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1. 发明授权

US5872010A Microscale fluid handling system 失效
标题翻译：微型流体处理系统
公开(公告)号：US5872010A
公开(公告)日：1999-02-16
申请号：US675177
申请日：1996-07-03
申请人： Barry L. Karger , Frantisek Foret , Paul M. Zavracky , E. Nicol McGruer , Qifeng Xue , Yuriy M. Dunayevskiy
发明人： Barry L. Karger , Frantisek Foret , Paul M. Zavracky , E. Nicol McGruer , Qifeng Xue , Yuriy M. Dunayevskiy
IPC分类号： G01N27/62 , B01J4/00 , B01J19/00 , B01L3/00 , B01L3/02 , G01N30/02 , G01N30/28 , G01N30/46 , G01N30/60 , G01N30/62 , G01N30/72 , G01N35/08 , G01N35/10 , G01N37/00 , H01J49/04 , G01N24/00 , G01N30/00
CPC分类号： H01J49/165 , B01J19/0093 , B01L3/0268 , B01L3/502715 , G01N30/7266 , H01J49/0445 , B01J2219/00783 , B01J2219/00822 , B01J2219/00824 , B01J2219/00828 , B01J2219/00831 , B01J2219/00833 , B01J2219/00853 , B01J2219/00873 , B01J2219/00889 , B01J2219/00891 , B01J2219/0093 , B01J2219/00932 , B01L2300/0803 , B01L2300/0816 , B01L2400/027 , B01L2400/0421 , G01N2030/027 , G01N2030/285 , G01N2030/628 , G01N2035/1044 , G01N30/466 , G01N30/6095 , Y10T436/117497 , Y10T436/14 , Y10T436/142222 , Y10T436/143333 , Y10T436/24 , Y10T436/25 , Y10T436/25125 , Y10T436/25375
摘要： A microscale fluid handling system that permits the efficient transfer of nanoliter to picoliter quantities of a fluid sample from the spatially concentrated environment of a microfabricated chip to "off-chip" analytical or collection devices for further off-chip sample manipulation and analysis is disclosed. The fluid handling system is fabricated in the form of one or more channels, in any suitable format, provided in a microchip body or substrate of silica, polymer or other suitable non-conductive material, or of stainless steel, noble metal, silicon or other suitable conductive or semi-conductive material. The microchip fluid handling system includes one or more exit ports integral with the end of one or more of the channels for consecutive or simultaneous off-chip analysis or collection of the sample. The exit port or ports may be configured, for example, as an electrospray interface for transfer of a fluid sample to a mass spectrometer.
摘要翻译：公开了一种微量流体处理系统，其允许将纳升剂有效转移到微胶囊数量的流体样品从微细堆芯片的空间集中环境到“片外”分析或收集装置，用于进一步的片外样品操作和分析。流体处理系统以一种或多种通道的形式，以任何合适的格式制成，设置在微芯片体或二氧化硅，聚合物或其它合适的非导电材料或不锈钢，贵金属，硅或其他合适的导电或半导体材料。微芯片流体处理系统包括与一个或多个通道的末端一体化的一个或多个出口，用于连续或同时片外分析或收集样品。出口或端口可以被配置为例如用于将流体样品转移到质谱仪的电喷雾界面。

2. 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。

3. 发明授权

US06175112B1 On-line liquid sample deposition interface for matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectroscopy 失效
标题翻译：在线液体样品沉积界面，用于基质辅助激光解吸电离 - 飞行时间（MALDI-TOF）质谱
公开(公告)号：US06175112B1
公开(公告)日：2001-01-16
申请号：US09083815
申请日：1998-05-22
申请人： Barry L. Karger , Frantisek Foret , Jan Preisler
发明人： Barry L. Karger , Frantisek Foret , Jan Preisler
IPC分类号： H01J4900
CPC分类号： H01J49/0431 , H01J49/0418
摘要： A universal interface for continuous on-line liquid sample introduction directly to the time-of-flight mass spectrometer, which can further promote throughput and utility of MALDI-TOF MS, is disclosed. Preferably, the liquid sample includes a matrix, either solid or liquid, for use in matrix-assisted-laser-desorption-ionization, most particularly in a time-of-flight mass spectrometer which can further promote throughput and utility of MALDI-TOF MS. In the method of the invention, the same samples and matrices, both solid and liquid, can be used as in conventional MALDI. In practice of the method of the invention, a solution of sample containing, e.g., peptide and matrix is infused directly into the source chamber of a mass spectrometer at subatmospheric pressure, deposited on a moving sample holder, such as a rotating quartz wheel, and desorbed by, e.g., a nitrogen laser. The method of the invention is particularly amenable to multiplexing, the parallel deposition of multiple samples, e.g., from a capillary array or microchip channels, with subsequent sequential desorption with a scanning laser. This format is particularly useful for high throughput MS analysis.
摘要翻译：公开了用于连续在线液体样品直接引入飞行时间质谱仪的通用界面，其可进一步促进MALDI-TOF MS的产量和效用。优选地，液体样品包括用于基质辅助激光解吸电离的固体或液体基质，最特别是在飞行时间质谱仪中，其可以进一步促进MALDI-TOF MS的通过量和效用。在本发明的方法中，可以像常规的MALDI一样使用固体和液体两种相同的样品和基质。在本发明方法的实践中，将含有例如肽和基质的样品溶液直接注入质谱仪的源室中，沉积在移动的样品架上，例如旋转的石英砂轮，以及由氮激光器解吸。本发明的方法特别适合多路复用，例如来自毛细管阵列或微芯片通道的多个样品的平行沉积，随后用扫描激光随后的顺序解吸。此格式对于高通量MS分析特别有用。

4. 发明授权

US07323092B2 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：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。

5. 发明授权

US06825463B2 On-line and off-line deposition of liquid samples for matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectroscopy 失效
标题翻译：用于基质辅助激光解吸电离 - 飞行时间（MALDI-TOF）质谱的液体样品的在线和离线沉积
公开(公告)号：US06825463B2
公开(公告)日：2004-11-30
申请号：US10132064
申请日：2002-04-25
申请人： Barry L. Karger , Frantisek Foret , Jan Preisler
发明人： Barry L. Karger , Frantisek Foret , Jan Preisler
IPC分类号： H01J4900
CPC分类号： H01J49/0418 , G01N1/2214 , H01J49/0431
摘要： A universal interface for continuous on-line liquid sample introduction directly to the time-of-flight mass spectrometer, which can further promote throughput and utility of MALDI-TOF MS, is disclosed. Preferably, the liquid sample includes a matrix, either solid or liquid, for use in matrix-assisted-laser-desorption-ionization, most particularly in a time-of-flight mass spectrometer which can further promote throughput and utility of MALDI-TOF MS. In the method of the invention, the same samples and matrices, both solid and liquid, can be used as in conventional MALDI. In practice of the method of the invention, a solution of sample containing, e.g., peptide and matrix is infused directly into the source chamber of a mass spectrometer at subatmospheric pressure, deposited on a moving sample holder, such as a rotating quartz wheel, and desorbed by, e.g., a nitrogen laser. The method of the invention is particularly amenable to multiplexing, the parallel deposition of multiple samples, e.g., from a capillary array or microchip channels, with subsequent sequential desorption with a scanning laser. This format is particularly useful for high throughput MS analysis. Also disclosed is an off-line deposition chamber and a general method of preparing a sample for analysis that results in the homogeneous deposition of small quantities of sample at improved reproducibility on any appropriately configured sample receptor. This format of sample preparation is particularly useful with existing commercial mass spectrometers.
摘要翻译：公开了用于连续在线液体样品直接引入飞行时间质谱仪的通用界面，其可进一步促进MALDI-TOF MS的产量和效用。优选地，液体样品包括用于基质辅助激光解吸电离的固体或液体基质，最特别是在飞行时间质谱仪中，其可以进一步促进MALDI-TOF MS的通过量和效用。在本发明的方法中，可以像常规的MALDI一样使用固体和液体两种相同的样品和基质。在本发明方法的实践中，将含有例如肽和基质的样品溶液直接注入质谱仪的源室中，沉积在移动的样品架上，例如旋转的石英砂轮，以及由氮激光器解吸。本发明的方法特别适合多路复用，例如来自毛细管阵列或微芯片通道的多个样品的平行沉积，随后用扫描激光随后的顺序解吸。此格式对于高通量MS分析特别有用。还公开了离线沉积室和制备用于分析的样品的一般方法，其导致在任何适当配置的样品受体上以改善的再现性均匀沉积少量样品。样品制备的这种格式对于现有的商业质谱仪是特别有用的。

6. 发明授权

US5633129A Electrophoretic detection and separation of mutant DNA using replaceable polymer matrices 失效
标题翻译：使用可替换的聚合物基质进行电泳检测和分离突变体DNA
公开(公告)号：US5633129A
公开(公告)日：1997-05-27
申请号：US190919
申请日：1994-02-03
申请人： Barry L. Karger , William G. Thilly , Frantisek Foret , Konstaintin Khrapko , Phouthone Koehavong , Aharon S. Cohen , Roger W. Giese
发明人： Barry L. Karger , William G. Thilly , Frantisek Foret , Konstaintin Khrapko , Phouthone Koehavong , Aharon S. Cohen , Roger W. Giese
IPC分类号： C12N15/09 , C12Q1/68 , G01N33/566
CPC分类号： C12Q1/6827 , C12Q1/6809 , Y10S435/81
摘要： The disclosure relates to a method for resolving double-stranded DNA species differing by at least one base pair. Each of the species is characterized by an iso-melting domain with a unique melting temperature contiguous with a melting domain of higher thermal stability.
摘要翻译：本公开涉及一种解决由至少一个碱基对不同的双链DNA种的方法。每个物种的特征在于具有与具有较高热稳定性的熔融区域相邻的独特熔融温度的等熔融区域。

7. 发明授权

US5571398A Precise capillary electrophoretic interface for sample collection or analysis 失效
标题翻译：精确的毛细管电泳界面，用于样品收集或分析
公开(公告)号：US5571398A
公开(公告)日：1996-11-05
申请号：US363474
申请日：1994-12-23
申请人： Barry L. Karger , Frantisek Foret , Odilo M uller
发明人： Barry L. Karger , Frantisek Foret , Odilo M uller
IPC分类号： G01N27/447 , C25B9/00
CPC分类号： B01D57/02 , G01N27/44717 , G01N27/44721
摘要： A capillary electrophoretic system and method for accurate and precise post-column manipulation of molecules separated by capillary electrophoresis is disclosed. The system of the invention includes a separation capillary; a detector positioned close to, and preferably less than approximately one cm from the outlet end of the capillary; and a sheath which surrounds and directs a collection buffer over the capillary outlet end. With the detector positioned as described, precise and accurate correlation is possible between detection of the separated components of a sample and their emergence from the capillary. The detector preferably includes optical fibers connected to a spectrophotometric detection method, such as UV detection or fluorescence, including laser induced fluorescence. The sheath collection buffer, the capillary and an electrophoresis buffer reservoir, for supplying buffer to the inlet end of the capillary, are in electrical contact in an electrical circuit and provide the electric field required for separation of a sample of molecules. The separated components of the sample are mixed with collection buffer as they emerge from the outlet end of the capillary. They are then collected into or on any collection device, such as vials, collection capillaries or membranes, or they are transferred to other devices for further analysis, such as mass spectroscopy.
摘要翻译：公开了一种用于通过毛细管电泳分离的分子的精确和精确的后柱操作的毛细管电泳系统和方法。本发明的系统包括分离毛细管; 位于离毛细管出口端近似近似一厘米处的检测器; 以及护套，其围绕毛细管出口端引导收集缓冲液。利用如上所述定位检测器，可以在检测样品的分离组分和从毛细管出现之间进行精确和准确的相关性。检测器优选地包括连接到分光光度检测方法的光纤，例如UV检测或荧光，包括激光诱导的荧光。用于向毛细管的入口端供应缓冲液的鞘收集缓冲液，毛细管和电泳缓冲液储存器在电路中电接触并提供分离样品分子所需的电场。当样品的分离成分从毛细管的出口端出现时与收集缓冲液混合。然后将它们收集到任何收集装置中的任何收集装置上，例如小瓶，收集毛细管或膜，或者将它们转移到其他装置进行进一步分析，例如质谱法。

8. 发明授权

US5322608A Siloxandediol coating for capillary electrophoresis and for general surface modification 失效
标题翻译：用于毛细管电泳和一般表面改性的硅氧烷二醇涂层
公开(公告)号：US5322608A
公开(公告)日：1994-06-21
申请号：US994832
申请日：1992-12-23
申请人： Barry L. Karger , Dieter Schmalzing , Frantisek Foret
发明人： Barry L. Karger , Dieter Schmalzing , Frantisek Foret
IPC分类号： B01J20/283 , B01D57/02 , B01J20/281 , G01N27/447 , G01N30/88 , C25B9/00
CPC分类号： G01N27/44752
摘要： A coated microcapillary column for high performance electrophoresis is disclosed. A preferred microcapillary includes a column; a universal sub-layer of coating material that has been highly crosslinked using a crosslinking agent and attached covalently or non-covalently to the column wall; and a variable top layer of a monomer or polymer, preferably crosslinked, attached to the sub-layer. The microcapillary preferably is prepared by covalently bonding a highly crosslinked siloxanediol sub-layer to the inner surface of the microcapillary wall and then causing a mixture of monomers or polymers to react in the bore of the microcapillary to form a top layer. The bilayer coating as used in a microcapillary prevents adsorption of solutes during electrophoresis and eliminates or controls electroosmotic flow. The disclosed coating may also be formed on other kinds of surfaces where similar surface modification is desired. The sub-layer, which can be formed from other siloxane derivatives having two nucleophilic end groups, e.q., diamino or dithiol, may be used independently, or as a base layer for bilayer or even multilayer surface formation.
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柱; 已经使用交联剂高度交联并与塔壁共价或非共价附着的涂层材料的通用子层; 以及连接到子层上的优选交联的单体或聚合物的可变顶层。微毛细管优选通过将高度交联的硅氧烷二醇亚层共价结合到微毛细管壁的内表面，然后使单体或聚合物的混合物在微毛细孔的孔中反应以形成顶层来制备。在微毛细管中使用的双层涂层防止电泳期间溶质的吸附，并消除或控制电渗流。所公开的涂层也可以在需要类似表面改性的其它种类的表面上形成。可以独立地使用具有两个亲核端基的其它硅氧烷衍生物，即二氨基或二硫醇形成的亚层，或作为双层或甚至多层表面形成的基层。

9. 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。

10. 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。

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