当前问题，例如高噪声与信号比和困难的鉴别，将许多核酸片段连接到表面，制备许多更长或更复杂的探针并标记更多的物质 。

    Large-scale parallelized DNA sequencing
    80.
    发明申请
    Large-scale parallelized DNA sequencing 审中-公开

    公开(公告)号：US20060110764A1

    公开(公告)日：2006-05-25

    申请号：US11281188

    申请日：2005-11-16

    申请人： Tom Tang ,  Radoje Drmanac

    发明人： Tom Tang ,  Radoje Drmanac

    IPC分类号： C12Q1/68 ,  C12P19/34

    CPC分类号： C12Q1/6874 ,  C12Q2600/156 ,  C12Q2525/179 ,  C12Q2527/101 ,  C12Q2535/101 ,  C12Q2565/125 ,  C12Q2565/537

    摘要： We provide a DNA sequencing method and a sequencing system where large numbers of sequence reads can be obtained in parallel by running traditional electrophoresis in a special format. Parallelization is obtained either through a 3-dimensional gel-cube or through bundled capillary tubes including fiber-optic tubes or other types of micro channels in a bundle or matrix format. Various ways of capturing sequence traces are provided. We also provide two distinct methods for preparing genomic DNA/cDNA fragments: one through universal primer site anchoring and amplification of single molecules, and the other through micro-array/bead oligomer extension and dye-terminator incorporation using target sequence specific primers. The invention can perform large-scale genomic sequencing including sequencing a complete human genome in one or a few runs.