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1. 发明授权

US07022515B2 Waveguide immunosensor with coating chemistry and providing enhanced sensitivity 失效
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.

2. 发明授权

US06340598B1 Apparatus for multichannel fluorescent immunoassays 有权
标题翻译：波导免疫传感器具有涂层化学和提供更高的灵敏度
公开(公告)号：US06340598B1
公开(公告)日：2002-01-22
申请号：US09207187
申请日：1998-12-08
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： G01N33543
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.
摘要翻译：公开了消逝光荧光免疫测定法的方法和装置。该装置采用平面波导并且可选地具有多阱特征和改善的消逝场强度。优选的生物传感器和测定方法通过位点特异性偶联化学将捕获分子固定在波导表面上。另外，用于固定捕获分子的涂层提供降低的非特异性蛋白质吸附。

3. 发明授权

US06316274B1 Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays 有权
标题翻译：多分析物均匀荧光免疫测定的装置和方法
公开(公告)号：US06316274B1
公开(公告)日：2001-11-13
申请号：US09516307
申请日：2000-03-01
申请人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin Caldwell , Vera Janatová , Shao-Chie Huang
发明人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin Caldwell , Vera Janatová , Shao-Chie Huang
IPC分类号： G01N33543
CPC分类号： G01N21/6452 , C07C281/02 , C08G65/329 , G01N21/6428 , G01N21/648 , G01N21/7703 , G01N33/54353 , G01N33/54373 , G01N33/54393 , Y10S435/808 , Y10S436/805 , Y10S436/807
摘要： Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers which in turn are coupled to the waveguide surface or to a non-specific-binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers the selective irradiation involving a mask, a laser light source, or the like.
摘要翻译：公开了消逝光荧光免疫测定法的方法和装置。该装置采用具有整体半柱面透镜的平面波导，并具有多分析物特征和校准特征，以及改善的消逝场强度。生物传感器和测定方法的优选实施方案具有每个针对不同分析物特异性的捕获分子的斑块，其邻近设置在单个贮存器内。捕获分子通过捕获分子上的硫醇基团的特异性偶联而固定在波导表面上的贴片上，而光致亲和性交联剂又连接到波导表面或非特异性结合抗性涂层上表面。通过在涉及光亲和性交联剂的涉及掩模，激光光源等的选择性照射的过程中选择性地照射波导表面的一部分来产生不同抗体的斑块。

4. 发明授权

US06979567B2 Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays 失效
标题翻译：多分析物均匀荧光免疫测定的装置和方法
公开(公告)号：US06979567B2
公开(公告)日：2005-12-27
申请号：US10008339
申请日：2001-11-13
申请人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin Caldwell , Vera Janatová , Shao-Chie Huang
发明人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin Caldwell , Vera Janatová , Shao-Chie Huang
IPC分类号： C07C281/02 , C08G65/329 , G01N21/25 , G01N21/64 , G01N21/77 , G01N33/543 , C12M3/00
CPC分类号： G01N21/6452 , C07C281/02 , C08G65/329 , G01N21/6428 , G01N21/648 , G01N21/7703 , G01N33/54353 , G01N33/54373 , G01N33/54393 , Y10S435/808 , Y10S436/805 , Y10S436/807
摘要： Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semicylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method has patches of capture molecules, each specific for a different analyte disposed adjacently within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers, which in turn are coupled to the waveguide surface or to a nonspecific binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers, the selective irradiation involving a mask, a laser light source, or the like.
摘要翻译：公开了消逝光荧光免疫测定法的方法和装置。该装置采用具有整体半圆柱透镜的平面波导，并具有多分析物特征和校准特征，以及改善的消逝场强度。生物传感器和测定方法的优选实施方案具有捕获分子的斑块，每个捕获分子具有针对在单个贮存器内相邻设置的不同分析物的特征。捕获分子通过捕获分子上的硫醇基团的特异性偶联而固定在波导表面上的贴片上，而光致亲和交联剂依次耦合到波导表面或表面上的非特异性结合抗性涂层。在偶联光亲和性交联剂，涉及掩模的选择性照射，激光光源等的过程中，通过选择性地照射波导表面的一部分来产生不同抗体的贴片。

5. 发明授权

US5846842A Waveguide immunosensor with coating chemistry and providing enhanced sensitivity 失效
公开(公告)号：US5846842A
公开(公告)日：1998-12-08
申请号：US640141
申请日：1996-04-30
申请人： James N. Herron , Douglas A. Christensen , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang , Hsu-Kun Wang
发明人： James N. Herron , Douglas A. Christensen , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang , Hsu-Kun Wang
IPC分类号： G01N21/25 , G01N21/55 , G01N21/64 , G01N21/77 , G01N33/543 , G01N33/552
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.

6. 发明授权

US5919712A Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays 失效
公开(公告)号：US5919712A
公开(公告)日：1999-07-06
申请号：US748687
申请日：1996-11-13
申请人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang
发明人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang
IPC分类号： C07C281/02 , C08G65/329 , G01N21/25 , G01N21/64 , G01N21/77 , G01N33/543 , G01N33/552
CPC分类号： G01N21/6452 , C07C281/02 , C08G65/329 , G01N21/6428 , G01N21/648 , G01N21/7703 , G01N33/54353 , G01N33/54373 , G01N33/54393 , Y10S435/808 , Y10S436/805 , Y10S436/807
摘要： Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers which in turn are coupled to the waveguide surface or to a non-specific-binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers the selective irradiation involving a mask, a laser light source, or the like.

7. 发明授权

US5677196A Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays 失效
标题翻译：多分析物均匀荧光免疫测定的装置和方法
公开(公告)号：US5677196A
公开(公告)日：1997-10-14
申请号：US263522
申请日：1994-06-22
申请人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang
发明人： James N. Herron , Douglas A. Christensen , Hsu-Kun Wang , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang
IPC分类号： C08G65/329 , G01N21/64 , G01N21/77 , G01N33/543 , G01N33/552
CPC分类号： G01N21/7703 , C08G65/329 , G01N21/6428 , G01N21/648 , G01N2021/7786 , Y10S435/808 , Y10S436/805 , Y10S436/807 , Y10S436/809
摘要： Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers which in turn are coupled to the waveguide surface or to a non-specific-binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers the selective irradiation involving a mask, a laser light source, or the like.
摘要翻译：公开了消逝光荧光免疫测定法的方法和装置。该装置采用具有整体半柱面透镜的平面波导，并具有多分析物特征和校准特征，以及改善的消逝场强度。生物传感器和测定方法的优选实施方案具有每个针对不同分析物特异性的捕获分子的斑块，其邻近设置在单个贮存器内。捕获分子通过捕获分子上的硫醇基团的特异性偶联而固定在波导表面上的贴片上，而光致亲和性交联剂又连接到波导表面或非特异性结合抗性涂层上表面。通过在涉及光亲和性交联剂的涉及掩模，激光光源等的选择性照射的过程中选择性地照射波导表面的一部分来产生不同抗体的斑块。

8. 发明授权

US5512492A Waveguide immunosensor with coating chemistry providing enhanced sensitivity 失效
标题翻译：带涂层化学的波导免疫传感器提供更高的灵敏度
公开(公告)号：US5512492A
公开(公告)日：1996-04-30
申请号：US64608
申请日：1993-05-18
申请人： James N. Herron , Douglas A. Christensen , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang , Hsu-Kun Wang
发明人： James N. Herron , Douglas A. Christensen , Karin D. Caldwell , Vera Janatova , Shao-Chie Huang , Hsu-Kun Wang
IPC分类号： G01N21/25 , G01N21/55 , G01N21/64 , G01N21/77 , G01N33/543 , G01N33/544 , G01N33/552
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.
摘要翻译：公开了消逝光荧光免疫测定法的方法和装置。该装置采用平面波导并且可选地具有多阱特征和改善的消逝场强度。优选的生物传感器和测定方法通过位点特异性偶联化学将捕获分子固定在波导表面上。另外，用于固定捕获分子的涂层提供降低的非特异性蛋白质吸附。

9. 发明授权

US5832165A Composite waveguide for solid phase binding assays 失效
标题翻译：用于固相结合测定的复合波导
公开(公告)号：US5832165A
公开(公告)日：1998-11-03
申请号：US705893
申请日：1996-08-28
申请人： W. Monty Reichert , James N. Herron , Douglas A. Christensen , Hsu-Kun Wang
发明人： W. Monty Reichert , James N. Herron , Douglas A. Christensen , Hsu-Kun Wang
IPC分类号： G01N21/77 , G01N33/543 , G02B6/12 , G02B6/34 , G02B6/10
CPC分类号： G01N21/7703 , G01N21/05 , G01N21/274 , G01N21/648 , G01N33/543 , G01N2021/058 , G01N2021/7709 , G01N2021/7763 , G01N2021/7786 , G02B2006/12038 , G02B2006/12107 , G02B2006/12173 , G02B2006/12176 , G02B6/34 , Y10S435/808 , Y10S436/805
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。

10. 发明授权

US5814565A Integrated optic waveguide immunosensor 失效
公开(公告)号：US5814565A
公开(公告)日：1998-09-29
申请号：US393450
申请日：1995-02-23
申请人： W. Monty Reichert , James N. Herron , Douglas A. Christensen , Hsu-Kun Wang
发明人： W. Monty Reichert , James N. Herron , Douglas A. Christensen , Hsu-Kun Wang
IPC分类号： G01N21/64 , G01N21/05 , G01N21/55 , G01N21/77 , G01N33/543 , G01N33/53 , G01N21/17
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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