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    • 1. 发明授权
    • Fluorescent haloalkyl derivatives of reporter molecules well retained in
cells
    • 报道分子的荧光卤代烷基衍生物保留在细胞中
    • US5362628A
    • 1994-11-08
    • US26633
    • 1993-03-05
    • Richard P. HauglandYu-Zhong ZhangRam SabnisNels A. OlsonJohn J. NalewayRosaria P. Haugland
    • Richard P. HauglandYu-Zhong ZhangRam SabnisNels A. OlsonJohn J. NalewayRosaria P. Haugland
    • C12Q1/04C12Q1/34G01N33/535C12Q1/00A61K37/02C07H15/24G01N33/40
    • C12Q1/04C12Q1/34G01N33/535C12Q2334/00C12Q2334/20C12Q2334/40C12Q2337/20G01N2333/924Y10S530/802
    • The subject invention provides a method for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The method for analyzing metabolic activity of cells involves the use of a substrate having the formXR-REPORTER-BLOCKwherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate,-REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properities different from those of the substrate, andXR-- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z--S--H) to form a thioether conjugate (Z--S--R--).After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.
    • 本发明提供了通过仅在存在特定酶的完整细胞中改善可检测报道分子的保留来分析细胞中的代谢活性的方法。 特别地,涉及将报道分子的卤代烷基取代的衍生物与含细胞内半胱氨酸的肽结合的两部分方法的改进的保留结果,同时解除报道分子的阻断。 用于分析细胞代谢活性的方法涉及使用具有XR-REPORTER-BLOCK形式的底物,其中-BLOCK是通过特定分析物的作用被选择为可去除的基团,以产生与底物的不同的REPORTER光谱性质 -REPORTER-是一个分子,当不再通过BLOCK-REPORTER键与BLOCK结合时,具有与底物不同的光谱性质,XR-是可以与胞内硫醇(ZSH)共价反应的卤代烷基部分, 以形成硫醚缀合物(ZSR-)。 在底物进入细胞后,分析物除去BLOCK以通过光谱性质的变化使REPORTER可检测到,并且卤代烷基XR与细胞内硫醇反应以在细胞内形成硫醚缀合物,其在细胞中良好保留。
    • 2. 发明授权
    • Haloalkyl derivatives of reporter molecules used to analyze metabolic
activity in cells
    • 用于分析细胞代谢活性的报道分子的卤代烷基衍生物
    • US5576424A
    • 1996-11-19
    • US336285
    • 1994-11-08
    • Fei MaoRam SabnisJohn NalewayNels OlsonRichard P. Haugland
    • Fei MaoRam SabnisJohn NalewayNels OlsonRichard P. Haugland
    • C12Q1/04C12Q1/34G01N33/535C07H17/00C07D309/00
    • G01N33/535C12Q1/04C12Q1/34C12Q2334/00C12Q2334/20C12Q2334/40C12Q2337/20G01N2333/924
    • The subject invention provides substrates useful for analyzing the metabolic activity in cells by improving the retention of a detectable reporter molecule only in intact cells where a particular enzyme is present. In particular, improved retention results from a two part process involving conjugation of haloalkyl-substituted derivatives of a reporter molecule with intracellular cysteine-containing peptides while unblocking the reporter molecule. The substrates have the formXR-SPACER-REPORTER-BLOCKwherein -BLOCK is a group selected to be removable by action of a specific analyte, to give REPORTER spectral properties different from those of the substrate,-REPORTER- is a molecule that, when no longer bound to BLOCK by a BLOCK-REPORTER bond, has spectral properties different from those of the substrate,-SPACER- is a covalent linkage, andXR- is a haloalkyl moiety that can covalently react with an intracellular thiol (Z-S-H) to form a thioether conjugate (Z-S-R-).After the substrate enters the cells, the analyte removes BLOCK to make REPORTER detectable by the change in spectral properties, and the haloalkyl XR reacts with the intracellular thiol to form the thioether conjugate inside the cells, which is well-retained in the cells.
    • 本发明提供了用于通过仅在存在特定酶的完整细胞中改善可检测报道分子的保留来分析细胞中代谢活性的底物。 特别地,涉及将报道分子的卤代烷基取代的衍生物与含细胞内半胱氨酸的肽结合的两部分方法的改进的保留结果,同时解除报道分子的阻断。 底物具有形式XR-SPACER-REPORTER-BLOCK,其中-BLOCK是选择通过特定分析物的作用可除去的基团,使得REPORTER光谱性质与底物不同,-REPORTER-是不再存在的分子 通过BLOCK-REPORTER键与BLOCK结合,具有与底物不同的光谱性质,-SPACER-是共价连接,XR-是可与胞内硫醇(ZSH)共价反应形成硫醚的卤代烷基部分 缀合物(ZSR-)。 在底物进入细胞后,分析物除去BLOCK以通过光谱性质的变化使REPORTER可检测到,并且卤代烷基XR与细胞内硫醇反应以在细胞内形成硫醚缀合物,其在细胞中良好保留。
    • 5. 发明申请
    • Lithography pattern shrink process and articles
    • 平版印刷图案收缩工艺和文章
    • US20050147901A1
    • 2005-07-07
    • US11063411
    • 2005-02-23
    • Ram SabnisJames Lamb
    • Ram SabnisJames Lamb
    • H01L21/28B32B3/10G03C5/00G03F7/00G03F7/16G03F7/40H01L21/00H01L21/027H01L21/312H01L21/768
    • H01L21/02274G03F7/40H01L21/02118H01L21/0212H01L21/312H01L21/76816H01L21/76885Y10T428/24331Y10T428/24562
    • Novel processes of applying a thin, uniform, conformal organic polymeric film by a wide variety of deposition processes into lithography pattern substrates are provided. The inventive processes result in shrinking of the gaps in the lithography pattern equally, thus producing a smaller dimension. The amount of pattern shrinkage is selectively controlled by controlling the deposition rate to provide the desired final structure dimension. A wide variety of organic films is used as materials for these films. The inventive methods are applicable to any patterning technique used in lithography to provide a reduction in pattern sizes. Examples of the applicable device levels include the production of gate layers, ion implantation of active device layers and substantive metal layers, dielectric patterning, interconnect processes produced by damascene, dual damascene, backend packaging layers, and devices requiring multiple layers deposited by electrodeposition, CVD or sputtering. The inventive methods are useful for providing highly conformal coatings on large surface substrates having super submicron (i.e., 0.15 μm or smaller) features. The process is environmentally friendly and relatively low cost compared to other options.
    • 提供了通过各种各样的沉积工艺将薄的,均匀的共形有机聚合物膜应用于光刻图案衬底的新方法。 本发明的方法导致平版印刷图案中间隙的缩小,从而产生更小的尺寸。 通过控制沉积速率以提供期望的最终结构尺寸来选择性地控制图案收缩量。 使用各种有机薄膜作为这些薄膜的材料。 本发明的方法适用于在光刻中使用的任何图案化技术以提供图案尺寸的减小。 可应用的器件级别的实例包括栅极层的生产,有源器件层的离子注入和实质金属层,电介质图案化,由镶嵌生成的互连工艺,双镶嵌,后端封装层以及需要通过电沉积沉积多层的器件 或溅射。 本发明的方法可用于在具有超亚微米(即0.15μm或更小)特征的大表面基底上提供高保形涂层。 与其他选项相比,该过程是环保的,成本相对较低。