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1. 发明申请

WO2009146157A2 METHODS OF GENERATING FLORESCENCE RESONANCE ENERGY TRANSFER (FRET) BETWEEN SEMICONDUCTOR QUANTUM DOTS AND FLUORESCENT DYES/PROTEINS VIA MULTI-PHOTON EXCITATION, ACHIEVING ZERO BACKGROUND OR DIRECT EXCITATION CONTRIBUTIONS TO THE FRET SIGNATURE 审中-公开
标题翻译：通过多光子激发产生半导体量子点和荧光染料/蛋白质之间的花色共振能量转移（FRET）的方法，实现零背景或直接激发对FRET签名的贡献
公开(公告)号：WO2009146157A2
公开(公告)日：2009-12-03
申请号：PCT/US2009/040062
申请日：2009-04-09
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE NAVY , MATTOUSSI, Hedi, M , MEDINTZ, Igor, L , CLAPP, Aaron, R
发明人： MATTOUSSI, Hedi, M , MEDINTZ, Igor, L , CLAPP, Aaron, R
IPC分类号： G01J5/02 , G01N33/554
CPC分类号： G01N21/6428 , G01N21/6408 , G01N21/6458 , G01N21/6489 , G01N33/542 , Y02A90/26
摘要： A system and method of sensing physiological conditions in biological applications includes a laser source for optically exciting a plurality of luminescent quantum dots and a plurality of biomolecules in a nanoscale sensing system having a nanocrystal structure, where the plurality of biomolecules is stained with dye. In a multi-photon excitation process, a laser system optically excites, the plurality of luminescent quantum dots and the plurality of biomolecules in the nanoscale sensing system, where fluorescence resonance energy transfer (FRET) occurs between the plurality of quantum dots and the plurality of biomolecules. Stability of self assembly of quantum dot peptide conjugates within the plurality of biomolecules is investigated. Physiological conditions at the cellular level are determined, using a spectrometer to sense fluorosence spectra. The sensing of physiological conditions includes transducing signals into immunoassays, clinical diagnostics and cellular imaging to provide treatment to biological subjects including human patients.
摘要翻译：在生物学应用中感测生理条件的系统和方法包括用于在具有纳米晶体结构的纳米级感测系统中光学激发多个发光量子点的激光源和多个生物分子，其中多个生物分子被染料染色。在多光子激发过程中，激光系统在纳米级感测系统中光学激发多个发光量子点和多个生物分子，其中在多个量子点与多个量子点之间发生荧光共振能量转移（FRET）生物分子。研究了多个生物分子内量子点肽缀合物自组装的稳定性。使用光谱仪检测荧光光谱，测定细胞水平的生理条件。对生理条件的检测包括将信号转导到免疫测定，临床诊断和细胞成像中，以向包括人类患者在内的生物学受试者提供治疗。

2. 发明申请

WO2011056575A3 COVALENT ATTACHMENT OF PEPTIDES AND BIOLOGICAL MOLECULES TO LUMINESCENT SEMICONDUCTOR NANOCRYSTALS 审中-公开
标题翻译：共价连接多肽和生物分子发光半导体纳米晶
公开(公告)号：WO2011056575A3
公开(公告)日：2011-09-15
申请号：PCT/US2010054099
申请日：2010-10-26
申请人： US GOV SEC NAVY , MATTOUSSI HEDI M , DAWSON PHILIP E , UYEDA HARRY TETSUO , MEDINTZ IGOR L , SCHEINOST JOHANNA
发明人： MATTOUSSI HEDI M , DAWSON PHILIP E , UYEDA HARRY TETSUO , MEDINTZ IGOR L , SCHEINOST JOHANNA
IPC分类号： G01N33/68 , B82B3/00 , G01N33/53 , G01N33/58
CPC分类号： C07K1/13 , B82Y15/00 , C07K1/042 , G01N33/587 , G01N33/588
摘要： A method is described for covalent attachment of peptides to luminescent quantum dots or other inorganic nanoparticles. The first step in the method involves functionalizing at least a portion of a surface of the quantum dot or nanoparticle with one or more materials having at least one reactive functional group therein. Subsequently, a peptide having a reactive functional group is reacted with at least some of the quantum dot or nanoparticle reactive functional groups to covalently bond at least some of the peptide to the quantum dots or nanoparticles. Modifications of the basic method are disclosed which provide methods allowing customized fabrication of quantum dots having a variety of different functional properties and combinations of functional properties. Also disclosed are quantum dots and nanoparticles made by the methods described herein.
摘要翻译：描述了将肽共价连接至发光量子点或其他无机纳米粒子的方法。该方法的第一步包括用一种或多种其中具有至少一个反应性官能团的材料使量子点或纳米粒子的至少一部分表面功能化。随后，使具有反应性官能团的肽与至少一些量子点或纳米颗粒反应性官能团反应，以将至少一些肽与量子点或纳米颗粒共价键合。公开了基本方法的修改，其提供了允许定制制造具有多种不同功能性质和功能性质组合的量子点的方法。还公开了通过本文所述的方法制备的量子点和纳米粒子。

3. 发明申请

WO2010123973A1 MULTIFUNCTIONAL METAL-CHELATING LIGANDS 审中-公开
标题翻译：多功能金属联锁配置
公开(公告)号：WO2010123973A1
公开(公告)日：2010-10-28
申请号：PCT/US2010/031868
申请日：2010-04-21
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE NAVY , STEWART, Michael , SUSUMU, Kimihiro , MEI, Bing, C. , MATTOUSSI, Hedi, M
发明人： STEWART, Michael , SUSUMU, Kimihiro , MEI, Bing, C. , MATTOUSSI, Hedi, M
IPC分类号： B32B5/16
CPC分类号： C07C323/60 , C07D339/04 , Y02P20/55
摘要： Disclosed herein are the compounds shown below and methods of their synthesis. The value m is a positive integer. R comprises an alkyl chain or an alkoxy chain. Each X comprises a metal binding group. Each E is a methoxy group or comprises a biomolecule reactive group or a residue thereof. E optionally comprises a protecting group. The value n is a positive integer. The value p is zero or one. Y is OCH3, OH, NH2, or COOH.
摘要翻译：本文公开了下文所示的化合物及其合成方法。值m是正整数。 R包括烷基链或烷氧基链。每个X包含金属结合基团。每个E是甲氧基或包含生物分子反应性基团或其残基。 E任选地包含保护基团。值n为正整数。值p为零或一。 Y是OCH 3，OH，NH 2或COOH。

4. 发明申请

WO2009146157A3 METHODS OF GENERATING FLORESCENCE RESONANCE ENERGY TRANSFER 审中-公开
标题翻译：生成花生共振能量转移的方法
公开(公告)号：WO2009146157A3
公开(公告)日：2010-02-25
申请号：PCT/US2009040062
申请日：2009-04-09
申请人： US GOV SEC NAVY , MATTOUSSI HEDI M , MEDINTZ IGOR L , CLAPP AARON R
发明人： MATTOUSSI HEDI M , MEDINTZ IGOR L , CLAPP AARON R
IPC分类号： G01J5/02 , G01N33/554
CPC分类号： G01N21/6428 , G01N21/6408 , G01N21/6458 , G01N21/6489 , G01N33/542 , Y02A90/26
摘要： A system and method of sensing physiological conditions in biological applications includes a laser source for optically exciting a plurality of luminescent quantum dots and a plurality of biomolecules in a nanoscale sensing system having a nanocrystal structure, where the plurality of biomolecules is stained with dye. In a multi-photon excitation process, a laser system optically excites, the plurality of luminescent quantum dots and the plurality of biomolecules in the nanoscale sensing system, where fluorescence resonance energy transfer (FRET) occurs between the plurality of quantum dots and the plurality of biomolecules. Stability of self assembly of quantum dot peptide conjugates within the plurality of biomolecules is investigated. Physiological conditions at the cellular level are determined, using a spectrometer to sense fluorosence spectra. The sensing of physiological conditions includes transducing signals into immunoassays, clinical diagnostics and cellular imaging to provide treatment to biological subjects including human patients.
摘要翻译：在生物学应用中感测生理条件的系统和方法包括用于在具有纳米晶体结构的纳米级感测系统中光学激发多个发光量子点的激光源和多个生物分子，其中多个生物分子被染料染色。在多光子激发过程中，激光系统在纳米级感测系统中光学激发多个发光量子点和多个生物分子，其中在多个量子点与多个量子点之间发生荧光共振能量转移（FRET）生物分子。研究了多个生物分子内量子点肽缀合物自组装的稳定性。使用光谱仪检测荧光光谱，测定细胞水平的生理条件。对生理条件的检测包括将信号转导到免疫测定，临床诊断和细胞成像中，以向包括人类患者在内的生物学受试者提供治疗。

5. 发明申请

WO2006036646A1 THE FIELD OF MODULAR MULTIFUNCTIONAL LIGANDS 审中-公开
标题翻译：模块化多功能配置领域
公开(公告)号：WO2006036646A1
公开(公告)日：2006-04-06
申请号：PCT/US2005/033591
申请日：2005-09-20
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF THE NAVY , UYEDA, Harry, T. , MATTOUSSI, Hedi , MEDINTZ, Igor, L.
发明人： UYEDA, Harry, T. , MATTOUSSI, Hedi , MEDINTZ, Igor, L.
IPC分类号： G01N33/551
CPC分类号： B82Y15/00 , B82Y5/00 , B82Y10/00 , G01N33/532 , G01N33/588 , Y10T436/182
摘要： This invention pertains to a surface ligand; preparation of the ligand; colloidal nanoparticle, such as quantum dot bearing one or more of the ligand; and a bioconjugate characterized by a nanoparticle bearing one or more of the ligand conjugated to a biomolecule. The ligand is characterized by the presence of a first module containing atoms that can attach to an inorganic surface; a second module that imparts water-solubility to the ligand and to the inorganic surface that may be attached to the ligand; and a third module that contains a functional group that can, directly or indirectly, conjugate to a biomolecule. Order of the modules can be different and other modules and groups can be on the ligand. Preparation of the ligand includes the steps of reacting a compound having atoms that can attach to an inorganic surface with a water-solubilizing compound that imparts the property of water-solubility to the ligand and the inorganic surface to which it may be attached and purification thereof. Colloidal nanoparticle is characterized by an inorganic surface having attached to it one or more of the ligands. The colloidal bioconjugate is characterized by an inorganic surface having attached thereto one or more of the ligand wherein at least some of the ligand have a biomolecule conjugated thereto.
摘要翻译：本发明涉及表面配体; 配体的制备; 胶体纳米颗粒，例如带有一个或多个配体的量子点; 其特征在于具有一个或多个与生物分子缀合的配体的纳米颗粒。该配体的特征在于存在可以附着到无机表面上的原子的第一模块; 赋予配体和附着于配体的无机表面的水溶性的第二模块; 以及包含可以直接或间接缀合到生物分子的官能团的第三模块。模块的顺序可以不同，其他模块和组可以在配体上。配体的制备包括以下步骤：将具有可附着于无机表面的原子的化合物与赋予其可配位的无机表面和赋予其水溶性的水溶性化合物反应。胶体纳米颗粒的特征在于其上连接有一个或多个配体的无机表面。胶体生物缀合物的特征在于其上附着有一种或多种配体的无机表面，其中至少一些配体具有与其缀合的生物分子。

6. 发明申请

WO2011050039A3 MODULAR FUNCTIONAL PEPTIDES FOR THE INTRACELLULAR DELIVERY OF NANOPARTICLES 审中-公开
标题翻译：纳米颗粒细胞递送的模块功能肽
公开(公告)号：WO2011050039A3
公开(公告)日：2011-08-18
申请号：PCT/US2010053341
申请日：2010-10-20
申请人： US GOV SEC NAVY , DELEHANTY JAMES B , MEDINTZ IGOR L , MATTOUSSI HEDI M , DESCHAMPS JEFFREY R , DAWSON GLYN , DAWSON PHILIP E , BLANCO-CANOSA JUAN BAUTISTA , BOENEMAN KELLY
发明人： DELEHANTY JAMES B , MEDINTZ IGOR L , MATTOUSSI HEDI M , DESCHAMPS JEFFREY R , DAWSON GLYN , DAWSON PHILIP E , BLANCO-CANOSA JUAN BAUTISTA , BOENEMAN KELLY
IPC分类号： A61K9/127 , A61K9/38 , A61K9/51 , A61K47/02 , A61K47/30 , A61K47/42 , G01N33/68
CPC分类号： C07H21/04 , A61K47/6921 , A61K49/0093 , B82Y5/00 , C07H19/00
摘要： Described are peptides for delivery of a nanoparticle to the cytosol, the peptide comprising: (a) a nanoparticle association domain; (b) a proline-rich spacer domain; (c) an uptake domain; and (d) a vesicle escape domain comprising a non-hydrolyzable lipid moiety, wherein the spacer domain is between the nanoparticle association domain and the uptake and vesicle escape domains, and wherein the peptide, when attached to an extracellular nanoparticle, is effective to induce uptake of the nanoparticle by a cell and delivery of the nanoparticle to the cytosol of the cell. Also described are methods of delivery of a nanoparticle to the cytosol of a cell, the method comprising providing to a cell a nanoparticle attached to such a peptide. Exemplary nanoparticles include quantum dots.
摘要翻译：描述了用于将纳米颗粒递送到细胞溶质的肽，所述肽包含：（a）纳米颗粒缔合结构域; （b）富含脯氨酸的间隔区; （c）摄取域; 和（d）包含不可水解脂质部分的囊泡逃逸结构域，其中所述间隔区位于纳米颗粒缔合结构域和吸收和囊泡逃逸结构域之间，并且其中所述肽在附着于细胞外纳米颗粒时有效诱导通过细胞摄取纳米颗粒并将纳米颗粒递送到细胞的胞质溶胶。还描述了将纳米颗粒递送到细胞的细胞溶质的方法，该方法包括向细胞提供与这种肽连接的纳米颗粒。示例性纳米颗粒包括量子点。

7. 发明申请

WO2011056575A2 COVALENT ATTACHMENT OF PEPTIDES AND BIOLOGICAL MOLECULES TO LUMINESCENT SEMICONDUCTOR NANOCRYSTALS 审中-公开
标题翻译：肽和生物分子共价连接到发光半导体纳米晶体
公开(公告)号：WO2011056575A2
公开(公告)日：2011-05-12
申请号：PCT/US2010/054099
申请日：2010-10-26
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by the secretary of THE NAVY , MATTOUSSI, Hedi, M. , DAWSON, Philip, E. , UYEDA, Harry, Tetsuo , MEDINTZ, Igor, L. , SCHEINOST, Johanna
发明人： MATTOUSSI, Hedi, M. , DAWSON, Philip, E. , UYEDA, Harry, Tetsuo , MEDINTZ, Igor, L. , SCHEINOST, Johanna
IPC分类号： G01N33/68 , G01N33/53 , G01N33/58 , B82B3/00
CPC分类号： C07K1/13 , B82Y15/00 , C07K1/042 , G01N33/587 , G01N33/588
摘要： A method is described for covalent attachment of peptides to luminescent quantum dots or other inorganic nanoparticles. The first step in the method involves functionalizing at least a portion of a surface of the quantum dot or nanoparticle with one or more materials having at least one reactive functional group therein. Subsequently, a peptide having a reactive functional group is reacted with at least some of the quantum dot or nanoparticle reactive functional groups to covalently bond at least some of the peptide to the quantum dots or nanoparticles. Modifications of the basic method are disclosed which provide methods allowing customized fabrication of quantum dots having a variety of different functional properties and combinations of functional properties. Also disclosed are quantum dots and nanoparticles made by the methods described herein.
摘要翻译：描述了将肽共价连接到发光量子点或其它无机纳米粒子的方法。该方法的第一步包括用其中具有至少一个反应性官能团的一种或多种材料官能化量子点或纳米颗粒的表面的至少一部分。随后，具有反应性官能团的肽与至少一些量子点或纳米颗粒反应性官能团反应，以将至少一些肽共价结合到量子点或纳米颗粒上。公开了基本方法的修改，其提供允许定制制造具有各种不同功能特性和功能性质的组合的量子点的方法。还公开了通过本文所述的方法制备的量子点和纳米颗粒。

8. 发明申请

WO0171354A3 INORGANIC PARTICLE CONJUGATES 审中-公开
标题翻译：无机颗粒混合物
公开(公告)号：WO0171354A3
公开(公告)日：2002-08-01
申请号：PCT/US0108788
申请日：2001-03-20
申请人： MASSACHUSETTS INST TECHNOLOGY , NAVAL RES LAB , MATTOUSSI HEDI , ANDERSON GEORGE P , MAURO J MATTHEW , BAWENDI MOUNGI G , SUNDAR VIKRAM C
发明人： MATTOUSSI HEDI , ANDERSON GEORGE P , MAURO J MATTHEW , BAWENDI MOUNGI G , SUNDAR VIKRAM C
IPC分类号： G01N33/566 , G01N33/53 , G01N33/551 , G01N33/58 , G01N33/543 , G01N33/547
CPC分类号： B82Y15/00 , G01N33/551 , G01N33/588
摘要： The ionic conjugates include an inorganic particle electrostatically associated with a macromolecule which can interact specifically with predetermined chemical species or biological targets.
摘要翻译：离子共轭物包括与大分子静电相关的无机颗粒，其可以与预定的化学物质或生物靶相互作用。

9. 发明申请

WO2011050039A2 MODULAR FUNCTIONAL PEPTIDES FOR THE INTRACELLULAR DELIVERY OF NANOPARTICLES 审中-公开
标题翻译：用于纳米颗粒胞内传递的模块化功能肽
公开(公告)号：WO2011050039A2
公开(公告)日：2011-04-28
申请号：PCT/US2010/053341
申请日：2010-10-20
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE NAVY , DELEHANTY, James, B. , MEDINTZ, Igor, L. , MATTOUSSI, Hedi, M. , DESCHAMPS, Jeffrey, R. , DAWSON, Glyn , DAWSON, Philip, E. , BLANCO-CANOSA, Juan Bautista , BOENEMAN, Kelly
发明人： DELEHANTY, James, B. , MEDINTZ, Igor, L. , MATTOUSSI, Hedi, M. , DESCHAMPS, Jeffrey, R. , DAWSON, Glyn , DAWSON, Philip, E. , BLANCO-CANOSA, Juan Bautista , BOENEMAN, Kelly
IPC分类号： A61K9/127 , A61K9/38 , A61K9/51 , A61K47/30 , A61K47/42 , A61K47/02 , G01N33/68
CPC分类号： C07H21/04 , A61K47/6921 , A61K49/0093 , B82Y5/00 , C07H19/00
摘要： Described are peptides for delivery of a nanoparticle to the cytosol, the peptide comprising: (a) a nanoparticle association domain; (b) a proline-rich spacer domain; (c) an uptake domain; and (d) a vesicle escape domain comprising a non-hydrolyzable lipid moiety, wherein the spacer domain is between the nanoparticle association domain and the uptake and vesicle escape domains, and wherein the peptide, when attached to an extracellular nanoparticle, is effective to induce uptake of the nanoparticle by a cell and delivery of the nanoparticle to the cytosol of the cell. Also described are methods of delivery of a nanoparticle to the cytosol of a cell, the method comprising providing to a cell a nanoparticle attached to such a peptide. Exemplary nanoparticles include quantum dots.
摘要翻译：描述了用于递送纳米颗粒至胞质溶胶的肽，所述肽包含：（a）纳米颗粒缔合结构域; （b）富含脯氨酸的间隔区; （c）摄取域; 和（d）包含非可水解脂质部分的囊泡逃逸结构域，其中所述间隔结构域位于纳米颗粒缔合结构域与摄取和囊泡逃逸结构域之间，并且其中所述肽在附着至细胞外纳米颗粒时有效诱导通过细胞摄取纳米颗粒并将纳米颗粒递送至细胞的胞质溶胶。还描述了将纳米颗粒递送至细胞的胞质溶胶的方法，所述方法包括向细胞提供附着于此类肽的纳米颗粒。示例性的纳米粒子包括量子点。

10. 发明申请

WO2009023320A3 MODULAR LINKERS FOR CONJUGATION OF ORGANIC SUBSTANCES TO SUBSTANTIALLY INORGANIC SUBSTANCES AND METHODS OF MANUFACTURE AND USE THEREOF 审中-公开
公开(公告)号：WO2009023320A3
公开(公告)日：2009-02-19
申请号：PCT/US2008/063591
申请日：2008-05-14
申请人： THE GOVERNMENT OF THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY OF THE NAVY , MEDINTZ, Igor, L , BERTI, Lorenzo , FACCI, Paolo , MATTOUSSI, Hedi, M.
发明人： MEDINTZ, Igor, L , BERTI, Lorenzo , FACCI, Paolo , MATTOUSSI, Hedi, M.
IPC分类号： A61K39/00 , A61K31/70
摘要： A modular linker includes an inorganic binding entity having an affinity for a substantially inorganic substance, and an organic binding entity capable of binding with an organic substance covalently bonded thereto. The modular linker is capable of being stored in a stable condition for later use. The modular linker may be synthesized by modifying the inorganic binding entity to be covalently bonded to an organic binding entity and storing the modular linker in an inert environment from about a day up to at least 1 week. The modular linker may be conjugated to an organic substance and to a substantially inorganic substance in substantially a 1 : 1 ratio. The modular linker may have more than one organic binding entity covalently bonded to an inorganic binding entity or vice-versa. Also, a particular modular linker may have an organic binding entity capable of binding with a nucleic acid sequence.

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