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1. 发明授权

US6008892A Optical substrate for enhanced detectability of fluorescence 失效
标题翻译：用于增强荧光检测性的光学基底
公开(公告)号：US6008892A
公开(公告)日：1999-12-28
申请号：US864363
申请日：1997-05-23
申请人： Robert C. Kain , Eric G. Marason , Richard F. Johnston
发明人： Robert C. Kain , Eric G. Marason , Richard F. Johnston
IPC分类号： G01N21/01 , G01N21/64 , G01N1/00
CPC分类号： G01N21/6456 , G01N21/6452 , G01N21/6428
摘要： A sample substrate for use in a fluorescence imaging system includes a rigid base with a specularly reflective surface, typically metal, on which is deposited a transparent coating layer. The coating layer has a thickness selected so that a particular fluorescence excitation wavelength, corresponding to a specified fluorescent constituent to be sought in sample material, has an optical path from the top of the coating layer to the reflecting surface in the base of substantially an odd multiple of one-quarter wavelength, so that the standing wave of the fluorescence excitation wavelength of light incident on the substrate has an antinode located at or near where sample material would be disposed on top of the coating layer. This maximizes fluorescence excitation of the sample on the reflective substrate. The transparent coating layer may be a dielectric material (e.g. silica) or may be a multilayer structure with a top layer of biologically active material for binding a specified sample constituent.
摘要翻译：用于荧光成像系统的样品衬底包括具有镜面反射表面（通常为金属）的刚性基底，其上沉积有透明涂层。涂层具有选择的厚度，使得对应于在样品材料中寻找的特定荧光成分的特定荧光激发波长具有从涂层的顶部到基底中的反射表面的基本上奇数的光路使得入射到基板上的光的荧光激发波长的驻波具有位于或附近的样品材料将设置在涂层顶部上的波腹。这使得样品在反射基板上的荧光激发最大化。透明涂层可以是介电材料（例如二氧化硅），也可以是具有用于结合特定样品成分的生物活性材料顶层的多层结构。

2. 发明授权

US06177990B1 Optical substrate for enhanced detectability of fluorescence 有权
标题翻译：用于增强荧光检测性的光学基底
公开(公告)号：US06177990B1
公开(公告)日：2001-01-23
申请号：US09468750
申请日：1999-12-21
申请人： Robert C. Kain , Eric G. Marason , Richard F. Johnston
发明人： Robert C. Kain , Eric G. Marason , Richard F. Johnston
IPC分类号： G01N100
CPC分类号： G01N21/6456 , G01N21/6428 , G01N21/6452
摘要： A sample substrate for use in a fluorescence imaging system includes a rigid base with a specularly reflective surface, typically metal, on which is deposited a transparent coating layer. The coating layer has a thickness selected so that a particular fluorescence excitation wavelength, corresponding to a specified fluorescent constituent to be sought in sample material, has an optical path from the top of the coating layer to the reflecting surface in the base of substantially an odd multiple of one-quarter wavelength, so that the standing wave of the fluorescence excitation wavelength of light incident on the substrate has an antinode located at or near where sample material would be disposed on top of the coating layer. This maximizes fluorescence excitation of the sample on the reflective substrate. The transparent coating layer may be a dielectric material (e.g. silica) or may be a multilayer structure with a top layer of biologically active material for binding a specified sample constituent.
摘要翻译：用于荧光成像系统的样品衬底包括具有镜面反射表面（通常为金属）的刚性基底，其上沉积有透明涂层。涂层具有选择的厚度，使得对应于在样品材料中寻找的特定荧光成分的特定荧光激发波长具有从涂层的顶部到基底中的反射表面的基本上奇数的光路使得入射到基板上的光的荧光激发波长的驻波具有位于或附近的样品材料将设置在涂层顶部上的波腹。这使得样品在反射基板上的荧光激发最大化。透明涂层可以是介电材料（例如二氧化硅），也可以是具有用于结合特定样品成分的生物活性材料顶层的多层结构。

3. 发明授权

US5347139A Dual energy tracer quantitative analysis 失效
标题翻译：双能量示踪剂定量分析
公开(公告)号：US5347139A
公开(公告)日：1994-09-13
申请号：US4229
申请日：1993-01-12
申请人： David L. Barker , Richard F. Johnston , Siobhan C. Pickett
发明人： David L. Barker , Richard F. Johnston , Siobhan C. Pickett
IPC分类号： G01T1/29 , G03G5/16 , G01J5/04
CPC分类号： G03G5/16 , G01T1/2012 , Y10T436/13
摘要： Using storage phosphor recording media, two exposures are made of a sample containing two target substances tagged with different radiative emitters, for example 32-P and 35-S. The first exposure, image 1, is of the sample directly on the phosphor screen. The second exposure, image 2, is made with the appropriate absorption material between the sample and screen. Both images are captured. By using simultaneous equations isotope contributions of each label can be determined. Quantitative assessment of the contributions of the isotopes, and hence the target substances, are made by calculating isotope efficiencies both with and without the absorption filter.
摘要翻译：使用存储磷光体记录介质，对包含两个不同辐射发射体标记的目标物质的样品进行两次曝光，例如32-P和35-S。第一次曝光，图像1是直接在荧光屏上的样品。第二次曝光，图像2由样品和荧光屏之间的适当的吸收材料制成。两个图像被捕获。通过使用联立方程可以确定每个标签的同位素贡献。通过计算具有和不具有吸收滤光器的同位素效率，对同位素和因此的目标物质的贡献进行定量评估。

4. 发明授权

US06551839B2 Method of merging chemical reactants in capillary tubes 有权
标题翻译：将化学反应物并入毛细管中的方法
公开(公告)号：US06551839B2
公开(公告)日：2003-04-22
申请号：US09770412
申请日：2001-01-25
申请人： Stevan B. Jovanovich , Gregory J. Ronan , David J. Roach , Richard F. Johnston
发明人： Stevan B. Jovanovich , Gregory J. Ronan , David J. Roach , Richard F. Johnston
IPC分类号： G01N110
CPC分类号： G01N35/1097 , B01L3/5025 , B01L3/561 , B01L3/565 , B01L2200/026 , B01L2300/0838 , B01L2400/0406 , B01L2400/0622 , B01L2400/0644 , G01N30/20 , G01N30/24 , G01N30/6039 , G01N30/6078 , G01N2030/8827 , G02B6/3504 , G02B6/3558 , G02B6/381 , G02B6/3818 , G02B6/3825 , G02B6/3851 , G02B6/3854 , G02B6/3869 , G02B6/3877 , G02B6/3878 , G02B6/3887 , G02B6/3894 , G02B6/403 , Y10T137/86549 , Y10T436/143333 , Y10T436/2575
摘要： A capillary valve, connector and router where one or more cylindrical fibers, which may be capillaries, plugged capillaries, optical fibers, or the like, including at least one capillary tube are contained in a first bundle of fibers that terminates at a first face. A second cylindrical bundle of fibers also containing one or more fibers including at least one capillary tube terminates in a second face abutting the first face. A fastener or adapter holds the members together with faces in mutually biased alignment. Connection of a plurality of macroscale pumps enables push-pull fluid motion, with routing, in a capillary system formed by a plurality of fibers coupled by switches, connectors and routers. Chemical reactions, separations and analysis may be carried out with microliter volumes or smaller.
摘要翻译：毛细阀，连接器和路由器，其中一个或多个圆柱形纤维（其可以是毛细管，堵塞的毛细管，光纤等）包括至少一个毛细管，其包含在终止于第一面的第一束纤维中。还包含一个或多个包括至少一个毛细管的纤维的第二圆柱形纤维束终止于邻接第一面的第二面。紧固件或适配器将构件与面对齐地保持在彼此偏置的对准中。多个宏观泵的连接使得能够通过布线在由被开关，连接器和路由器耦合的多个光纤形成的毛细管系统中的推挽流体运动。化学反应，分离和分析可以用微升体积或更小的量进行。

5. 发明授权

US06764648B1 Robotic microchannel bioanalytical instrument 有权
标题翻译：机器人微通道生物分析仪器
公开(公告)号：US06764648B1
公开(公告)日：2004-07-20
申请号：US09556897
申请日：2000-04-20
申请人： David J. Roach , Robert T. Loder, Jr. , Thomas M. Armstrong , Dennis W. Harris , Stevan B. Jovanovich , Richard F. Johnston
发明人： David J. Roach , Robert T. Loder, Jr. , Thomas M. Armstrong , Dennis W. Harris , Stevan B. Jovanovich , Richard F. Johnston
IPC分类号： G01N3500
CPC分类号： G01N27/44704 , B01L3/5027 , B01L99/00 , G01N27/44743 , G01N27/44782 , G01N27/44791 , G01N35/0099 , G01N35/1074 , G01N2035/00059 , G01N2035/00158 , G01N2035/0437 , Y10T436/11 , Y10T436/110833 , Y10T436/25 , Y10T436/2575
摘要： A substrate with a plurality of microchannels is movably deployed with other movable objects that will load sample into the microchannels, stimulate molecular migration, read the results of the migration, remove and replace the substrate, and prepare for a new run. The other objects include a gripper for engaging and moving the substrate, an electrode array of fine wires suitable for fitting into the microchannels for electromigration, and a scanning detector for reading migration results. A sequence of automatic operations is established so that one substrate after another may be moved into position, loaded with sample, stimulated for molecular migration, read with a beam, and then removed and replaced with a fresh substrate.
摘要翻译：具有多个微通道的基板可移动地与其他可移动物体一起展开，其中可移动物体将样品载入微通道，刺激分子迁移，读取迁移结果，去除和替换基底，并准备新的运行。其他目的包括用于接合和移动衬底的夹持器，适于安装到用于电迁移的微通道中的细线的电极阵列，以及用于读取迁移结果的扫描检测器。建立了一系列自动操作，使得一个接一个的衬底可以移动到位置，装载样品，刺激分子迁移，用光束读取，然后移除并用新鲜的底物代替。

6. 发明授权

US5728282A Denaturing separation matrix having hydroxyethyl cellulose for nucleic acid electrophoresis 失效
公开(公告)号：US5728282A
公开(公告)日：1998-03-17
申请号：US631353
申请日：1996-04-12
申请人： John S. Bashkin , David L. Barker , Richard F. Johnston
发明人： John S. Bashkin , David L. Barker , Richard F. Johnston
IPC分类号： G01N27/447 , G01N27/26
CPC分类号： G01N27/44747
摘要： A capillary electrophoresis separation matrix for single-stranded nucleic acids, along with methods for using and preparing the matrix, are disclosed. The separation matrix provides denaturing conditions and contains hydroxyethyl cellulose (HEC) in combination with urea, and preferably also includes formamide. The separation matrix may be used for DNA sizing and sequencing applications and provides a single-base resolution to approximately 500 base pairs. The separation matrix is inexpensive, easy to prepare, requires no polymerization steps, and is of low enough viscosity to be pumped easily into and out of capillary tubes for electrophoresis. The low viscosity allows for high throughput of samples and reuse of the capillary tubes for numerous separations.

7. 发明授权

US5424841A Apparatus for measuring spatial distribution of fluorescence on a substrate 失效
标题翻译：用于测量衬底上荧光的空间分布的装置
公开(公告)号：US5424841A
公开(公告)日：1995-06-13
申请号：US069150
申请日：1993-05-28
申请人： Ezra Van Gelder , Bee C. Liang , Richard F. Johnston , Robert T. Loder, Jr.
发明人： Ezra Van Gelder , Bee C. Liang , Richard F. Johnston , Robert T. Loder, Jr.
IPC分类号： G01N21/64
CPC分类号： G01N21/6456 , G01N21/6428 , G01N2021/6441
摘要： A fluorescence detection scanner and method employing a fiberoptic collector, positioned adjacent to the scanning plane of the excitation beam, with a light collecting surface which is oriented to reject back-scattered excitation light from the incident surface of the sample support. The scanning plane of the excitation beam is off normal relative to the incident surface of the sample support and the light collecting surface is located within the area defined by the resulting acute angle of incidence. The light collecting surface is angled away from the location at which the incident excitation beam intersects the surface of the sample support so that back-scattered excitation light does not enter the optical fibers. The orientation of the light collector results in a four to five-fold decrease in excitation-light background without attenuation of the fluorescence emitted by the sample. Long-pass interference filters, selected to reject the excitation wavelength, are located at the input and output surfaces of the fiberoptic light collector to further reduce background excitation light. Multiple fluorophores are discriminated by sequentially scanning the sample with a different interchangeable narrow bandpass filter for each fluorophore. Internal fluorescence standards in the sample are used to determine filter efficiencies for each label in each filter image and the quantity of each fluorophore is computed by linear analysis. Increased detector sensitivity allows linear quantitation of multiple fluorophores in the femto-mole range.
摘要翻译：一种荧光检测扫描器和采用与激发光束的扫描平面相邻的光纤收集器的方法，该光收集表面被定向成阻止来自样品支架的入射表面的反向散射的激发光。激发光束的扫描平面相对于样品支架的入射表面正常，并且光收集表面位于由所产生的锐角入射限定的区域内。光收集表面远离入射激发光束与样品支架表面相交的位置成角度，使得后向散射的激发光不进入光纤。光收集器的取向导致激发光背景下降4-5倍，而不会使样品发射的荧光发生衰减。被选择以抑制激发波长的长通干涉滤光器位于光纤集光器的输入和输出表面，以进一步减少背景激发光。通过用每个荧光团的不同可互换的窄带通滤光器顺序扫描样品来区分多个荧光团。使用样品中的内部荧光标准来确定每个过滤图像中每个标记的过滤效率，并且通过线性分析计算每个荧光团的量。增加的检测器灵敏度允许在毫微微摩尔范围内的多个荧光团的线性定量。

8. 发明授权

US06787111B2 Apparatus and method for filling and cleaning channels and inlet ports in microchips used for biological analysis 有权
标题翻译：用于生物分析的微芯片中填充和清洁通道和入口的装置和方法
公开(公告)号：US06787111B2
公开(公告)日：2004-09-07
申请号：US09737675
申请日：2000-12-13
申请人： David J. Roach , Robert T. Loder, Jr. , Thomas M. Armstrong , Dennis W. Harris , Stevan B. Jovanovich , Richard F. Johnston
发明人： David J. Roach , Robert T. Loder, Jr. , Thomas M. Armstrong , Dennis W. Harris , Stevan B. Jovanovich , Richard F. Johnston
IPC分类号： G01N2726
CPC分类号： G01N27/44791 , B01J2219/0099 , B01L3/5027 , B01L99/00 , G01N27/44704 , G01N27/44743 , G01N27/44782 , G01N35/0099 , G01N35/1074 , G01N2035/00059 , G01N2035/00158 , G01N2035/0437
摘要： An apparatus for filling and cleaning channels and inlet ports of a microchip substrate is disclosed. A device of the apparatus comprising an array of tubes is inserted into each of the inlet ports of the microchip. The array of tubes of the device comprises a plurality of pressure tubes, surrounded by a plurality of vacuum tubes. In conjunction with this, pressurized solutions such as matrix or wash are introduced into common openings on the microchip that provide a passage to microchannels of the microchip with the use of pressure tip injectors of the apparatus. As matrix or wash solutions are pumped through the common openings and microchannels of the microchip substrate, wash solutions are pumped through the plurality of pressure tubes and everything is vacuumed through the plurality of vacuum tubes surrounding the plurality of pressure tubes. Various reservoirs of solutions are selected and allowed to flow by proper valve actuation. This process can be performed manually or easily automated by utilizing appropriate valves and control hardware/software.
摘要翻译：公开了一种用于填充和清洁微芯片衬底的通道和入口的装置。将包括管阵列的装置的装置插入到微芯片的每个入口端口中。该装置的管阵列包括由多个真空管包围的多个压力管。与此同时，诸如基质或洗涤剂的加压溶液被引入到微芯片上的共同的开口中，通过使用该装置的压头喷射器提供通向微芯片的微通道的通道。当将基质或洗涤溶液泵送通过微芯片衬底的共同的开口和微通道时，将洗涤溶液泵送通过多个压力管，并且通过围绕多个压力管的多个真空管将一切都抽真空。选择各种储存的溶液并通过适当的阀驱动使其流动。该过程可以通过使用适当的阀门和控制硬件/软件手动或容易地进行自动化。

9. 发明授权

US06627446B1 Robotic microchannel bioanalytical instrument 失效
标题翻译：机器人微通道生物分析仪器
公开(公告)号：US06627446B1
公开(公告)日：2003-09-30
申请号：US09109676
申请日：1998-07-02
申请人： David J. Roach , Robert T. Loder, Jr. , Thomas M. Armstrong , Dennis W. Harris , Stevan B. Jovanovich , Richard F. Johnston
发明人： David J. Roach , Robert T. Loder, Jr. , Thomas M. Armstrong , Dennis W. Harris , Stevan B. Jovanovich , Richard F. Johnston
IPC分类号： G01N2726
CPC分类号： G01N27/44704 , B01L3/5027 , B01L99/00 , G01N27/44743 , G01N27/44782 , G01N27/44791 , G01N35/0099 , G01N35/1074 , G01N2035/00059 , G01N2035/00158 , G01N2035/0437 , Y10T436/11 , Y10T436/110833 , Y10T436/25 , Y10T436/2575
摘要： A substrate with a plurality of microchannels is movably deployed with other movable objects that will load sample into the microchannels, stimulate molecular migration, read the results of the migration, remove and replace the substrate, and prepare for a new run. The other objects include a gripper for engaging and moving the substrate, an electrode array of fine wires suitable for fitting into the microchannels for electromigration, and a scanning detector for reading migration results. A sequence of automatic operations is established so that one substrate after another may be moved into position, loaded with sample, stimulated for molecular migration, read with a beam, and then removed and replaced with a fresh substrate.
摘要翻译：具有多个微通道的基板可移动地与其他可移动物体一起展开，其中可移动物体将样品载入微通道，刺激分子迁移，读取迁移结果，去除和替换基底，并准备新的运行。其他目的包括用于接合和移动衬底的夹持器，适于安装到用于电迁移的微通道中的细线的电极阵列，以及用于读取迁移结果的扫描检测器。建立了一系列自动操作，使得一个接一个的衬底可以移动到位置，装载样品，刺激分子迁移，用光束读取，然后移除并用新鲜的底物代替。

10. 发明授权

US06190616B1 Capillary valve, connector, and router 失效
标题翻译：毛细管阀，连接器和路由器
公开(公告)号：US06190616B1
公开(公告)日：2001-02-20
申请号：US08927645
申请日：1997-09-11
申请人： Stevan B. Jovanovich , Gregory J. Ronan , David J. Roach , Richard F. Johnston
发明人： Stevan B. Jovanovich , Gregory J. Ronan , David J. Roach , Richard F. Johnston
IPC分类号： G01N120
CPC分类号： G01N35/1097 , B01L3/5025 , B01L3/561 , B01L3/565 , B01L2200/026 , B01L2300/0838 , B01L2400/0406 , B01L2400/0622 , B01L2400/0644 , G01N30/20 , G01N30/24 , G01N30/6039 , G01N30/6078 , G01N2030/8827 , G02B6/3504 , G02B6/3558 , G02B6/381 , G02B6/3818 , G02B6/3825 , G02B6/3851 , G02B6/3854 , G02B6/3869 , G02B6/3877 , G02B6/3878 , G02B6/3887 , G02B6/3894 , G02B6/403 , Y10T137/86549 , Y10T436/143333 , Y10T436/2575
摘要： A capillary valve, connector and router where one or more cylindrical fibers, which may be capillaries, plugged capillaries, optical fibers, or the like, including at least one capillary tube are contained in a first cylindrical bundle of fibers that terminates at a first face. A second cylindrical bundle of fibers also containing one or more fibers including at least one capillary tube terminates in a second face abutting the first face. A fastener or adapter holds the members together with faces in mutually biased alignment, allowing relative rotation of the two cylindrical bundles which terminate in rotatable ferrules. Various functions achieved by rotation include a zero dead volume slide valve, a fluid router and a manifold. The fibers in each sleeve are preferably of uniform size for close symmetrical packing, but could be of disparate sizes, allowing connection of macroscale tubes to capillary tubes. A single connector member may be attached by a fastener to a reservoir or other macroscale device to bring one or more capillary tubes into fluid communication with a macroscale device. A plurality of fibers in one ferrule could allow dispensing of fluid from a single fiber in the other ferrule so that a single fiber could feed a plurality of wells through the plurality of fibers. Connection of a plurality of macroscale pumps enables push-pull fluid motion, with routing, in a capillary system formed by a plurality of fibers coupled by switches, connectors and routers. Chemical reactions, separations and analysis may be carried out with microliter volumes and smaller.
摘要翻译：一种毛细阀，连接器和路由器，其中一个或多个圆柱形纤维（其可以是毛细管，堵塞的毛细管，光纤等）包括至少一个毛细管，其包含在第一圆柱形纤维束中，其终止于第一面。还包含一个或多个包括至少一个毛细管的纤维的第二圆柱形纤维束终止于邻接第一面的第二面。紧固件或适配器将构件以与相对偏压对准的面保持在一起，允许两个圆柱形束的相对旋转，其终止于可旋转的套圈中。通过旋转实现的各种功能包括零死体积滑阀，流体路由器和歧管。每个套管中的纤维优选地具有均匀的尺寸以用于紧密对称的包装，但是可以具有不同的尺寸，允许宏观尺管连接到毛细管。单个连接器构件可以通过紧固件附接到储存器或其他宏观尺寸装置以使一个或多个毛细管与宏观尺寸装置流体连通。一个套圈中的多个纤维可以允许从另一个套圈中的单个纤维分配流体，使得单个纤维可以通过多个纤维供给多个孔。多个宏观泵的连接使得能够通过布线在由被开关，连接器和路由器耦合的多个光纤形成的毛细管系统中的推挽流体运动。化学反应，分离和分析可以用微升体积和更小的方式进行。

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