公开(公告)号：US20060228713A1

公开(公告)日：2006-10-12

申请号：US10941289

申请日：2004-09-09

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

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

IPC分类号： C12Q1/68 ,  C12P19/34

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。

公开(公告)号：US20050153320A1

公开(公告)日：2005-07-14

申请号：US10984629

申请日：2004-11-08

申请人： James Herron ,  Samuel Tolley

发明人： James Herron ,  Samuel Tolley

IPC分类号： C12P19/34 ,  C12Q1/68

CPC分类号： C12Q1/6825 ,  C12Q1/683 ,  C12Q2565/607 ,  C12Q2565/537 ,  C12Q2535/125

摘要： Genetic polymorphisms can change protein structure and function, altering dispositions to diseases and conditions. A single nucleotide polymorphism is the smallest genetic mutation and the most difficult to detect. However, single nucleotide polymorphisms also make up 90% of known genetic mutations, thus identifying such polymorphisms is essential. Single base extension uses the affinity of one base for its complementary base to detect polymorphisms, including single nucleotide polymorphisms. Planar waveguides are used as the platform for single base extension enabling rapid, real time detection of genetic polymorphisms. Detection limits in the picomolar range can be obtained. Signals from the non-matched DNA bases are in the range of the blank signal. Detection times of 5 minutes are reported.

摘要翻译： 遗传多态性可以改变蛋白质的结构和功能，改变疾病和状况。 单核苷酸多态性是最小的遗传突变，最难检测。 然而，单核苷酸多态性也占已知遗传突变的90％，因此识别这种多态性是至关重要的。 单碱基延伸使用一个碱基的互补碱基的亲和力来检测多态性，包括单核苷酸多态性。 平面波导用作单碱基扩增的平台，可以快速，实时地检测遗传多态性。 可以获得皮摩尔范围内的检测限。 来自非匹配DNA碱基的信号在空白信号的范围内。 报告检测时间为5分钟。

公开(公告)号：US08747751B2

公开(公告)日：2014-06-10

申请号：US12481799

申请日：2009-06-10

申请人： Reuven Duer ,  James Herron

发明人： Reuven Duer ,  James Herron

IPC分类号： G02B27/56 ,  G02B6/10 ,  G02B6/24 ,  C12Q1/68 ,  C12N15/10

CPC分类号： G02B27/56 ,  B01J2219/00529 ,  B01J2219/00596 ,  B01J2219/00659 ,  B01J2219/00704 ,  B01J2219/00711 ,  B01J2219/00722 ,  B01L3/502715 ,  B01L2300/0654 ,  B01L2300/0819 ,  B82Y30/00 ,  C12N15/1068 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N21/6452 ,  G01N21/648 ,  G01N2021/6441 ,  G02B6/24 ,  C12Q2523/319 ,  C12Q2535/107 ,  C12Q2565/607

摘要： A system and methods of sequencing a nucleic acid by detecting the identity of a fluorescent nucleotide analogue incorporated at the 3′ end of a growing nucleic acid strand are provided. The system may include a substrate comprising a plurality of substantially parallel excitation waveguides, and a plurality of substantially parallel collection waveguides, the excitation waveguides and collection waveguides crossing to form a two-dimensional array of intersection regions, a plurality of optical sensing sites in optical communication with the intersection regions, one or more switchable light sources and a detector coupled to the light dispersive module. Methods of using these systems are also described.

摘要翻译： 提供了通过检测在生长的核酸链的3'末端引入的荧光核苷酸类似物的身份来测序核酸的系统和方法。 该系统可以包括包括多个基本上平行的激励波导和多个基本上平行的收集波导的基板，所述激励波导和收集波导交叉以形成二维阵列的交叉区域，光学中的多个光学感测位置 与交叉区域的通信，一个或多个可切换光源和耦合到光色散模块的检测器。 还描述了使用这些系统的方法。

公开(公告)号：US20090312188A1

公开(公告)日：2009-12-17

申请号：US12481799

申请日：2009-06-10

申请人： Reuven Duer ,  James Herron

发明人： Reuven Duer ,  James Herron

IPC分类号： C40B20/08 ,  C40B60/10

CPC分类号： G02B27/56 ,  B01J2219/00529 ,  B01J2219/00596 ,  B01J2219/00659 ,  B01J2219/00704 ,  B01J2219/00711 ,  B01J2219/00722 ,  B01L3/502715 ,  B01L2300/0654 ,  B01L2300/0819 ,  B82Y30/00 ,  C12N15/1068 ,  C12Q1/6869 ,  C12Q1/6874 ,  G01N21/6452 ,  G01N21/648 ,  G01N2021/6441 ,  G02B6/24 ,  C12Q2523/319 ,  C12Q2535/107 ,  C12Q2565/607

摘要： A system and methods of sequencing a nucleic acid by detecting the identity of a fluorescent nucleotide analogue incorporated at the 3′ end of a growing nucleic acid strand are provided. One method includes the steps of (a) immobilizing a plurality of complexes comprising a template nucleic acid, a primer configured to hybridize to the template and a polymerase, at a plurality of optical sensing sites of a substrate, wherein the substrate is part of a waveguide-based optical scanning system; (b) extending the primer by a single nucleotide with the polymerase and one or more fluorescent nucleotide analogues using a polymerase extension reaction, wherein each type of fluorescent nucleotide analogue comprises a unique fluorescent tag optionally configured to inhibit further primer extension and/or a blocking agent at the 3′ end and wherein incorporation of the fluorescent nucleotide analogue reversibly terminates the polymerase extension reaction; (c) detecting the unique tag of the fluorescent nucleotide analogue by optically scanning the substrate using the optical scanning system to identify the fluorescent nucleotide analogue incorporated by the polymerase reaction; (d) recording the results of the optical scanning of the substrate; (e) reversing the termination of the polymerase extension reaction by providing a photo-cleaving pulse of light to one or more of the optical sensing sites of the substrate to cleave the fluorescent tag or the blocking agent; and (f) repeating steps (b) through (e).

摘要翻译： 提供了通过检测在生长的核酸链的3'末端引入的荧光核苷酸类似物的身份来测序核酸的系统和方法。 一种方法包括以下步骤：（a）在衬底的多个光学感测位置处固定包含模板核酸的多个复合物，配置为与模板杂交的引物和聚合酶，其中所述底物是 基于波导的光学扫描系统; （b）使用聚合酶延伸反应，使用聚合酶和一个或多个荧光核苷酸类似物将引物延伸单个核苷酸，其中每种类型的荧光核苷酸类似物包含独特的荧光标签，其可选地配置为抑制进一步的引物延伸和/或阻断 3'端的试剂，其中掺入荧光核苷酸类似物可逆地终止聚合酶延伸反应; （c）通过使用光学扫描系统光学扫描底物来检测荧光核苷酸类似物的唯一标记，以鉴定通过聚合酶反应引入的荧光核苷酸类似物; （d）记录基板的光学扫描的结果; （e）通过向衬底的一个或多个光学感测位置提供光切割脉冲以切割荧光标签或封闭剂来反转聚合酶延伸反应的终止; 和（f）重复步骤（b）至（e）。

公开(公告)号：US5135876A

公开(公告)日：1992-08-04

申请号：US100935

申请日：1987-09-24

申请人： Joseph D. Andrade ,  James Herron

发明人： Joseph D. Andrade ,  James Herron

IPC分类号： G01N33/543

CPC分类号： G01N33/54373 ,  Y10S436/805

摘要： A reusable biosensor is disclosed. A molecule containing a moiety of an antibody-antigen complex and photosensitive polymers are bonded to an optical conduit. When placed in a solution, the presence or absence of a second complementary moiety of an antibody-antigen complex can be determined by sensing whether or not the first moiety is complexed. The first moiety of an antibody-antigen complex can then be regenerated by transmitting light through the optical conduit which alters the structure of the photosensitive polymers to cause interference with said complex, thereby dissociating the second complementary moiety from the first moiety. The ability to regulate and control specific binding has applications can be useful in information storage devices, bioorganic electronic devices, and optical devices.

摘要翻译： 公开了可重复使用的生物传感器。 含有抗体 - 抗原复合物部分和感光性聚合物的分子被结合到光导管上。 当置于溶液中时，抗体 - 抗原复合物的第二互补部分的存在或不存在可以通过检测第一部分是否复合来确定。 抗体 - 抗原复合物的第一部分然后可以通过透过光导管来再生，该光导管改变光敏聚合物的结构以引起与所述复合物的干扰，从而使第二互补部分与第一部分解离。 调节和控制特异性结合的能力可用于信息存储设备，生物有机电子设备和光学设备中。