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1. 发明授权

US5846726A Detection of nucleic acids by fluorescence quenching 失效
公开(公告)号：US5846726A
公开(公告)日：1998-12-08
申请号：US855085
申请日：1997-05-13
申请人： James G. Nadeau , J. Bruce Pitner , James L. Schram , C. Preston Linn , Glenn P. Vonk , G. Terrance Walker
发明人： James G. Nadeau , J. Bruce Pitner , James L. Schram , C. Preston Linn , Glenn P. Vonk , G. Terrance Walker
IPC分类号： G01N21/64 , C07H21/00 , C12N15/09 , C12Q1/68 , G01N33/58 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6818 , C12Q1/6825
摘要： Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.

2. 发明授权

US5919630A Detection of nucleic acids by fluorescence quenching 失效
公开(公告)号：US5919630A
公开(公告)日：1999-07-06
申请号：US186030
申请日：1998-11-04
申请人： James G. Nadeau , J. Bruce Pitner , James L. Schram , C. Preston Linn , Glenn P. Vonk , G. Terrance Walker
发明人： James G. Nadeau , J. Bruce Pitner , James L. Schram , C. Preston Linn , Glenn P. Vonk , G. Terrance Walker
IPC分类号： G01N21/64 , C07H21/00 , C12N15/09 , C12Q1/68 , G01N33/58 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/6818 , C12Q1/6825
摘要： Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.

3. 发明授权

US6054279A Detection of nucleic acids by fluorescence quenching 失效
标题翻译：通过荧光猝灭检测核酸
公开(公告)号：US6054279A
公开(公告)日：2000-04-25
申请号：US120916
申请日：1998-07-20
申请人： James G. Nadeau , J. Bruce Pitner , James L. Schram , C. Preston Linn , Glenn P. Vonk , G. Terrance Walker
发明人： James G. Nadeau , J. Bruce Pitner , James L. Schram , C. Preston Linn , Glenn P. Vonk , G. Terrance Walker
IPC分类号： G01N21/64 , C07H21/00 , C12N15/09 , C12Q1/68 , G01N33/58 , C21Q1/68
CPC分类号： C12Q1/6818 , C12Q1/6825
摘要： Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.
摘要翻译：通过连接到形成供体/受体染料对的两种染料来修饰单链信号引物。这两种染料位于信号引物足够接近的空间上，第一种染料的荧光被第二种染料淬灭。信号引物还可以包含两种染料之间的限制性内切核酸酶识别位点（RERS）。由于信号引物最初是单链的，并且在不存在靶标的情况下保持单链，限制性内切核酸酶识别位点不受限制性内切核酸酶的切割或切割。然而，在靶的存在下，信号引物和限制性内切核酸酶识别位点被限制性内切核酸酶双链和切割或切割。切割或切口分离两种染料，并且由于猝灭降低引起的荧光变化被检测为目标序列或靶序列扩增的存在的指示。

4. 发明授权

US5691145A Detection of nucleic acids using G-quartets 失效
标题翻译：使用G四重奏检测核酸
公开(公告)号：US5691145A
公开(公告)日：1997-11-25
申请号：US703755
申请日：1996-08-27
申请人： J. Bruce Pitner , Glenn P. Vonk , James G. Nadeau
发明人： J. Bruce Pitner , Glenn P. Vonk , James G. Nadeau
IPC分类号： G01N33/58 , C07H21/04 , C12N15/09 , C12Q1/68 , G01N21/78 , C07H21/02 , C12P19/34
CPC分类号： C12Q1/6818 , Y10S436/80 , Y10S436/805 , Y10T436/143333
摘要： Oligonucleotides which form G-quartet structures have been found to be useful in fluorescence assays to detect a selected nucleic acid sequence. When one end of the oligonucleotide is labeled with a donor fluorophore and the other end is labeled with an acceptor dye, the folding of the molecule in the G-quartet structure brings the donor-acceptor pair into close proximity, allowing an interaction between the two labels which results in quenching of donor fluorescence or a change in other fluorescence properties which are the result of the interaction of two dyes in close proximity. The G-quartet structure unfolds upon hybridization to its complementary sequence, increasing the distance between the two dye labels. This results in decreased donor quenching or a change in another proximity-related fluorescence parameter. The associated increase in donor fluorescence intensity or the change in another fluorescence parameter may be monitored as an indication of the presence of a selected nucleic acid sequence. Alternatively, in some cases a decrease in acceptor fluorescence may be monitored as an indication of the presence of the selected nucleic acid sequence when the acceptor is also a fluorophore.
摘要翻译：已经发现形成G-四重结构的寡核苷酸可用于荧光测定以检测所选择的核酸序列。当寡核苷酸的一端用供体荧光团标记，另一端用受体染料标记时，分子在G四重结构中的折叠使供体 - 受体对紧密接近，允许两者之间的相互作用导致供体荧光猝灭的标记或其他荧光性质的变化，这两种染料是两种染料相互作用的结果。 G-四重结构在与其互补序列杂交时展开，增加两个染料标记之间的距离。这导致供体猝灭减少或另一邻近相关荧光参数的变化。可以监测供体荧光强度的相关增加或另一荧光参数的变化作为选择的核酸序列的存在的指示。或者，在一些情况下，当受体也是荧光团时，可以监测受体荧光的降低作为选择的核酸序列的存在的指示。

5. 发明授权

US5888739A Detection of nucleic acids using G-quartets and I-tetraplexes 失效
标题翻译：使用G四重奏和I-tetraplexes检测核酸
公开(公告)号：US5888739A
公开(公告)日：1999-03-30
申请号：US926054
申请日：1997-09-09
申请人： J. Bruce Pitner , James G. Nadeau , Glenn P. Vonk
发明人： J. Bruce Pitner , James G. Nadeau , Glenn P. Vonk
IPC分类号： G01N33/58 , C07H21/04 , C12N15/09 , C12Q1/68 , G01N21/78
CPC分类号： C12Q1/6818 , Y10S436/80 , Y10S436/805 , Y10T436/143333
摘要： G-quartet structures have been found to be useful in fluorescence assays to detect a selected nucleic acid sequence. When oligonucleotides containing these structures are labeled with a donor fluorophore and an acceptor dye, the folding or interaction of the oligonucleotides in the G-quartet structure brings the donor-acceptor pair into close proximity, allowing an interaction between the two labels which results in quenching of donor fluorescence or a change in other fluorescence properties which are the result of the interaction of two dyes in close proximity. The G-quartet structure unfolds or is otherwise disrupted upon hybridization to its complementary sequence, increasing the distance between the two dye labels. This results in decreased donor quenching or a change in another proximity-related fluorescence parameter. The associated increase in donor fluorescence intensity or the change in another fluorescence parameter may be monitored as an indication of the presence of a selected nucleic acid sequence. Alternatively, in some cases a decrease in acceptor fluorescence may be monitored as an indication of the presence of the selected nucleic acid sequence when the acceptor is also a fluorophore. Related structures, such as the i-tetraplex, may also be useful in similar methods for detection of a selected nucleic acid sequence.
摘要翻译：已经发现G-四重结构在荧光测定中可用于检测选定的核酸序列。当含有这些结构的寡核苷酸用供体荧光团和受体染料标记时，G-四重结构中寡核苷酸的折叠或相互作用使供体 - 受体对紧密接近，允许两个标记之间的相互作用导致淬灭的供体荧光或其他荧光性质的变化，这两种染料是两种染料相互作用的结果。 G-四重结构在与其互补序列杂交时展开或以其它方式被破坏，增加了两个染料标记之间的距离。这导致供体猝灭减少或另一邻近相关荧光参数的变化。可以监测供体荧光强度的相关增加或另一荧光参数的变化作为选择的核酸序列的存在的指示。或者，在一些情况下，当受体也是荧光团时，可以监测受体荧光的降低作为选择的核酸序列的存在的指示。相关结构，例如i-tetraplex，也可用于检测所选择的核酸序列的相似方法中。

6. 发明授权

US5650275A Target detection method using spectroscopically detectable nucleic acid ligands 失效
标题翻译：使用光谱可检测的核酸配体的靶标检测方法
公开(公告)号：US5650275A
公开(公告)日：1997-07-22
申请号：US276271
申请日：1994-07-18
申请人： J. Bruce Pitner , Douglas P. Malinowski , Glenn P. Vonk , Larry Gold
发明人： J. Bruce Pitner , Douglas P. Malinowski , Glenn P. Vonk , Larry Gold
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68
摘要： The invention relates to methods of using spectroscopically detectable labeled receptor molecules to determine the presence or absence of a target compound in a sample. In one embodiment, spectroscopically detectable labeled nucleic acid ligands are used to determine the presence or absence of biological targets of interest in biological samples.
摘要翻译：本发明涉及使用光谱可检测标记的受体分子来确定样品中目标化合物的存在或不存在的方法。在一个实施方案中，使用光谱可检测的标记的核酸配体来确定生物样品中感兴趣的生物靶标的存在或不存在。

7. 发明授权

US5314801A Probes to Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium paratuberculosis 失效
标题翻译：对鸟分枝杆菌，胞内分枝杆菌和副结核分枝杆菌的探针
公开(公告)号：US5314801A
公开(公告)日：1994-05-24
申请号：US973342
申请日：1992-11-06
申请人： Colleen M. Nycz , James L. Schram , Daryl D. Shank , Glenn P. Vonk
发明人： Colleen M. Nycz , James L. Schram , Daryl D. Shank , Glenn P. Vonk
IPC分类号： C12Q1/68 , C07H21/00 , C12P19/34
CPC分类号： C12Q1/689
摘要： The invention provides methods and nucleic acid probes for deleting, amplifying, and isolating sequences of Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium paratuberculosis.
摘要翻译：本发明提供了用于缺失，扩增和分离鸟分枝杆菌，胞内分枝杆菌和副结核分枝杆菌序列的方法和核酸探针。

8. 发明授权

US4978625A Fluorescence immunoassay using water insoluble dyes 失效
标题翻译：荧光免疫测定使用水不溶性染料
公开(公告)号：US4978625A
公开(公告)日：1990-12-18
申请号：US109689
申请日：1987-10-19
申请人： Daniel B. Wagner , Glenn P. Vonk , Thomas J. Mercolino
发明人： Daniel B. Wagner , Glenn P. Vonk , Thomas J. Mercolino
IPC分类号： G01N33/58
CPC分类号： G01N33/586 , Y10S436/80 , Y10S436/808 , Y10S436/829
摘要： In a method for fluorescence immunoassay of an analyte, an antianalyte attached to the surface of a solid support is contacted with the analyte and a tracer which includes a substantially water insoluble fluorescent dye occluded in the nonaqueous portion of a sac. After binding reactions involving the antianalyte, analyte and tracer, the solid support is separated, excitation light is applied and fluorescence from dye in intact sacs bound to the solid support is measured and compared to fluorescence measured when known quantities of analyte are assayed. The invention includes a kit of materials useful in performing an immunoassay in accordance with the method of the invention.
摘要翻译：在用于分析物的荧光免疫测定的方法中，附着在固体支持物表面的抗分析物与分析物和示踪剂接触，所述示踪剂包括封闭在囊的非水部分中的基本上不溶于水的荧光染料。在涉及抗分析物，分析物和示踪剂的结合反应之后，分离固体支持物，施加激发光，并测量与固体支持物结合的完整囊中来自染料的荧光，并与测定已知量的分析物时测量的荧光进行比较。本发明包括用于根据本发明的方法进行免疫测定的材料试剂盒。

9. 发明授权

US07369919B2 Medication adherence system 有权
标题翻译：药物依从系统
公开(公告)号：US07369919B2
公开(公告)日：2008-05-06
申请号：US10497310
申请日：2002-11-26
申请人： Glenn P. Vonk , Richard C. Rumbaugh , Colleen Ryan
发明人： Glenn P. Vonk , Richard C. Rumbaugh , Colleen Ryan
IPC分类号： G06F17/00
CPC分类号： A61J7/0481 , A61J7/0454 , A61J2200/30 , G06F19/00 , G06F19/3462 , G06Q50/24
摘要： A system comprising a medication tray (10) and a docking station (20) for facilitating effective self-management of medication treatment by patients is provided. The medication tray (10) accepts medication filled containers (30) and mates with the docking station (20). The medication tray (10) receives prescription data at the time the medication tray (10) accepts the medication filled containers (30), which is then downloaded to the docking station (20). The docking station (20) monitors and reports to third parties, via a network (160), a patient's compliance with various medication treatment regimens. Medication containers (30) are provided with low bit tags (35) that provide container presence information to the docking station (20). The docking station (20) provides visual and/or audio signals regarding prescription data to a patient. The docking station (20) can query patients and appliances regarding patient's medication usage and health status.
摘要翻译：提供了一种包括用于促进患者药物治疗的有效自我管理的药物托盘（10）和对接站（20）的系统。药物托盘（10）接受药物填充的容器（30）并与对接站（20）配合。药物托盘（10）在药物托盘（10）接受药物填充容器（30）时接收处方数据，然后将其下载到对接站（20）。对接站（20）通过网络（160）监视和向第三方报告患者对各种药物治疗方案的遵守情况。药物容器（30）具有向对接站（20）提供容器存在信息的低位标签（35）。对接站（20）向患者提供关于处方数据的视觉和/或音频信号。对接站（20）可以查询患者和器具关于患者的药物使用情况和健康状况。

10. 发明授权

US5139934A Substrate composition and method for solid phase urease immunoassay 失效
标题翻译：基质组合物和固相免疫免疫法的方法
公开(公告)号：US5139934A
公开(公告)日：1992-08-18
申请号：US528526
申请日：1990-05-25
申请人： Thomas N. Stewart , Glenn P. Vonk , James P. Mapes
发明人： Thomas N. Stewart , Glenn P. Vonk , James P. Mapes
IPC分类号： C12Q1/58 , G01N33/535 , G01N33/543 , G01N33/58
CPC分类号： C12Q1/58 , G01N33/54366 , G01N33/54386 , G01N33/581 , Y10S435/805 , Y10S435/97 , Y10S436/81 , Y10S436/904
摘要： A method for enzyme immunoassay of a ligand includes urease as a label. A bound fraction of ligand and antiligand conjugated to urease is formed on a solid support. The urease component of the bound fraction is contacted with a substrate composition for urease which includes a compound converted to ammonia by the urease, a tetrazolium salt and a pH dependent reducing agent which reduces the tetrazolium salt when the pH of the assay medium has been raised by the ammonia. The tetrazolium salt is reduced to a colored insoluble formazan which precipitates as a detectable spot on the support. The invention includes the substrate composition and a kit of materials for performing the assay.

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