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51. 发明授权

US07871811B2 Method for eliminating crosstalk between waveguide grating-based biosensors located in a microplate and the resulting microplate 失效
标题翻译：用于消除位于微板中的基于波导光栅的生物传感器与所得微板之间的串扰的方法
公开(公告)号：US07871811B2
公开(公告)日：2011-01-18
申请号：US11101096
申请日：2005-04-07
申请人： Ye Fang , Ann M. Ferrie , Norman H. Fontaine , Anthony G. Frutos , Eric J. Mozdy , Chuan-Che Wang , Po Ki Yuen
发明人： Ye Fang , Ann M. Ferrie , Norman H. Fontaine , Anthony G. Frutos , Eric J. Mozdy , Chuan-Che Wang , Po Ki Yuen
IPC分类号： C12M1/00 , C12Q1/68 , G01N1/00
CPC分类号： G01N21/7743 , G01N21/253
摘要： The present invention includes several methods for modifying the current processes of manufacturing optical sensing microplates that use continuous waveguide films to reduce/eliminate crosstalk between the biosensors that are incorporated within wells. The methods include (1) physically deteriorating/removing the waveguide film between individual biosensors; (2) chemically depositing highly absorbing materials within the waveguide film between individual biosensors; (3) patterning disordered (scattering) regions between the diffraction gratings that define individual biosensors; (4) using a specific mask and depositing individual patches of waveguide film, where each patch defines at least one biosensor. Each of these methods and several other methods described herein prevent the propagation of light between individual sensing regions, thereby eliminating optical crosstalk between the biosensors. The present invention also includes the resulting microplate.
摘要翻译：本发明包括几种用于修改制造光学感测微板的当前工艺的方法，其使用连续波导膜来减少/消除结合在孔内的生物传感器之间的串扰。所述方法包括（1）在各个生物传感器之间物理劣化/去除波导膜; （2）在各个生物传感器之间在波导膜内化学沉积高吸收材料; （3）在限定单个生物传感器的衍射光栅之间图形化无序（散射）区域; （4）使用特定掩模并沉积波导膜的各个贴片，其中每个贴片限定至少一个生物传感器。这些方法和本文所描述的其它方法中的每一种都防止光在各个感测区域之间的传播，从而消除了生物传感器之间的光学串扰。本发明还包括所得到的微孔板。

52. 发明授权

US07867700B2 Porous substrate plates and the use thereof 失效
标题翻译：多孔基板及其用途
公开(公告)号：US07867700B2
公开(公告)日：2011-01-11
申请号：US11870742
申请日：2007-10-11
申请人： Ye Fang , Ann M. Ferrie , Yulong Hong , Brian L. Webb
发明人： Ye Fang , Ann M. Ferrie , Yulong Hong , Brian L. Webb
IPC分类号： C12Q1/00
CPC分类号： B01L3/5085 , B01L2200/12 , B01L2300/069 , B01L2300/0829 , Y10S435/81 , Y10S436/809 , Y10T29/49885
摘要： A substrate plate or device adapted for use with biological or chemical assays is disclosed. The device may take the form of a multi-well plate having a three-dimensional, porous layer as part of a support surface within each well for immobilizing probe species. The porous layer is characterized as having a plurality of interconnected voids defined by a matrix of contiguous solid material. A method and its variants are also described.
摘要翻译：公开了适用于生物或化学测定的底物板或装置。该装置可以采用具有三维多孔层的多孔板的形式，作为每个孔内的支撑表面的一部分，用于固定探针物质。多孔层的特征在于具有由连续的固体材料的基体限定的多个相互连接的空隙。还描述了一种方法及其变体。

53. 发明申请

US20100087332A1 High-Throughput High-Information Content Label-Free Cell Biology Screening Methods 有权
标题翻译：高通量高信息内容无标签免疫细胞生物学筛选方法
公开(公告)号：US20100087332A1
公开(公告)日：2010-04-08
申请号：US12569407
申请日：2009-09-29
申请人： Ye Fang , Anthony Glenn Frutos , David H. Randle , Elizabeth Tran
发明人： Ye Fang , Anthony Glenn Frutos , David H. Randle , Elizabeth Tran
IPC分类号： C40B30/06
CPC分类号： C12Q1/025 , G01N33/5008 , G01N33/54373 , G01N33/566 , G01N33/74 , G01N2333/71 , G01N2333/726 , G01N2500/10
摘要： A method for hit compound identification in a high throughput, label-free biosensor cellular assay, one method including, for example: generating at least one pathway-specific kinetic profile for a target receptor; generating a relational table that integrates each kinetic profile; determining a delta response with the relational table for candidate compounds screened against the target receptor; and identifying one or more hit compounds based upon the separation of the delta response from a threshold.
摘要翻译：一种在高通量，无标记的生物传感器细胞测定中的命中化合物鉴定的方法，一种方法包括例如：为靶受体产生至少一种途径特异性动力学分布; 生成集合每个动力学轮廓的关系表; 用针对靶受体筛选的候选化合物的关系表确定δ响应; 以及基于所述δ响应与阈值的分离来识别一个或多个命中化合物。

54. 发明申请

US20090298166A1 CELL CULTURE APPARATUS HAVING VARIABLE TOPOGRAPHY 审中-公开
标题翻译：具有可变地形图的细胞培养装置
公开(公告)号：US20090298166A1
公开(公告)日：2009-12-03
申请号：US12471879
申请日：2009-05-26
申请人： Ye Fang , Jianguo Wang , Ying Zhang
发明人： Ye Fang , Jianguo Wang , Ying Zhang
IPC分类号： C12M1/00 , B44C1/22
CPC分类号： C12M23/16 , B01L3/50857 , B01L2200/12 , B01L2300/0829 , B01L2300/0838 , B01L2300/0893 , C12M23/12
摘要： A cell culture apparatus includes a substrate having formed therein a micro-pillared well array. The micro-pillared well array includes a plurality of micro-pillared wells. Each micro-pillared structure includes a plurality of spaced-apart micro-pillars having distal ends shaped to form a well. The well is suitable for cell culture.
摘要翻译：细胞培养装置包括其中形成有微柱状阵列的基板。微支柱阵列包括多个微柱孔。每个微支柱结构包括多个间隔开的微柱，其具有成形为形成井的远端。该井适合细胞培养。

55. 发明申请

US20060105371A1 Method and device for protein delivery into cells 失效
公开(公告)号：US20060105371A1
公开(公告)日：2006-05-18
申请号：US11261198
申请日：2005-10-27
申请人： Ye Fang , Fang Lai , Laurent Picard , Brian Webb
发明人： Ye Fang , Fang Lai , Laurent Picard , Brian Webb
IPC分类号： C12Q1/70 , C12Q1/68
CPC分类号： C12N5/0068 , C12N2503/00 , C12N2535/10
摘要： Methods for performing surface-mediated protein delivery into living cells, and fabricating protein-transfected cell cluster arrays are provided. The method comprises providing a protein-containing mixture; depositing said protein-containing mixture onto a surface at defined locations; affixing the protein-containing mixture to the surface as microspots; and plating cells onto the surface in sufficient density and under conditions for the proteins to be delivered into the cells. The protein-containing mixture comprises any suitable amino acid sequence, including peptides, proteins, protein-domains, antibodies, or protein-nucleic acid conjugates, etc., with a carrier reagent. Protein-transfected cell arrays may be used for rapid and direct, screening of protein or enzymatic functions or any given intracellular protein interaction in the natural environment of a living cell, as well as for high-throughput screening of other biological and chemical analytes, which affect the functions of these proteins.

56. 发明授权

US08426148B2 Label-free methods using a resonant waveguide grating biosensor to determine GPCR signaling pathways 失效
标题翻译：使用谐振波导光栅生物传感器确定GPCR信号通路的无标记方法
公开(公告)号：US08426148B2
公开(公告)日：2013-04-23
申请号：US11998711
申请日：2007-11-30
申请人： Ye Fang , Y. Alice Gao , Elizabeth Tran
发明人： Ye Fang , Y. Alice Gao , Elizabeth Tran
IPC分类号： G01N33/567 , G01N33/53
CPC分类号： G01N33/74 , G01N33/54373 , G01N33/554 , G01N2333/726
摘要： A system and method for GPCR signaling pathway analysis and elucidation using a biosensor, a live-cell, and a pathway active compound, as defined herein.
摘要翻译：使用如本文所定义的生物传感器，活细胞和途径活性化合物的GPCR信号传导途径分析和阐明的系统和方法。

57. 发明授权

US08288113B2 Method and device for protein delivery into cells 失效
标题翻译：用于蛋白质递送到细胞中的方法和装置
公开(公告)号：US08288113B2
公开(公告)日：2012-10-16
申请号：US12893412
申请日：2010-09-29
申请人： Ye Fang , Fang Lai , Laurent A. G. Picard , Brian L. Webb
发明人： Ye Fang , Fang Lai , Laurent A. G. Picard , Brian L. Webb
IPC分类号： G01N33/53
CPC分类号： C12N5/0068 , C12N2503/00 , C12N2535/10
摘要： Methods for performing surface-mediated protein delivery into living cells, and fabricating protein-transfected cell cluster arrays are provided. The method comprises providing a protein-containing mixture; depositing said protein-containing mixture onto a surface at defined locations; affixing the protein-containing mixture to the surface as microspots; and plating cells onto the surface in sufficient density and under conditions for the proteins to be delivered into the cells. The protein-containing mixture comprises any suitable amino acid sequence, including peptides, proteins, protein-domains, antibodies, or protein-nucleic acid conjugates, etc., with a carrier reagent. Protein-transfected cell arrays may be used for rapid and direct, screening of protein or enzymatic functions or any given intracellular protein interaction in the natural environment of a living cell, as well as for high-throughput screening of other biological and chemical analytes, which affect the functions of these proteins.
摘要翻译：提供了将表面介导的蛋白质递送到活细胞中并制备蛋白质转染的细胞簇阵列的方法。该方法包括提供含蛋白质的混合物; 将所述含蛋白质的混合物在限定的位置沉积在表面上; 将含蛋白质的混合物作为微滴固定在表面上; 并以足够的密度和将蛋白质递送到细胞中的条件将细胞电镀在表面上。含蛋白质的混合物包含任何合适的氨基酸序列，包括肽，蛋白质，蛋白质结构域，抗体或蛋白质 - 核酸缀合物等与载体试剂。蛋白质转染的细胞阵列可用于在活细胞的天然环境中快速和直接地筛选蛋白质或酶功能或任何给定的细胞内蛋白质相互作用，以及用于其他生物和化学分析物的高通量筛选，其中影响这些蛋白质的功能。

58. 发明申请

US20100152060A1 ASSAY SOLUTION COMPOSITIONS AND METHODS FOR GPCR ARRAYS 失效
标题翻译：测试解决方案组合物和GPCR阵列的方法
公开(公告)号：US20100152060A1
公开(公告)日：2010-06-17
申请号：US12697664
申请日：2010-02-01
申请人： Ye Fang , Ann M. Ferrie , Yulong Hong , Sadashiva K. Pai , Jinlin Peng , Brian L. Webb
发明人： Ye Fang , Ann M. Ferrie , Yulong Hong , Sadashiva K. Pai , Jinlin Peng , Brian L. Webb
IPC分类号： C40B30/04
CPC分类号： G01N33/52 , G01N2333/726
摘要： Buffered assay solutions for performing 1) binding or 2) functional assays on GPCR arrays, along with methods for their use are described. The buffered assay solution has an underlying composition having: a buffer reagent with a pH in the range of about 6.5 to about 7.9; an inorganic salt of either a monovalent or divalent species, at a concentration from about 1 mM to about 500 mM; and optionally a combination of: c) a blocker reagent at a concentration of about 0.01 wt. % to about 2 wt. % of the composition, or d) protease-inhibitor at a concentration of about 0.001 mM to about 100 mM. In an embodiment for functional assay uses, the composition is modified to also include a GTP-analogue, a guanosine 5′-diphosphate (GDP) salt, and/or an anti-oxidant reagent.
摘要翻译：描述了用于执行1）GPCR阵列上的结合或2）功能测定的缓冲测定溶液及其使用方法。缓冲测定溶液具有下列组成，其具有：pH在约6.5至约7.9范围内的缓冲试剂; 浓度为约1mM至约500mM的单价或二价物质的无机盐; 和任选的以下组合：c）浓度为约0.01wt。％至约2wt。％的组合物，或d）浓度为约0.001mM至约100mM的蛋白酶抑制剂。在功能测定用途的实施方案中，组合物被修饰为还包括GTP类似物，鸟苷5'-二磷酸（GDP）盐和/或抗氧化试剂。

59. 发明申请

US20100129854A1 LIVER CELL TOXICITY ASSAY 失效
标题翻译：肝细胞毒性测定
公开(公告)号：US20100129854A1
公开(公告)日：2010-05-27
申请号：US12613966
申请日：2009-11-06
申请人： Ye Fang , Ann M. Ferrie , Haiyan Sun , Elizabeth Tran , Ying Wei
发明人： Ye Fang , Ann M. Ferrie , Haiyan Sun , Elizabeth Tran , Ying Wei
IPC分类号： C12Q1/02
CPC分类号： G01N33/5067 , C12N2503/00 , C12Q1/025 , G01N33/5014 , G01N33/54373
摘要： The disclosure provides methods for characterizing the toxicity of a candidate molecule to liver cells as defined herein; methods of culturing metabolically active liver cells on a biosensor as defined herein; and biosensor liver culture systems as defined herein.
摘要翻译：本公开提供了表征候选分子对本文定义的肝细胞的毒性的方法; 在本文定义的生物传感器上培养代谢活性肝细胞的方法; 和如本文所定义的生物传感器肝脏培养系统。

60. 发明授权

US07691580B2 Reverse protein delivery into cells on coded microparticles 失效
标题翻译：反向蛋白质递送到编码微粒上的细胞
公开(公告)号：US07691580B2
公开(公告)日：2010-04-06
申请号：US10353496
申请日：2003-01-29
申请人： Ye Fang , Brian L. Webb
发明人： Ye Fang , Brian L. Webb
IPC分类号： G01N33/53
CPC分类号： G01N33/5005 , G01N33/5432
摘要： Systems, methods and kits that utilize uniquely coded microparticles for performing protein assays are provided. The uniquely coded microparticles are used as a substrate for reverse protein delivery into cells. The microparticles and methods offer the possibility of studying the biological functions of either a single protein of interest in multiple cell types per assay or multiple proteins in a single cell type.
摘要翻译：提供了使用唯一编码的微粒进行蛋白质测定的系统，方法和试剂盒。唯一编码的微粒用作反向蛋白递送到细胞中的底物。微粒和方法提供了研究在每种测定的多种细胞类型中的单一目的蛋白或单细胞类型的多种蛋白质的生物学功能的可能性。

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