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1. 发明授权

US08580570B2 Narrow bore porous layer open tube capillary column and uses thereof 失效
标题翻译：窄孔多孔层开管毛细管柱及其用途
公开(公告)号：US08580570B2
公开(公告)日：2013-11-12
申请号：US13184075
申请日：2011-07-15
申请人： Barry L. Karger , Jian Zhang
发明人： Barry L. Karger , Jian Zhang
IPC分类号： G01N30/00 , G01N30/02
CPC分类号： G01N30/60 , B01J20/28085 , B01J20/285 , B01J20/289 , B01J20/327 , B01J20/3282 , B01J2220/54 , B01J2220/84 , B01J2220/86 , G01N30/6073 , G01N30/7266 , G01N2030/528 , Y10T436/11 , Y10T436/117497
摘要： A polymer-based PLOT capillary column prepared by in situ copolymerization of a functional monomer, which usually contains the retentive chemistries, and a crosslinking monomer, which enhances the strength of the polymer matrix, is disclosed. Also disclosed is a system comprising the polymer-based PLOT column coupled to a mass flow or concentration sensitive detector, for carrying out a chemical analysis method on samples separated by liquid chromatography using the column, and a process for using the system. Columns of the invention can be prepared in a robust fashion with a very narrow i.d., e.g., 5-15 μm. Thus, they are suitable for commercial use in ultratrace LC/MS proteomic analysis. Columns according to the invention are characterized by high resolving power and high column-to-column reproducibility. When these columns are coupled on-line with, e.g., ESI-MS detection, the resulting systems are capable of detecting the component parts of complex proteomic samples down to the low attomole to sub-attomole level.
摘要翻译：公开了通过含有保持性化学物质的官能单体的原位共聚制备的聚合物基PLOT毛细管柱和增强聚合物基质的强度的交联单体。还公开了一种系统，其包含与质量流量或浓度敏感检测器相连的基于聚合物的PLOT柱，用于对通过使用该柱的液相色谱分离的样品进行化学分析方法，以及使用该系统的方法。可以以非常窄的i.d.例如5-15mum的稳健方式制备本发明的色谱柱。因此，它们适用于超临界LC / MS蛋白质组学分析中的商业用途。根据本发明的色谱柱的特征在于高分辨能力和高柱色谱重现性。当这些柱在线与例如ESI-MS检测偶联时，所得到的系统能够检测复合蛋白质组样品的组分部分，直至低阿托莫尔至亚阿托莫尔水平。

2. 发明申请

US20110290009A1 NARROW BORE POROUS LAYER OPEN TUBE CAPILLARY COLUMN AND USES THEREOF 失效
标题翻译： NARROW BORE POROUS LAYER OPEN TUBE CAPILLARY COLUMN及其用途
公开(公告)号：US20110290009A1
公开(公告)日：2011-12-01
申请号：US13184075
申请日：2011-07-15
申请人： Barry L. Karger , Jian Zhang
发明人： Barry L. Karger , Jian Zhang
IPC分类号： G01N30/02 , G01N30/72 , B01D15/22
CPC分类号： G01N30/60 , B01J20/28085 , B01J20/285 , B01J20/289 , B01J20/327 , B01J20/3282 , B01J2220/54 , B01J2220/84 , B01J2220/86 , G01N30/6073 , G01N30/7266 , G01N2030/528 , Y10T436/11 , Y10T436/117497
摘要： A polymer-based PLOT capillary column prepared by in situ copolymerization of a functional monomer, which usually contains the retentive chemistries, and a crosslinking monomer, which enhances the strength of the polymer matrix, is disclosed. Also disclosed is a system comprising the polymer-based PLOT column coupled to a mass flow or concentration sensitive detector, for carrying out a chemical analysis method on samples separated by liquid chromatography using the column, and a process for using the system. Columns of the invention can be prepared in a robust fashion with a very narrow i.d., e.g., 5-15 μm. Thus, they are suitable for commercial use in ultratrace LC/MS proteomic analysis. Columns according to the invention are characterized by high resolving power and high column-to-column reproducibility. When these columns are coupled on-line with, e.g., ESI-MS detection, the resulting systems are capable of detecting the component parts of complex proteomic samples down to the low attomole to sub-attomole level.
摘要翻译：公开了通过含有保持性化学物质的官能单体的原位共聚制备的聚合物基PLOT毛细管柱和增强聚合物基质的强度的交联单体。还公开了一种系统，其包含与质量流量或浓度敏感检测器相连的基于聚合物的PLOT柱，用于对通过使用该柱的液相色谱分离的样品进行化学分析方法，以及使用该系统的方法。可以以非常窄的i.d.例如5-15μm的稳健方式制备本发明的色谱柱。因此，它们适用于超临界LC / MS蛋白质组学分析中的商业用途。根据本发明的色谱柱的特征在于高分辨能力和高柱色谱重现性。当这些柱在线与例如ESI-MS检测偶联时，所得到的系统能够检测复合蛋白质组样品的组分部分，直至低阿托莫尔至亚阿托莫尔水平。

3. 发明申请

US20090203146A1 NARROW BORE LAYER OPEN TUBE CAPILLARY COLUMN AND USES THEREOF 审中-公开
标题翻译： NARROW BORE LAYER OPEN TUBE CAPILLARY COLUMN及其用途
公开(公告)号：US20090203146A1
公开(公告)日：2009-08-13
申请号：US12306232
申请日：2007-06-20
申请人： Barry L. Karger , Jian Zhang
发明人： Barry L. Karger , Jian Zhang
IPC分类号： G01N27/26 , B05D5/00 , G01N35/00 , G01N27/06
CPC分类号： G01N30/60 , B01J20/28085 , B01J20/285 , B01J20/289 , B01J20/327 , B01J20/3282 , B01J2220/54 , B01J2220/84 , B01J2220/86 , G01N30/6073 , G01N30/7266 , G01N2030/528 , Y10T436/11 , Y10T436/117497
摘要： A polymer-based PLOT column prepared by in situ copolymerization of a functional monomer, which usually contains the retentive chemistries, and a crosslinking monomer, which enhances the strength of the polymer matrix, is disclosed. Styrenic based monomers such as styrene and divinylbenzene or meth/acrylic based monomers such as butyl or stearyl methacrylate and ethylene glycol dimethacrylate, are preferred. Columns of the invention can be prepared in a robust fashion with a very narrow i.d., e.g., 5-15 μm. Thus, they are suitable for commercial use in ultratrace LC/MS proteomic analysis. Columns according to the invention are characterized by high resolving power, high column-to-column reproducibility and relatively high loading capacity. When these columns are coupled on-line with, e.g., ESI-MS detection, the resulting systems provide high sensitivity for analysis of complex proteomic samples, even down to the low attomole to sub-attomole level.
摘要翻译：公开了通过包含保持性化学物质的官能单体的原位共聚制备的聚合物基PLOT柱和提高聚合物基质的强度的交联单体。苯乙烯类单体如苯乙烯和二乙烯基苯或甲基丙烯酸类单体如甲基丙烯酸丁酯或硬脂基酯和乙二醇二甲基丙烯酸酯是优选的。可以以非常窄的i.d.例如5-15mum的稳健方式制备本发明的色谱柱。因此，它们适用于超临界LC / MS蛋白质组学分析中的商业用途。根据本发明的色谱柱的特征在于高分辨能力，高柱色谱重现性和相对较高的负载能力。当这些色谱柱与ESI-MS检测在线偶联时，所得到的系统为复杂蛋白质组样品的分析提供了高灵敏度，甚至低至低阿托莫尔至亚阿托莫尔水平。

4. 发明授权

US07409298B2 Matched filtration with experimental noise determination for denoising, peak picking and quantitation in LC-MS 失效
标题翻译：在LC-MS中进行去噪，峰值采集和定量的实验噪声测定的匹配滤波
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。

5. 发明授权

US06939452B2 Parallel sample loading and injection device for multichannel microfluidic devices 失效
标题翻译：用于多通道微流体装置的平行样品装载和注射装置
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。

6. 发明授权

US06929731B2 Parallel array of independent thermostats for column separations 失效
标题翻译：用于柱分离的独立恒温器的并联阵列
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。

7. 发明授权

US5783397A Screening natural samples for new therapeutic compounds using capillary electrophoresis 失效
标题翻译：使用毛细管电泳筛选新的治疗化合物的天然样品
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。

8. 发明授权

US4865706A High performance microcapillary gel electrophoresis 失效
标题翻译：高性能微毛细管凝胶电泳
公开(公告)号：US4865706A
公开(公告)日：1989-09-12
申请号：US921311
申请日：1986-10-21
申请人： Barry L. Karger , Aharon Cohen
发明人： Barry L. Karger , Aharon Cohen
IPC分类号： G01N27/447
CPC分类号： G01N27/44721 , G01N27/44704 , G01N27/44747 , Y10T29/49885
摘要： A microcapillary column for high performance electrophoresis includes a fused silica microcapillary, a gel of crosslinked polyacrylamide polymerized in the tube, and a thin layer of connecting material covalently bonded to the inner surface of the microcapillary wall and to the polymeric gel. The gel-containing microcapillary is prepared by first covalently bonding a suitable bifunctional reagent to the inner surface of the microcapillary wall, and then causing a mixture of monomer, crosslinking agent, and polymerization catalyst to react in the bore of the microcapillary to form a polymeric matrix which is covalently bonded to the microcapillary wall via the bifunctional reagent. In electrophoresis, the gel-containing microcapillary provides peak efficiencies in excess of 100,000 theoretical plates within separation times of less than thirty minutes, and permits trace level determinations of molecular weights.
摘要翻译：用于高性能电泳的微毛细管柱包括熔融二氧化硅微毛细管，在管中聚合的交联聚丙烯酰胺的凝胶和共价键合到微毛细管壁的内表面和聚合物凝胶的薄层连接材料。通过首先将合适的双功能试剂共价结合到微毛细管壁的内表面，然后使单体，交联剂和聚合催化剂的混合物在微毛细孔的孔中反应以形成聚合物，制备含凝胶的微毛细管通过双功能试剂共价结合到微毛细管壁上的基质。在电泳过程中，含凝胶微毛细管提供超过100,000理论塔板的峰值效率，分离时间少于30分钟，并允许痕量水平测定分子量。

9. 发明申请

US20090221430A1 Proteomic Methods For The Identification And Use Of Putative Biomarkers Associated With The Dysplastic State In Cervical Cells Or Other Cell Types 审中-公开
标题翻译：用于鉴定和使用与宫颈细胞或其他细胞类型中的发育不良状态相关的推定生物标志物的蛋白质组学方法
公开(公告)号：US20090221430A1
公开(公告)日：2009-09-03
申请号：US12224973
申请日：2007-03-12
申请人： Shiaw-Lin Wu , William S. Hancock , Barry L. Karger , James Linder , David W. Hanlon
发明人： Shiaw-Lin Wu , William S. Hancock , Barry L. Karger , James Linder , David W. Hanlon
IPC分类号： C40B30/00 , C12Q1/68 , G01N33/68 , G01N33/536 , C12Q1/02
CPC分类号： G01N33/57411
摘要： The invention relates to methods for detecting and identifying potential biomarkers of high-grade cervical dysplasia in an individual human subject. The invention also relates to newly discovered biomarkers, as set forth in Tables 1-4 herein, which are associated with the dysplastic state of cervical cells. It has been discovered that a differential level of expression of any of these markers or combination of these markers correlates with a dysplastic condition in a human subject, e.g., a patient.
摘要翻译：本发明涉及用于检测和鉴定个体人类受试者高级宫颈发育不良的潜在生物标志物的方法。本发明还涉及新发现的与本发明的表1-4所示的生物标志物，其与子宫颈细胞的发育不良状态相关。已经发现，这些标记物或这些标记物的组合的表达差异水平与人受试者例如患者中的发育异常状况相关。

10. 发明授权

US06660149B1 Multichannel microscale system for high throughput preparative separation with comprehensive collection and analysis 失效
标题翻译：用于高通量制备分离的多通道微量系统，具有全面的收集和分析
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。

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