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    • 1. 发明授权
    • Methods for generating a distribution of optimal solutions to nondeterministic polynomial optimization problems
    • 用于生成非确定性多项式优化问题的最优解的分布的方法
    • US08126649B2
    • 2012-02-28
    • US12181056
    • 2008-07-28
    • Wayne FraschDavid SpetzlerJustin YorkFusheng Xiong
    • Wayne FraschDavid SpetzlerJustin YorkFusheng Xiong
    • G01N33/48C12Q1/68G06G7/58
    • G06F19/24G06F19/22
    • The present invention provides methods for generating a distribution of optimal answers to a nondeterministic polynomial optimization problem by providing a plurality of solutions comprising input polynucleotides, wherein each solution comprises identical input polynucleotides; and wherein the number of solutions comprising polynucleotides equals a number of data inputs in the problem to be answered, and wherein each input polynucleotide comprises an x segment and a y segment; providing a plurality of solutions comprising connection polynucleotides wherein each solution comprises identical connection polynucleotides; and wherein the number of solutions comprising connection polynucleotides equals a number of unique connections that can be made between the different data inputs, and wherein each polynucleotide in the set of connection polynucleotides is complementary to the x segment of one input polynucleotide and to the y segment of one different input polynucleotide; combining the solutions comprising the input polynucleotides with the solutions comprising the connection polynucleotides to form a hybridization mixture, wherein the combining is done under conditions to promote formation of hybridization complexes between complementary polynucleotides, and wherein each individual connection polynucleotide is added at a concentration based on a weighted value assigned to the individual connection polynucleotide; ligating the polynucleotides that are present in the hybridization complexes to form ligation products; and determining a concentration of the ligation products, wherein the ligation products present at the highest concentration represent optimal answers to the nondeterministic polynomial optimization problem.
    • 本发明提供了通过提供包括输入多核苷酸的多种解决方案来产生对非确定性多项式优化问题的最优答案的分布的方法,其中每个溶液包含相同的输入多核苷酸; 并且其中包含多核苷酸的溶液的数量等于要回答的问题中的多个数据输入,并且其中每个输入多核苷酸包括x区段和y区段; 提供包含连接多核苷酸的多种溶液,其中每种溶液包含相同的连接多核苷酸; 并且其中包含连接多核苷酸的溶液的数量等于可以在不同数据输入之间进行的多个唯一连接,并且其中连接多核苷酸组中的每个多核苷酸与一个输入多核苷酸的x片段和y片段互补 的一种不同的输入多核苷酸; 将包含输入多核苷酸的溶液与包含连接多核苷酸的溶液组合以形成杂交混合物,其中组合在促进互补多核苷酸之间形成杂交复合物的条件下进行,并且其中每个单独的连接多核苷酸以基于 分配给个体连接多核苷酸的加权值; 连接存在于杂交复合物中的多核苷酸以形成连接产物; 并确定连接产物的浓度,其中以最高浓度存在的连接产物表示非确定性多项式优化问题的最佳答案。
    • 7. 发明申请
    • Single Molecule Detection Using Molecular Motors
    • 使用分子电机的单分子检测
    • US20090035751A1
    • 2009-02-05
    • US10582820
    • 2004-12-17
    • Lyian HeWayne Frasch
    • Lyian HeWayne Frasch
    • C12Q1/68
    • C12Q1/6825C12Q1/6834C12Q2565/619C12Q2531/137C12Q2533/107C12Q2565/601C12Q2565/629C12Q2563/125
    • The present invention provides methods and compositions for highly sensitive nucleic acid detection, down to the single nucleic acid molecule level. In one aspect, the present invention provides methods for detecting a target nucleic acid comprising: (a) providing first and second target-specific nucleic acids, wherein the first and second target-specific nucleic acids each comprise sequences complementary to the target nucleic acid; wherein the first target specific nucleic acid is bound to a first affinity tag and the second target-specific nucleic acid is bound to a second affinity tag, wherein the first affinity tag is capable of binding to a molecular motor, and wherein the second affinity tag is capable of binding to a detection probe; (b) contacting the first and second target-specific nucleic acids to a sample under conditions whereby the first and second target-specific nucleic acids will hybridize to the target nucleic acid if the target nucleic acid is present in the sample, wherein upon hybridization to the target nucleic acid the first and second target-specific nucleic acids are directly adjacent to each other; (c) ligating the first and second target-specific nucleic acids together; (d) binding the molecular motor t˜ the first affinity tag and the detection probe to the second affinity tag; (e) inducing movement of the molecular motor; and (f) detecting movement of the molecular motor through the detection probe, wherein the movement of the molecular motor serves to detect the target nucleic acid in the sample.
    • 本发明提供用于高度敏感的核酸检测的方法和组合物,直到单个核酸分子水平。 一方面,本发明提供了用于检测靶核酸的方法,包括:(a)提供第一和第二靶特异性核酸,其中第一和第二靶特异性核酸各自包含与靶核酸互补的序列; 其中所述第一靶特异性核酸与第一亲和标签结合,并且所述第二靶特异性核酸与第二亲和标签结合,其中所述第一亲和标签能够结合分子马达,并且其中所述第二亲和标签 能够结合检测探针; (b)在条件下使第一和第二靶特异性核酸与样品接触,其中如果靶核酸存在于样品中,则第一和第二靶特异性核酸将与靶核酸杂交,其中在与 靶核酸第一和第二靶特异性核酸彼此直接相邻; (c)将第一和第二靶特异性核酸连接在一起; (d)将第一亲和标签和检测探针的分子马达结合到第二亲和标签上; (e)诱导分子马达的运动; 和(f)检测分子马达通过检测探针的运动,其中分子马达的移动用于检测样品中的靶核酸。
    • 9. 发明授权
    • Single molecule detection using molecular motors
    • 使用分子马达进行单分子检测
    • US08076079B2
    • 2011-12-13
    • US10582820
    • 2004-12-17
    • Wayne FraschLyian He
    • Wayne FraschLyian He
    • C12Q1/68C12M1/34C07H21/04C07H21/02
    • C12Q1/6825C12Q1/6834C12Q2565/619C12Q2531/137C12Q2533/107C12Q2565/601C12Q2565/629C12Q2563/125
    • The present invention provides methods and compositions for highly sensitive nucleic acid detection, down to the single nucleic acid molecule level. In one aspect, the present invention provides methods for detecting a target nucleic acid comprising: (a) providing first and second target-specific nucleic acids, wherein the first and second target-specific nucleic acids each comprise sequences complementary to the target nucleic acid; wherein the first target specific nucleic acid is bound to a first affinity tag and the second target-specific nucleic acid is bound to a second affinity tag, wherein the first affinity tag is capable of binding to a molecular motor, and wherein the second affinity tag is capable of binding to a detection probe; (b) contacting the first and second target-specific nucleic acids to a sample under conditions whereby the first and second target-specific nucleic acids will hybridize to the target nucleic acid if the target nucleic acid is present in the sample, wherein upon hybridization to the target nucleic acid the first and second target-specific nucleic acids are directly adjacent to each other; (c) ligating the first and second target-specific nucleic acids together; (d) binding the molecular motor t˜ the first affinity tag and the detection probe to the second affinity tag; (e) inducing movement of the molecular motor; and (f) detecting movement of the molecular motor through the detection probe, wherein the movement of the molecular motor serves to detect the target nucleic acid in the sample.
    • 本发明提供用于高度敏感的核酸检测的方法和组合物,直到单个核酸分子水平。 一方面,本发明提供了用于检测靶核酸的方法,包括:(a)提供第一和第二靶特异性核酸,其中第一和第二靶特异性核酸各自包含与靶核酸互补的序列; 其中所述第一靶特异性核酸与第一亲和标签结合,并且所述第二靶特异性核酸与第二亲和标签结合,其中所述第一亲和标签能够结合分子马达,并且其中所述第二亲和标签 能够结合检测探针; (b)在条件下使第一和第二靶特异性核酸与样品接触,其中如果靶核酸存在于样品中,则第一和第二靶特异性核酸将与靶核酸杂交,其中在与 靶核酸第一和第二靶特异性核酸彼此直接相邻; (c)将第一和第二靶特异性核酸连接在一起; (d)将分子马达t〜第一亲和标签和检测探针结合到第二亲和标签上; (e)诱导分子马达的运动; 和(f)检测分子马达通过检测探针的运动,其中分子马达的移动用于检测样品中的靶核酸。