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41. 发明授权

US06447724B1 DNA sequencing using multiple fluorescent labels being distinguishable by their decay times 有权
标题翻译：使用多个荧光标记的DNA测序可通过其衰变时间来区分
公开(公告)号：US06447724B1
公开(公告)日：2002-09-10
申请号：US09213297
申请日：1998-12-15
申请人： Morten Jensen , J. Wallace Parce
发明人： Morten Jensen , J. Wallace Parce
IPC分类号： G01N1506
CPC分类号： G01N15/06 , B01L3/5027 , C12Q1/6869 , G01N21/6408 , G01N2015/0693 , G01N2021/6413 , G01N2021/6441 , C12Q2561/12 , C12Q2565/629
摘要： A method is provided for identifying components of a mixture by labeling the individual components with fluorescent agents having different fluorescence lifetimes. The components are subsequently separated, fluorescent labels detected and their lifetimes measured. Based on the measured fluorescent lifetimes, the components of mixtures of small organic molecules, polymers, peptides, saccharides and nucleic acids can be identified.
摘要翻译：提供了通过用具有不同荧光寿命的荧光剂标记各个组分来鉴定混合物组分的方法。随后分离组分，检测荧光标记物并测定其寿命。基于测量的荧光寿命，可以鉴定小有机分子，聚合物，肽，糖和核酸的混合物的组分。

42. 发明申请

US20010055773A1 Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction 有权
标题翻译：通过核酸配体 - 配体信标相互作用均匀检测靶
公开(公告)号：US20010055773A1
公开(公告)日：2001-12-27
申请号：US09907074
申请日：2001-07-17
申请人： Gilead Sciences, Inc.
发明人： Sumedha Jayasena , Larry Gold
IPC分类号： C12Q001/68
CPC分类号： C07H21/00 , C12Q1/6818 , C12Q1/682 , Y10T436/143333 , C12Q2561/12 , C12Q2537/101
摘要： A homogeneous assay that utilizes molecular beacons as the reporter and nucleic acid ligands as the sensor is described. This assay, called the ligand beacon assay, is for the detection of target molecules in a test mixture. The concept of the ligand beacon assay was tested using several proteins to which high affinity and specific nucleic acid ligands are available. The assay specifically detects the molecular target that binds the nucleic acid ligand with high affinity and specificity. The range of the assay is dictated by the concentration of the nucleic acid ligand/ligand beacon pair used in the assay. Target proteins were detected in buffer as well as in plasma, expanding its applicability to clinical use. This is a simple to use and fast assay format with the potential for automation for high throughput screening applications.
摘要翻译：描述了使用分子信标作为报告物和核酸配体作为传感器的均一测定法。称为配体信标测定的该测定法用于检测测试混合物中的靶分子。使用高亲和性和特异性核酸配体可用的几种蛋白质来测试配体信标测定的概念。该测定法以高亲和力和特异性特异性检测结合核酸配体的分子靶标。测定的范围由测定中使用的核酸配体/配体信标对的浓度决定。在缓冲液和血浆中检测到靶蛋白，扩大其临床应用范围。这是一种易于使用和快速测定的方法，具有高通量筛选应用的自动化潜力。

43. 发明公开

US20240279721A1 HIGHLY STABLE AND SPECIFIC MOLECULAR BEACONS ENCAPSULATED IN CATIONIC LIPOPLEX NANOPARTICLES AND APPLICATION THEREOF 审中-公开
公开(公告)号：US20240279721A1
公开(公告)日：2024-08-22
申请号：US18350566
申请日：2023-07-11
申请人： Spot Biosystems Ltd.
发明人： Ly James LEE , Jiaming HU , Kwang Joo KWAK
IPC分类号： C12Q1/6827 , C12Q1/6818 , C12Q1/6886
CPC分类号： C12Q1/6827 , C12Q1/6818 , C12Q1/6886 , C12N2310/141 , C12N2310/3517 , C12N2310/531 , C12Q2561/12 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/178
摘要： The present invention discloses a method of detecting the presence of mutated genes, mRNAs or microRNAs in a subject. The method comprises the following steps: (1) Provide a body fluid sample containing cells, circulating tumor cells (CTCs), and/or extracellular vesicles (EVs); and use an analyzer having overhang molecular beacons to measure fluorescence signals generated by interactions between the body fluid sample and the overhang molecular beacons, so as to detect the presence of the mutated genes, mRNAs or microRNA. Furthermore, a biochip comprising a gold coating substrate and tethered lipoplex nanoparticles encapsulating the overhang molecular beacons is also provided in the invention.

44. 发明申请

US20160168633A1 APPARATUS AND METHODS FOR KINETIC ANALYSIS AND DETERMINATION OF NUCLEIC ACID SEQUENCES 审中-公开
标题翻译：用于动力学分析和核酸序列测定的装置和方法
公开(公告)号：US20160168633A1
公开(公告)日：2016-06-16
申请号：US15009246
申请日：2016-01-28
申请人： Illumina, Inc.
发明人： Michael Previte , Molly He , Rigo Pantoja , Cheng-Yao Chen , Chunhong Zhou
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12Q1/6869 , C12Q2537/149 , C12Q2561/12 , C12Q2565/518 , C12Q2565/537
摘要： A system for determining nucleic acid sequences, including (a) an array of nucleic acid features; (b) a fluidic apparatus configured to deliver sequencing reagents, including polymerases and nucleotides, to the array; (c) a detector configured to obtain pre-equilibrium kinetic measurements from the array at a resolution that distinguishes individual nucleic acid features; (d) a control module having instructions for (i) directing the fluidic apparatus to deliver the sequencing reagents to the array, and (ii) directing the detection apparatus to obtain the kinetic measurements; and (e) an analysis module having instructions for (i) processing the kinetic measurements to determine binding of the polymerase molecules to the nucleic acid features at several pre-equilibrium time points, thereby determining a transient state of the polymerase molecules at the nucleic acid features, and (ii) identifying nucleic acid features that correctly incorporate the nucleotide molecules based on the transient state of the polymerase molecules.
摘要翻译：一种用于测定核酸序列的系统，包括（a）核酸特征阵列; （b）流体装置，其配置为将测序试剂（包括聚合酶和核苷酸）递送到阵列; （c）检测器，被配置为以区分各个核酸特征的分辨率从阵列获得预平衡动力学测量; （d）控制模块，其具有用于（i）引导流体装置将测序试剂递送到阵列的指令，以及（ii）引导检测装置获得动力学测量; 和（e）具有以下指令的分析模块：（i）处理动力学测量以在几个预平衡时间点确定聚合酶分子与核酸特征的结合，从而确定核酸处的聚合酶分子的瞬态特征，和（ii）鉴定基于聚合酶分子的瞬态的正确掺入核苷酸分子的核酸特征。

45. 发明授权

US09279154B2 Apparatus and methods for kinetic analysis and determination of nucleic acid sequences 有权
标题翻译：用于核酸序列的动力学分析和测定的装置和方法
公开(公告)号：US09279154B2
公开(公告)日：2016-03-08
申请号：US13722979
申请日：2012-12-20
申请人： ILLUMINA, INC.
发明人： Michael Previte , Molly He , Rigo Pantoja , Cheng-Yao Chen , Chunhong Zhou
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , C12Q1/6869 , C12Q2537/149 , C12Q2561/12 , C12Q2565/518 , C12Q2565/537
摘要： A method of distinguishing nucleotide sequences for different nucleic acid molecules including the steps of (a) mixing a plurality of different nucleic acid molecules with polymerase molecules and nucleotide molecules, wherein the different nucleic acid molecules are attached to a surface in the form of an array of nucleic acid features; (b) determining a transient state of the polymerase molecules at the nucleic acid features; and (c) identifying a subset of nucleic acid features that correctly incorporate the nucleotide molecules based on the transient state of the polymerase molecules at the nucleic acid features, thereby distinguishing the nucleotide sequences for the different nucleic acid molecules.
摘要翻译：区分不同核酸分子的核苷酸序列的方法，包括以下步骤：（a）将多种不同的核酸分子与聚合酶分子和核苷酸分子混合，其中不同的核酸分子以阵列的形式附着在表面上的核酸特征; （b）确定聚合酶分子在核酸特征处的瞬时状态; 和（c）鉴定核酸特征的子集，其核酸分子基于聚合酶分子在核酸特征处的瞬时状态正确地掺入，从而区分不同核酸分子的核苷酸序列。

46. 发明授权

US09194007B2 Double-stranded probes for the fluorescent detection of nucleic acids 有权
标题翻译：用于核酸荧光检测的双链探针
公开(公告)号：US09194007B2
公开(公告)日：2015-11-24
申请号：US12445099
申请日：2007-10-12
申请人： Typhaine Dagland , Francois Rieunier
发明人： Typhaine Dagland , Francois Rieunier
IPC分类号： C07H21/04 , G01N33/542 , G01N33/533 , G01N33/53 , G01N21/76 , G01N21/00 , G01N33/566 , C12Q1/68 , C12M1/36 , C12M1/34 , C12P7/12 , C12Q1/70
CPC分类号： C12Q1/706 , C12Q1/6818 , C12Q1/6844 , C12Q1/703 , Y02A50/59 , C12Q2565/525 , C12Q2537/161 , C12Q2525/161 , C12Q2561/12 , C12Q2561/113 , C12Q2531/113
摘要： The present invention relates to a double-stranded probe intended for the fluorescent detection of at least one single-stranded or double-stranded target nucleic acid, comprising: —a first strand of formula X1-(L1)a-S1-S′1-(L′1)b-Y1 intended for the detection of a first strand of the target nucleic acid which comprises a sequence of formula T′1-T1; —a second strand of formula X2-(L2)c-S2-S′2-(L′2)d-Y2 intended for the detection of a second strand of the target nucleic acid, if present, the second strand of the target nucleic acid comprising a sequence of formula T′2-T2; wherein two of X1, X2, Y1, and Y2 represent a fluorescent donor, while the two others represent a fluorescent acceptor, and X1 and Y2 can not both represent a fluorescent donor.
摘要翻译：本发明涉及用于荧光检测至少一种单链或双链靶核酸的双链探针，包括： - 式X1-（L1）a-S1-S'1的第一链 - （L'1）b-Y1，用于检测包含式T'1-T1序列的靶核酸的第一链; - 式X2-（L2）c-S2-S'2-（L'2）d-Y2的第二链，其用于检测靶核酸的第二链（如果存在）靶的第二链包含式T'2-T2的序列的核酸; 其中X1，X2，Y1和Y2中的两个表示荧光供体，而另外两个表示荧光受体，X1和Y2不能都表示荧光供体。

47. 发明授权

US09150909B2 Determination of the integrity of RNA 有权
标题翻译：确定RNA的完整性
公开(公告)号：US09150909B2
公开(公告)日：2015-10-06
申请号：US12548226
申请日：2009-08-26
申请人： Vladimir Denisov
发明人： Vladimir Denisov
IPC分类号： G01N27/26 , C12Q1/68 , G06F19/00
CPC分类号： C12Q1/6816 , C12Q1/6806 , C12Q2545/113 , C12Q2563/107 , C12Q2565/125 , G01N2333/4728 , G01N2800/34 , C12Q2561/12 , C12Q2539/101
摘要： Methods, systems, and apparatus make a determination of a level of integrity of a sample of biomolecules. For example, the determination of the integrity of RNA in a sample may be done in a fast and reproducible manner, such that the user can be assured of accuracy of a test (e.g. quantitative polymerase chain reaction qPCR) on the sample and compare results of different samples. The determination of integrity of an RNA sample is performed by comparing a size profile to reference size profiles (degradation standards) obtained from degradation over different lengths of times. As the reference scale of the level of integrity is derived from the actual degradation that occurs in a sample, high accuracy, reproducibility, and efficiency is provided.
摘要翻译：方法，系统和装置确定生物分子样品的完整性水平。例如，样品中RNA的完整性的确定可以以快速和可再现的方式进行，使得用户可以确保样品的测试准确性（例如定量聚合酶链式反应qPCR）并比较结果不同样品。 RNA样品的完整性的确定通过将尺寸分布与不同长度的降解获得的参考尺寸分布（降解标准）进行比较来进行。由于完整性水平的参考比例来源于样品中发生的实际降解，因此提供了高精度，重复性和效率。

48. 发明申请

US20110143350A1 PRIMERS AND METHODS FOR THE DETECTION AND DISCRIMINATION OF NUCLEIC ACIDS 审中-公开
标题翻译：用于检测和鉴别核酸的原理和方法
公开(公告)号：US20110143350A1
公开(公告)日：2011-06-16
申请号：US12240914
申请日：2008-09-29
申请人： IRINA NAZARENKO , AYOUB RASHTCHIAN
发明人： IRINA NAZARENKO , AYOUB RASHTCHIAN
IPC分类号： C12Q1/68 , C07H21/00
CPC分类号： C12Q1/6827 , C12Q1/6816 , C12Q1/6818 , C12Q1/6832 , C12Q1/6851 , C12Q1/6858 , C12Q2565/107 , C12Q2563/107 , C12Q2561/12 , C12Q2561/119 , C12Q2525/301 , C12Q2525/101
摘要： The present invention provides novel primers and methods for the detection of specific nucleic acid sequences. The primers and methods of the invention are useful in a wide variety of molecular biology applications and are particularly useful in allele specific PCR.
摘要翻译：本发明提供用于检测特异性核酸序列的新型引物和方法。本发明的引物和方法可用于多种分子生物学应用，并且特别适用于等位基因特异性PCR。

49. 发明授权

US07943307B2 Methods for analyzing nucleic acid sequences 有权
标题翻译：分析核酸序列的方法
公开(公告)号：US07943307B2
公开(公告)日：2011-05-17
申请号：US11336122
申请日：2006-01-19
申请人： Jonas Korlach , Watt W. Webb , Michael Levene , Stephen Turner , Harold G. Craighead , Mathieu Foquet
发明人： Jonas Korlach , Watt W. Webb , Michael Levene , Stephen Turner , Harold G. Craighead , Mathieu Foquet
IPC分类号： C12Q1/68 , C12P19/34 , C12N9/00 , C12M3/00 , C07H21/04 , G01N33/53
CPC分类号： C12Q1/6874 , C12Q1/6869 , Y10S436/80 , Y10S436/805 , Y10T436/143333 , C12Q2565/537 , C12Q2537/149 , C12Q2561/113 , C12Q2521/543 , C12Q2565/518 , C12Q2561/12
摘要： The present invention is directed to a method of sequencing a target nucleic acid. The method provides a complex comprising a polymerase enzyme, a target nucleic acid molecule, and a primer, wherein the complex is immobilized on a support Fluorescent label is attached to a terminal phosphate group of the nucleotide or nucleotide analog. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The time duration of the signal from labeled nucleotides or nucleotide analogs that become incorporated is distinguished from freely diffusing labels by a longer retention in the observation volume for the nucleotides or nucleotide analogs that become incorporated than for the freely diffusing labels.
摘要翻译：本发明涉及对靶核酸进行测序的方法。该方法提供了一种包含聚合酶，靶核酸分子和引物的复合物，其中复合物被固定在载体上荧光标记附着于核苷酸或核苷酸类似物的末端磷酸基团。通过使用聚合酶将核酸类似物加入到核酸链中来延长生长的核酸链。鉴定作为聚合步骤的结果添加到寡核苷酸引物中的核苷酸类似物。来自被引入的标记核苷酸或核苷酸类似物的信号的持续时间与自由扩散标记的区别在于，对于被掺入的核苷酸或核苷酸类似物的观察体积比对于自由扩散标记物的观察体积更长的保留。

50. 发明授权

US07416844B2 Composition for nucleic acid sequencing 有权
标题翻译：用于核酸测序的组合物
公开(公告)号：US07416844B2
公开(公告)日：2008-08-26
申请号：US11285422
申请日：2005-11-21
申请人： Jonas Korlach , Watt W. Webb , Michael Levene , Stephen Turner , Harold G. Craighead , Mathieu Foquet
发明人： Jonas Korlach , Watt W. Webb , Michael Levene , Stephen Turner , Harold G. Craighead , Mathieu Foquet
IPC分类号： C12Q1/68 , C12P19/34 , C12P21/06 , C12M1/34 , C12N11/00 , G01N33/00 , G01N33/53 , C07H21/00 , C07H21/04
CPC分类号： C12Q1/6874 , C12Q1/6869 , Y10S436/80 , Y10S436/805 , Y10T436/143333 , C12Q2565/537 , C12Q2537/149 , C12Q2561/113 , C12Q2521/543 , C12Q2565/518 , C12Q2561/12
摘要： The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site. A plurality of labelled types of nucleotide analogs are provided proximate to the active site, with each distinguishable type of nucleotide analog being complementary to a different nucleotide in the target nucleic acid sequence. The growing nucleic acid strand is extended by using the polymerase to add a nucleotide analog to the nucleic acid strand at the active site, where the nucleotide analog being added is complementary to the nucleotide of the target nucleic acid at the active site. The nucleotide analog added to the oligonucleotide primer as a result of the polymerizing step is identified. The steps of providing labelled nucleotide analogs, polymerizing the growing nucleic acid strand, and identifying the added nucleotide analog are repeated so that the nucleic acid strand is further extended and the sequence of the target nucleic acid is determined.
摘要翻译：本发明涉及对具有多个碱基的靶核酸分子进行测序的方法。在其原理中，聚合反应中碱添加的时间顺序是在核酸分子上测量的，即核酸聚合酶在待测序的模板核酸分子上的活性被实时跟踪。通过在碱添加序列的每个步骤中通过核酸聚合酶的催化活性鉴定哪个碱基被掺入靶核酸的生长互补链中来推断该序列。在靶核酸分子复合物上提供聚合酶，其适于沿着靶核酸分子移动并在活性位点延伸寡核苷酸引物。多个标记类型的核苷酸类似物在活性位点附近提供，每种可区分类型的核苷酸类似物与靶核酸序列中的不同核苷酸互补。生长的核酸链通过使用聚合酶延伸到活性位点处的核酸链的核苷酸类似物，其中加入的核苷酸类似物与活性位点上的靶核酸的核苷酸互补。鉴定作为聚合步骤的结果添加到寡核苷酸引物中的核苷酸类似物。重复提供标记的核苷酸类似物，聚合生长的核酸链和鉴定添加的核苷酸类似物的步骤，使得核酸链进一步延长并确定靶核酸的序列。

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