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    Electrophoretic nucleic acid purification method
    2.
    发明授权
    Electrophoretic nucleic acid purification method 失效
    电泳核酸纯化方法

    公开(公告)号：US6146511A

    公开(公告)日：2000-11-14

    申请号：US016531

    申请日：1998-01-30

    申请人： Gary Slater ,  J. William Efcavitch ,  Guy Drouin ,  Pascal Mayer ,  Jean Rousseau ,  Hong Yan Zhou ,  Claudia Chiesa ,  Robert Ruhfel ,  Roger O'Neill

    发明人： Gary Slater ,  J. William Efcavitch ,  Guy Drouin ,  Pascal Mayer ,  Jean Rousseau ,  Hong Yan Zhou ,  Claudia Chiesa ,  Robert Ruhfel ,  Roger O'Neill

    IPC分类号： B01D57/02 ,  B03C5/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/09 ,  C12N15/10 ,  G01N27/447 ,  G01N27/26

    CPC分类号： C12N15/101 ,  G01N27/447

    摘要： An electrophoretic method for purifying a nucleic acid sample is disclosed. The method generally comprises the steps of (1) providing a nucleic acid sample comprising a desired nucleic acid and one or more contaminants, (2) providing an electrophoresis matrix having a loading well and a recovery well formed therein, (3) placing the nucleic acid sample into the loading well, (4) performing a first electrophoresis comprising electrophoresing the nucleic acid sample for a first time effective to transport the desired nucleic acid out of the loading well and into the electrophoresis matrix; and (5) performing a second electrophoresis comprising electrophoresing the nucleic acid sample for a second time effective to transport the desired nucleic acid out of the electrophoresis matrix and into the recovery well. According to the method, the first and second electrophoresis steps are effective to substantially reduce the concentration of contaminants relative to the concentration of desired nucleic acid in the nucleic acid sample, thereby producing a purified nucleic acid. In the method, the loading and recovery wells may be the same or different, and the electric fields may be DC or alternating. Also disclosed is a preparative electrophoresis method employing an alternating electrical field.

    摘要翻译： 公开了一种用于纯化核酸样品的电泳方法。 该方法通常包括以下步骤：（1）提供包含所需核酸和一种或多种污染物的核酸样品，（2）提供具有载体孔的电泳基质和其中形成的回收孔，（3） （4）进行第一次电泳，其中包括使核酸样品首次有效地将所需核酸转运到载体孔中并进入电泳基质中; 包括进行第二次电泳，其包括将核酸样品电泳第二次，有效将所需核酸转运到电泳基质内并进入回收井。 根据该方法，第一和第二电泳步骤对于相对于核酸样品中所需核酸浓度显着降低污染物的浓度是有效的，从而产生纯化的核酸。 在该方法中，加载和回收井可以相同或不同，并且电场可以是直流或交替的。 还公开了采用交流电场的制备电泳方法。

    Ion source and accelerator for improved dynamic range and mass selection in a time of flight mass spectrometer
    3.
    发明授权
    Ion source and accelerator for improved dynamic range and mass selection in a time of flight mass spectrometer 失效
    离子源和加速器，用于在飞行时间质谱仪中改善动态范围和质量选择

    公开(公告)号：US06080985A

    公开(公告)日：2000-06-27

    申请号：US940576

    申请日：1997-09-30

    申请人： David G. Welkie ,  Dar Bahatt

    发明人： David G. Welkie ,  Dar Bahatt

    IPC分类号： G01N27/62 ,  G01N30/72 ,  H01J49/40

    CPC分类号： H01J49/147 ,  H01J49/40

    摘要： In a mass spectrometer, an ion source in combination with an accelerator comprising an electron source, a gate electrode constructed so as to block the flow of electrons from the source when a potential is applied, a sample introduction means for transporting carrier gas containing analytes, an ionization chamber positioned to receive the flow of electrons and the carrier gas, wherein the flow of electrons ionizes the carrier gas, a pulsed accelerator, and an ion transfer region situated so that the ionized carrier gas travels from the ionization chamber, through the ion transfer region and into an accelerator. The gate electrode and the pulsed accelerator are controlled in a timed relationship to control the amount off carrier gas being ionized and traveling into the accelerator between accelerator pulses so as to improve the dynamic range of the mass spectrometer and to selectively accelerate a particular mass range.

    摘要翻译： 在质谱仪中，与包含电子源的加速器组合的离子源，构成为当施加电位时阻挡电子从源极流动的栅电极，用于输送含有分析物的载气的样品引入装置， 定位成接收电子流和载气的电离室，其中电子流使载气离子化，脉冲加速器和离子转移区域，使离子化的载气从电离室通过离子 转移区域并进入加速器。 以定时关系控制栅电极和脉冲加速器，以控制离子化的载气量和加速器脉冲之间的加速器中的量，从而改善质谱仪的动态范围并选择性地加速特定的质量范围。

    Method and system for velocity-normalized position-based scanning
    4.
    发明授权
    Method and system for velocity-normalized position-based scanning 失效
    用于速度归一化位置扫描的方法和系统

    公开(公告)号：US6040586A

    公开(公告)日：2000-03-21

    申请号：US73130

    申请日：1998-05-05

    申请人： Tor Slettnes

    发明人： Tor Slettnes

    IPC分类号： G06T1/00 ,  G01N27/447 ,  H04N1/19 ,  G01N15/06

    CPC分类号： G01N27/44717 ,  G01N27/44721

    摘要： A data collection method for scanning a scan window comprising one or more channels is described. In the method of the invention an integrated signal (S) is measured across a scan window including one or more channels using an integrating detector. Next, a velocity-normalized integrated signal (Sn) is determined based on the integrated signal (S) and a scan velocity.

    摘要翻译： 描述了用于扫描包括一个或多个信道的扫描窗口的数据收集方法。 在本发明的方法中，使用积分检测器在包括一个或多个通道的扫描窗口之间测量积分信号（S）。 接下来，基于积分信号（S）和扫描速度来确定速度归一化积分信号（Sn）。

    4,7-Dichlororhodamine dyes
    5.
    发明授权
    4,7-Dichlororhodamine dyes 失效
    4,7-二氯罗丹明染料

    公开(公告)号：US6025505A

    公开(公告)日：2000-02-15

    申请号：US38191

    申请日：1998-03-10

    申请人： Linda G. Lee ,  Scott C. Benson ,  Barnett B. Rosenblum ,  Sandra L. Spurgeon ,  Jonathan M. Cassel ,  Ronald J. Graham

    发明人： Linda G. Lee ,  Scott C. Benson ,  Barnett B. Rosenblum ,  Sandra L. Spurgeon ,  Jonathan M. Cassel ,  Ronald J. Graham

    IPC分类号： C12N15/09 ,  C07D311/80 ,  C07D311/82 ,  C07D405/12 ,  C07D491/22 ,  C07F9/6561 ,  C07H19/06 ,  C07H19/14 ,  C07H19/16 ,  C07H21/00 ,  C07H21/04 ,  C09B11/24 ,  C09B11/28 ,  C09K11/06 ,  C09K11/07 ,  C12P19/34 ,  C12Q1/68 ,  G01N21/78 ,  G01N27/447 ,  G01N33/58 ,  C07D311/78 ,  C07D311/88

    CPC分类号： C07H21/00 ,  C09B11/24

    摘要： A class of 4,7-dichlororhodamine compounds useful as fluorescent dyes are disclosed having the structure ##STR1## wherein R.sub.1 -R.sub.6 are hydrogen, fluorine, chlorine, lower alkyl, lower alkene, lower alkyne, sulfonate, sulfone, amino, amido, nitrile, lower alkoxy, linking group, or combinations thereof, or, when taken together, R.sub.1 and R.sub.6 is benzo, or, when taken together, R.sub.4 and R.sub.5 is benzo; Y.sub.1 -Y.sub.4 are hydrogen or lower alkyl, or, when taken together, Y.sub.1 and R.sub.2, Y.sub.2 and R.sub.1 Y.sub.3 and R.sub.3, or Y.sub.4 and R.sub.4 is propano, ethano, or substituted forms thereof, and X.sub.1 -X.sub.3 taken separately are selected from the group consisting of hydrogen, chlorine, fluorine, lower alkyl, carboxylate, sulfonic acid, --CH.sub.2 OH, and linking group. In another aspect, the invention includes reagents labeled with the 4,7-dichlororhodamine dye compounds, including deoxynucleotides, dideoxynucleotides, and polynucleotides. In an additional aspect, the invention includes methods utilizing such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.

    摘要翻译： 公开了一类用作荧光染料的4,7-二氯罗丹明化合物，其结构是其中R 1 -R 6是氢，氟，氯，低级烷基，低级烯烃，低级炔烃，磺酸酯，砜，氨基，酰氨基，腈，低级烷氧基 或连接基团，或其组合，或者当R 1和R 6一起时为苯并，或者一起使用时，R 4和R 5为苯并; Y1-Y4是氢或低级烷基，或者当Y1和R2，Y2和R1Y3和R3，或Y4和R4是它们的丙酰，乙酸或取代形式时，分别选择的X1-X3选自 由氢，氯，氟，低级烷基，羧酸酯，磺酸，-CH 2 OH和连接基组成的组。 另一方面，本发明包括用4,7-二氯罗丹明染料化合物标记的试剂，包括脱氧核苷酸，双脱氧核苷酸和多核苷酸。 在另一方面，本发明包括利用这种染料化合物的方法和包括双脱氧多核苷酸测序和片段分析方法的试剂。

    Method of detecting aneuploidy by amplified short-tandem repeats
    6.
    发明授权
    Method of detecting aneuploidy by amplified short-tandem repeats 失效
    通过扩增的短串联重复检测非整倍体的方法

    公开(公告)号：US5994057A

    公开(公告)日：1999-11-30

    申请号：US199722

    申请日：1994-02-22

    申请人： Elaine S. Mansfield

    发明人： Elaine S. Mansfield

    IPC分类号： C12Q1/68

    CPC分类号： C12Q1/6876 ,  C12Q2600/156 ,  C12Q2600/16

    摘要： A method is provided for determining aneuploidy of selected chromosomes. An important feature of the invention is the quantitative amplification of STR markers with repeat units of at least 3 nucleotides. The amplified STR DNA is separated by size and the respective quantities of the amplified components are determined and related to chromosome copy number. The highly polymorphic nature of the STR markers permits a more sensitive and reliable quantitative analysis of the amplified DNA.

    摘要翻译： 提供了一种用于确定所选染色体非整倍体的方法。 本发明的一个重要特征是具有至少3个核苷酸的重复单元的STR标记的定量扩增。 扩增的STR DNA按大小分开，并确定扩增组分的相应量并与染色体拷贝数相关。 STR标记的高度多态性质允许对扩增的DNA进行更灵敏和可靠的定量分析。

    Kits for DNA sequencing employing a mixed DNA-polymer chain probe
    7.
    发明授权
    Kits for DNA sequencing employing a mixed DNA-polymer chain probe 失效
    使用混合DNA-聚合物链探针进行DNA测序的试剂盒

    公开(公告)号：US5989871A

    公开(公告)日：1999-11-23

    申请号：US800641

    申请日：1997-02-14

    申请人： Paul D. Grossman ,  Steven Fung ,  Steven M. Menchen ,  Sam Lee Woo ,  Emily S. Winn-Deen

    发明人： Paul D. Grossman ,  Steven Fung ,  Steven M. Menchen ,  Sam Lee Woo ,  Emily S. Winn-Deen

    IPC分类号： C12N15/09 ,  B01D57/02 ,  C12Q1/68 ,  G01N27/447 ,  G01N30/88 ,  G01N33/566 ,  C12P19/34 ,  C07H21/04

    CPC分类号： C12Q1/6869 ,  C12Q1/6816 ,  C12Q1/6827 ,  C12Q1/6858 ,  C12Q1/686 ,  C12Q1/6862 ,  C12Q1/6818 ,  Y10T436/143333

    摘要： Method and composition for detecting one or more selected polynucleotide regions in a target polynucleotide. In the method, a mixture of sequence-specific probes are reacted with the target polynucleotide under hybridization conditions, and the hybridized probes are treated to selectively modify those probes which are bound to the target polynucleotide in a base-specific manner. The resulting labeled probes include a polymer chain which imparts to each different-sequence probe, a distinctive ratio of charge/translational frictional drag, and a detectable label. The labeled probes are fractionated by electrophoresis in a non-sieving matrix, and the presence of one or more selected sequences in the target polynucleotide are detected according to the observed electrophoretic migration rates of the labeled probes in a non-sieiving medium.

    摘要翻译： 用于检测靶多核苷酸中的一个或多个选择的多核苷酸区域的方法和组合物。 在该方法中，将序列特异性探针的混合物与靶多核苷酸在杂交条件下反应，并对杂交的探针进行处理以选择性地修饰以碱基特异性方式结合靶多核苷酸的那些探针。 所得到的标记探针包括赋予每个不同序列探针的聚合物链，电荷/平移摩擦阻力的独特比例和可检测标记。 标记的探针通过在非筛选基质中的电泳进行分级，并且根据在非筛选培养基中标记的探针的观察到的电泳迁移速率来检测靶多核苷酸中一个或多个选定序列的存在。

    Detection of specific sequences in nucleic acids
    8.
    发明授权
    Detection of specific sequences in nucleic acids 失效
    检测核酸中的特定序列

    公开(公告)号：US5962223A

    公开(公告)日：1999-10-05

    申请号：US574826

    申请日：1995-12-19

    申请人： Norman M. Whiteley ,  Michael W. Hunkapiller ,  Alexander N. Glazer

    发明人： Norman M. Whiteley ,  Michael W. Hunkapiller ,  Alexander N. Glazer

    IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12P19/34

    CPC分类号： C12Q1/6862 ,  C12Q1/6813 ,  C12Q1/6827 ,  Y10S435/803 ,  Y10S435/81

    摘要： The invention provides a method for diagnosis of genetic abnormalities or other genetic conditions which can be readily automated. The method is used to determine the presence or absence of a target sequence in a sample of denatured nucleic acid and entails hybridizing the sample with a probe complementary to a diagnostic portion of the target sequence (the diagnostic probe), and with a probe complementary to a nucleotide sequence contiguous with the diagnostic portion (the contiguous probe), under conditions wherein the diagnostic probe remains bound substantially only to the sample nucleic acid containing the target sequence. The diagnostic probe and contiguous probe are then covalently attached to yield a target probe which is complementary to the target sequence, and the probes which are not attached are removed. In the preferred mode, one of the probes is labeled so that the presence or absence of the target sequence can then be tested by melting the sample nucleic acid-target probe duplex, eluting the dissociated target probe, and testing for the label. In another embodiment, the testing is accomplished without first removing probes not covalently attached, by attaching a hook to the probe that is not labeled, so that the labeled target probe may be recovered by catching the hook. In both instances, the presence of both the diagnostic probe and the contiguous probe is required for the label to appear in the assay. The above method is then applied to the detection of genetic diseases.

    摘要翻译： 本发明提供了一种用于诊断遗传异常或其他遗传病症的方法，其可以容易地自动化。 该方法用于确定变性核酸样品中靶序列的存在或不存在，并且需要将样品与与靶序列（诊断探针）的诊断部分互补的探针杂交，并且与探针互补 在诊断探针保持基本上仅与包含靶序列的样品核酸结合的条件下，与诊断部分（连续探针）连续的核苷酸序列。 然后将诊断探针和连续探针共价连接以产生与靶序列互补的靶探针，并且除去未连接的探针。 在优选模式中，其中一个探针被标记，使得靶序列的存在或不存在可以通过熔化样品核酸 - 靶标探针双链体，洗脱解离的靶标探针和测试标签来测试。 在另一个实施方案中，通过将钩连接到未标记的探针上，而无需首先除去未共价连接的探针，从而可以通过捕捉钩来回收标记的靶探针而进行测试。 在这两种情况下，诊断探针和连续探针的存在是标签出现在测定中所必需的。 然后将上述方法应用于遗传疾病的检测。

    Method and apparatus for reducing the distortion of a sample zone eluting from a capillary electrophoresis capillary
    10.
    发明授权
    Method and apparatus for reducing the distortion of a sample zone eluting from a capillary electrophoresis capillary 失效
    用于减少从毛细管电泳毛细管洗脱的样品区变形的方法和装置

    公开(公告)号：US5833826A

    公开(公告)日：1998-11-10

    申请号：US766009

    申请日：1996-12-13

    申请人： Eric S. Nordman

    发明人： Eric S. Nordman

    IPC分类号： G01N27/447 ,  G01N27/26

    CPC分类号： G01N27/44717

    摘要： An electrophoresis system including means for reducing the distortion of a sample zone eluting from a capillary electrophoresis separation capillary is disclosed. The system includes one or more separation capillaries, each separation capillary having an inlet end and an outlet end; a first electrode in electrical communication with the inlet ends of the separation capillaries; a second electrode in electrical communication with the outlet ends of the separation capillaries; and one or more focusing electrodes in electrical communication with the outlet ends of the separation capillaries. In operation, the voltage of each of the electrodes is adjusted such that (i) the sample zone is transported from the inlet end to the outlet end of the separation capillaries and (ii) the distortion of the sample zone eluting from the separation capillaries is reduced.

    摘要翻译： 公开了一种包括用于减少从毛细管电泳分离毛细管洗脱的样品区变形的装置的电泳系统。 该系统包括一个或多个分离毛细管，每个分离毛细管具有入口端和出口端; 与分离毛细管的入口端电连通的第一电极; 与分离毛细管的出口端电连通的第二电极; 以及一个或多个聚焦电极与分离毛细管的出口端电连通。 在操作中，调节每个电极的电压，使得（i）样品区域从分离毛细管的入口端输出到出口端，和（ii）从分离毛​​细管洗脱的样品区域的变形是 减少