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    Biosensors including metallic nanocavities
    1.
    发明授权
    Biosensors including metallic nanocavities 有权
    生物传感器包括金属纳米孔

    公开(公告)号：US09012207B2

    公开(公告)日：2015-04-21

    申请号：US11497581

    申请日：2006-08-02

    申请人： Steven M. Blair ,  Farhad Mahdavi ,  Yongdong Liu ,  James N. Herron ,  Ajay Nahata

    发明人： Steven M. Blair ,  Farhad Mahdavi ,  Yongdong Liu ,  James N. Herron ,  Ajay Nahata

    IPC分类号： C12M1/34 ,  G01N33/543 ,  B82Y15/00 ,  B82Y20/00 ,  B82Y30/00 ,  G01N21/64 ,  G01N21/77 ,  G02B5/00

    CPC分类号： G01N21/648 ,  B82Y15/00 ,  B82Y20/00 ,  B82Y30/00 ,  G01N21/6428 ,  G01N21/7746 ,  G01N33/54373 ,  G01N2021/6439 ,  G02B5/008 ,  G02B2207/101

    摘要： A biomolecular assay includes a substrate with a metallic layer on at least one surface thereof. The metallic film includes nanocavities. The nanocavities are configured to enhance signals that are representative of the presence or amount of one or more analytes in a sample or sample solution, and may be configured to enhance the signal by a factor of about two or more or by a factor of about three or more. Such signal enhancement may be achieved with nanocavities that are organized in an array, randomly positioned nanocavities, or nanocavities that are surrounded by increased surface area features, such as corrugation or patterning, or nanocavities that have quadrilateral or triangular shapes with tailored edge lengths, or with a plurality of nanoparticles. Methods for fabricating biomolecular substrates and assay techniques in which such biomolecular substrates are used are also disclosed.

    摘要翻译： 生物分子测定包括在其至少一个表面上具有金属层的基底。 金属膜包括纳米孔。 纳米结构被配置为增强代表样品或样品溶液中一种或多种分析物的存在或量的信号，并且可以被配置为将信号增强约两个或更多个因子或约三分之一 或者更多。 这种信号增强可以通过以阵列，随机定位的纳米空间或纳米空间组织的纳米腔实现，纳米空间被增加的表面积特征（例如波纹或图案化）或具有具有定制的边缘长度的四边形或三角形形状的纳米腔包围，或 与多个纳米颗粒。 还公开了制备生物分子底物的方法和其中使用这种生物分子底物的测定技术。

    Biosensors including metallic nanocavities
    2.
    发明申请
    Biosensors including metallic nanocavities 有权
    生物传感器包括金属纳米孔

    公开(公告)号：US20100256016A1

    公开(公告)日：2010-10-07

    申请号：US11497581

    申请日：2006-08-02

    申请人： Steven M. Blair ,  Farhad Mahdavi ,  Yongdong Liu ,  James N. Herron ,  Ajay Nahata

    发明人： Steven M. Blair ,  Farhad Mahdavi ,  Yongdong Liu ,  James N. Herron ,  Ajay Nahata

    IPC分类号： C40B40/00 ,  C40B30/04 ,  C40B50/02 ,  C40B50/14

    CPC分类号： G01N21/648 ,  B82Y15/00 ,  B82Y20/00 ,  B82Y30/00 ,  G01N21/6428 ,  G01N21/7746 ,  G01N33/54373 ,  G01N2021/6439 ,  G02B5/008 ,  G02B2207/101

    摘要： A biomolecular assay includes a substrate with a metallic layer on at least one surface thereof. The metallic film includes nanocavities. The nanocavities are configured to enhance signals that are representative of the presence or amount of one or more analytes in a sample or sample solution, and may be configured to enhance the signal by a factor of about two or more or by a factor of about three or more. Such signal enhancement may be achieved with nanocavities that are organized in an array, randomly positioned nanocavities, or nanocavities that are surrounded by increased surface area features, such as corrugation or patterning, or nanocavities that have quadrilateral or triangular shapes with tailored edge lengths, or with a plurality of nanoparticles. Methods for fabricating biomolecular substrates and assay techniques in which such biomolecular substrates are used are also disclosed.

    摘要翻译： 生物分子测定包括在其至少一个表面上具有金属层的基底。 金属膜包括纳米孔。 纳米结构被配置为增强代表样品或样品溶液中一种或多种分析物的存在或量的信号，并且可以被配置为将信号增强约两个或更多个因子或约三分之一 或者更多。 这种信号增强可以通过以阵列，随机定位的纳米空间或纳米空间组织的纳米腔实现，纳米空间被增加的表面积特征（例如波纹或图案化）或具有具有定制的边缘长度的四边形或三角形形状的纳米腔包围，或 与多个纳米颗粒。 还公开了制备生物分子底物的方法和其中使用这种生物分子底物的测定技术。

    Oscillation apparatus and methods for multi-analyte homogeneous fluoro-immunoassays
    3.
    发明授权
    Oscillation apparatus and methods for multi-analyte homogeneous fluoro-immunoassays 失效
    用于多分析物均匀荧光免疫测定的振荡装置和方法

    公开(公告)号：US06242267B1

    公开(公告)日：2001-06-05

    申请号：US09142946

    申请日：1998-09-18

    申请人： James N. Herron ,  Douglas A. Christensen ,  Scott D. Miles

    发明人： James N. Herron ,  Douglas A. Christensen ,  Scott D. Miles

    IPC分类号： G01N33552

    CPC分类号： G01N33/54386 ,  G01N33/54373 ,  Y10S435/808 ,  Y10S436/807

    摘要： An apparatus and method for rapidly analyzing samples for analytes of interest by an homogeneous immunofluorescence assay. The apparatus includes a sample test cartridge having a high control sample section, a low control sample section, and at least one test sample section. Each of these sections contain at least one pre-loaded reagent housed in a well within the cartridge wherein the low control sample section contains a known low amount of an analyte of interest and the high control sample section contains a known high amount of an analyte of interest. The cartridge includes a biosensor comprising a planar waveguide having first and second parallel plane surfaces and an edge extending between them, the edge having a receiving region for receiving a light beam. Each of the high control sample section, the low control sample section, and the test sample control sections have a well which includes a waveguide surface, wherein the contents of each section contacts capture molecules immobilized on the waveguide surface. The capture molecules are configured to specifically bind a chosen analyte and fluoresce when interacting with light passing through the waveguide surface. The concentration of said analyte of interest in said sample fluid is determined by a comparison of intensities of fluorescence of between said capture molecule areas of said sample capture molecule well, said low control capture molecule well, and said high control capture molecule well.

    摘要翻译： 用于通过均匀免疫荧光测定快速分析感兴趣的分析物的样品的装置和方法。 该装置包括具有高控制样品部分，低对照样品部分和至少一个测试样品部分的样品测试盒。 这些部分中的每一个包含至少一个预先加载的试剂，其容纳在筒内的孔中，其中低对照样品部分含有已知的低量感兴趣的分析物，并且高对照样品部分含有已知的大量分析物 利益。 所述盒包括生物传感器，所述生物传感器包括具有第一和第二平行平面的平面波导和在它们之间延伸的边缘，所述边缘具有用于接收光束的接收区域。 高控制采样部分，低控制样品部分和测试样品控制部分中的每一个具有包括波导表面的阱，其中每个部分的内容物接触固定在波导表面上的捕获分子。 捕获分子被配置为特异性地结合所选择的分析物并且当与通过波导表面的光相互作用时发出荧光。 通过比较所述样品捕获分子阱的所述捕获分子区域，所述低对照捕获分子阱和所述高对照捕获分子阱之间的荧光强度来确定所述样品流体中所述目标分析物的浓度。

    Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays
    6.
    发明授权
    Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays 有权
    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。

    Composite waveguide for solid phase binding assays
    9.
    发明授权
    Composite waveguide for solid phase binding assays 失效
    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。

    Detection of single nucleotide polymorphisms using planar waveguides
    10.
    发明授权
    Detection of single nucleotide polymorphisms using planar waveguides 有权
    使用平面波导检测单核苷酸多态性

    公开(公告)号：US07811754B2

    公开(公告)日：2010-10-12

    申请号：US10941289

    申请日：2004-09-09

    申请人： James N. Herron ,  Samuel Tolley ,  Hsu-Kun Wang

    发明人： James N. Herron ,  Samuel Tolley ,  Hsu-Kun Wang

    IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04 ,  C07H21/00

    CPC分类号： C12Q1/6827 ,  C12Q1/6874 ,  C12Q2565/501 ,  C12Q2563/107 ,  C12Q2561/113

    摘要： Methods and apparatus for detecting single nucleotide polymorphisms in genes of interest are disclosed. A plurality of probes is immobilized on a planar waveguide. The probes comprise sequences complementary to a wildtype sequence of the gene of interest and complementary to a sequence of a known SNP in the gene of interest. A fluorescently-labeled analyte is flowed over the planar waveguide. The binding between the labeled analyte and each of the probes causes a change in the fluorescence signal. The SNP is detected by comparing the hybridization kinetics of the analyte with each of the probes. A method of detecting single nucleotide polymorphisms in a gene of interest by sequencing by hybridization is also disclosed.

    摘要翻译： 公开了用于检测感兴趣的基因中单核苷酸多态性的方法和装置。 多个探针固定在平面波导上。 探针包含与感兴趣的基因的野生型序列互补的序列，并与感兴趣的基因中已知SNP的序列互补。 荧光标记的分析物在平面波导上流动。 标记的分析物与每个探针之间的结合导致荧光信号的变化。 通过比较分析物与每个探针的杂交动力学来检测SNP。 还公开了通过杂交测序检测目的基因中的单核苷酸多态性的方法。