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公开(公告)号：US07022515B2
公开(公告)日：2006-04-04
申请号：US09971467
申请日：2001-10-05
申请人： James N. Herron , Douglas A. Christensen , Karin D. Caldwell , Vera Janatová , Shao-Chie Huang , Hsu-Kun Wang
发明人： James N. Herron , Douglas A. Christensen , Karin D. Caldwell , Vera Janatová , Shao-Chie Huang , Hsu-Kun Wang
IPC分类号： C12M3/00
CPC分类号： G01N21/648 , G01N21/6428 , G01N21/6452 , G01N21/7703 , G01N33/54373 , Y10S435/808 , Y10S436/805
摘要： Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide and optionally has multi-well features and improved evanescent field intensity. The preferred biosensor and assay method have the capture molecules immobilized to the waveguide surface by site-specific coupling chemistry. Additionally, the coatings used to immobilize the capture molecules provide reduced non-specific protein adsorption.
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公开(公告)号：US06611634B2
公开(公告)日：2003-08-26
申请号：US10095540
申请日：2002-03-11
申请人： James N. Herron , Douglas A. Christensen , Victor A. Pollak , Richard D. McEachern , Eric M. Simon
发明人： James N. Herron , Douglas A. Christensen , Victor A. Pollak , Richard D. McEachern , Eric M. Simon
IPC分类号： G02B600
CPC分类号： G01N21/0303 , G01N21/05 , G01N2021/0346 , G01N2021/058
摘要： Improvements in a biosensor are disclosed. A biosensor includes a waveguide, at least a portion of which is substantially planar. One or more reservoirs may be formed adjacent to a chemistry-bearing surface of the waveguide. The biosensor may include a gasket to form a seal between the waveguide and side walls of the reservoir. A sample solution may be introduced into the reservoir or otherwise onto the surface of a waveguide through an input port. Waveguides of varying composition (e.g., plastic, quartz, glass, or other suitable waveguide materials) may be used in the biosensor. Also disclosed is a sled-shaped waveguide, which includes a planar portion and a lens at an end thereof and angled relative thereto for coupling light into the waveguide.
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公开(公告)号：US06482655B1
公开(公告)日：2002-11-19
申请号：US08096338
申请日：1993-07-23
申请人： Ai-Ping Wei , James N. Herron
发明人： Ai-Ping Wei , James N. Herron
IPC分类号： G01N3353
CPC分类号： G01N33/582 , C12Q1/6818 , Y10S436/80 , Y10S436/805
摘要： Disclosed are fluorescent energy transfer dyes which are capable of moving between a more stacked configuration to exhibit fluorescent quenching and a more spaced configuration to exhibit fluorescence can be conjugated to a peptide epitope for use in the detection of an unknown antibody in bulk solution. The resulting labeled peptide reagent can be used in an immunoassay procedure by placing it in bulk solution along with the unknown antibody to be detected. When the antibody binds to the peptide epitope, the pair of dyes carried by the peptide epitope will have their configuration altered from a stacked to an unstacked configuration and will exhibit a fluorescent increase in response thereto.
摘要翻译： 公开了能够在更叠层的配置之间移动以展示荧光猝灭和更间隔的构型以显示荧光的荧光能量转移染料可以缀合到肽表位，以用于检测本体溶液中的未知抗体。 所得标记的肽试剂可以在免疫测定程序中使用，将其与待检测的未知抗体一起放入本体溶液中。 当抗体与肽表位结合时，由肽表位携带的一对染料将具有从堆叠到未堆叠构型的改变，并且对其反应将呈现荧光增加。
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公开(公告)号：US5814565A
公开(公告)日：1998-09-29
申请号：US393450
申请日：1995-02-23
CPC分类号： G01N33/54373 , G01N21/648 , G01N21/7703 , G01N21/05
摘要： A step-gradient composite waveguide for evanescent sensing in fluorescent binding assays comprises a thick substrate layer having one or more thin film waveguide channels deposited thereon. In one embodiment, the substrate is silicon dioxide and the thin film is silicon oxynitride. Specific binding molecules having the property of binding with specificity to an analyte are immobilized on the surface of the thin film channels. In preferred embodiments, the composite waveguide further includes light input coupling means integrally adapted to the thin film channels. Such light coupling means can be a grating etched into the substrate prior to deposition of the thin film, or a waveguide coupler affixed to the upper surface of the thin film. The waveguide coupler has a thick input waveguide of high refractive index which receives the laser light through one end and propagates it by total internal reflection. The propagated light is then coupled evanescently into the thin film waveguide across a spacer layer of precise thickness and having an index of refraction lower than either the input waveguide or the thin-film waveguide. The composite waveguide can be constructed by plasma vapor deposition of silicon oxynitride onto the silicon dioxide substrate, masking the channel waveguides with a photoresist, and using reactive ion etching to expose the substrate in the unmasked regions.
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15.发明授权Method of determining energy transfer efficiency of a donor-acceptor pair of fluorescent dyes 失效确定荧光染料供体 - 受体对能量转移效率的方法
公开(公告)号：US5237515A
公开(公告)日：1993-08-17
申请号：US683146
申请日：1991-04-10
申请人： James N. Herron , Ai-Ping Wei
发明人： James N. Herron , Ai-Ping Wei
IPC分类号： G01N21/64
CPC分类号： G01N21/6428 , G01N2021/6421 , G01N2201/129
摘要： The energy transfer efficiency of a donor-acceptor pair of fluorescent dyes can be determined by first measuring the fluorescence and absorption spectra of donor-protein, acceptor-protein, mixture of donor-protein and acceptor-protein, and donor-acceptor-protein conjugates, then separating the respective spectra into their respective donor-protein complex and acceptor-protein complex components using multiple linear regression, and then determining the transfer efficiency on the basis of the quenching of the donor fluorescence based on the spectral data thus obtained.
摘要翻译： 供体 - 受体对荧光染料的能量转移效率可以通过首先测量供体 - 蛋白质，受体 - 蛋白质，供体 - 蛋白质和受体 - 蛋白质的混合物和供体 - 受体 - 蛋白质缀合物的荧光和吸收光谱来确定 ，然后使用多元线性回归将相应的光谱分离成它们各自的供体 - 蛋白质复合物和受体 - 蛋白质复合物组分，然后基于由此获得的光谱数据基于供体荧光的猝灭确定转移效率。
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公开(公告)号：US07537734B2
公开(公告)日：2009-05-26
申请号：US09973557
申请日：2001-10-10
CPC分类号： G01N33/54373 , G01N21/05 , G01N21/648 , G01N21/7703
摘要： A composite waveguide for evanescent sensing in fluorescent binding assays comprising a substrate layer having one or more thin-film waveguide channels deposited thereon. Binding molecules having the property of binding with specificity to an analyte are immobilized on the surface of the thin-film channels. In preferred embodiments, the composite waveguide includes integral light input coupling means adapted to the thin-film channels. Light coupling means may include a grating etched into the substrate prior to deposition of the thin film, or a waveguide coupler affixed to the upper surface of the thin film. The waveguide coupler has an input waveguide of high refractive index which receives the laser light through one end, propagating it by total internal reflection. Propagated light is coupled evanescently into the thin film across a spacer layer of precise thickness with a lower index of refraction than that of the input waveguide or the thin-film waveguide.
摘要翻译： 一种用于荧光结合测定中的ev逝感测的复合波导，包括其上沉积有一个或多个薄膜波导通道的基底层。 具有与分析物特异性结合的性质的结合分子固定在薄膜通道的表面上。 在优选实施例中，复合波导包括适于薄膜通道的整体光输入耦合装置。 光耦合装置可以包括在沉积薄膜之前蚀刻到衬底中的光栅，或者固定到薄膜的上表面的波导耦合器。 波导耦合器具有高折射率的输入波导，其通过一端接收激光，通过全内反射传播。 传播光通过具有比输入波导或薄膜波导的折射率更低的精确厚度的间隔层逐渐耦合到薄膜中。
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公开(公告)号：US07153654B2
公开(公告)日：2006-12-26
申请号：US10286600
申请日：2002-10-31
申请人： Ai-Ping Wei , James N. Herron
发明人： Ai-Ping Wei , James N. Herron
CPC分类号： G01N33/582 , C12Q1/6818
摘要： Fluorescent energy transfer dyes capable of moving between a more stacked configuration to exhibit fluorescent quenching and a more spaced configuration to exhibit fluorescence can be conjugated to a peptide epitope or nucleic acid for use in the detection of an unknown antibody in bulk solution. The resulting labeled peptide reagent can be used in an immunoassay procedure by placing it in bulk solution along with the unknown antibody to be detected. When the antibody binds to the peptide epitope, the pair of dyes carried by the peptide epitope will have their configuration altered from a stacked to an unstacked configuration and will exhibit a fluorescent increase in response thereto.
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公开(公告)号：US06576419B1
公开(公告)日：2003-06-10
申请号：US08891114
申请日：1997-07-10
申请人： Ai-Ping Wei , James N. Herron
发明人： Ai-Ping Wei , James N. Herron
IPC分类号： C12Q108
CPC分类号： G01N33/582 , C12Q1/6818
摘要： Fluorescent energy transfer dyes capable of moving between a more stacked configuration to exhibit fluorescent quenching and a more spaced configuration to exhibit fluorescence can be conjugated to a peptide epitope or nucleic acid for use in the detection of an unknown antibody in bulk solution. The resulting labeled peptide reagent can be used in an immunoassay procedure by placing it in bulk solution along with the unknown antibody to be detected. When the antibody binds to the peptide epitope, the pair of dyes carried by the peptide epitope will have their configuration altered from a stacked to an unstacked configuration and will exhibit a fluorescent increase in response thereto.
摘要翻译： 能够在更叠层的配置之间移动以展现荧光猝灭和更间隔的配置以显示荧光的荧光能量转移染料可以缀合到肽表位或核酸上，以用于检测本体溶液中的未知抗体。 所得标记的肽试剂可以在免疫测定程序中使用，将其与待检测的未知抗体一起放入本体溶液中。 当抗体与肽表位结合时，由肽表位携带的一对染料将具有从堆叠到未堆叠构型的改变，并且对其反应将呈现荧光增加。
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公开(公告)号：US06350413B1
公开(公告)日：2002-02-26
申请号：US09412731
申请日：1999-10-05
IPC分类号： G01N3353
CPC分类号： G01N33/54373 , G01N21/05 , G01N21/648 , G01N21/7703
摘要： A step-gradient composite waveguide for evanescent sensing in fluorescent binding assays comprises a thick substrate layer having one or more thin film waveguide channels deposited thereon. In one embodiment, the substrate is silicon dioxide and the thin film is silicon oxynitride. Specific binding molecules having the property of binding with specificity to an analyte are immobilized on the surface of the thin film channels. In preferred embodiments, the composite waveguide further includes light input coupling means integrally adapted to the thin film channels. Such light coupling means can be a grating etched into the substrate prior to deposition of the thin film, or a waveguide coupler affixed to the upper surface of the thin film. The waveguide coupler has a thick input waveguide of high refractive index which receives the laser light through one end and propagates it by total internal reflection. The propagated light is then coupled evanescently into the thin film waveguide across a spacer layer of precise thickness and having an index of refraction lower than either the input waveguide or the thin-film waveguide. The composite waveguide can be constructed by plasma vapor deposition of silicon oxynitride onto the silicon dioxide substrate, masking the channel waveguides with a photoresist, and using reactive ion etching to expose the substrate in the unmasked regions.
摘要翻译： 在荧光结合测定中用于ev逝感测的梯度梯度复合波导包括其上沉积有一个或多个薄膜波导通道的厚基底层。 在一个实施例中，衬底是二氧化硅，薄膜是氮氧化硅。 具有与分析物特异性结合的特性的特异性结合分子被固定在薄膜通道的表面上。 在优选实施例中，复合波导还包括与薄膜通道整体适配的光输入耦合装置。 这种光耦合装置可以是在沉积薄膜之前蚀刻到基板中的光栅，或者固定到薄膜的上表面的波导耦合器。 波导耦合器具有高折射率的厚输入波导，其通过一端接收激光并通过全内反射传播。 然后将传播的光ev逝地穿过精确厚度的间隔层并且具有低于输入波导或薄膜波导的折射率的薄膜波导。 复合波导可以通过将氧氮化硅等离子体气相沉积到二氧化硅衬底上，用光致抗蚀剂掩蔽通道波导，并且使用反应离子蚀刻来暴露未掩模区域中的衬底。
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公开(公告)号：US06287871B1
公开(公告)日：2001-09-11
申请号：US09142947
申请日：1998-09-18
IPC分类号： G01N2164
CPC分类号： G01N21/648 , G01N21/6452 , G01N33/54373
摘要： The present invention relates to a system (80) for determining analyte concentration. The system (80) includes an optical detection system (92) that detects fluorescence from fluorescent binding assays in a biosensor (88). A processing system (96) may be used to determine analyte concentration from the fluorescence detected by the optical detection system (92). The optical detection system (92) may include photodetectors with or without in series lenses. Alternatively, a CCD camera (146) may be used.
摘要翻译： 本发明涉及一种用于确定分析物浓度的系统（80）。 系统（80）包括在生物传感器（88）中检测来自荧光结合测定的荧光的光学检测系统（92）。 处理系统（96）可用于根据由光学检测系统（92）检测的荧光来确定分析物浓度。 光学检测系统（92）可以包括具有或不具有串联透镜的光电探测器。 或者，可以使用CCD照相机（146）。
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