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1. 发明申请

WO2008018933A2 DETECTION OF PROTEASE AND PROTEASE ACTIVITY USING A SINGLE NANOCRESCENT SERS PROBE 审中-公开
标题翻译：使用单个纳米复合物探针检测蛋白质和蛋白酶活性
公开(公告)号：WO2008018933A2
公开(公告)日：2008-02-14
申请号：PCT/US2007/010722
申请日：2007-05-02
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , LIU, Gang, L. , ELLMAN, Jonathan, A. , LEE, Luke, P. , CHEN, Fanqing, Frank
发明人： LIU, Gang, L. , ELLMAN, Jonathan, A. , LEE, Luke, P. , CHEN, Fanqing, Frank
IPC分类号： G01N33/53
CPC分类号： C12Q1/37 , G01N33/57434 , G01N33/587 , G01N2333/96433 , G01N2333/96466 , G01N2333/974
摘要： This invention pertains to the in vitro detection of proteases using a single peptide-conjugate nanocrescent surface enhanced Raman scattering (SERS) probes with at least nanomolar sensitivity. The probe enables detection of proteolytic activity in extremely small volume and at low concentration. In certain embodiments the probes comprise an indicator for the detection of an active protease, where the indicator comprises a nanocrescent attached to a peptide, where said peptide comprises a recognition site for the protease and a Raman tag attached to the peptide.
摘要翻译：本发明涉及使用具有至少纳摩尔灵敏度的单个肽 - 缀合的纳米新生表面增强拉曼散射（SERS）探针来体外检测蛋白酶。该探针能够以非常小的体积和低浓度检测蛋白水解活性。在某些实施方案中，探针包含用于检测活性蛋白酶的指示剂，其中指示剂包含连接到肽的纳米新月形，其中所述肽包含蛋白酶的识别位点和与肽连接的拉曼标签。

2. 发明申请

WO2009088779A2 SERS-BASED, SINGLE STEP, REAL-TIME DETECTION OF PROTEIN KINASE AND/OR PHOSPHATASE ACTIVITY 审中-公开
标题翻译：基于SERS的单步，实时检测蛋白激酶和/或磷酸酶活性
公开(公告)号：WO2009088779A2
公开(公告)日：2009-07-16
申请号：PCT/US2008/088195
申请日：2008-12-23
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , CHEN, Fanqing, Frank , LIU, Gang, L. , ELLMAN, Jonathan, A.
发明人： CHEN, Fanqing, Frank , LIU, Gang, L. , ELLMAN, Jonathan, A.
IPC分类号： C12M3/00 , G01N33/53
CPC分类号： C12Q1/42 , B01J19/0046 , B01J2219/00382 , B01J2219/00527 , B01J2219/00576 , B01J2219/00585 , B01J2219/00596 , B01J2219/00605 , B01J2219/00612 , B01J2219/00621 , B01J2219/00626 , B01J2219/0063 , B01J2219/00635 , B01J2219/00637 , B01J2219/00648 , B01J2219/00659 , B01J2219/00677 , B01J2219/00702 , B01J2219/00725 , B01J2219/00734 , B01J2219/0074 , B81B2201/0214 , B81C1/00206 , B82Y30/00 , C12Q1/485 , C40B50/18 , C40B60/12 , G01N21/658 , G01N2500/04
摘要： This invention provides novel compositions and methods for the detection, and/or quantification, of the presence and/or activity of one or more kinases and/or phosphatases. In certain embodiments this invention a device for the detection of kinase and/or phosphatase activity where the device comprises a Raman active surface comprising features that enhance Raman scattering having attached thereto a plurality of kinase and/or phosphatase substrate molecules.
摘要翻译：本发明提供用于检测和/或定量一种或多种激酶和/或磷酸酶的存在和/或活性的新型组合物和方法。在某些实施方案中，本发明是用于检测激酶和/或磷酸酶活性的装置，其中该装置包括拉曼活性表面，其包括增强拉曼散射的特征，其附着有多个激酶和/或磷酸酶底物分子。

3. 发明申请

WO2009094058A9 REAL-TIME, SINGLE-STEP BIOASSAY USING NANOPLASMONIC RESONATOR WITH ULTRA-HIGH SENSITIVITY 审中-公开
公开(公告)号：WO2009094058A9
公开(公告)日：2009-07-30
申请号：PCT/US2008/082266
申请日：2008-11-03
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
发明人： CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
IPC分类号： G01N21/65
摘要： Enzymatic activity measurement has broad application in drug screening, diagnosis and disease staging, and molecular profiling. However, conventional immunopeptidemetric assays (IMPA) exhibit low fluorescence signal-to-noise ratios, preventing reliable measurements at lower concentrations in the clinically important pM~nM range. Here, we demonstrated a highly sensitive measurement of protease activity using nanoplasmonic resonator (NPR). NPRs enhance Raman signals by 6.1x10 10 times in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at sensitivity level at 6 pM (0.2 ng/ml) with a dynamic range of 3 orders of magnitude. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background. This method offers a fast, sensitive, accurate, and one-step approach to detect the proteases activities in very small sample volumes.

4. 发明申请

WO2009094058A3 REAL-TIME, SINGLE-STEP BIOASSAY USING NANOPLASMONIC RESONATOR WITH ULTRA-HIGH SENSITIVITY 审中-公开
公开(公告)号：WO2009094058A3
公开(公告)日：2009-07-30
申请号：PCT/US2008/082266
申请日：2008-11-03
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
发明人： CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
IPC分类号： G01J3/44
摘要： Enzymatic activity measurement has broad application in drug screening, diagnosis and disease staging, and molecular profiling. However, conventional immunopeptidemetric assays (IMPA) exhibit low fluorescence signal-to-noise ratios, preventing reliable measurements at lower concentrations in the clinically important pM~nM range. Here, we demonstrated a highly sensitive measurement of protease activity using nanoplasmonic resonator (NPR). NPRs enhance Raman signals by 6.1x10 10 times in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at sensitivity level at 6 pM (0.2 ng/ml) with a dynamic range of 3 orders of magnitude. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background. This method offers a fast, sensitive, accurate, and one-step approach to detect the proteases activities in very small sample volumes.

5. 发明申请

WO2009094058A2 REAL-TIME, SINGLE-STEP BIOASSAY USING NANOPLASMONIC RESONATOR WITH ULTRA-HIGH SENSITIVITY 审中-公开
标题翻译：使用具有超高灵敏度的纳米平衡共振器的实时，单步生物
公开(公告)号：WO2009094058A2
公开(公告)日：2009-07-30
申请号：PCT/US2008/082266
申请日：2008-11-03
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
发明人： CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
IPC分类号： G01N21/65
CPC分类号： G01N21/658 , B82Y15/00 , B82Y20/00 , C12Q1/37
摘要： Enzymatic activity measurement has broad application in drug screening, diagnosis and disease staging, and molecular profiling. However, conventional immunopeptidemetric assays (IMPA) exhibit low fluorescence signal-to-noise ratios, preventing reliable measurements at lower concentrations in the clinically important pM~nM range. Here, we demonstrated a highly sensitive measurement of protease activity using nanoplasmonic resonator (NPR). NPRs enhance Raman signals by 6.1x10 10 times in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at sensitivity level at 6 pM (0.2 ng/ml) with a dynamic range of 3 orders of magnitude. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background. This method offers a fast, sensitive, accurate, and one-step approach to detect the proteases activities in very small sample volumes.
摘要翻译：酶活性测定在药物筛选，诊断和疾病分期以及分子谱分析中具有广泛的应用。然而，传统的免疫肽测定（IMPA）表现出低的荧光信噪比，防止在临床上重要的pM〜nM范围内在较低浓度下的可靠测量。在这里，我们使用纳米弹性共振器（NPR）展示了对蛋白酶活性的高度灵敏度测量。 NPR以高度可重复的方式增强了6.1x1010倍的拉曼信号，实时快速检测蛋白酶和酶活性，如前列腺特异抗原（paPSA），灵敏度水平为6 pM（0.2 ng / ml），具有动态范围3个数量级。来自paPSA阳性细胞的细胞外液（ECF）的实验在复杂的生物流体背景中表现出特异性检测。该方法提供了一种快速，灵敏，准确和一步法在非常小的样品体积中检测蛋白酶活性。

6. 发明申请

WO2011046842A1 TARGETED NANOCLUSTERS AND METHODS OF THEIR USE 审中-公开
标题翻译：目标纳米技术及其使用方法
公开(公告)号：WO2011046842A1
公开(公告)日：2011-04-21
申请号：PCT/US2010/052087
申请日：2010-10-08
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , WENG, Kevin, C. , CHEN, Fanqing, Frank , GRAY, Joe W.
发明人： WENG, Kevin, C. , CHEN, Fanqing, Frank , GRAY, Joe W.
IPC分类号： B32B5/16
CPC分类号： A61K49/0002 , A61K47/6907 , A61K49/0058 , A61K49/0067 , B82Y15/00 , G01N33/54346 , G01N33/574 , G01N33/57415 , G01N33/587 , G01N33/588
摘要： This invention provides targeted nanoclusters comprising multiple polyvalent nanoparticle core units or nanoscaffolds, each nanoparticle core unit attached to multiple targeting moieties and multiple detectable moieties. The nanoclusters find use in a broad range of analytical assays, diagnostic assays and as targeted therapeutics.
摘要翻译：本发明提供了包含多个多价纳米颗粒核心单元或纳米支架的靶向纳米团簇，每个纳米颗粒核心单元连接到多个靶向部分和多个可检测部分。纳米团簇用于广泛的分析测定，诊断测定和靶向治疗。

7. 发明申请

WO2009045579A2 MULTIMODAL IMAGING PROBES FOR IN VIVO TARGETED AND NON-TARGETED IMAGING AND THERAPEUTICS 审中-公开
标题翻译：多目标成像和非目标成像和治疗方法的多模式成像探针
公开(公告)号：WO2009045579A2
公开(公告)日：2009-04-09
申请号：PCT/US2008/067009
申请日：2008-06-13
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNIA , CHEN, Fanqing, Frank , GERION, Daniele , GRAY, Joe, W. , BUDINGER, Thomas, F.
发明人： CHEN, Fanqing, Frank , GERION, Daniele , GRAY, Joe, W. , BUDINGER, Thomas, F.
IPC分类号： C12M3/00
CPC分类号： G01N21/6428 , A61K41/0071 , A61K47/6923 , A61K47/6929 , A61K49/0002 , A61K49/0065 , A61K49/0067 , A61K49/085 , A61K49/106 , A61K49/1881 , A61K51/1244 , B82Y5/00
摘要： In certain embodiments this invention provides a nanoparticle-based technology platform for multimodal in vivo imaging and therapy. The nanoparticle-based probes detects diseased cells by MRI, PET or deep tissue Near Infrared (NIR) imaging, and are capable of detecting diseased cells with greater sensitivity than is possible with existing technologies. The probes also target molecules that localize to normal or diseased cells, and initiates apoptosis of diseased cells.
摘要翻译：在某些实施方案中，本发明提供了一种用于多峰体内成像和治疗的基于纳米颗粒的技术平台。基于纳米颗粒的探针通过MRI，PET或深部组织近红外（NIR）成像来检测患病细胞，并且能够以比现有技术可能更高的灵敏度检测患病细胞。探针还靶向定位于正常或患病细胞的分子，并引发患病细胞的凋亡。

8. 发明申请

WO2008073175A2 NANOPLASMONIC MOLECULAR RULER FOR NUCLEASE ACTIVITY AND DNA FOOTPRINTING 审中-公开
标题翻译：用于核酸酶活性和DNA覆盖的纳米分子量规
公开(公告)号：WO2008073175A2
公开(公告)日：2008-06-19
申请号：PCT/US2007/020026
申请日：2007-09-14
申请人： THE REGENTS OF THE UNIVERSITY OF CALIFORNINA , CHEN, Fanqing, Frank , LIU, Gang, L. , LEE, Luke, P.
发明人： CHEN, Fanqing, Frank , LIU, Gang, L. , LEE, Luke, P.
IPC分类号： C12Q1/68 , C12M3/00
CPC分类号： C12Q1/683 , C12Q1/6825 , C12Q1/6827 , C12Q1/6834 , C12Q1/6876 , G01N21/554 , C12Q2565/628 , C12Q2563/155 , C12Q2521/319
摘要： This invention provides a nanoplasmonic molecular ruler, which can perform label-free and real-time monitoring of nucleic acid (e.g., DNA) length changes and perform nucleic acid footprinting. In various embodiments the ruler comprises a nucleic acid attached to a nanoparticle, such that changes in the nucleic acid length are detectable using surface plasmon resonance. The nanoplamonic ruler provides a fast and convenient platform for mapping nucleic acid -protein interactions, for nuclease activity monitoring, and for other footprinting related methods.
摘要翻译：本发明提供了纳米等离子体分子尺，其可以执行核酸（例如DNA）长度变化的无标记和实时监测并且执行核酸足迹。在各种实施方案中，标尺包含附着于纳米颗粒的核酸，使得使用表面等离子体共振可检测核酸长度的变化。纳米电子标尺为绘制核酸 - 蛋白质相互作用，核酸酶活性监测以及其他足迹相关方法提供了快速便捷的平台。

9. 发明公开

EP2210072A2 REAL-TIME, SINGLE-STEP BIOASSAY USING NANOPLASMONIC RESONATOR WITH ULTRA-HIGH SENSITIVITY 审中-公开
标题翻译：单级REAL-TIME使用生物测定具有超高灵敏度NANOPLASMONISCHEM谐振器
公开(公告)号：EP2210072A2
公开(公告)日：2010-07-28
申请号：EP08871173.4
申请日：2008-11-03
申请人： The Regents of the University of California
发明人： CHEN, Fanqing, Frank , ELLMAN, Jonathan, A. , ZHANG, Xiang
IPC分类号： G01J3/44
CPC分类号： G01N21/658 , B82Y15/00 , B82Y20/00 , C12Q1/37
摘要： Enzymatic activity measurement has broad application in drug screening, diagnosis and disease staging, and molecular profiling. However, conventional immunopeptidemetric assays (IMPA) exhibit low fluorescence signal-to-noise ratios, preventing reliable measurements at lower concentrations in the clinically important pM~nM range. Here, we demonstrated a highly sensitive measurement of protease activity using nanoplasmonic resonator (NPR). NPRs enhance Raman signals by 6.1x10
10 times in a highly reproducible manner, enabling fast detection of protease and enzyme activity, such as Prostate Specific Antigen (paPSA), in real-time, at sensitivity level at 6 pM (0.2 ng/ml) with a dynamic range of 3 orders of magnitude. Experiments on extracellular fluid (ECF) from paPSA-positive cells demonstrate specific detection in a complex bio-fluid background. This method offers a fast, sensitive, accurate, and one-step approach to detect the proteases activities in very small sample volumes.
摘要翻译：甲纳米等离子体激元共振器（NPR），其包括具有交替屏蔽层（一个或多个）金属纳米盘，具有结合或束缚到所述纳米等离子体激元共振器的表面，用于酶活性的高灵敏度的测定一个标记的生物分子。 NPR增强在高度可再现的方式的拉曼信号，使几乎检测蛋白酶和酶的活性，：如前列腺特异性抗原（paPSA）在实时的，在皮摩尔灵敏度水平。对细胞外流体从paPSA阳性细胞（ECF）的实验证明在非常小的样品体积中的实时单步检测的复合物的生物流体背景特异性检测。

10. 发明公开

EP2019587A2 DETECTION OF PROTEASE AND PROTEASE ACTIVITY USING A SINGLE NANOCRESCENT SERS PROBE 有权
标题翻译：蛋白酶和蛋白酶活动检测使用单纳米增强SERS PROBE
公开(公告)号：EP2019587A2
公开(公告)日：2009-02-04
申请号：EP07835744.9
申请日：2007-05-02
申请人： The Regents of the University of California
发明人： LIU, Gang, L. , ELLMAN, Jonathan, A. , LEE, Luke, P. , CHEN, Fanqing, Frank
IPC分类号： A01N37/18 , A61K38/00
CPC分类号： C12Q1/37 , G01N33/57434 , G01N33/587 , G01N2333/96433 , G01N2333/96466 , G01N2333/974
摘要： This invention pertains to the in vitro detection of proteases using a single peptide-conjugate nanocrescent surface enhanced Raman scattering (SERS) probes with at least nanomolar sensitivity. The probe enables detection of proteolytic activity in extremely small volume and at low concentration. In certain embodiments the probes comprise an indicator for the detection of an active protease, where the indicator comprises a nanocrescent attached to a peptide, where said peptide comprises a recognition site for the protease and a Raman tag attached to the peptide.

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