公开(公告)号：US5207886A

公开(公告)日：1993-05-04

申请号：US767345

申请日：1991-09-27

申请人： Henk H. Lauer ,  Paul D. Grossman ,  Dennis E. Mead

发明人： Henk H. Lauer ,  Paul D. Grossman ,  Dennis E. Mead

IPC分类号： G01N27/447

CPC分类号： G01N27/44756 ,  G01N27/44743

摘要： An apparatus is disclosed for providing capillary electrophoresis, which includes an electronically controlled valve system for automatically introducing a sample into the capillary by means of a vacuum at the end of the capillary tube. This approach of sucking in the sample is extremely accurate and reproducible, and results in a minimum of band broadening. Furthermore, it enables the entire capillary electrophoresis system to be easily automated. An automated temperature control system is provided which enables the temperature of the capillary tube (and hence the solvent/solute system) to be controlled during electrophoresis, thereby very directly controlling pH and electrophoretic mobility. In another embodiment, the capillary is prewashed and equilibrated to achieve substantially zero charge on the capillary wall, thereby essentially eliminating electroosmotic flow and substantially improving resolution.

摘要翻译： 公开了一种用于提供毛细管电泳的装置，其包括电子控制阀系统，用于通过毛细管末端的真空将样品自动引入毛细管。 吸入样品的这种方法是非常准确和可重复的，并且导致最小的带宽变宽。 此外，它使得整个毛细管电泳系统能够容易地自动化。 提供了一种自动温度控制系统，其能够在电泳期间控制毛细管（因此溶剂/溶质系统）的温度，从而非常直接地控制pH和电泳迁移率。 在另一个实施方案中，毛细管被预洗和平衡以在毛细管壁上实现基本上零的电荷，从而基本上消除电渗流并显着提高分辨率。

公开(公告)号：US5597468A

公开(公告)日：1997-01-28

申请号：US324359

申请日：1994-10-17

申请人： Henk H. Lauer ,  Paul D. Grossman ,  Dennis E. Mead

发明人： Henk H. Lauer ,  Paul D. Grossman ,  Dennis E. Mead

IPC分类号： G01N27/447 ,  G01N27/26

CPC分类号： G01N27/44756 ,  G01N27/44743

摘要： An apparatus is disclosed for providing capillary electrophoresis, which includes an electronically controlled valve system for automatically introducing a sample into the capillary by means of a vacuum at the end of the capillary tube. This approach of sucking in the sample is extremely accurate and reproducible, and results in a minimum of band broadening. Furthermore, it enables the entire capillary electrophoresis sytem to be easily automated. An automated temperature control system is provided which enables the temperature of the capillary tube (and hence the solvent/solute system) to be controlled during electrophoresis, thereby very directly controlling pH and electrophoretic mobility. In another embodiment, the capillary is prewashed and equilibrated to achieve substantially zero charge on the capillary wall, thereby essentially eliminating electroosmotic flow and substantially improving resolution.

摘要翻译： 公开了一种用于提供毛细管电泳的装置，其包括电子控制阀系统，用于通过毛细管末端的真空将样品自动引入毛细管。 吸入样品的这种方法是非常准确和可重复的，并且导致最小的带宽变宽。 此外，它使得整个毛细管电泳系统能够容易地自动化。 提供了一种自动温度控制系统，其能够在电泳期间控制毛细管（因此溶剂/溶质系统）的温度，从而非常直接地控制pH和电泳迁移率。 在另一个实施方案中，毛细管被预洗和平衡以在毛细管壁上实现基本上零的电荷，从而基本上消除电渗流并显着提高分辨率。

公开(公告)号：US5240576A

公开(公告)日：1993-08-31

申请号：US461568

申请日：1990-01-05

申请人： Henk H. Lauer ,  Paul D. Grossman ,  Dennis E. Mead

发明人： Henk H. Lauer ,  Paul D. Grossman ,  Dennis E. Mead

IPC分类号： G01N27/447

CPC分类号： G01N27/44756 ,  G01N27/44743

摘要： an apparatus is disclosed for providing capillary electrophoresis, which includes an electronically controlled valve system for automatically introducing a sample into the capillary by means of a vacuum at the end of the capillary tube. This approach of sucking in the sample is extremely accurate and reproducible, and results in a minimum of band broadening. Furthermore, it enables the entire capillary electrophoresis sytem to be easily automated. An automated temperature control system is provided which enables the temperature of the capillary tube (and hence the solvent/solute system) to be controlled during electrophoresis, thereby very directly controlling pH and electrophoretic mobility. In another embodiment, the capillary is prewashed and equilibrated to achieve substantially zero charge on the capillary wall, thereby essentially eliminating electroosmotic flow and substantially improving resolution.

摘要翻译： 公开了一种用于提供毛细管电泳的装置，其包括用于通过毛细管末端的真空将样品自动引入毛细管的电子控制阀系统。 吸入样品的这种方法是非常准确和可重复的，并且导致最小的带宽变宽。 此外，它使得整个毛细管电泳系统能够容易地自动化。 提供了一种自动温度控制系统，其能够在电泳期间控制毛细管（因此溶剂/溶质系统）的温度，从而非常直接地控制pH和电泳迁移率。 在另一个实施方案中，毛细管被预洗和平衡以在毛细管壁上实现基本上零的电荷，从而基本上消除电渗流并显着提高分辨率。

公开(公告)号：US5552028A

公开(公告)日：1996-09-03

申请号：US458525

申请日：1995-06-02

申请人： Ramakrishna S. Madabhushi ,  Steven M. Menchen ,  J. William Efcavitch ,  Paul D. Grossman

发明人： Ramakrishna S. Madabhushi ,  Steven M. Menchen ,  J. William Efcavitch ,  Paul D. Grossman

IPC分类号： C08F20/52 ,  C08F26/10 ,  C08F122/38 ,  C08F126/10 ,  C08G63/06 ,  C08G63/08 ,  G01N27/447 ,  C07K1/26 ,  B01J13/00 ,  C25B7/00

CPC分类号： G01N27/44752 ,  G01N27/44747

摘要： The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20.degree. C. to about 50.degree. C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5.times.10.sup.3 to about 1.times.10.sup.6 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9. In one embodiment, polymers of the invention are selected from the group consisting of polylactams, such as polyvinylpyrrolidone; N,N-disubstituted polyacrylamides; and N-substituted polyacrylamides. In accordance with the method of the invention, a sufficient amount of polymer adsorbs to the capillary surface to establish a zone of high viscosity that shields the analyte from the wall and impedes the movement of an electrical double layer under an electric field.

公开(公告)号：US5514543A

公开(公告)日：1996-05-07

申请号：US102372

申请日：1993-08-04

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

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

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

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 one embodiment of the invention, a plurality of different-sequence probe pairs are added to a target polynucleotide, where each probe pair includes two polynucleotide probe elements which are complementary in sequence to adjacent portions of a selected one of the target sequences in the target polynucleotide. In each probe pair, one of the probe elements contains a non-polynucleotide polymer chain which imparts a distinctive mobility to the associated probe pair, when the elements in the pair are ligated. The other element in the pair contains a detectable reporter label. After the probe pairs have been allowed to hybridize with the target polynucleotide, the hybridized polynucleotides are treated under conditions effective to ligate the end subunits of target-bound probe elements when their end subunits are base-paired with adjacent target bases. The ligated probe pairs are then released from the target polynucleotide and separated electrophoretically in a sieving matrix, or chromatographically.

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。 在本发明的一个实施方案中，将多个不同序列探针对加入到靶多核苷酸中，其中每个探针对包含两个多核苷酸探针元件，该多核苷酸探针元件与目标中所选择的一个目标序列的相邻部分互补 多核苷酸。 在每个探针对中，探针元件中的一个包含非多核苷酸聚合物链，当对中的元件被连接时，赋予相关探针对的特异性移动性。 该对中的另一个元素包含可检测的报告物标记。 在探针对已被允许与靶多核苷酸杂交后，杂交的多核苷酸在有效连接靶结合探针元件的末端亚基的条件下处理，当它们的末端亚基与相邻的靶基碱基配对时。 然后将连接的探针对从目标多核苷酸中释放，并在筛分基质中电泳分离，或进行色谱分离。

公开(公告)号：US06734296B1

公开(公告)日：2004-05-11

申请号：US09724730

申请日：2000-11-28

申请人： Paul D. Grossman

发明人： Paul D. Grossman

IPC分类号： C12Q168

CPC分类号： C12Q1/6834 ,  C12Q1/6813 ,  C12Q1/6827 ,  C12Q1/6858 ,  C12Q2563/179 ,  C12Q2535/125 ,  C12Q2537/143 ,  C12Q2525/161

摘要： Compositions and methods for the analysis of multiple nucleic acid target sequences are disclosed. The compositions comprise a probe comprising a target-specific portion for sequence-specific hybridization to a target nucleic acid sequence, and a tag; and a mobility-modifier comprising a tail and a tag complement for binding to the tag. The associated methods generally comprise the steps of providing a sample potentially containing one or more target nucleic acid sequences; providing one or more probes, each probe comprising a target-specific portion and a tag; providing one or more mobility modifiers, each mobility modifier comprising a tag complement and a tail; contacting the probe(s) and the target nucleic acid sequence(s) under conditions effective for sequence-dependent hybridization of the probe(s) and the target nucleic acid sequence(s); contacting the probe(s) and the mobility-modifier(s) under conditions suitable for selectively binding the probe(s) to the mobility modifier(s), thereby forming one or more a probe/mobility modifier complex(s); and analyzing the probe/mobility modifier complex(s) using a mobility-dependent analysis technique.

摘要翻译： 公开了用于分析多个核酸靶序列的组合物和方法。 所述组合物包含探针，所述探针包含用于靶核酸序列的序列特异性杂交的靶特异性部分和标签; 和包含尾部的移动性修饰剂和用于结合标签的标签互补物。 相关方法通常包括提供潜在含有一个或多个靶核酸序列的样品的步骤; 提供一个或多个探针，每个探针包括目标特异性部分和标签; 提供一个或多个移动性修饰符，每个移动性修饰物包含标签补体和尾部; 在对探针和靶核酸序列的序列依赖性杂交有效的条件下使探针和靶核酸序列接触; 在适于选择性地将探针结合到迁移率改性剂的条件下，使探针和迁移率调节剂接触，从而形成一种或多种探针/迁移率调节剂复合物; 并使用迁移率依赖性分析技术分析探针/迁移率调节剂复合物。

公开(公告)号：US5567292A

公开(公告)日：1996-10-22

申请号：US350852

申请日：1994-12-06

申请人： Ramakrishna S. Madabhushi ,  Steven M. Menchen ,  J. William Efcavitch ,  Paul D. Grossman

发明人： Ramakrishna S. Madabhushi ,  Steven M. Menchen ,  J. William Efcavitch ,  Paul D. Grossman

IPC分类号： C08F20/52 ,  C08F26/10 ,  C08F122/38 ,  C08F126/10 ,  C08G63/06 ,  C08G63/08 ,  G01N27/447 ,  C07K1/26 ,  C25B7/00 ,  C25B15/00

CPC分类号： G01N27/44752 ,  G01N27/44747

摘要： The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20.degree. C. to about 50.degree. C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5.times.10.sup.3 to about 1.times.10.sup.6 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9. In one embodiment, polymers of the invention are selected from the group consisting of polylactams, such as polyvinylpyrrolidone; N,N-disubstituted polyacrylamides; and N-substituted polyacrylamides. In accordance with the method of the invention, a sufficient amount of polymer adsorbs to the capillary surface to establish a zone of high viscosity that shields the analyte from the wall and impedes the movement of an electrical double layer under an electric field.

公开(公告)号：US07381315B2

公开(公告)日：2008-06-03

申请号：US10455986

申请日：2003-06-07

申请人： Paul D. Grossman ,  Jeffery D. Frazier

发明人： Paul D. Grossman ,  Jeffery D. Frazier

IPC分类号： G01N27/26 ,  B03C11/00

CPC分类号： G01N27/44782 ,  G01N27/44721

摘要： A side-entry excitation arrangement is provided with a multi-channel analyte-separation device. In various embodiments, a plurality of channels are disposed in an array, with a laser disposed to direct an excitation beam of light along a beam path that crosses the longitudinal axes of the channels, so as to simultaneously irradiate a region of each of the channels. Devices of the invention can be useful, for example, in the separation and analysis of bio-molecules, such as DNA, RNA, etc.

摘要翻译： 侧入口激励装置设置有多通道分析物分离装置。 在各种实施例中，多个通道被布置成阵列，激光器设置成沿着与通道的纵向轴线交叉的光束路径引导激发光束，以便同时照射每个通道的区域 。 本发明的装置可用于例如生物分子如DNA，RNA等的分离和分析。

公开(公告)号：US06627433B2

公开(公告)日：2003-09-30

申请号：US09938767

申请日：2001-08-24

申请人： Jeffery D. Frazier ,  Paul D. Grossman

发明人： Jeffery D. Frazier ,  Paul D. Grossman

IPC分类号： C12M134

CPC分类号： G01N27/44782 ,  G01N27/44721

摘要： A side-entry excitation arrangement is provided with a multi-channel analyte-separation device. In various embodiments, a plurality of channels are disposed in an array, with a laser disposed to direct an excitation beam of light along a beam path that crosses the longitudinal axes of the channels, so as to simultaneously irradiate a region of each of the channels. Devices of the invention can be useful, for example, in the separation and analysis of bio-molecules, such as DNA, RNA, etc.

公开(公告)号：US06358385B1

公开(公告)日：2002-03-19

申请号：US09228991

申请日：1999-01-11

申请人： Ramakrishna S. Madabhushi ,  Steven M. Menchen ,  J. William Efcavitch ,  Paul D. Grossman

发明人： Ramakrishna S. Madabhushi ,  Steven M. Menchen ,  J. William Efcavitch ,  Paul D. Grossman

IPC分类号： B01D5702

CPC分类号： G01N27/44752 ,  G01N27/44747

摘要： The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20° C. to about 50° C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5×103 to about 1×106 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9. In one embodiment, polymers of the invention are selected from the group consisting of polylactams, such as polyvinylpyrrolidone; N,N-disubstituted polyacrylamides; and N-substituted polyacrylamides. In accordance with the method of the invention, a sufficient amount of polymer adsorbs to the capillary surface to establish a zone of high viscosity that shields the analyte from the wall and impedes the movement of an electrical double layer under an electric field.

摘要翻译： 本发明提供了不带电的水溶性二氧化硅吸附聚合物，用于抑制毛细管电泳中的电渗流和降低毛细管电泳中的分析物 - 壁相互作用。 在本发明的一个方面，一种或多种这样的聚合物用作用于通过毛细管电泳分离生物分子例如多核苷酸，多糖，蛋白质等的分离介质的组分。 通常，这种聚合物的特征在于（i）在约20℃至约50℃之间的温度范围内的水溶性，（ii）分离介质中的浓度在约0.001％至约10％（重量） /体积），（iii）约5×10 3至约1×10 6道尔顿范围内的分子量，和（iv）在pH为约6至约9范围内的水性介质中不存在带电基团。在一个实施方案中， 本发明选自聚内酰胺类，如聚乙烯吡咯烷酮; N，N-二取代的聚丙烯酰胺; 和N-取代的聚丙烯酰胺。 根据本发明的方法，足够量的聚合物吸附到毛细管表面以建立一个高粘度的区域，从而将分析物与壁隔离并阻止双电层在电场下移动。