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    • 7. 发明授权
    • Homogeneous detection of a target through nucleic acid ligand-ligand beacon interaction
    • 通过核酸配体 - 配体信标相互作用均匀检测靶
    • US06261783B1
    • 2001-07-17
    • US09581326
    • 2000-08-11
    • Sumedha JayasenaLarry Gold
    • Sumedha JayasenaLarry Gold
    • C12Q168
    • C07H21/00C12Q1/6818C12Q1/682Y10T436/143333C12Q2561/12C12Q2537/101
    • A method for detecting a target molecule in a test mixture suspected of containing said target molecule is described. The nucleic acid ligand capable of binding to the target molecule has a first sequence A and a second sequence B, which are partially complementary sequences that form an imperfect intramolecular duplex, which unwinds upon the binding of the target to the nucleic acid ligand. Sequences A and B are able to participate in extramolecular hybridization reactions only when the duplex is unwound. Three different cascade nucleic acids contain a first sequence and a second sequence, which are partially complementary sequences. At least one sequence is exactly complementary to A or B. The second sequence may be complementary to A or B, or may be a third sequence C, or its complement. The test mixture suspected of containing the target molecule is contacted with the nucleic acid ligand, causing the duplex of the nucleic acid ligand to unwind such that sequences A and B become available for extramolecular hybridization. This mixture is contacted with the first, second, and third cascade nucleic acids so that the unpaired A and B sequences triggers a cascade of intermolecular hybridization involving the cascade nucleic acids in which intermolecular hybridization takes place between A and its complement, B and its complement, and between C its complement, leading to the formation of a multimolecular hybridization complex. The presence of the multimolecular hybridization complex is then detected.
    • 描述了一种用于检测怀疑含有所述靶分子的试验混合物中的靶分子的方法。 能够结合靶分子的核酸配体具有第一序列A和第二序列B,它们是形成不完全分子内双链体的部分互补序列,其解离靶核酸与核酸配体的结合。 序列A和B只有当双链体解卷时才能参与分子内杂交反应。 三种不同的级联核酸含有第一序列和第二序列,其是部分互补序列。 至少一个序列与A或B完全互补。第二个序列可以与A或B互补,或者可以是第三个序列C或其补体。 怀疑含有靶分子的试验混合物与核酸配体接触,导致核酸配体的双链体解开,使得序列A和B可用于分子内杂交。 该混合物与第一级,第二级和第三级联核酸接触,使得不成对的A和B序列引发级联的分子间杂交,其涉及级联核酸,其中分子间杂交发生在A与其补体之间,B及其补体 ,和C之间的补体,导致形成多分子杂交复合物。 然后检测多分子杂交复合物的存在。
    • 9. 发明授权
    • Nucleic acid ligand diagnostic biochip
    • 核酸配体诊断生物芯片
    • US06503715B1
    • 2003-01-07
    • US09723394
    • 2000-11-28
    • Larry GoldDan DroletDom ZichiSumedha JayasenaSteve CreightonStanley Gill
    • Larry GoldDan DroletDom ZichiSumedha JayasenaSteve CreightonStanley Gill
    • C12Q168
    • C12Q1/6839C07B2200/11C12Q1/6834C12Q1/6837C40B40/00Y10S977/924C12Q2565/514C12Q2565/101C12Q2541/101C12Q2525/205
    • A Nucleic acid ligand “Biochip” is disclosed, consisting of a solid support to which one or more specific Nucleic acid ligands is attached in a spatially defined manner. Each Nucleic acid ligand binds specifically and avidly to a particular Target molecule contained within a Test mixture, such as a Bodily fluid. The Target molecules include, but are not limited to, proteins (cellular, viral, bacterial, etc.) hormones, sugars, metabolic byproducts, cofactor, and intermediates, drugs, and toxins. Contacting the Test mixture with the Biochip leads to the binding of a Target molecule to its cognate Nucleic acid ligand. Binding of Target to the Nucleic acid ligand results in a detectable change at each specific location on the Biochip. The detectable change can include, but is not limited to, a change in fluorescence, or a change in a physical parameter, such as electrical conductance or refractive index, at each location on the Biochip. The Biochip will then be read by a device, such as a fluorescence scanner or a surface plasmon resonance detector, that can measure the magnitude of the change at each location on the Biochip. The location of the change reveals what Target molecule has been detected, and the magnitude of the change indicates how much of it is present. The combination of these two pieces of information will yield diagnostic and prognostic medical information when signal patterns are compared with those obtained from Bodily fluids of individuals with diagnosed disorders (FIG. 1). In principle, the Biochip could be used to test any chemically complex mixture provided that Nucleic acid ligands to components suspected of being present in the mixture are attached to the Biochip. Thus, the Nucleic acid ligand Biochip will have a wider use in environmental testing, etc.
    • 披露了一种核酸配体“生物芯片”,由一种或多种特定的核酸配体以空间限定的方式连接的固体支持物组成。 每个核酸配体特异性地和特异性地结合到包含在测试混合物例如体液内的特定靶分子。 靶分子包括但不限于蛋白质(细胞,病毒,细菌等)激素,糖,代谢副产物,辅因子和中间体,药物和毒素。 将测试混合物与Biochip接触导致Target分子与其同源核酸配体的结合。 靶向核酸配体的结合在Biochip上的每个特定位置产生可检测的变化。 可检测的变化可以包括但不限于在生物芯片上的每个位置的荧光的变化或物理参数的变化,例如电导率或折射率。 然后,生物芯片将被诸如荧光扫描仪或表面等离子体共振检测器的装置读取,该检测器可以测量Biochip上每个位置的变化幅度。 变化的位置揭示了目标分子被检测到的,变化的大小表明它有多少存在。 当将信号模式与从具有诊断障碍的个体的体液获得的信号模式进行比较时,这两条信息的组合将产生诊断和预后的医学信息(图1)。 原则上,生物芯片可以用于测试任何化学复合物混合物,只要核酸配体与怀疑存在于混合物中的组分连接在Biochip上即可。 因此,核酸配体生物芯片将在环境测试等方面有更广泛的应用。
    • 10. 发明授权
    • Nucleic acid ligand diagnostic Biochip
    • 核酸配体诊断生物芯片
    • US06242246B1
    • 2001-06-05
    • US08990436
    • 1997-12-15
    • Larry GoldDan DroletDom ZichiSumedha JayasenaSteve CreightonStanley Gill
    • Larry GoldDan DroletDom ZichiSumedha JayasenaSteve CreightonStanley Gill
    • C12M136
    • C12Q1/6839C07B2200/11C12Q1/6834C12Q1/6837C40B40/00Y10S977/924C12Q2565/514C12Q2565/101C12Q2541/101C12Q2525/205
    • A Nucleic acid ligand “Biochip” is disclosed, consisting of a solid support to which one or more specific Nucleic acid ligands is attached in a spatially defined manner. Each Nucleic acid ligand binds specifically and avidly to a particular Target molecule contained within a Test mixture, such as a Bodily fluid The Target molecules include, but are not limited to, proteins (cellular, viral, bacterial, etc.) hormones, sugars, metabolic byproducts, cofactor, and intermediates, drugs, and toxins. Contacting the Test mixture with the Biochip leads to the binding of a Target molecule to its cognate Nucleic acid ligand. Binding of Target to the Nucleic acid ligand results in a detectable change at each specific location on the Biochip. The detectable change can include, but is not limited to, a change in fluorescence, or a change in a physical parameter, such as electrical conductance or refractive index, at each location on the Biochip. The Biochip will then be read by a device, such as a fluorescence scanner or a surface plasma resonance detector, that can measure the magnitude of the change at each location on the Biochip. The location of the change reveals what Target molecule has been detected, and the magnitude of the change indicates how much of it is present The combination of these two pieces of information will yield diagnostic and prognostic medical information when signal patterns are compared with those obtained from Bodily fluids of individuals with diagnosed disorders FIG. 1). In principle, the Biochip could be used to test any chemically complex mixture provided that Nucleic acid ligands to components suspected of being present in the mixture are attached to the Biochip. Thus, the Nucleic acid ligand Biochip will have a wider use in environmental testing, etc.
    • 披露了一种核酸配体“生物芯片”,由一种或多种特定的核酸配体以空间限定的方式连接的固体支持物组成。 每个核酸配体特异性地和特异性地结合在测试混合物(例如体液)中的特定靶分子。靶分子包括但不限于蛋白质(细胞,病毒,细菌等)激素,糖, 代谢副产物,辅因子和中间体,药物和毒素。 将测试混合物与Biochip接触导致Target分子与其同源核酸配体的结合。 靶向核酸配体的结合在Biochip上的每个特定位置产生可检测的变化。 可检测的变化可以包括但不限于在生物芯片上的每个位置的荧光的变化或物理参数的变化,例如电导率或折射率。 然后,生物芯片将被诸如荧光扫描仪或表面等离子体共振检测器等器件读取,可以测量Biochip上每个位置的变化幅度。 变化的位置揭示了目标分子被检测到的,变化的幅度表明它存在多少这两个信息的组合将产生诊断和预后的医学信息,当信号模式与从 患有诊断障碍的个体的体液。 1)。 原则上,生物芯片可以用于测试任何化学复合物混合物,只要核酸配体与怀疑存在于混合物中的组分连接在Biochip上即可。 因此,核酸配体生物芯片将在环境测试等方面有更广泛的应用。