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31. 发明授权

US5667972A Method of sequencing of genoms by hybridization of oligonucleotide probes 失效
标题翻译：通过寡核苷酸探针杂交测序基因组的方法
公开(公告)号：US5667972A
公开(公告)日：1997-09-16
申请号：US461106
申请日：1995-06-05
申请人： Radoje T. Drmanac , Radomir B. Crkvenjakov
发明人： Radoje T. Drmanac , Radomir B. Crkvenjakov
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6874 , C12Q1/6827 , Y10T436/143333
摘要： The conditions under which oligonucleotides hybridize only with entirely homologous sequences are recognized. The sequence of a given DNA fragment is read by the hybridization and assembly of positively hybridizing probes through overlapping portions. By simultaneous hybridization of DNA molecules applied as dots and bound onto a filter, representing single-stranded phage vector with the cloned insert, with about 50,000 to 100,000 groups of probes, the main type of which is (A,T,C,G)(A,T,C,G)N8(A,T,C,G), information for computer determination of a sequence of DNA having the complexity of a mammalian genome are obtained in one step. To obtain a maximally completed sequence, three libraries are cloned into the phage vector, M13, bacteriophage are used: with the 0.5 kb and 7 kbp insert consisting of two sequences, with the average distance in genomic DNA of 100 kbp. For a million bp of genomic DNA, 25,000 subclones of the 0.5 kbp are required as well as 700 subclones 7 kb long and 170 jumping subclones. Subclones of 0.5 kb are applied on a filter in groups of 20 each, so that the total number of samples is 2,120 per million bp. The process can be easily and entirely robotized for factory reading of complex genomic fragments or DNA molecules.
摘要翻译：识别寡核苷酸仅与完全同源序列杂交的条件。通过重叠部分杂交和组装阳性杂交探针来读取给定DNA片段的序列。通过作为点应用的DNA分子的同时杂交并结合到过滤器上，用克隆的插入物代表单链噬菌体载体，其具有约50,000至100,000组的探针，其主要类型是（A，T，C，G）（A，T，C，G）N8（A，T，C，G），在一个步骤中获得了具有哺乳动物基因组复杂性的DNA序列的计算机测定的信息。为了获得最大完成的序列，将三个文库克隆到噬菌体载体M13中，使用噬菌体：0.5kb和7kbp插入片段由两个序列组成，基因组DNA的平均距离为100kbp。对于一百万bp的基因组DNA，需要25,000个0.5kb的亚克隆以及7kb长的700个亚克隆和170个跳跃亚克隆。将0.5kb的亚克隆以20个组的过滤器施加，使得样品的总数为2,120个百万分之一bp。该过程可以容易且完全自动化，以便工厂读取复杂的基因组片段或DNA分子。

32. 发明授权

US5525464A Method of sequencing by hybridization of oligonucleotide probes 失效
标题翻译：通过寡核苷酸探针杂交测序的方法
公开(公告)号：US5525464A
公开(公告)日：1996-06-11
申请号：US203502
申请日：1994-02-28
申请人： Radoje T. Drmanac , Radomir B. Crkvenjakov
发明人： Radoje T. Drmanac , Radomir B. Crkvenjakov
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6874 , G06F19/22 , C12Q2600/156
摘要： The conditions under which oligonucleotide probes hybridize preferentially with entirely complementary and homologous nucleic acid targets are described. Using these hybridization conditions, overlapping oligonucleotide probes associate with a target nucleic acid. Following washes, positive hybridization signals are used to assemble the sequence of a given nucleic acid fragment. Representative target nucleic acids are applied as dots. Up to to 100,000 probes of the type (A,T,C,G)(A,T,C,G)N8(A,T,C,G) are used to determine sequence information by simultaneous hybridization with nucleic acid molecules bound to a filter. Additional hybridization conditions are provided that allow stringent hybridization of 6-10 nucleotide long oligomers which extends the utility of the invention. A computer process determines the information sequence of the target nucleic acid which can include targets with the complexity of mammalian genomes. Sequence generation can be obtained for a large complex mammalian genome in a single process.
摘要翻译：描述寡核苷酸探针优先与完全互补和同源的核酸靶物杂交的条件。使用这些杂交条件，重叠的寡核苷酸探针与靶核酸结合。洗涤后，使用阳性杂交信号来组装给定核酸片段的序列。代表性靶核酸作为点应用。（A，T，C，G）（A，T，C，G）N8（A，T，C，G）多达100,000个探针用于通过与结合核酸分子的同时杂交来确定序列信息到一个过滤器。提供额外的杂交条件，其允许6-10个核苷酸长的寡聚体的严格杂交，其延伸了本发明的效用。计算机过程确定目标核酸的信息序列，其可以包括具有哺乳动物基因组复杂性的靶标。可以在单个过程中为大型复合哺乳动物基因组获得序列产生。

33. 发明授权

US09334490B2 Methods and compositions for large-scale analysis of nucleic acids using DNA deletions 有权
标题翻译：使用DNA缺失大规模分析核酸的方法和组合物
公开(公告)号：US09334490B2
公开(公告)日：2016-05-10
申请号：US11938096
申请日：2007-11-09
申请人： Radoje T. Drmanac
发明人： Radoje T. Drmanac
IPC分类号： C12Q1/68 , C12N15/10 , C12N15/66
CPC分类号： C12N15/10 , C12N15/66
摘要： The present invention is related generally to analysis of polynucleotides, particularly polynucleotides derived from genomic DNA. The invention provides methods, compositions and systems for such analysis. Encompassed by the invention are constructs that include pairs of target sequences which are separated by a known distance in the polynucleotide from which they are derived.
摘要翻译：本发明一般涉及多核苷酸的分析，特别是衍生自基因组DNA的多核苷酸。本发明提供了用于这种分析的方法，组合物和系统。本发明所涵盖的是构建物，其包括在衍生自它们的多核苷酸中被分离已知距离的靶序列对。

34. 发明授权

US08722326B2 High throughput genome sequencing on DNA arrays 有权
标题翻译： DNA阵列上的高通量基因组测序
公开(公告)号：US08722326B2
公开(公告)日：2014-05-13
申请号：US11981661
申请日：2007-10-31
申请人： Radoje T. Drmanac , Matthew Callow , Snezana Drmanac
发明人： Radoje T. Drmanac , Matthew Callow , Snezana Drmanac
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6837 , C12Q1/6874 , C12Q2531/125 , C12Q2525/151 , C12Q2521/313
摘要： The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.
摘要翻译：本发明涉及使用分散在靶多核苷酸中的衔接子获得靶序列的核苷酸序列信息的方法和组合物。序列信息可以是新的，例如测序未知核酸，重新测序或基因分型。本发明优选地包括在多核苷酸的靶多核苷酸或片段内的间隔位置插入多个衔接子的方法。这样的衔接子可以用作使用各种测序化学品询问相邻序列的平台，例如通过引物延伸，探针连接等鉴定核苷酸的测序化学物质。在本发明中包括用于将已知衔接子序列插入靶序列的方法和组合物，使得与适配器存在连续靶序列的中断。通过对适配器的“上游”和“下游”进行排序，可以完成整个靶序列的识别。

35. 发明申请

US20090155781A1 High throughput genome sequencing on DNA arrays 有权
公开(公告)号：US20090155781A1
公开(公告)日：2009-06-18
申请号：US11981761
申请日：2007-10-31
申请人： Radoje T. Drmanac , Matthew Callow , Snezana Drmanac
发明人： Radoje T. Drmanac , Matthew Callow , Snezana Drmanac
IPC分类号： C12Q1/68 , C12N15/64
CPC分类号： C12Q1/6874 , C12N15/64 , C12N15/66 , Y10T436/143333 , C12Q2521/313 , C12Q2525/191 , C12Q2525/151 , C12Q2525/131 , C12Q2565/518 , C12Q2533/107 , C12Q2531/125
摘要： The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.

36. 发明申请

US20090118488A1 High throughput genome sequencing on DNA arrays 审中-公开
公开(公告)号：US20090118488A1
公开(公告)日：2009-05-07
申请号：US11981793
申请日：2007-10-31
申请人： Radoje T. Drmanac , Matthew Callow , Snezana Drmanac
发明人： Radoje T. Drmanac , Matthew Callow , Snezana Drmanac
IPC分类号： C07H21/04
CPC分类号： C12Q1/6874 , C12N15/64 , C12N15/66 , Y10T436/143333 , C12Q2521/313 , C12Q2525/191 , C12Q2525/151 , C12Q2525/131 , C12Q2565/518 , C12Q2533/107 , C12Q2531/125
摘要： The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.

37. 发明申请

US20080171331A1 Methods and Compositions for Large-Scale Analysis of Nucleic Acids Using DNA Deletions 审中-公开
公开(公告)号：US20080171331A1
公开(公告)日：2008-07-17
申请号：US11938106
申请日：2007-11-09
申请人： Radoje T. Drmanac
发明人： Radoje T. Drmanac
IPC分类号： C12Q1/68 , C12P21/00 , C40B50/14 , C40B50/06 , C40B40/06
CPC分类号： C12N15/10 , C12N15/66
摘要： The present invention is related generally to analysis of polynucleotides, particularly polynucleotides derived from genomic DNA. The invention provides methods, compositions and systems for such analysis. Encompassed by the invention are constructs that include pairs of target sequences which are separated by a known distance in the polynucleotide from which they are derived.

38. 发明授权

US06451996B1 Method of sequencing of genomes by hybridization of oligonucleotide probes 失效
标题翻译：通过寡核苷酸探针杂交测序基因组的方法
公开(公告)号：US06451996B1
公开(公告)日：2002-09-17
申请号：US09489421
申请日：2000-01-21
申请人： Radoje T. Drmanac , Radomir B. Crkvenjakov
发明人： Radoje T. Drmanac , Radomir B. Crkvenjakov
IPC分类号： C07H2104
CPC分类号： C12Q1/6874 , C12Q1/6827 , Y10T436/143333 , C12Q2565/518 , C12Q2525/204
摘要： The conditions under which oligonucleotides hybridize only with entirely homologous sequences are recognized. The sequence of a given DNA fragment is read by the hybridization and assembly of positively hybridizing probes through overlapping portions. By simultaneous hybridization of DNA molecules applied as dots and bound onto a filter, representing single-stranded phage vector with the cloned insert, with about 50,000 to 100,000 groups of probes, the main type of which is (A,T,C,G)(A,T,C,G)N8(A,T,C,G), information for computer determination of a sequence of DNA having the complexity of a mammalian genome are obtained in one step. To obtain a maximally completed sequence, three libraries are cloned into the phage vector, M13, bacteriophage are used: with the 0.5 kb and 7 kbp insert consisting of two sequences, with the average distance in genomic DNA of 100 kbp. For a million bp of genomic DNA, 25,000 subclones of the 0.5 kbp are required as well as 700 subclones 7 kb long and 170 jumping subclones. Subclones of 0.5 kb are applied on a filter in groups of 20 each, so that the total number of samples is 2,120 per million bp. The process can be easily and entirely robotized for factory reading of complex genomic fragments or DNA molecules.
摘要翻译：识别寡核苷酸仅与完全同源序列杂交的条件。通过重叠部分杂交和组装阳性杂交探针来读取给定DNA片段的序列。通过作为点应用的DNA分子的同时杂交并结合到过滤器上，用克隆的插入物代表单链噬菌体载体，其具有约50,000至100,000组的探针，其主要类型是（A，T，C，G）（A，T，C，G）N8（A，T，C，G），在一个步骤中获得了具有哺乳动物基因组复杂性的DNA序列的计算机测定的信息。为了获得最大完成的序列，将三个文库克隆到噬菌体载体M13中，使用噬菌体：0.5kb和7kbp插入片段由两个序列组成，基因组DNA的平均距离为100kbp。对于一百万bp的基因组DNA，需要25,000个0.5kb的亚克隆以及7kb长的700个亚克隆和170个跳跃亚克隆。将0.5kb的亚克隆以20个组的过滤器施加，使得样品的总数为2,120个百万分之一bp。该过程可以容易且完全自动化，以便工厂读取复杂的基因组片段或DNA分子。

39. 发明授权

US06309824B1 Methods for analyzing a target nucleic acid using immobilized heterogeneous mixtures of oligonucleotide probes 失效
标题翻译：使用寡核苷酸探针的固定异构混合物分析靶核酸的方法
公开(公告)号：US06309824B1
公开(公告)日：2001-10-30
申请号：US08784747
申请日：1997-01-16
申请人： Radoje T. Drmanac
发明人： Radoje T. Drmanac
IPC分类号： C12Q168
CPC分类号： C12Q1/6869 , C12Q2537/143 , C12Q2533/107 , C12Q2525/197
摘要： The present invention provides a method for detecting a target nucleic acid species including the steps of providing an array of probes affixed to a substrate and a plurality of labeled probes wherein each labeled probe is selected to have a first nucleic acid sequence which is complementary to a first portion of a target nucleic acid and wherein the nucleic acid sequence of at least one probe affixed to the substrate is complementary to a second portion of the nucleic acid sequence of the target, the second portion being adjacent to the first portion; applying a target nucleic acid to the array under suitable conditions for hybridization of probe sequences to complementary sequences; introducing a labeled probe to the array; hybridizing a probe affixed to the substrate to the target nucleic acid; hybridizing the labeled probe to the target nucleic acid; affixing the labeled probe to an adjacently hybridized probe in the array; and detecting the labeled probe affixed to the probe in the array.
摘要翻译：本发明提供了一种用于检测靶核酸物种的方法，包括以下步骤：提供固定在底物上的探针阵列和多个标记的探针，其中每个标记的探针被选择为具有与第一个核酸序列互补的第一个核酸序列靶核酸的第一部分，并且其中固定于所述底物的至少一个探针的核酸序列与所述靶的核酸序列的第二部分互补，所述第二部分与所述第一部分相邻; 在合适的条件下将靶核酸应用于探针序列与互补序列的杂交; 将标记的探针引入阵列; 将附着于底物的探针与目标核酸杂交; 将标记的探针与靶核酸杂交; 将标记的探针附着到阵列中的相邻杂交探针; 并且检测固定在阵列中的探针的标记探针。

40. 发明授权

US06268210B1 Sandwich arrays of biological compounds 失效
标题翻译：三明治阵列的生物化合物
公开(公告)号：US06268210B1
公开(公告)日：2001-07-31
申请号：US09251303
申请日：1999-02-17
申请人： Joerg Baier , Brian Hauser , Radoje T. Drmanac
发明人： Joerg Baier , Brian Hauser , Radoje T. Drmanac
IPC分类号： C12M134
CPC分类号： B82Y30/00 , B01J19/0046 , B01J2219/00542 , B01J2219/00547 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/0063 , B01J2219/00637 , B01J2219/00659 , B01J2219/00677 , B01J2219/00702 , B01J2219/00722 , B01L3/508 , B01L3/5085 , B01L9/52 , B01L2200/0689 , B01L2300/0636 , B01L2300/0822 , B01L2300/0887 , C07B2200/11 , C07H21/00 , C40B40/06 , C40B70/00
摘要： The present invention relates to spatially-addressable sandwich arrays of compounds, particularly biological compounds such as peptides and polynucleotide probes, and methods of making and using the same. The present invention also relates to a method and device for holding together the substrates of the sandwich array, more particularly, a clamping device for securely yet safely holding substrates of a sandwich array together during assembly, use, storage, and/or transport of the sandwich array.
摘要翻译：本发明涉及化合物，特别是生物化合物如肽和多核苷酸探针的空间可寻址三明治阵列，以及制备和使用它们的方法。本发明还涉及一种用于将三明治阵列的基板保持在一起的方法和装置，更具体地说，涉及一种夹紧装置，用于在组装，使用，储存和/或运输三明治阵列。

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