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1. 发明授权

US07578915B2 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：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。

2. 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。

3. 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。

4. 发明授权

US06476118B1 Polymer mixtures for high performance/high temperature separation in capillary electrophoresis, especially for long read DNA sequencing 有权
标题翻译：用于毛细管电泳中高性能/高温分离的聚合物混合物，特别是长读DNA测序
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。

5. 发明申请

US20090181385A1 Reagents, methods, and libraries for bead-based sequencing 审中-公开
公开(公告)号：US20090181385A1
公开(公告)日：2009-07-16
申请号：US12220201
申请日：2008-07-21
申请人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
发明人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , B82Y15/00 , B82Y30/00 , C12Q1/68 , C12Q1/6837 , C12Q1/6844 , C12Q1/6869 , C12Q2565/537 , C12Q2565/518 , C12Q2565/513 , C12Q2565/137 , C12Q2565/102 , C12Q2533/107 , C12Q2537/165
摘要： The present invention provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles comprise steps of extension, ligation, and, preferably, cleavage. In certain embodiments the methods make use of extension probes containing phosphorothiolate linkages and employ agents appropriate to cleave such linkages. The invention provides methods of determining information about a sequence using at least two distinguishably labeled probe families. In certain embodiments the methods acquire less than 2 bits of information from each of a plurality of nucleotides in the template in each cycle. In certain embodiments the sequencing reactions are performed on templates attached to immobilized beads. The invention further provides sets of labeled probes containing phosphorothiolate linkages. In addition, the invention includes performing multiple sequencing reactions on a single template by removing initializing oligonucleotides and extended strands and performing subsequent reactions using different initializing oligonucleotides.

6. 发明授权

US08431691B2 Reagents, methods, and libraries for bead-based sequencing 有权
公开(公告)号：US08431691B2
公开(公告)日：2013-04-30
申请号：US12220208
申请日：2008-07-21
申请人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
发明人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
IPC分类号： C07H21/04
CPC分类号： C12Q1/6874 , B82Y15/00 , B82Y30/00 , C12Q1/68 , C12Q1/6837 , C12Q1/6844 , C12Q1/6869 , C12Q2565/537 , C12Q2565/518 , C12Q2565/513 , C12Q2565/137 , C12Q2565/102 , C12Q2533/107 , C12Q2537/165
摘要： The present invention provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles comprise steps of extension, ligation, and, preferably, cleavage. In certain embodiments the methods make use of extension probes containing phosphorothiolate linkages and employ agents appropriate to cleave such linkages. The invention provides methods of determining information about a sequence using at least two distinguishably labeled probe families. In certain embodiments the methods acquire less than 2 bits of information from each of a plurality of nucleotides in the template in each cycle. In certain embodiments the sequencing reactions are performed on templates attached to immobilized beads. The invention further provides sets of labeled probes containing phosphorothiolate linkages. In addition, the invention includes performing multiple sequencing reactions on a single template by removing initializing oligonucleotides and extended strands and performing subsequent reactions using different initializing oligonucleotides.

7. 发明申请

US20080003571A1 Reagents, methods, and libraries for bead-based sequencing 审中-公开
公开(公告)号：US20080003571A1
公开(公告)日：2008-01-03
申请号：US11345979
申请日：2006-02-01
申请人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
发明人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , B82Y15/00 , B82Y30/00 , C12Q1/68 , C12Q1/6837 , C12Q1/6844 , C12Q1/6869 , C12Q2565/537 , C12Q2565/518 , C12Q2565/513 , C12Q2565/137 , C12Q2565/102 , C12Q2533/107 , C12Q2537/165
摘要： The present invention provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles comprise steps of extension, ligation, and, preferably, cleavage. In certain embodiments the methods make use of extension probes containing phosphorothiolate linkages and employ agents appropriate to cleave such linkages. In certain embodiments the methods make use of extension probes containing an abasic residue or a damaged base and employ agents appropriate to cleave linkages between a nucleoside and an abasic residue and/or agents appropriate to remove a damaged base from a nucleic acid. The invention provides methods of determining information about a sequence using at least two distinguishably labeled probe families. In certain embodiments the methods acquire less than 2 bits of information from each of a plurality of nucleotides in the template in each cycle. In certain embodiments the sequencing reactions are performed on templates attached to beads, which are immobilized in or on a semi-solid support. The invention further provides sets of labeled extension probes containing phosphorothiolate linkages or trigger residues that are suitable for use in the method. In addition, the invention includes performing multiple sequencing reactions on a single template by removing initializing oligonucleotides and extended strands and performing subsequent reactions using different initializing oligonucleotides. The invention further provides efficient methods for preparing templates, particularly for performing sequencing multiple different templates in parallel. The invention also provides methods for performing ligation and cleavage. The invention also provides new libraries of nucleic acid fragments containing paired tags, and methods of preparing microparticles having multiple different templates (e.g., containing paired tags) attached thereto and of sequencing the templates individually. The invention also provides automated sequencing systems, flow cells, image processing methods, and computer-readable media that store computer-executable instructions (e.g., to perform the image-processing methods) and/or sequence information. In certain embodiments the sequence information is stored in a database.

8. 发明授权

US08329404B2 Reagents, methods, and libraries for bead-based sequencing 有权
标题翻译：用于珠基测序的试剂，方法和文库
公开(公告)号：US08329404B2
公开(公告)日：2012-12-11
申请号：US13410919
申请日：2012-03-02
申请人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
发明人： Kevin McKernan , Alan Blanchard , Lev Kotler , Gina Costa
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6874 , B82Y15/00 , B82Y30/00 , C12Q1/68 , C12Q1/6837 , C12Q1/6844 , C12Q1/6869 , C12Q2565/537 , C12Q2565/518 , C12Q2565/513 , C12Q2565/137 , C12Q2565/102 , C12Q2533/107 , C12Q2537/165
摘要： The present invention provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles comprise steps of extension, ligation, and, preferably, cleavage. In certain embodiments the methods make use of extension probes containing phosphorothiolate linkages and employ agents appropriate to cleave such linkages. The invention provides methods of determining information about a sequence using at least two distinguishably labeled probe families. In certain embodiments the methods acquire less than 2 bits of information from each of a plurality of nucleotides in the template in each cycle. In certain embodiments the sequencing reactions are performed on templates attached to immobilized beads. The invention further provides sets of labeled extension probes containing phosphorothiolate linkages. In addition, the invention includes performing multiple sequencing reactions on a single template by removing initializing oligonucleotides and extended strands and performing subsequent reactions using different initializing oligonucleotides.
摘要翻译：本发明提供了通过沿着单链模板进行连续循环的双链延伸来确定核酸序列的方法。循环包括延伸，连接和优选切割的步骤。在某些实施方案中，所述方法利用含有硫代磷酸酯键的延伸探针，并使用适合切割这种连接的试剂。本发明提供使用至少两个可区分标记的探针家族确定关于序列的信息的方法。在某些实施方案中，该方法在每个周期中从模板中的多个核苷酸中的每一个获取少于2位的信息。在某些实施方案中，测序反应在附着于固定化珠粒的模板上进行。本发明还提供了含有硫代磷酸酯键的标记的延伸探针的集合。此外，本发明包括通过除去初始化寡核苷酸和延伸的链并使用不同的初始化寡核苷酸进行后续反应，在单个模板上进行多个测序反应。

9. 发明授权

US07883265B2 Devices, systems, and methods for preparing emulsions 失效
标题翻译：用于制备乳液的装置，系统和方法
公开(公告)号：US07883265B2
公开(公告)日：2011-02-08
申请号：US12130502
申请日：2008-05-30
申请人： Lev Kotler , John Andrew Sheridan , Gina Costa , Joseph Podhasky
发明人： Lev Kotler , John Andrew Sheridan , Gina Costa , Joseph Podhasky
IPC分类号： B01F11/00 , B67D7/74
CPC分类号： B01F11/0014 , B01F11/0008
摘要： A vortex mixer and method for forming an emulsion wherein the mixer is adapted to form an emulsion with a desired droplet size and having a desired volume. The vortex mixer provides improved uniformity in emulsion preparation and may be used to create multiple emulsions simultaneously.
摘要翻译：涡流混合器和形成乳液的方法，其中混合器适于形成具有所需液滴尺寸并具有所需体积的乳液。涡流混合器提供了乳液制备中的改进的均匀性，并可用于同时产生多个乳液。

10. 发明申请

US20090035825A1 Devices, Systems, and Methods for Preparing Emulsions 失效
标题翻译：仪器，系统和准备乳液的方法
公开(公告)号：US20090035825A1
公开(公告)日：2009-02-05
申请号：US12130502
申请日：2008-05-30
申请人： Lev Kotler , John Andrew Sheridan , Gina Costa , Joseph Podhasky
发明人： Lev Kotler , John Andrew Sheridan , Gina Costa , Joseph Podhasky
IPC分类号： C12P19/34 , B01F11/00 , B01F15/02
CPC分类号： B01F11/0014 , B01F11/0008
摘要： A vortex mixer and method for forming an emulsion wherein the mixer is adapted to form an emulsion with a desired droplet size and having a desired volume. The vortex mixer provides improved uniformity in emulsion preparation and may be used to create multiple emulsions simultaneously.
摘要翻译：涡流混合器和形成乳液的方法，其中混合器适于形成具有所需液滴尺寸并具有所需体积的乳液。涡流混合器提供了乳液制备中的改进的均匀性，并可用于同时产生多个乳液。

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