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公开(公告)号：US07067322B2
公开(公告)日：2006-06-27
申请号：US10099424
申请日：2002-03-15
申请人： Robert M. Corn , Emily A. Smith , Bernard Weisblum , Matthew G. Erickson , Andrew T. Ulijasz , Matthew J. Wanat
发明人： Robert M. Corn , Emily A. Smith , Bernard Weisblum , Matthew G. Erickson , Andrew T. Ulijasz , Matthew J. Wanat
IPC分类号： G01N33/00 , G01N33/53 , C07C319/02
CPC分类号： C40B40/06 , B01J2219/00274 , B01L2300/0636 , B82Y30/00 , C40B30/10 , C40B40/10 , C40B50/18 , G01N33/54353 , Y10T436/18 , Y10T436/182
摘要： Disclosed are methods for making surface plasmon resonance-capable arrays wherein molecules, such as proteins or nucleic acids, or cells, are adhered to a metal substrate. The metal substrates are modified by depositing an ω-modified alkanethiol monolayer to the substrate and then contacting the ω-modified monolayer with a heterobifunctional linking compound. Biomolecules or cells can then be attached to the heterobifunctional linking compound. Also disclosed are arrays wherein glutathione-containing molecules are immobilized on the substrate and GST-containing molecules are then specifically immobilized onto the substrate, taking advantage of the affinity between glutathione and GST.
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公开(公告)号：US07002004B2
公开(公告)日：2006-02-21
申请号：US10260923
申请日：2002-09-30
CPC分类号： B82Y30/00 , B01J19/0046 , B01J2219/00317 , B01J2219/00432 , B01J2219/00497 , B01J2219/00527 , B01J2219/00576 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00686 , B01J2219/00722 , B01J2219/00743 , B82Y40/00 , C40B40/06 , C40B60/14
摘要： Disclosed is a process to construct multi-component biomolecule or cellular arrays suitable for use in SPR imaging studies of large molecule, cellular/molecular, and cell/cell interactions. Also disclosed are the resulting arrays. The success of the procedure hinges on the use of a reversible protecting group to modify reversibly ω-functionalized alkanethiols self-assembled on metal substrates. The arrays themselves include a metal substrate, a continuous layer of an identical ω-modified alkanthiol adhered to the metal substrate, and one or more discrete spots of biomolecules or cells directly bonded to the continuous layer of ω-modified alkenthiol. The areas of the continuous layer of ω-modified alkenthiol not covered by one of the discrete spots are covered by a background material resistant to non-specific protein binding.
摘要翻译： 公开了一种构建适用于大分子，细胞/分子和细胞/细胞相互作用的SPR成像研究的多组分生物分子或细胞阵列的方法。 还公开了所得到的阵列。 该方法的成功取决于使用可逆保护基团来修饰在金属底物上自组装的可逆的ω-官能化的烷硫醇。 阵列本身包括金属基底，附着到金属基底上的相同的ω-改性的烷基醇的连续层，以及直接连接到ω-改性的链烷醇的连续层的生物分子或细胞的一个或多个离散点。 未被一个离散斑点覆盖的欧米加修饰的硫醇的连续层的区域被抗非特异性蛋白质结合的背景材料覆盖。
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公开(公告)号：US09651487B2
公开(公告)日：2017-05-16
申请号：US12037332
申请日：2008-02-26
申请人： Lloyd M. Smith , Matthew R. Lockett , Michael R. Shortreed , Robert M. Corn , Stephen Weibel , Robert J. Hamers , Bin Sun
发明人： Lloyd M. Smith , Matthew R. Lockett , Michael R. Shortreed , Robert M. Corn , Stephen Weibel , Robert J. Hamers , Bin Sun
IPC分类号： G02B5/04 , G01N21/552
CPC分类号： G01N21/553 , G02B5/04
摘要： SPR-compatible substrates for high density microarray fabrication and analyses are provided. Novel carbon-on-metal thin film substrate architecture permits the integration of surface plasmon resonance detection with photolithographically fabricated biomolecule arrays for the analysis of biomolecular interactions. The utility of the technology is shown in the analysis of specific DNA-DNA, DNA-RNA and DNA-protein binding interactions. These new substrates may be used to determine the secondary structure of RNA molecules, to probe the sequence-specific binding kinetics and affinity of proteins and small molecules, and as substrates for small-molecule combinatorial chemistry platforms for drug discovery applications.
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公开(公告)号：US06849397B2
公开(公告)日：2005-02-01
申请号：US09998551
申请日：2001-11-29
IPC分类号： C07H21/04 , C12M1/34 , C12P13/14 , C12Q1/68 , C12Q1/70 , G01J4/00 , G01N20060101 , G01N33/48 , G01N33/50 , G06F19/00
CPC分类号： B82Y30/00 , B82Y15/00 , C12Q1/6837 , C12Q2565/628
摘要： Disclosed is a method to detect unlabeled nucleic acids (DNA and/or RNA) in a taxa, species, and organelle-specific fashion using surface plasmon resonance (SPR) imaging. Taxa-specific, species-specific, or organelle-specific nucleic acids are affixed to an SPR-suitable substrate. A nucleic acid sample to be analyzed is then contacted with the SPR-substrate and the substrate analyzed to determine the presence or absence of specific hybridization between the nucleic acids bound to the substrate and the nucleic acids contained in the sample. The method does not require that either the bound nucleic acids nor the sample nucleic acids be labeled. The method can be used to identify the source of nucleic acids, their sequence, as well as to identify organisms and place them within a given taxonomic hierarchy.
摘要翻译： 公开了一种使用表面等离子体共振（SPR）成像检测分类群，物种和细胞器特异性方式中的未标记核酸（DNA和/或RNA）的方法。 分子标记特异性，物种特异性或细胞器特异性核酸固定在适合SPR的底物上。 待分析的核酸样品然后与SPR-底物接触并分析底物，以确定与底物结合的核酸与样品中所含核酸之间是否存在特异性杂交。 该方法不要求结合的核酸和样品核酸都被标记。 该方法可用于鉴定核酸的来源，其序列，以及鉴定生物体并将其置于给定的分类层级中。
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5.发明授权Process to create biomolecule and/or cellular arrays on metal surfaces and product produced thereby 失效在金属表面上产生生物分子和/或细胞阵列的方法和由此产生的产物
公开(公告)号：US6127129A
公开(公告)日：2000-10-03
申请号：US368991
申请日：1999-08-05
IPC分类号： G01N33/566 , B01J19/00 , C12M1/00 , C12N15/09 , C12Q1/68 , G01N33/53 , G01N33/543 , G01N33/553 , G01N37/00 , G03F9/00
CPC分类号： B82Y30/00
摘要： Disclosed is a process to construct multi-component biomolecule or cellular arrays suitable for use in SPR imaging studies of large molecule, cellular/molecular, and cell/cell interactions. The success of the procedure hinges on the use of a reversible protecting group to modify reversibly .omega.-functionalized alkanethiols self-assembled on metal substrates.
摘要翻译： 本发明提供编码哺乳动物甘氨酸转运蛋白的分离的核酸分子，编码人甘氨酸转运蛋白的分离的核酸分子，作为哺乳动物甘氨酸转运蛋白的分离的蛋白质，作为人甘氨酸转运蛋白的分离的蛋白质，包含编码哺乳动物的分离的核酸分子的载体 或人甘氨酸转运蛋白，包含此类载体的哺乳动物细胞，针对哺乳动物甘氨酸转运蛋白的抗体，针对人甘氨酸转运蛋白的抗体，用于检测编码哺乳动物甘氨酸转运蛋白的核酸的核酸探针，用于检测核酸编码的核酸探针 人甘氨酸转运蛋白，与编码哺乳动物甘氨酸转运蛋白的核酸分子的任何序列互补的反义寡核苷酸，与编码人甘氨酸转运蛋白的核酸所述分子的任何序列互补的反义寡核苷酸，ph 与哺乳动物甘氨酸转运蛋白和非人转运蛋白相关的药物化合物，与人甘氨酸转运蛋白相关的药物化合物和非人类转基因动物，其表达编码正常或突变型哺乳动物或人甘氨酸转运蛋白的DNA。 本发明还提供了用于确定配体结合，检测表达，药物筛选和用于减轻与哺乳动物甘氨酸转运蛋白相关的异常的治疗的方法。 本发明还提供了用于确定配体结合，检测表达，药物筛选和用于减轻与人甘氨酸转运蛋白相关的异常的治疗的方法。
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6.发明授权公开(公告)号：US07265844B2
公开(公告)日：2007-09-04
申请号：US10602243
申请日：2003-06-24
申请人： Eric P. Codner , Robert M. Corn
发明人： Eric P. Codner , Robert M. Corn
IPC分类号： G01N21/55
CPC分类号： G01N21/553
摘要： A surface plasmon resonance imaging apparatus provides an improved optical assembly allowing fixed source and detector operating with a horizontal test surface for a more compact design. In a preferred embodiment, a mechanical linkage of planar mirrors provides a single point adjustment of angle of incidence and angle of refraction while maintaining a constant optical axis of the source and detector.
摘要翻译： 表面等离子体共振成像装置提供改进的光学组件，其允许固定的源和检测器与水平测试表面一起操作以用于更紧凑的设计。 在优选实施例中，平面镜的机械连杆提供入射角和折射角的单点调整，同时保持源和检测器的恒定的光轴。
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7.发明授权Biomolecule and/or cellular arrays on metal surfaces and product produced thereby 有权金属表面上的生物分子和/或细胞阵列以及由此产生的产物公开(公告)号：US06489102B2
公开(公告)日：2002-12-03
申请号：US09456038
申请日：1999-12-03
IPC分类号： C12Q168
CPC分类号： B82Y30/00 , B01J19/0046 , B01J2219/00317 , B01J2219/00432 , B01J2219/00497 , B01J2219/00527 , B01J2219/00576 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00612 , B01J2219/00617 , B01J2219/00626 , B01J2219/00637 , B01J2219/00659 , B01J2219/00686 , B01J2219/00722 , B01J2219/00743 , B82Y40/00 , C40B40/06 , C40B60/14
摘要： Disclosed is a process to construct multi-component biomolecule or cellular arrays suitable for use in SPR imaging studies of large molecule, cellular/molecular, and cell/cell interactions. The success of the procedure hinges on the use of a reversible protecting group to modify reversibly &ohgr;-functionalized alkanethiols self-assembled on metal substrates.
摘要翻译： 公开了一种构建适用于大分子，细胞/分子和细胞/细胞相互作用的SPR成像研究的多组分生物分子或细胞阵列的方法。 该方法的成功取决于使用可逆保护基团来修饰在金属底物上自组装的可逆的ω-官能化的烷硫醇。
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公开(公告)号：US07670556B2
公开(公告)日：2010-03-02
申请号：US10192026
申请日：2002-07-10
申请人： Robert M. Corn , Hye Jin Lee , Terry T. Goodrich
发明人： Robert M. Corn , Hye Jin Lee , Terry T. Goodrich
CPC分类号： B01J19/0046 , B01J2219/00274 , B01L3/502707 , B01L2200/12 , B01L2200/16 , B01L2300/0636 , B82Y15/00 , B82Y30/00 , C12Q1/6837 , G01N21/253 , G01N21/553 , G01N21/6458 , C12Q2565/629
摘要： Disclosed is a method for fabricating 1-dimensional micro-arrays using parallel micro-fluidic channels on chemically-modified metal, carbon, silicon, and/or germanium surfaces; a μL detection volume method that uses 2-dimensional nucleic acid micro-arrays formed by employing the 1-dimensional DNA micro-arrays in conjunction with a second set of parallel micro-fluidic channels for solution delivery, and the 1-dimensional and 2-dimensional arrays used in the methods. The methodology allows the rapid creation of 1- and 2-dimensional arrays for SPR imaging and fluorescence imaging of DNA-DNA, DNA-RNA, DNA-protein, and protein-protein binding events. The invention enables very small volumes necessary for a variety of bioassay applications to be analyzed by SPR. Target solution volumes as small as 200 pL can be analyzed.
摘要翻译： 公开了一种在化学改性的金属，碳，硅和/或锗表面上使用平行微流体通道制造一维微阵列的方法; 一种检测体积方法，其使用通过使用一维DNA微阵列与第二组平行微流体通道结合形成的二维核酸微阵列用于溶液递送，以及1维和2- 方法中使用的三维数组。 该方法允许快速创建用于SPR成像和DNA-DNA，DNA-RNA，DNA-蛋白和蛋白质 - 蛋白质结合事件的荧光成像的1维和2维阵列。 本发明使得通过SPR分析各种生物测定应用所需的非常小的体积。 可以分析小至200 pL的目标溶液体积。
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公开(公告)号：US20090141376A1
公开(公告)日：2009-06-04
申请号：US12037332
申请日：2008-02-26
申请人： Lloyd M. Smith , Matthew R. Lockett , Michael R. Shortreed , Robert M. Corn , Stephen Weibel , Robert J. Hamers , Bin Sun
发明人： Lloyd M. Smith , Matthew R. Lockett , Michael R. Shortreed , Robert M. Corn , Stephen Weibel , Robert J. Hamers , Bin Sun
CPC分类号： G01N21/553 , G02B5/04
摘要： SPR-compatible substrates for high density microarray fabrication and analyses are provided. Novel carbon-on-metal thin film substrate architecture permits the integration of surface plasmon resonance detection with photolithographically fabricated biomolecule arrays for the analysis of biomolecular interactions. The utility of the technology is shown in the analysis of specific DNA-DNA, DNA-RNA and DNA-protein binding interactions. These new substrates may be used to determine the secondary structure of RNA molecules, to probe the sequence-specific binding kinetics and affinity of proteins and small molecules, and as substrates for small-molecule combinatorial chemistry platforms for drug discovery applications.
摘要翻译： 提供了用于高密度微阵列制造和分析的SPR兼容基板。 新的碳 - 金属薄膜基板架构允许将表面等离子体共振检测与光刻制造的生物分子阵列整合以用于生物分子相互作用的分析。 该技术的实用性在特异性DNA-DNA，DNA-RNA和DNA-蛋白结合相互作用的分析中显示。 这些新的底物可用于确定RNA分子的二级结构，以探测序列特异性结合动力学和蛋白质和小分子的亲和力，以及作为用于药物发现应用的小分子组合化学平台的底物。
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公开(公告)号：US07148968B2
公开(公告)日：2006-12-12
申请号：US10411583
申请日：2003-04-10
申请人： Eric P. Codner , Robert M. Corn
发明人： Eric P. Codner , Robert M. Corn
IPC分类号： G01N21/55
CPC分类号： G01N21/553
摘要： A surface plasmon resonant device provides practical portable operation through the use of a low power high efficiency LED source and a high-efficiency prism sample cell pre-loaded with probe molecules and sealed for field use. A simple mechanical control allows adjustment of angulation of the light and camera for accurate response outside of the laboratory.
摘要翻译： 表面等离子体共振装置通过使用低功率高效率LED源和预先加载探针分子的高效棱镜样品池提供实用的便携式操作，并且密封用于现场使用。 简单的机械控制允许调整光和照相机的角度，以便在实验室外部进行准确的响应。
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