Nanopore device for reversible ion and molecule sensing or migration
    1.
    发明授权
    Nanopore device for reversible ion and molecule sensing or migration 有权
    用于可逆离子和分子感测或迁移的纳米孔装置

    公开(公告)号:US08980073B2

    公开(公告)日:2015-03-17

    申请号:US13411221

    申请日:2012-03-02

    摘要: Disclosed are methods and devices for detection of ion migration and binding, utilizing a nanopipette adapted for use in an electrochemical sensing circuit. The nanopipette may be functionalized on its interior bore with metal chelators for binding and sensing metal ions or other specific binding molecules such as boronic acid for binding and sensing glucose. Such a functionalized nanopipette is comprised in an electrical sensor that detects when the nanopipette selectively and reversibly binds ions or small molecules. Also disclosed is a nanoreactor, comprising a nanopipette, for controlling precipitation in aqueous solutions by voltage-directed ion migration, wherein ions may be directed out of the interior bore by a repulsing charge in the bore.

    摘要翻译: 公开了用于检测离子迁移和结合的方法和装置,利用适用于电化学感测电路的纳米管。 可以在其内孔上用金属螯合剂官能化纳米针管,用于结合和感测金属离子或其它特异性结合分子,例如用于结合和感测葡萄糖的硼酸。 这种功能化的纳米移液管包含在电传感器中,该传感器检测纳米管片何时选择性地和可逆地结合离子或小分子。 还公开了一种纳米反应器,其包括纳米管,用于通过电压导向的离子迁移控制水溶液中的沉淀,其中离子可以通过孔中的排斥电荷引出到内孔内。

    Nanopore Device for Reversible Ion and Molecule Sensing or Migration
    2.
    发明申请
    Nanopore Device for Reversible Ion and Molecule Sensing or Migration 有权
    用于可逆离子和分子感测或迁移的纳米孔装置

    公开(公告)号:US20120222958A1

    公开(公告)日:2012-09-06

    申请号:US13411221

    申请日:2012-03-02

    摘要: Disclosed are methods and devices for detection of ion migration and binding, utilizing a nanopipette adapted for use in an electrochemical sensing circuit. The nanopipette may be functionalized on its interior bore with metal chelators for binding and sensing metal ions or other specific binding molecules such as boronic acid for binding and sensing glucose. Such a functionalized nanopipette is comprised in an electrical sensor that detects when the nanopipette selectively and reversibly binds ions or small molecules. Also disclosed is a nanoreactor, comprising a nanopipette, for controlling precipitation in aqueous solutions by voltage-directed ion migration, wherein ions may be directed out of the interior bore by a repulsing charge in the bore.

    摘要翻译: 公开了用于检测离子迁移和结合的方法和装置,利用适用于电化学感测电路的纳米管。 可以在其内孔上用金属螯合剂官能化纳米针管,用于结合和感测金属离子或其它特异性结合分子,例如用于结合和感测葡萄糖的硼酸。 这种功能化的纳米移液管包含在电传感器中,该传感器检测纳米管片何时选择性地和可逆地结合离子或小分子。 还公开了一种纳米反应器,其包括纳米管,用于通过电压导向的离子迁移控制水溶液中的沉淀,其中离子可以通过孔中的排斥电荷被引导出内孔。

    Biomolecule Immobilization on Biosensors
    3.
    发明申请
    Biomolecule Immobilization on Biosensors 有权
    生物传感器上的生物分子固定

    公开(公告)号:US20080161200A1

    公开(公告)日:2008-07-03

    申请号:US11949442

    申请日:2007-12-03

    IPC分类号: C40B40/00 C40B50/18

    摘要: A highly specific and versatile surface chemistry for immobilization of amine-terminated probes is disclosed. A bi-layered polymer thin film serves as the platform for coupling the probes, which are preferably oligonucleotides. The process involves sequentially coating a substrate with polyamine and polyacid anhydride. Hydrolyzed polyacid anhydride groups may be converted to non-hydrolyzed groups at about 100° C. prior to probe attachment. The process of coating the substrate requires no harsh chemical pretreatment of substrates such as RCA or Piranha cleaning. In addition, simple thermal activation of the anhydride groups has a low requirement for storage, leading to a long shelf life of modified surfaces. The disclosed surface chemistry is especially compatible with microfabrication processes, and its effective application to magnetic biosensors is demonstrated.

    摘要翻译: 公开了用于固定胺封端的探针的高度特异性和多功能的表面化学。 双层聚合物薄膜用作耦合探针的平台,优选为寡核苷酸。 该方法包括依次用多胺和多酸酐涂覆底物。 在探针附着之前,水解的多酸酐基团可以在约100℃下转化为非水解基团。 涂覆基材的过程不需要对基材进行苛刻的化学预处理,例如RCA或Piranha清洗。 此外,酸酐基团的简单热活化对储存的要求较低,导致改性表面的保质期长。 所公开的表面化学特性与微细加工工艺特别兼容,并且证明了其在磁性生物传感器中的有效应用。

    DNA template tailoring using PNA and modified nucleotides
    5.
    发明授权
    DNA template tailoring using PNA and modified nucleotides 有权
    使用PNA和修饰的核苷酸定制DNA模板

    公开(公告)号:US09187782B2

    公开(公告)日:2015-11-17

    申请号:US13027926

    申请日:2011-02-15

    IPC分类号: C12Q1/68

    摘要: Disclosed is a method whereby a repetitive nucleic acid sequence, such as a short tandem repeat (STR), may be characterized as to its length. Pyrosequencing is used to sequence an STR repetitive region to measure the length of STRs in a rapid manner. A combinatorial approach is disclosed for the addition of multiple nucleotides (e.g., two mononucleotides) at a time by the polymerase, which reduces the sample analysis time by half. In addition, modified nucleic acids, such as peptide nucleic acids, are used as blocking probe to stop polymerization on the flanking region which makes it possible to use pyrosequencing for DNA length measurement both in the case of homozygous or heterozygous samples for varying repeat patterns of different markers. Further, dideoxynucleotides are added to stop polymerization in the flanking region of the STR.

    摘要翻译: 公开了一种重复核酸序列,例如短串联重复(STR)的方法,其特征可在于其长度。 焦磷酸测序用于对STR重复区域进行排序,以快速方式测量STR的长度。 公开了通过聚合酶一次添加多个核苷酸(例如两个单核苷酸)的组合方法,其将样品分析时间减少了一半。 此外,修饰的核酸,例如肽核酸,被用作阻断探针以阻止侧翼区域的聚合,这使得可以在纯合或杂合样品的情况下使用焦磷酸测序进行DNA长度测量,以改变重复模式 不同的标记。 此外,加入双脱氧核苷酸以在STR的侧翼区停止聚合。

    Charge perturbation detection system for DNA and other molecules
    6.
    发明授权
    Charge perturbation detection system for DNA and other molecules 有权
    用于DNA和其他分子的电荷扰动检测系统

    公开(公告)号:US08313907B2

    公开(公告)日:2012-11-20

    申请号:US13170607

    申请日:2011-06-28

    摘要: Methods and apparatus for direct detection of chemical reactions are provided. In a preferred embodiment, electric charge perturbations of the local environment during enzyme-catalyzed reactions are sensed by an electrode system with an immobilized target molecule. The target molecule is preferably DNA. The charge perturbation caused by the polymerase reaction can uniquely identify a DNA sequence. The polymerization process generates local perturbations of charge in the solution near the electrode surface and induces a charge in a polarazible gold electrode. This event is detected as a transient current by a voltage clamp amplifier. Detection of single nucleotides in a sequence can be determined by dispensing individual dNTPs to the electrode solution and detecting the charge perturbations. Alternatively, multiple bases can be determined at the same time using a mix of all dNTPs with subsequent analysis of the resulting signal. The initial enzyme attachment to the DNA molecule can be detected prior to polymerization, with electrode capacitance measurement using the same voltage-clamp amplifier. This technique and device may be adapted to other reaction determinations, such as enzymatic reactions, other electrode configurations, and other amplifying circuits.

    摘要翻译: 提供了用于直接检测化学反应的方法和装置。 在优选的实施方案中,酶催化反应期间局部环境的电荷扰动由具有固定化靶分子的电极系统检测。 靶分子优选为DNA。 由聚合酶反应引起的电荷扰动可以唯一地识别DNA序列。 聚合过程在电极表面附近的溶液中产生电荷的局部扰动,并在极化金电极中引起电荷。 该事件由电压钳位放大器检测为瞬态电流。 可以通过将单个dNTP分配到电极溶液并检测电荷扰动来确定序列中单个核苷酸的检测。 或者,可以使用所有dNTP的混合物同时测定多个碱基,随后分析所得信号。 可以在聚合前检测到DNA分子的初始酶附着,使用相同的电压钳位放大器进行电极电容测量。 该技术和装置可以适用于其他反应测定,例如酶反应,其它电极配置和其它放大电路。

    Charge Perturbation Detection System for DNA and Other Molecules
    7.
    发明申请
    Charge Perturbation Detection System for DNA and Other Molecules 有权
    DNA和其他分子的电荷扰动检测系统

    公开(公告)号:US20110281739A1

    公开(公告)日:2011-11-17

    申请号:US13170607

    申请日:2011-06-28

    摘要: Methods and apparatus for direct detection of chemical reactions are provided. In a preferred embodiment, electric charge perturbations of the local environment during enzyme-catalyzed reactions are sensed by an electrode system with an immobilized target molecule. The target molecule is preferably DNA. The charge perturbation caused by the polymerase reaction can uniquely identify a DNA sequence. The polymerization process generates local perturbations of charge in the solution near the electrode surface and induces a charge in a polarazible gold electrode. This event is detected as a transient current by a voltage clamp amplifier. Detection of single nucleotides in a sequence can be determined by dispensing individual dNTPs to the electrode solution and detecting the charge perturbations. Alternatively, multiple bases can be determined at the same time using a mix of all dNTPs with subsequent analysis of the resulting signal. The initial enzyme attachment to the DNA molecule can be detected prior to polymerization, with electrode capacitance measurement using the same voltage-clamp amplifier. This technique and device may be adapted to other reaction determinations, such as enzymatic reactions, other electrode configurations, and other amplifying circuits.

    摘要翻译: 提供了用于直接检测化学反应的方法和装置。 在优选的实施方案中,酶催化反应期间局部环境的电荷扰动由具有固定化靶分子的电极系统检测。 靶分子优选为DNA。 由聚合酶反应引起的电荷扰动可以唯一地识别DNA序列。 聚合过程在电极表面附近的溶液中产生电荷的局部扰动,并在极化金电极中引起电荷。 该事件由电压钳位放大器检测为瞬态电流。 可以通过将单个dNTP分配到电极溶液并检测电荷扰动来确定序列中单个核苷酸的检测。 或者,可以使用所有dNTP的混合物同时测定多个碱基,随后分析所得信号。 可以在聚合前检测到DNA分子的初始酶附着,使用相同的电压钳位放大器进行电极电容测量。 该技术和装置可以适用于其他反应测定,例如酶反应,其它电极配置和其它放大电路。

    Multiplexed assay and probes for identification of HPV types
    8.
    发明授权
    Multiplexed assay and probes for identification of HPV types 有权
    用于鉴定HPV类型的多重测定和探针

    公开(公告)号:US07875428B2

    公开(公告)日:2011-01-25

    申请号:US11707832

    申请日:2007-02-13

    CPC分类号: C12Q1/708

    摘要: A DNA microarray, preferably in the form of a chip, contains probes which hybridize to generate primers capable of amplifying approximately 89 HPV types. These target the E1 region of the gene. The design of the chip allows for the detection of any known HPV type, based on a unique probe sequence derived from the HPV E1 region. The present assay utilizes a number of primers that can amplify from about one to six different types of HPV. A large number of primers can be used together. After amplification, the amplicons are contacted with specific probes that are unique for each HPV type. The array further employs a control sequence, which normalizes variability due to sample size.

    摘要翻译: 优选以芯片形式的DNA微阵列含有杂交以产生能够扩增大约89种HPV类型的引物的探针。 这些靶基因的E1区域。 基于来自HPV E1区域的唯一探针序列,芯片的设计允许检测任何已知的HPV类型。 本测定使用可以扩增大约一至六种不同类型的HPV的许多引物。 大量的引物可以一起使用。 扩增后,扩增子与特定的探针接触,这些探针对于每种HPV类型是独特的。 该阵列进一步采用控制序列,其归一化由于样本大小引起的变异性。

    Rapid, Informative Diagnostic Assay For Influenza Viruses Including H5N1
    9.
    发明申请
    Rapid, Informative Diagnostic Assay For Influenza Viruses Including H5N1 有权
    包括H5N1在内的流感病毒的快速,详细的诊断测定

    公开(公告)号:US20090123909A1

    公开(公告)日:2009-05-14

    申请号:US11945960

    申请日:2007-11-27

    IPC分类号: C12Q1/70 C12Q1/68

    CPC分类号: C12Q1/701

    摘要: A rapid diagnostic assay for influenza virus, particularly avian influenza and more particularly H5N1, is described. The assay is based on amplification of a significant portion of the hemagglutinin (HA) gene and sequencing of several loci within the HA gene, using techniques which can obtain real time sequence information from multiple sites of a target DNA, in particular pyrosequencing and bioluminescence regenerative cycle. The assay contemplates the use of information-rich subsequences within the HA gene, e.g., (1) a glycosylation sequon; (2) receptor binding site; and (3) HA1/HA2 cleavage site. Other subsequences for sequencing include strain and clade markers, which vary among H5N1 strains.

    摘要翻译: 描述了流感病毒,特别是禽流感,特别是H5N1的快速诊断测定。 该测定基于使用可从靶DNA的多个位点获得实时序列信息的技术,特别是焦磷酸测序和生物发光再生的技术,基于对血凝素(HA)基因的重要部分的扩增和HA基因内几个基因座的测序 周期。 该测定考虑了在HA基因内使用富含信息的子序列,例如(1)糖基化序列; (2)受体结合位点; 和(3)HA1 / HA2切割位点。 用于测序的其他子序列包括菌株和进化枝标记,其在H5N1菌株中不同。

    Multiplexed assay and probes for identification of HPV types
    10.
    发明申请
    Multiplexed assay and probes for identification of HPV types 有权
    用于鉴定HPV类型的多重测定和探针

    公开(公告)号:US20070207456A1

    公开(公告)日:2007-09-06

    申请号:US11707832

    申请日:2007-02-13

    IPC分类号: C12Q1/70 C12Q1/68 C12M1/34

    CPC分类号: C12Q1/708

    摘要: A DNA microarray, preferably in the form of a chip, contains probes which hybridize to generate primers capable of amplifying approximately 89 HPV types. These target the E1 region of the gene. The design of the chip allows for the detection of any known HPV type, based on a unique probe sequence derived from the HPV E1 region. The present assay utilizes a number of primers that can amplify from about one to six different types of HPV. A large number of primers can be used together. After amplification, the amplicons are contacted with specific probes that are unique for each HPV type. The array further employs a control sequence, which normalizes variability due to sample size.

    摘要翻译: 优选以芯片形式的DNA微阵列含有杂交以产生能够扩增大约89种HPV类型的引物的探针。 这些靶基因的E1区域。 基于来自HPV E1区域的唯一探针序列,芯片的设计允许检测任何已知的HPV类型。 本测定使用可以扩增大约一至六种不同类型的HPV的许多引物。 大量的引物可以一起使用。 扩增后,扩增子与特定的探针接触,这些探针对于每种HPV类型是独特的。 该阵列进一步采用控制序列,其归一化由于样本大小引起的变异性。