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    Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing
    13.
    发明授权
    Method and apparatus for identifying, classifying, or quantifying DNA sequences in a sample without sequencing 失效

    公开(公告)号：US5871697A

    公开(公告)日：1999-02-16

    申请号：US547214

    申请日：1995-10-24

    申请人： Jonathan Marc Rothberg ,  Michael W. Deem ,  John W. Simpson

    发明人： Jonathan Marc Rothberg ,  Michael W. Deem ,  John W. Simpson

    IPC分类号： C12N15/10 ,  C12Q1/68 ,  G06F19/22 ,  G06F19/24 ,  G01N15/06 ,  C07H21/04 ,  G06G7/58

    CPC分类号： G06F19/24 ,  C12N15/10 ,  C12Q1/68 ,  C12Q1/6809 ,  C12Q1/6855 ,  G06F19/22 ,  Y10S707/99936

    摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.

    Method and apparatus for identifying, classifying, or quantifying protein sequences in a sample without sequencing
    15.
    发明授权
    Method and apparatus for identifying, classifying, or quantifying protein sequences in a sample without sequencing 失效
    用于在不测序的情况下鉴定，分类或定量样品中蛋白质序列的方法和装置

    公开(公告)号：US06453245B1

    公开(公告)日：2002-09-17

    申请号：US09757528

    申请日：2001-01-10

    申请人： Jonathan Marc Rothberg ,  Michael W. Deem ,  John W. Simpson

    发明人： Jonathan Marc Rothberg ,  Michael W. Deem ,  John W. Simpson

    IPC分类号： G01N1506

    CPC分类号： G06F19/24 ,  C12N15/10 ,  C12Q1/68 ,  C12Q1/6809 ,  C12Q1/6855 ,  G06F19/22 ,  Y10S707/99936

    摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.

    摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。

    Method and apparatus for indentifying, classifying, or quantifying protein sequences in a sample without sequencing
    16.
    发明授权
    Method and apparatus for indentifying, classifying, or quantifying protein sequences in a sample without sequencing 失效
    用于在不测序的情况下对样品中的蛋白质序列进行鉴定，分类或定量的方法和装置

    公开(公告)号：US06231812B1

    公开(公告)日：2001-05-15

    申请号：US09322617

    申请日：1999-05-28

    申请人： Jonathan Marc Rothberg ,  Michael W. Deem ,  John W. Simpson

    发明人： Jonathan Marc Rothberg ,  Michael W. Deem ,  John W. Simpson

    IPC分类号： G01N1506

    CPC分类号： G06F19/24 ,  C12N15/10 ,  C12Q1/68 ,  C12Q1/6809 ,  C12Q1/6855 ,  G06F19/22 ,  Y10S707/99936

    摘要： This invention provides methods by which biologically derived DNA sequences in a mixed sample or in an arrayed single sequence clone can be determined and classified without sequencing. The methods make use of information on the presence of carefully chosen target subsequences, typically of length from 4 to 8 base pairs, and preferably the length between target subsequences in a sample DNA sequence together with DNA sequence databases containing lists of sequences likely to be present in the sample to determine a sample sequence. The preferred method uses restriction endonucleases to recognize target subsequences and cut the sample sequence. Then carefully chosen recognition moieties are ligated to the cut fragments, the fragments amplified, and the experimental observation made. Polymerase chain reaction (PCR) is the preferred method of amplification. Another embodiment of the invention uses information on the presence or absence of carefully chosen target subsequences in a single sequence clone together with DNA sequence databases to determine the clone sequence. Computer implemented methods are provided to analyze the experimental results and to determine the sample sequences in question and to carefully choose target subsequences in order that experiments yield a maximum amount of information.

    摘要翻译： 本发明提供了可以确定和分类混合样品或排列单序列克隆中的生物衍生DNA序列而不进行测序的方法。 这些方法利用关于精确选择的目标子序列的存在的信息，通常长度为4至8个碱基对，优选样品DNA序列中目标子序列之间的长度以及含有可能存在的序列的DNA序列数据库 在样品中确定样品序列。 优选的方法是使用限制性核酸内切酶识别目标子序列并切割样品序列。 然后仔细选择识别部分连接到切割片段，扩增片段，并进行实验观察。 聚合酶链反应（PCR）是优选的扩增方法。 本发明的另一个实施方案使用关于在单个序列克隆中与DNA序列数据库一起存在或不存在仔细选择的目标子序列的信息来确定克隆序列。 提供计算机实现的方法来分析实验结果并确定所讨论的样本序列，并仔细选择目标子序列，以便实验产生最大量的信息。

    Apparatus and method for the generation, separation, detection, and recognition of biopolymer fragments
    17.
    发明授权
    Apparatus and method for the generation, separation, detection, and recognition of biopolymer fragments 失效
    用于产生，分离，检测和识别生物聚合物片段的装置和方法

    公开(公告)号：US5993634A

    公开(公告)日：1999-11-30

    申请号：US644073

    申请日：1996-05-09

    申请人： John W. Simpson ,  Jonathan M. Rothberg ,  Gregory T. Went

    发明人： John W. Simpson ,  Jonathan M. Rothberg ,  Gregory T. Went

    IPC分类号： B01J19/00 ,  G01N27/447 ,  G01N27/26

    CPC分类号： B01J19/0093 ,  G01N27/44708 ,  G01N27/44782 ,  G01N27/44791 ,  B01J2219/00783 ,  B01J2219/00828 ,  B01J2219/00831 ,  B01J2219/00833 ,  B01J2219/00873 ,  B01J2219/00995 ,  G01N27/44721 ,  Y10S436/80 ,  Y10T436/143333

    摘要： This invention is an integrated instrument for high-capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which the migration lanes are formed between a bottom plate and a plurality of etched grooves in a top plate, the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype. Optionally post-processing is done by a Monte-Carlo simulated annealing algorithm to improve results. Optionally, an array of micro-reactors can be integrated into the instrument for the generation of sequencing reaction fragments directly from crude DNA samples.

    摘要翻译： 本发明是用于生物聚合物样品的高容量电泳分析的集成仪器。 它包括专门的高压电泳模块，其中迁移通道形成在顶板和顶板中的多个蚀刻凹槽之间，该模块允许同时分离80个或更多个单独的样品。 与底板热接触的是热控制模块，其包括用于控制电泳介质中的温度和梯度的多个珀尔贴热传递装置。 通过透射成像光谱仪检测片段，其同时空间聚焦并光谱地解析所有迁移通道的检测区域。 该光谱仪包括用于检测信号的透射色散元件和CCD阵列。 信号分析包括噪声滤波，配置空间与信号原型的比较以及最佳原型的选择。 可选地，后处理通过蒙特卡罗模拟退火算法完成以改善结果。 任选地，可以将微反应器阵列整合到仪器中，以直接从粗DNA样品产生测序反应片段。

    Flux focusing eddy current probe
    19.
    发明授权
    Flux focusing eddy current probe 失效
    助焊剂聚焦涡流探头

    公开(公告)号：US5617024A

    公开(公告)日：1997-04-01

    申请号：US649851

    申请日：1996-05-08

    申请人： John W. Simpson ,  C. Gerald Clendenin ,  James P. Fulton ,  Russell A. Wincheski ,  Ronald G. Todhunter ,  Min Namkung ,  Shridhar C. Nath

    发明人： John W. Simpson ,  C. Gerald Clendenin ,  James P. Fulton ,  Russell A. Wincheski ,  Ronald G. Todhunter ,  Min Namkung ,  Shridhar C. Nath

    IPC分类号： G01N27/90 ,  G01R33/12

    CPC分类号： G01N27/9033 ,  G01N27/902

    摘要： A flux-focusing electromagnetic sensor which uses a ferromagnetic flux-focusing lens simplifies inspections and increases detectability of fatigue cracks and material loss in high conductivity material. The unique feature of the device is the ferrous shield isolating a high-turn pick-up coil from an excitation coil. The use of the magnetic shield is shown to produce a null voltage output across the receiving coil in the presence of an unflawed sample. A redistribution of the current flow in the sample caused by the presence of flaws, however, eliminates the shielding condition and a large output voltage is produced, yielding a clear unambiguous flaw signal.The maximum sensor output is obtained when positioned symmetrically above the crack. Hence, by obtaining the position of the maximum sensor output, it is possible to track the fault and locate the area surrounding its tip. The accuracy of tip location is enhanced by two unique features of the sensor; a very high signal-to-noise ratio of the probe's output which results in an extremely smooth signal peak across the fault, and a rapidly decaying sensor output outside a small area surrounding the crack tip which enables the region for searching to be clearly defined. Under low frequency operation, material thinning due to corrosion damage causes an incomplete shielding of the pick-up coil. The low frequency output voltage of the probe is therefore a direct indicator of the thickness of the test sample.

    摘要翻译： 使用铁磁通量聚焦透镜的助焊剂聚焦电磁传感器简化了检查并增加了高导电性材料中的疲劳裂纹和材料损失的可检测性。 该器件的独特之处在于，铁芯屏蔽了高频匝线圈与励磁线圈的隔离。 显示了使用磁屏蔽，在存在无裂纹的样品的情况下，在接收线圈上产生零电压输出。 然而，由于存在缺陷导致的样品中的电流的再分布消除了屏蔽状况，产生了大的输出电压，产生了明确的明确的缺陷信号。 当对称地位于裂缝上方时获得最大传感器输出。 因此，通过获得最大传感器输出的位置，可以跟踪故障并定位其尖端周围的区域。 通过传感器的两个独特功能增强了尖端位置的精度; 探头输出的非常高的信噪比导致故障之间的非常平滑的信号峰值，以及在裂纹尖端周围的小区域外的迅速衰减的传感器输出，使得该区域能够被清楚地定义。 在低频操作下，由于腐蚀损坏引起的材料变薄会导致拾取线圈的不完全屏蔽。 因此，探头的低频输出电压是测试样品厚度的直接指示。

    Eddy current probe for surface and sub-surface inspection
    20.
    发明授权
    Eddy current probe for surface and sub-surface inspection 有权
    用于表面和表面检查的涡流探头

    公开(公告)号：US08717012B2

    公开(公告)日：2014-05-06

    申请号：US13457687

    申请日：2012-04-27

    申请人： Russell A. Wincheski ,  John W. Simpson

    发明人： Russell A. Wincheski ,  John W. Simpson

    IPC分类号： G01N27/72 ,  G01N27/82 ,  G01R33/14 ,  G01R33/00 ,  G01B7/16

    CPC分类号： G01R33/091 ,  G01R33/12

    摘要： An eddy current probe includes an excitation coil for coupling to a low-frequency alternating current (AC) source. A magnetoresistive sensor is centrally disposed within and at one end of the excitation coil to thereby define a sensing end of the probe. A tubular flux-focusing lens is disposed between the excitation coil and the magnetoresistive sensor. An excitation wire is spaced apart from the magnetoresistive sensor in a plane that is perpendicular to the sensor's axis of sensitivity and such that, when the sensing end of the eddy current probe is positioned adjacent to the surface of a structure, the excitation wire is disposed between the magnetoresistive sensor and the surface of the structure. The excitation wire is coupled to a high-frequency AC source. The excitation coil and flux-focusing lens can be omitted when only surface inspection is required.

    摘要翻译： 涡流探头包括用于耦合到低频交流（AC）源的激励线圈。 磁阻传感器居中设置在励磁线圈的一端内并在其一端，从而限定探头的感测端。 管状磁通聚焦透镜设置在励磁线圈和磁阻传感器之间。 励磁线在垂直于传感器的灵敏度轴的平面中与磁阻传感器间隔开，并且当涡流探针的感测端位于结构的表面附近时，激励线被布置 在磁阻传感器和结构的表面之间。 励磁线耦合到高频AC电源。 当仅需要表面检查时，可以省略励磁线圈和磁通聚焦透镜。