公开(公告)号：US6108463A

公开(公告)日：2000-08-22

申请号：US142948

申请日：1998-09-18

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： G01N21/64 ,  G01N21/03 ,  G01N21/05 ,  G01N33/543 ,  G01N33/552 ,  G02B6/00 ,  G02B6/32 ,  G02B6/26 ,  G01N21/00 ,  G01N33/72 ,  G02B6/10

CPC分类号： G01N21/0303 ,  G01N2021/058

摘要： Improvements in a biosensor of the type having reservoirs or wells for analyzing a biological liquid are disclosed. A biosensor (190) includes a waveguide (164) placed between a plurality of members such as plates (100, 186), at least one of the members (100) being formed to define the walls (132, 134, 136) of the reservoirs where the liquid is biologically analyzed. The walls of the reservoirs are made of an inert, opaque material such as a metal. Although the biosensor may include a gasket (162), the gasket is associated with the members and waveguide in such a way (e.g. by recessing the gasket into a channel formed into a metal plate) so that the gasket does not form any significant portion of the reservoir wall. Waveguides of varying composition (e.g. plastic, quartz or glass) may be associated with the members to form the biosensor. The metal plate of the biosensor has input and output ports for infusing, draining, or oscillating the liquid to be analyzed in the reaction reservoir. Also disclosed is a sled-shaped waveguide associated with a rear lens to couple light out of the waveguide to serve as a quality control measure thus insuring that the biosensor is properly placed and that the light is working.

摘要翻译： PCT No.PCT / US97 / 04398 Sec。 371日期：1998年9月18日 102（e）1998年9月18日PCT PCT 1997年3月19日PCT公布。 公开号WO97 / 35176 日期1997年9月25日公开了具有用于分析生物液体的储库或井的类型的生物传感器的改进。 生物传感器（190）包括布置在诸如板（100,186）之间的多个构件之间的波导（164），所述构件（100）中的至少一个被形成以限定所述壁（132,134,136） 生物分析液体的储层。 储存器的壁由惰性的不透明材料如金属制成。 虽然生物传感器可以包括垫圈（162），但是垫圈以这样的方式（例如通过将垫圈凹入形成金属板的通道）与构件和波导相关联，使得垫圈不形成任何重要的部分 水库墙。 不同成分的波导（例如塑料，石英或玻璃）可与成员相关联以形成生物传感器。 生物传感器的金属板具有输入和输出端口，用于在反应槽中输入，排出或振荡待分析液体。 还公开了一种与后透镜相关联的雪橇形波导，以将光从波导耦合以用作质量控制措施，从而确保生物传感器被正确放置并且光正在工作。

公开(公告)号：US5961924A

公开(公告)日：1999-10-05

申请号：US961827

申请日：1997-10-31

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.

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。

公开(公告)号：USRE39772E1

公开(公告)日：2007-08-14

申请号：US10225687

申请日：1997-03-19

申请人： James N. Herron ,  Douglas A. Christensen ,  Victor A. Pollack ,  Richard D. McEachern ,  Eric M. Simon

发明人： James N. Herron ,  Douglas A. Christensen ,  Victor A. Pollack ,  Richard D. McEachern ,  Eric M. Simon

IPC分类号： G02B6/26 ,  G02B6/10 ,  G01N21/00 ,  G01N33/552 ,  G01N33/72

CPC分类号： G01N21/0303 ,  G01N2021/058

摘要： Improvements in a biosensor of the type having reservoirs or wells for analyzing a biological liquid are disclosed. A biosensor (190) includes a waveguide (164) placed between a plurality of members such as plates (100, 186), at least one of the members (100) being formed to define the walls (132, 134, 136) of the reservoirs where the liquid is biologically analyzed. The walls of the reservoirs are made of an inert, opaque material such as a metal. Although the biosensor may include a gasket (162), the gasket is associated with the members and waveguide in such a way (e.g. by recessing the gasket into a channel formed into a metal plate) so that the gasket does not form any significant portion of the reservoir wall. Waveguides of varying composition (e.g. plastic, quartz or glass) may be associated with the members to form the biosensor. The metal plate of the biosensor has input and output ports for infusing, draining, or oscillating the liquid to be analyzed in the reaction reservoir. Also disclosed is a sled-shaped waveguide associated with a rear lens to couple light out of the waveguide to serve as a quality control measure thus insuring that the biosensor is properly placed and that the light is working.

摘要翻译： 公开了具有用于分析生物液体的储存器或孔的类型的生物传感器的改进。 生物传感器（190）包括布置在诸如板（100,186）之间的多个构件之间的波导（164），所述构件（100）中的至少一个被形成以限定所述壁（132,134,136） 生物分析液体的储层。 储存器的壁由惰性的不透明材料如金属制成。 虽然生物传感器可以包括垫圈（162），但是垫圈以这样的方式（例如通过将垫圈凹入形成金属板的通道）与构件和波导相关联，使得垫圈不形成任何重要的部分 水库墙。 不同组成的波导（例如塑料，石英或玻璃）可以与成员相关联以形成生物传感器。 生物传感器的金属板具有输入和输出端口，用于在反应槽中输入，排出或振荡待分析液体。 还公开了一种与后透镜相关联的雪橇形波导，以将光从波导耦合以用作质量控制措施，从而确保生物传感器被正确放置并且光正在工作。

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。

公开(公告)号：US06911344B1

公开(公告)日：2005-06-28

申请号：US09185318

申请日：1998-11-03

申请人： W. Monty Reichert ,  James N. Herron ,  Douglas A. Christensen ,  Hsu-Kun Wang ,  Jacob D. Durtschi

发明人： W. Monty Reichert ,  James N. Herron ,  Douglas A. Christensen ,  Hsu-Kun Wang ,  Jacob D. Durtschi

IPC分类号： G01N21/77 ,  G01N33/543 ,  G02B6/12 ,  G02B6/34

CPC分类号： G01N21/7703 ,  G01N21/05 ,  G01N21/274 ,  G01N21/648 ,  G01N33/543 ,  G01N2021/058 ,  G01N2021/7709 ,  G01N2021/7763 ,  G01N2021/7786 ,  G02B6/34 ,  G02B2006/12038 ,  G02B2006/12107 ,  G02B2006/12173 ,  G02B2006/12176 ,  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。

公开(公告)号：US06632613B1

公开(公告)日：2003-10-14

申请号：US08483500

申请日：1995-06-07

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： G01N21/6428 ,  C07K14/59 ,  C12Q1/6818 ,  G01N21/6445 ,  G01N33/542 ,  G01N33/54373 ,  G01N33/582 ,  G01N2021/6441 ,  Y10S435/975

摘要： An improved oligopeptide composition for use in a fluorescent polarization immunoassay for a high molecular weight analyte is disclosed, along with a kit and a method using the composition. The composition comprises an oligopeptide selected by a screening procedure in which a plurality of different oligopeptides having respective amino acid sequences that represent sequential overlapping segments of the analyte amino acid sequence, and a fluorescent label bound thereto. In a preferred embodiment, the oligopeptide has an amino acid sequence which does not form internal disulfide bridges. Such a preferred oligopeptide will generally have no more than one cysteine residue. In a further preferred embodiment, the fluorescent label is tetramethylrhodamine or a cyanine dye. The kit may be packaged with instructions directing a user to prepare an assay solution containing the monoclonal antibody and the oligopeptide in certain respective concentrations. The composition, method and kit are preferably constructed to detect nanomolar concentrations of the analyte.

摘要翻译： 公开了用于高分子量分析物的荧光偏振免疫测定法的改进的寡肽组合物以及试剂盒和使用该组合物的方法。 该组合物包含通过筛选方法选择的寡肽，其中多个具有代表分析物氨基酸序列的顺序重叠片段的氨基酸序列的不同寡肽和与其结合的荧光标记。 在优选的实施方案中，寡肽具有不形成内部二硫桥的氨基酸序列。 这种优选的寡肽通常具有不超过一个半胱氨酸残基。 在另一优选实施方案中，荧光标记是四甲基罗丹明或花青染料。 试剂盒可以包装，指示用户在某些相应浓度下制备含有单克隆抗体和寡肽的测定溶液。 组合物，方法和试剂盒优选构建成检测纳摩尔浓度的分析物

公开(公告)号：US06356676B1

公开(公告)日：2002-03-12

申请号：US09608714

申请日：2000-06-30

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： G02B626

CPC分类号： G01N21/0303 ,  G01N21/05 ,  G01N2021/0346

摘要： Improvements in a biosensor of the type having reservoirs or wells for analyzing a biological liquid are disclosed. A biosensor includes a waveguide placed between a plurality of members such as plates at least one of the members being formed to define the walls of the reservoirs where the liquid is biologically analyzed. The walls of the reservoirs are made of an inert, opaque material such as a metal. Although the biosensor may include a gasket, the gasket is associated with the members and waveguide in such a way (e.g., by recessing the gasket into a channel formed into a metal plate) so that the gasket does not form any significant portion of the reservoir wall. Waveguides of varying composition (e.g., plastic, quartz or glass) may be associated with the members to form the biosensor. The metal plate of the biosensor has input and output ports for infusing, draining, or oscillating the liquid to be analyzed in the reaction reservoir. Also disclosed is a sled-shaped waveguide associated with a rear lens to couple light out of the waveguide to serve as a quality control measure thus insuring that the biosensor is properly placed and that the light is working.

摘要翻译： 公开了具有用于分析生物液体的储存器或孔的类型的生物传感器的改进。 生物传感器包括放置在诸如板之间的多个构件之间的波导，所述构件中的至少一个形成为限定储存器的壁，其中液体被生物分析。 储存器的壁由惰性的不透明材料如金属制成。 虽然生物传感器可以包括垫圈，但是垫圈以这样的方式（例如通过将垫圈凹入形成金属板的通道）与构件和波导相关联，使得垫圈不形成储存器的任何重要部分 壁。 不同组成的波导（例如，塑料，石英或玻璃）可以与成员相关联以形成生物传感器。 生物传感器的金属板具有输入和输出端口，用于在反应槽中输入，排出或振荡待分析液体。 还公开了一种与后透镜相关联的雪橇形波导，以将光从波导耦合以用作质量控制措施，从而确保生物传感器被正确放置并且光正在工作。

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。

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。