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1. 发明授权

US5602756A Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control 失效
标题翻译：热循环仪用于自动执行聚合酶链反应，并进行温度控制
公开(公告)号：US5602756A
公开(公告)日：1997-02-11
申请号：US569606
申请日：1995-12-08
申请人： John G. Atwood , Albert C. Mossa , Lisa M. Goven , Fenton Williams , Timothy M. Woudenberg , Marcel Margulies , Robert P. Ragusa , Richard Leath , Clive Miles
发明人： John G. Atwood , Albert C. Mossa , Lisa M. Goven , Fenton Williams , Timothy M. Woudenberg , Marcel Margulies , Robert P. Ragusa , Richard Leath , Clive Miles
IPC分类号： C12M1/00 , B01L3/00 , B01L3/14 , B01L7/00 , B01L9/00 , C12M1/02 , C12M1/34 , C12M1/36 , C12M1/38 , C12M1/40 , C12N15/00 , C12N15/09 , C12P19/34 , C12Q20060101 , C12Q1/00 , C12Q1/24 , C12Q1/68 , G01N35/00 , G05B13/00 , G05B15/00 , G05D23/00 , G05D23/19 , G06G7/58
CPC分类号： G05D23/1935 , B01L3/50851 , B01L3/50853 , B01L7/00 , B01L7/52 , G05D23/1917 , G05D23/1919 , B01L2200/147 , B01L2300/042 , B01L2300/046 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , B01L2300/185 , B01L3/5082
摘要： An instrument for performing highly accurate PCR employing a sample block in microtiter tray format. The sample block has local balance and local symmetry. A three zone film heater controlled by a computer and ramp cooling solenoid valves also controlled by the computer for gating coolant flow through the block controls the block temperature. Constant bias cooling is used for small changes. Sample temperature is calculated instead of measured. A platen deforms plastic caps to apply a minimum acceptable threshold force for seating the tubes and thermally isolates them. A cover isolates the block. The control software includes diagnostics. An install program tests and characterizes the instrument. A new user interface is used. Disposable, multipiece plastic microtiter trays to give individual freedom to sample tubes are taught.
摘要翻译：使用微量滴定盘格式的样品块进行高精度PCR的仪器。样品块具有局部平衡和局部对称性。由计算机控制的三区薄膜加热器也由计算机控制的斜坡冷却电磁阀用于选通通过块的冷却剂流控制块温度。恒定偏压冷却用于小的变化。计算样品温度而不是测量。压板使塑料盖变形，以施加最小可接受的阈值力，用于安置管并将其热隔离。盖子隔离块。控制软件包括诊断。安装程序测试和表征仪器。使用新的用户界面。教授了一次性的多片塑料微量滴定塔，以给予样品管的个体自由度。

2. 发明授权

US5475610A Thermal cycler for automatic performance of the polymerase chain reaction with close temperature control 失效
标题翻译：热循环仪用于自动执行聚合酶链反应，并进行温度控制
公开(公告)号：US5475610A
公开(公告)日：1995-12-12
申请号：US871264
申请日：1992-04-20
申请人： John G. Atwood , Albert C. Mossa , Lisa M. Goven , Fenton Williams , Timothy M. Woudenberg , Marcel Margoulies , Robert P. Ragusa , Richard Leath , Clive Miles
发明人： John G. Atwood , Albert C. Mossa , Lisa M. Goven , Fenton Williams , Timothy M. Woudenberg , Marcel Margoulies , Robert P. Ragusa , Richard Leath , Clive Miles
IPC分类号： C12M1/00 , B01L3/00 , B01L3/14 , B01L7/00 , B01L9/00 , C12M1/02 , C12M1/34 , C12M1/36 , C12M1/38 , C12M1/40 , C12N15/00 , C12N15/09 , C12P19/34 , C12Q20060101 , C12Q1/00 , C12Q1/24 , C12Q1/68 , G01N35/00 , G05B13/00 , G05B15/00 , G05D23/00 , G05D23/19 , G06G7/58
CPC分类号： G05D23/1935 , B01L3/50851 , B01L3/50853 , B01L7/00 , B01L7/52 , G05D23/1917 , G05D23/1919 , B01L2200/147 , B01L2300/042 , B01L2300/046 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , B01L2300/185 , B01L3/5082
摘要： An instrument for performing highly accurate PCR employing a sample block in microtiter tray format. The sample block has local balance and local symmetry. A three zone film heater controlled by a computer and ramp cooling solenoid valves also controlled by the computer for gating coolant flow through the block controls the block temperature. Constant bias cooling is used for small changes. Sample temperature is calculated instead of measured. A platen deforms plastic caps to apply a minimum acceptable threshold force for seating the tubes and thermally isolates them. A cover isolates the block. The control software includes diagnostics. An install program tests and characterizes the instrument. A new user interface is used. Disposable, multipiece plastic microtiter trays to give individual freedom to sample tubes are taught.
摘要翻译：使用微量滴定盘格式的样品块进行高精度PCR的仪器。样品块具有局部平衡和局部对称性。由计算机控制的三区薄膜加热器也由计算机控制的斜坡冷却电磁阀用于选通通过块的冷却剂流控制块温度。恒定偏压冷却用于小的变化。计算样品温度而不是测量。压板使塑料盖变形，以施加最小可接受的阈值力，用于安置管并将其热隔离。盖子隔离块。控制软件包括诊断。安装程序测试和表征仪器。使用新的用户界面。教授了一次性的多片塑料微量滴定塔，以给予样品管的个体自由度。

3. 发明授权

US09776187B2 Thermal cycler for PCR 有权
公开(公告)号：US09776187B2
公开(公告)日：2017-10-03
申请号：US12229404
申请日：2008-08-22
申请人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
发明人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
IPC分类号： B01L7/00 , C12Q1/68 , F25B21/04 , G01R27/20 , G05D23/19 , H01L35/30 , B01L3/00
CPC分类号： B01L7/52 , B01L3/50853 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , C12Q1/686 , F25B21/04 , F25B2321/021 , G01R27/205 , G05D23/1919 , H01L35/30 , Y10T137/1516
摘要： An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.

4. 发明授权

US4053236A Absorbance measuring photometer 失效
标题翻译：吸收式测光仪
公开(公告)号：US4053236A
公开(公告)日：1977-10-11
申请号：US703520
申请日：1976-07-08
申请人： John G. Atwood , Hamilton W. Marshall, Jr. , Charles F. DE Mey, II
发明人： John G. Atwood , Hamilton W. Marshall, Jr. , Charles F. DE Mey, II
IPC分类号： G01J1/16 , G01N21/25 , G01J3/50
CPC分类号： G01J1/1626 , G01N21/251
摘要： An absorbance measuring photometer, for measuring the absorbance of a sample in a sample cell, in which light of preselected wavelengths from one of two alternately utilizable sources of different wavelengths is formed into a beam and the etendu of the beam defined. The beam is then split into two separate beams one of which is directed through the sample cell onto a first detector and the other of which is passed directly onto a reference detector. The beam is so directed though the sample cell that it does not touch the cell walls and both beams are imaged on their respective detectors so as to be wholly within the photosensitive area thereof.

5. 发明授权

US08685717B2 Thermal cycler for PCR 有权
标题翻译：热循环仪用于PCR
公开(公告)号：US08685717B2
公开(公告)日：2014-04-01
申请号：US11654238
申请日：2007-01-17
申请人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
发明人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
IPC分类号： C12M1/34
CPC分类号： B01L7/52 , B01L3/50853 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , C12Q1/686 , F25B21/04 , F25B2321/021 , G01R27/205 , G05D23/1919 , H01L35/30 , Y10T137/1516
摘要： An apparatus comprising an assembly and a cover. The assembly comprises a sample block configured to receive a microtiter tray having a plurality of vials, each vial comprising a cap having a surface and a perimeter. The cover comprises a platen, vertically and horizontally displaceable in relationship to the sample block, the platen having a plurality of recesses. Each recess corresponds to a respective vial and is shaped and arranged to clear the surface of its respective cap when the cover is displaced onto the sample block. The cover includes a skirt in contact with and surrounding a perimeter of the platen. The skirt is configured for mating with a perimeter of a microtiter tray when a microtiter tray is received in the sample block, and also configured such that the cover contacts a microtiter tray when a microtiter tray is received in the sample block.
摘要翻译：一种包括组件和盖的装置。组件包括被配置为接收具有多个小瓶的微量滴定盘的样品块，每个小瓶包括具有表面和周边的盖。该盖包括一个与样品块相关的垂直和水平移位的压板，该压板具有多个凹槽。每个凹槽对应于相应的小瓶，并且当盖子移动到样品块上时，其形状和布置成使其相应盖的表面清除。所述盖包括与所述压板的周边接触并围绕所述压板的周边的裙部。当将微量滴定盘收纳在样品块中时，裙部配置成与微量滴定盘的周边配合，并且还构造成使得当微量滴定盘被接收在样品块中时，盖接触微量滴定盘。

6. 发明申请

US20100173400A1 Thermal Cycler for PCR 有权
标题翻译：热循环仪用于PCR
公开(公告)号：US20100173400A1
公开(公告)日：2010-07-08
申请号：US12686100
申请日：2010-01-12
申请人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
发明人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
IPC分类号： C12M1/00 , F25B21/02
CPC分类号： B01L7/52 , B01L3/50853 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , C12Q1/686 , F25B21/04 , F25B2321/021 , G01R27/205 , G05D23/1919 , H01L35/30 , Y10T137/1516
摘要： An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.
摘要翻译：提供了一种使用组件，加热盖和内部计算机执行高精度PCR的仪器。组件由样品块，多个珀耳帖热电器件和散热器组成，夹在一起。控制算法控制提供给热电冷却器的电流，使得可以控制块的动态热性能，从而可以执行样本温度的预定义热分布。计算样品温度，而不是使用设计特定的模型和方程来测量。控制软件包括校准诊断，其允许从仪器到仪器的热电冷却器的性能的变化被补偿，使得所有仪器执行相同的操作。块/散热器组件可以改变为相同或不同设计的另一个。该组件携带在板载存储器件中表征其自身性能所需的必要信息，允许组件在仪器之间可互换，同时保持其精密操作特性。

7. 发明授权

US07645070B2 Thermal cycler for PCR 有权
标题翻译：热循环仪用于PCR
公开(公告)号：US07645070B2
公开(公告)日：2010-01-12
申请号：US11804298
申请日：2007-05-17
申请人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
发明人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
IPC分类号： G01K1/14 , G01K17/00 , G01K13/12 , G01K25/00 , G12M1/34
CPC分类号： B01L7/52 , B01L3/50853 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , C12Q1/686 , F25B21/04 , F25B2321/021 , G01R27/205 , G05D23/1919 , H01L35/30 , Y10T137/1516
摘要： An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.
摘要翻译：提供了一种使用组件，加热盖和内部计算机执行高精度PCR的仪器。组件由样品块，多个珀耳帖热电器件和散热器组成，夹在一起。控制算法控制提供给热电冷却器的电流，使得可以控制块的动态热性能，从而可以执行样本温度的预定义热分布。计算样品温度，而不是使用设计特定的模型和方程来测量。控制软件包括校准诊断，其允许从仪器到仪器的热电冷却器的性能的变化被补偿，使得所有仪器执行相同的操作。块/散热器组件可以改变为相同或不同设计的另一个。该组件携带在板载存储器件中表征其自身性能所需的必要信息，允许组件在仪器之间可互换，同时保持其精密操作特性。

8. 发明申请

US20080314431A1 Thermal cycler for PCR 有权
标题翻译：热循环仪用于PCR
公开(公告)号：US20080314431A1
公开(公告)日：2008-12-25
申请号：US12229404
申请日：2008-08-22
申请人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
发明人： John G. Atwood , Adrian Fawcett , Keith S. Ferrara , Paul M. Hetherington , Richard W. Noreiks , Douglas E. Olsen , John R. Widomski , Charles M. Wittmer
IPC分类号： H01L35/28
CPC分类号： B01L7/52 , B01L3/50853 , B01L2300/0829 , B01L2300/1822 , B01L2300/1827 , C12Q1/686 , F25B21/04 , F25B2321/021 , G01R27/205 , G05D23/1919 , H01L35/30 , Y10T137/1516
摘要： An instrument for performing highly accurate PCR employing an assembly, a heated cover, and an internal computer, is provided. The assembly is made up of a sample block, a number of Peltier thermal electric devices, and a heat sink, clamped together. A control algorithm manipulates the current supplied to thermoelectric coolers such that the dynamic thermal performance of a block can be controlled so that pre-defined thermal profiles of sample temperature can be executed. The sample temperature is calculated instead of measured using a design specific model and equations. The control software includes calibration diagnostics which permit variation in the performance of thermoelectric coolers from instrument to instrument to be compensated for such that all instruments perform identically. The block/heat sink assembly can be changed to another of the same or different design. The assembly carries the necessary information required to characterize its own performance in an on-board memory device, allowing the assembly to be interchangeable among instruments while retaining its precision operating characteristics.
摘要翻译：提供了一种使用组件，加热盖和内部计算机执行高精度PCR的仪器。组件由样品块，多个珀耳帖热电器件和散热器组成，夹在一起。控制算法控制提供给热电冷却器的电流，使得可以控制块的动态热性能，从而可以执行样本温度的预定义热分布。计算样品温度，而不是使用设计特定的模型和方程来测量。控制软件包括校准诊断，其允许从仪器到仪器的热电冷却器的性能的变化被补偿，使得所有仪器执行相同的操作。块/散热器组件可以改变为相同或不同设计的另一个。该组件携带必要的信息，以在车载存储设备中表征自己的性能，允许组件在仪器之间可互换，同时保持其精确的操作特性。

9. 发明授权

US5766889A Method for determining the characteristics of the concentration growth of target nucleic acid molecules in polymerase chain reaction sample 失效
标题翻译：确定聚合酶链反应样品中靶核酸分子浓度增长特征的方法
公开(公告)号：US5766889A
公开(公告)日：1998-06-16
申请号：US255507
申请日：1994-06-08
申请人： John G. Atwood
发明人： John G. Atwood
IPC分类号： G01N33/58 , C07H21/04 , C12N15/09 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6816 , C12Q1/6851
摘要： Apparatus and method for determining an unknown starting molar concentration of target nucleic acid molecules at the beginning of a polymerase chain reaction in a sample reaction mixture containing suitable buffers, two complementary kinds of oligonucleotide primers, a molar excess of four kinds of nucleoside triphosphates, a DNA polymerase, and the unknown starting molar concentration of target nucleic acid molecules, wherein the two kinds of primers are provided in a known concentration (C.sub.po), the method including the steps of adding a reporter molecule which does not significantly interfere with the reaction and does not emit a strong signal in the absence of double-stranded DNA, but makes the dsDNA created by the reaction detectable and measurable at least once each cycle, thermal cycling one or more standard reaction mixtures which are substantially the same in every respect except they have known starting molar concentration of target mucleic acid molecules to obtain one or more growth curves with known starting molar concentrations of target nucleic acid molecules, exciting the reaction mixture during at least the extension portion of each cycle, detecting and measuring the intensity of the signal during at least the extension portion of each of the cycles, converting said intensity to molar concentration values of dsDNA and storing the molar concentration values for each of the extension portions of each of the cycles, generating a measured curve of molar concentration of dsDNA versus cycle number from the stored concentration values, using successive approximations, determining values of e.sub.v, e.sub.s, a, C.sub.z (n) and A.sub.z (n) which provide a best fit of the measured curve to the one or more known growth curves according to the following relation: C.sub.n+1 =C.sub.n e.sub.v plus the minimum of ##EQU1##
摘要翻译：在含有合适的缓冲液，两种互补种类的寡核苷酸引物，摩尔过量的四种核苷三磷酸酯的样品反应混合物中，在聚合酶链式反应开始时确定靶核酸分子的未知起始摩尔浓度的装置和方法， DNA聚合酶和目标核酸分子的未知起始摩尔浓度，其中两种引物以已知浓度（Cpo）提供，该方法包括添加不显着干扰反应的报道分子和在不存在双链DNA的情况下不会发出强信号，但是通过反应产生的dsDNA可以每个循环至少检测一次并测量至少一次，热循环一个或多个标准反应混合物，在各方面基本相同，除了它们已知已知起始摩尔浓度的靶核酸分子获得一个或多个具有已知的起始摩尔浓度的靶核酸分子的生长曲线，在每个循环的至少延伸部分期间激发反应混合物，在每个循环的至少延伸部分期间检测和测量信号的强度，将所述强度至dsDNA的摩尔浓度值，并存储每个循环的每个延伸部分的摩尔浓度值，根据存储的浓度值产生dsDNA的摩尔浓度与循环数的测量曲线，使用逐次逼近，确定ev ，es，a，Cz（n）和Az（n），其根据以下关系提供测量曲线与一个或多个已知生长曲线的最佳拟合：Cn + 1 = Cnev加上

10. 发明授权

US5364790A In situ PCR amplification system 失效
标题翻译：原位PCR扩增系统
公开(公告)号：US5364790A
公开(公告)日：1994-11-15
申请号：US17721
申请日：1993-02-16
申请人： John G. Atwood , Lawrence A. Haff
发明人： John G. Atwood , Lawrence A. Haff
IPC分类号： C12M1/00 , B01J19/00 , B01L3/00 , B01L7/00 , B01L9/00 , C12M1/14 , C12N15/09 , C12Q1/68 , C40B40/06 , G01N20060101 , G01N1/31 , G01N35/00 , C12M1/40
CPC分类号： G01N1/312 , B01J19/0046 , B01L3/508 , B01L7/52 , C12Q1/6841 , C12Q1/686 , B01J2219/00722 , B01L2200/0684 , B01L2200/0689 , B01L2300/041 , B01L2300/0822 , B01L2300/1827 , B01L2300/185 , B01L9/52 , C40B40/06 , Y10S435/809
摘要： A complete in situ PCR system for amplification of nucleic acids contained in a prepared cell or tissue sample. The containment system for the PCR sample comprises a glass microscope slide, a specimen sample containing the target nucleic acid sequence mounted on the slide, a flexible plastic cover over the sample, and a retaining assembly fastened to the slide and to the cover to retain and seal a reaction mixture against the sample during thermal cycling. The retaining assembly includes a rigid ring on a rim portion of the cover, a cross beam having spaced parallel rails joined by opposite flat ends, and a pair of clips which are pressed over the ends and opposite sides of the slide to fasten the cross beam and cover to the slide.
摘要翻译：用于扩增制备的细胞或组织样品中所含核酸的完整原位PCR系统。用于PCR样品的容纳系统包括玻璃显微镜载玻片，含有安装在载玻片上的靶核酸序列的样本样本，样品上的柔性塑料盖，以及固定到载玻片和保护盖的保持组件，在热循环期间将反应混合物密封在样品上。保持组件包括在盖的边缘部分上的刚性环，具有由相对的平坦端连接的间隔开的平行轨道的横梁和被压在滑块的端部和相对侧上的一对夹子，以将横梁并覆盖到幻灯片。

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