公开(公告)号：US06476118B1

公开(公告)日：2002-11-05

申请号：US09507496

申请日：2000-02-18

申请人： Barry L. Karger ,  Lev Kotler ,  Wolfgang Goetzinger ,  Haihong Zhou ,  Zoran Sosic ,  Oscar Salas-Solano

发明人： Barry L. Karger ,  Lev Kotler ,  Wolfgang Goetzinger ,  Haihong Zhou ,  Zoran Sosic ,  Oscar Salas-Solano

IPC分类号： C08L3104

CPC分类号： G01N27/44747 ,  C08L33/24 ,  C08L33/26 ,  C08L2205/02 ,  C08L2666/04 ,  C08L33/00

摘要： A method of separating a mixture of biopolymers of various lengths using a blend of two linear hydrophilic polymers, particularly polyacrylamides (LPA) or substituted polyacrylamides, one with high weight-average molecular mass and another with low weight-average molecular mass, each present at a low concentration but wherein the concentration of the high weight-average molecular mass LPA is above its entanglement threshold, is disclosed. The matrix is excellent for use in methods of nucleic acid analysis, particularly long read length DNA sequencing.

摘要翻译： 使用两种直链亲水性聚合物，特别是聚丙烯酰胺（LPA）或取代的聚丙烯酰胺（一种具有高重均分子量，另一种具有低重均分子量）的共混物的混合物分离各种长度的生物聚合物的混合物的方法， 公开了低浓度，但其中高重均分子量LPA的浓度高于其缠结阈值。 该基质非常适用于核酸分析方法，特别是长读长度DNA测序。

公开(公告)号：US06660149B1

公开(公告)日：2003-12-09

申请号：US09530118

申请日：2000-04-24

申请人： Barry L. Karger ,  Lev Kotler ,  Frantisek Foret ,  Marek Minarik ,  Karel Kleparnik

发明人： Barry L. Karger ,  Lev Kotler ,  Frantisek Foret ,  Marek Minarik ,  Karel Kleparnik

IPC分类号： G01N2726

CPC分类号： G01N30/80 ,  B01D15/08 ,  G01N27/44717 ,  G01N27/44782 ,  G01N27/44791 ,  G01N30/466 ,  G01N30/82

摘要： A modular multiple lane or capillary electrophoresis (chromatography) system that permits automated parallel separation and comprehensive collection of all fractions from samples in all lanes or columns, with the option of further on-line automated sample fraction analysis, is disclosed. Preferably, fractions are collected in a multi-well fraction collection unit, or plate (40). The multi-well collection plate (40) is preferably made of a solvent permeable gel, most preferably a hydrophilic, polymeric gel such as agarose or cross-linked polyacrylamide.

摘要翻译： 公开了一种模块化多通道或毛细管电泳（色谱）系统，其允许在所有泳道或色谱柱中的样品自动平行分离和全面收集所有级分，并进一步在线自动化样品分数分析。 优选地，将馏分收集在多孔馏分收集单元或板（40）中。 多孔收集板（40）优选由溶剂渗透性凝胶制成，最优选由亲水性聚合物凝胶如琼脂糖或交联聚丙烯酰胺制成。

公开(公告)号：US07578915B2

公开(公告)日：2009-08-25

申请号：US10652773

申请日：2003-08-29

申请人： Barry L. Karger ,  Lev Kotler ,  Frantisek Foret ,  Marek Minarik ,  Karel Kleparnik

发明人： Barry L. Karger ,  Lev Kotler ,  Frantisek Foret ,  Marek Minarik ,  Karel Kleparnik

IPC分类号： G01N27/447 ,  B01D57/02

CPC分类号： G01N30/80 ,  B01D15/08 ,  G01N27/44717 ,  G01N27/44782 ,  G01N27/44791 ,  G01N30/466 ,  G01N30/82

摘要： A modular multiple lane or capillary electrophoresis (chromatography) system that permits automated parallel separation and comprehensive collection of all fractions from samples in all lanes or columns, with the option of further on-line automated sample fraction analysis, is disclosed. Preferably, fractions are collected in a multi-well fraction collection unit, or plate. The multi-well collection plate is preferably made of a solvent permeable gel, most preferably a hydrophilic, polymeric gel such as agarose or cross-linked polyacrylamide.

摘要翻译： 公开了一种模块化多通道或毛细管电泳（色谱）系统，其允许在所有泳道或色谱柱中的样品自动平行分离和全面收集所有级分，并进一步在线自动化样品分数分析。 优选地，将馏分收集在多孔馏分收集单元或板中。 多孔收集板优选由溶剂可渗透的凝胶制成，最优选由亲水性聚合物凝胶如琼脂糖或交联聚丙烯酰胺制成。

公开(公告)号：US07323092B2

公开(公告)日：2008-01-29

申请号：US10653398

申请日：2003-09-02

申请人： Barry L. Karger ,  Lev Kotler ,  Frantisek Foret ,  Marek Minarik ,  Karel Kleparnik

发明人： Barry L. Karger ,  Lev Kotler ,  Frantisek Foret ,  Marek Minarik ,  Karel Kleparnik

IPC分类号： G01N27/453

CPC分类号： G01N30/80 ,  B01D15/08 ,  G01N27/44717 ,  G01N27/44782 ,  G01N27/44791 ,  G01N30/466 ,  G01N30/82

摘要： While the present invention has been described in conjunction with a preferred embodiment, one of ordinary skill, after reading the foregoing specification, will be able to effect various changes, substitutions of equivalents, and other alterations to the compositions and methods set forth herein. It is therefore intended that the protection granted by Letters Patent hereon be limited only by the definitions contained in the appended claims and equivalents thereof.

摘要翻译： 虽然已经结合优选实施例描述了本发明，但是在阅读前述说明书之后，普通技术人员将能够实现本文所阐述的组合物和方法的各种改变，替代等同物以及其它改变。 因此，专利文献授权的保护意图仅由所附权利要求及其等同物中所包含的定义来限制。

公开(公告)号：US5840388A

公开(公告)日：1998-11-24

申请号：US861906

申请日：1997-05-22

申请人： Barry L. Karger ,  Wolfgang Goetzinger

发明人： Barry L. Karger ,  Wolfgang Goetzinger

IPC分类号： G01N27/447 ,  C25B9/00

CPC分类号： B01J20/285 ,  B01J20/262 ,  G01N27/44752 ,  Y10T428/131 ,  Y10T428/1321 ,  Y10T428/1352 ,  Y10T428/1383 ,  Y10T428/1393 ,  Y10T428/31663 ,  Y10T428/31931 ,  Y10T428/31935

摘要： A coated microcapillary column for high performance electrophoresis is disclosed. A preferred microcapillary includes a fused silica capillary column, the inner surface of the column having an interconnected polymeric coating of a polyvinyl alcohol (PVA) based polymer covalently attached to the column wall by Si--O--Si bonds. The resulting coated microcapillary column has good hydrolytic and pH stability and minimizes electroosmotic flow and interactions between sample components and the capillary wall. Also disclosed are a method of forming a polymeric coating layer for any surface by polymerizing the appropriate organic compounds in an organic solvent and a method of forming a column with a hydrophilic polymeric coating by directly converting an attached hydrophobic polymeric coating material to a hydrophilic polymeric coating material.

摘要翻译： 公开了一种用于高性能电泳的涂层微毛细管柱。 优选的微毛细管包括熔融石英毛细管柱，柱的内表面具有通过Si-O-Si键共价连接到柱壁的聚乙烯醇（PVA）基聚合物的互连聚合物涂层。 所得涂层的微毛细管柱具有良好的水解和pH稳定性，并最小化电渗流和样品组分与毛细管壁之间的相互作用。 还公开了通过在有机溶剂中聚合合适的有机化合物来形成用于任何表面的聚合物涂层的方法，以及通过将附着的疏水性聚合物涂料直接转化为亲水性聚合物涂层的亲水性聚合物涂层形成柱的方法 材料。

公开(公告)号：US06372353B1

公开(公告)日：2002-04-16

申请号：US09197896

申请日：1998-11-23

申请人： Barry L. Karger ,  Wolfgang Goetzinger

发明人： Barry L. Karger ,  Wolfgang Goetzinger

IPC分类号： B32B904

摘要： Coatings suitable for surfaces such as are found in capillary electrophoresis columns and methods for their preparation are disclosed. A coated surface of the invention, preferably an interior surface of a microcapillary, generally includes a surface having an interconnected polymeric coating that includes a functional group attached to the surface and capable of copolymerizing with an organic compound in an organic solvent, and a polymer of the organic compound copolymerized with the functional group. The coating can be covalently or non-covalently attached to the surface and can further include an additional layer of coating material. Preferably, the organic compound is a vinyl ester, and most preferably, vinyl acetate, and the attached polymer forming the exposed surface of the coating is a polyvinyl alcohol, the hydroxyl groups of which can be further derivatized in any desired manner. The coating of the invention creates a new, stable surface, appropriate for CE columns or general surface modification. The coating is stable over a wide pH range and allows highly efficient grafting and/or adsorption of a variety of additional layers, if desired.

公开(公告)号：US07409298B2

公开(公告)日：2008-08-05

申请号：US10510992

申请日：2003-04-11

申请人： Victor P. Andreev ,  Tomas Rejtar ,  Barry L. Karger

发明人： Victor P. Andreev ,  Tomas Rejtar ,  Barry L. Karger

IPC分类号： G01N31/00

CPC分类号： H01J49/004 ,  G01N30/8603 ,  G01N30/8617 ,  G06F19/703 ,  H01J49/0036

摘要： An improved system and method of analyzing sample data that increases the reliability of peak (compound) detection and identification in the presence of chemical and/or random noise. The sample analysis system includes a compound-separating unit for separating constituent compounds in a sample mixture, a compound-analyzing unit for identifying and quantitating at least one of the separated compounds, and a computer for acquiring data from the compound-separating and compound-analyzing units, for generating a multi-dimensional data set incorporating the acquired data, for executing an algorithm for reducing noise in the data set and for detecting peaks (compounds) in the noise-reduced data set, and for identifying/quantitating the detected compounds.

摘要翻译： 一种改进的系统和方法，用于分析样本数据，提高在存在化学和/或随机噪声的情况下峰（复合）检测和识别的可靠性。 样品分析系统包括用于分离样品混合物中的组分化合物的化合物分离单元，用于鉴定和定量分离的化合物中的至少一种的化合物分析单元，以及用于从化合物分离和化合物分离单元中获取数据的计算机， 分析单元，用于生成包含所获取的数据的多维数据集，用于执行用于减少数据集中的噪声并且用于检测噪声减小的数据集中的峰值（化合物）的算法，以及用于识别/定量检测到的化合物 。

公开(公告)号：US06939452B2

公开(公告)日：2005-09-06

申请号：US10181503

申请日：2001-01-18

申请人： Frantisek Foret ,  Thomas Rejtar ,  Bailin Zhang ,  Barry L. Karger

发明人： Frantisek Foret ,  Thomas Rejtar ,  Bailin Zhang ,  Barry L. Karger

IPC分类号： B01L3/00 ,  G01N27/447 ,  G01N27/453

CPC分类号： B01L3/502715 ,  B01L3/5025 ,  B01L2200/027 ,  B01L2400/0415 ,  B01L2400/049 ,  G01N27/44743 ,  G01N27/44791

摘要： A sample load and injection device (10) includes sample introduction capillaries (11) attached to a microfluidic device (12). Sample introduction capillaries (11) are connected to sample introduction channels (18). Sample introduction capillaries (18) are connected to separation channels (20) at connection points (21). At a defined distance along the separation channels (20), auxilliary channels (23) originate at connection points (24). The sample load and injection device includes cover plate (28) which has connecting channels (26, 32). Connecting channel (26) is associated with ends (24) of sample introduction channels (18). Connecting channel (32) is associated with ends (20).

摘要翻译： 样品装载和注射装置（10）包括连接到微流体装置（12）的样品引入毛细管（11）。 样品引入毛细管（11）连接到样品引入通道（18）。 样品引入毛细管（18）在连接点（21）处连接到分离通道（20）。 在沿着分离通道（20）的限定距离处，辅助通道（23）起始于连接点（24）。 样品装载和注射装置包括具有连接通道（26,32）的盖板（28）。 连接通道（26）与样品引入通道（18）的端部（24）相关联。 连接通道（32）与端部（20）相关联。

公开(公告)号：US06929731B2

公开(公告)日：2005-08-16

申请号：US09979622

申请日：2001-03-07

申请人： Frantisek Foret ,  Barry L. Karger

发明人： Frantisek Foret ,  Barry L. Karger

IPC分类号： B01L3/00 ,  B01L7/00 ,  G01N27/447 ,  G01N30/28 ,  G01N30/30 ,  G01N30/46 ,  C02F11/18

CPC分类号： B01L7/54 ,  B01J2219/00452 ,  B01J2219/00585 ,  B01J2219/00587 ,  B01J2219/00698 ,  B01J2219/00702 ,  B01J2219/00707 ,  B01L3/5027 ,  B01L7/00 ,  B01L7/52 ,  B01L7/5255 ,  B01L2300/18 ,  B01L2300/1883 ,  B01L2400/0415 ,  G01N27/44704 ,  G01N27/44708 ,  G01N27/44782 ,  G01N30/30 ,  G01N2030/285 ,  G01N2030/3007 ,  G01N30/466

摘要： A thermostat array including an array of two or more capillary columns (10) or two or more channels in a microfabricated device is disclosed. A heat conductive material (12) surrounded each individual column or channel in array, each individual column or channel being thermally insulated from every other individual column or channel. One or more independently controlled heating or cooling elements (14) is positioned adjacent to individual columns or channels within the heat conductive material, each heating or cooling element being connected to a source of heating or cooling, and one or more independently controlled temperature sensing elements (16) is positioned adjacent to the individual columns or channels within the heat conductive material. Each temperature sensing element is connected to a temperature controller.

摘要翻译： 公开了一种包括两个或多个毛细管柱（10）的阵列或微加工装置中的两个或更多个通道的恒温器阵列。 导热材料（12）围绕阵列中的每个单独的柱或通道，每个单独的柱或通道与每个其他单独的柱或通道热绝缘。 一个或多个独立控制的加热或冷却元件（14）邻近于导热材料内的各个柱或通道定位，每个加热或冷却元件连接到加热或冷却源，以及一个或多个独立控制的温度感测元件 （16）定位成与导热材料内的各列或通道相邻。 每个温度感测元件连接到温度控制器。

公开(公告)号：US5783397A

公开(公告)日：1998-07-21

申请号：US662085

申请日：1996-06-12

申请人： Dallas E. Hughes ,  Barry L. Karger

发明人： Dallas E. Hughes ,  Barry L. Karger

IPC分类号： G01N27/447 ,  A61K36/00 ,  G01N33/537 ,  G01N33/561 ,  G01N33/68 ,  G01N33/53 ,  C25D13/00 ,  G01N21/00 ,  G01N33/00

CPC分类号： G01N33/561 ,  G01N33/537 ,  G01N33/6803 ,  G01N2500/00

摘要： A method in which natural sample components are simultaneously fractionated and screened for compounds that bind tightly to specific molecules of interest is disclosed. Such newly isolated ligands are good candidates for potential therapeutic or diagnostic compounds. The natural sample is first combined with a potential target molecule and then subjected to capillary electrophoresis (CE). Charged (or even neutral) compounds present in the natural sample that bind to the added target molecule can alter its normal migration time upon CE, by changing its charge-to-mass ratio, or will cause a variation in peak shape or area. Complex formation can be detected by simply monitoring the migration of the target molecule during electrophoresis. Any new ligands that bind to the target molecule will be good candidates for therapeutic or diagnostic compounds. Interfering, weak-binding ligands commonly present in crude extracts are not detected. Small, neutral ligands, as well as charged ligands, can be identified in competitive binding experiments with known, charged competitor molecules.

摘要翻译： 公开了一种方法，其中天然样品组分被同时分级并筛选与特定目的分子紧密结合的化合物。 这些新分离的配体是潜在的治疗或诊断化合物的良好候选物。 首先将天然样品与潜在的靶分子组合，然后进行毛细管电泳（CE）。 存在于与添加的靶分子结合的天然样品中的带电（或甚至中性）化合物可以通过改变其电荷质量比来改变其在CE上的正常迁移时间，或者将导致峰形或面积的变化。 络合物形成可以通过简单地监测靶分子在电泳过程中的迁移来检测。 与靶分子结合的任何新配体将是治疗或诊断化合物的良好候选物。 通常存在于粗提取物中的干扰，弱结合配体未被检测到。 可以在具有已知的带电竞争分子的竞争性结合实验中鉴定小的中性配体以及带电荷的配体。