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    • 4. 发明授权
    • Automated polymer-synthesis system
    • 自动聚合物合成系统
    • US08361396B2
    • 2013-01-29
    • US12932334
    • 2011-02-22
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • B01J19/00G01N21/00
    • B01J19/0046B01J2219/00286B01J2219/00315B01J2219/0036B01J2219/00414B01J2219/00423B01J2219/00722
    • Embodiments of the present invention are directed to automated-polymer-synthesis systems that include discrete reagent-solution-addition, wait-time, and reagent-solution-draining sub-systems which together significantly increase throughput and decrease sub-system idle time. The automated-polymer-synthesis systems that represent embodiments of the present invention additionally include switches at points in which carriers can be received from multiple input paths or output to multiple different output paths. The automated-polymer-synthesis systems that represent embodiments of the present invention generally include an input spur and output spur in addition to a main loop, allowing carriers containing only completed polymers to be removed and new carriers input, so that carriers traverse the automated-polymer-synthesis systems independently from one another.
    • 本发明的实施方案涉及自动聚合物合成系统,其包括离散的试剂 - 溶液添加,等待时间和试剂 - 溶液 - 排出子系统,这些子系统共同显着增加生产量并减少子系统空闲时间。 代表本发明实施例的自动化 - 聚合物合成系统另外包括在多个输入路径上可以接收载波或输出到多个不同输出路径的点处的交换机。 代表本发明实施例的自动化 - 聚合物 - 合成系统通常包括除了主回路之外的输入支线和输出支线,允许仅去除已完成的聚合物的载流子和新的载流子输入,使得载流子穿过自动化 - 聚合物合成系统彼此独立。
    • 5. 发明授权
    • Solid phase methods for polynucleotide production
    • 用于多核苷酸生产的固相方法
    • US07482119B2
    • 2009-01-27
    • US10965018
    • 2004-10-13
    • Hsing-Yeh ParkerJohn T. Mulligan
    • Hsing-Yeh ParkerJohn T. Mulligan
    • C12Q1/68C12P19/34C07H21/04
    • C12P19/34B01J19/0046B01J2219/00286B01J2219/00308B01J2219/00351B01J2219/00353B01J2219/00389B01J2219/00495B01J2219/00547B01J2219/00585B01J2219/00596B01J2219/00689B01J2219/00698B01J2219/00722C07H21/00
    • Polynucleotides having in excess of 1,000 nucleotides can be prepared using a solid phase synthesis technique. A feature of the technique is the use of a reusable solid support that contains covalently bound oligonucleotide. This covalently bound oligonucleotide is annealed to a bridge oligonucleotide, where the bridge is also annealed to a first oligonucleotide that forms a portion of the target polynucleotide. After the target polynucleotide is synthesized, it can be removed from the solid support under denaturing conditions, and the solid support re-used to prepare additional target polynucleotides. The yield of the target polynucleotide increases when shearing force is applied to the solid support that is linked to the growing oligonucleotide. This shearing force is thought to extend the growing end of the oligonucleotide away from contact with other oligonucleotide bound to the solid support and make that end more accessible to annealing with solution oligonucleotide. The synthesis is conveniently accomplished on a porous frit, where reagents and washing solutions are pumped through the frit.
    • 具有超过1,000个核苷酸的多核苷酸可以使用固相合成技术制备。 该技术的特征是使用含有共价结合的寡核苷酸的可重复使用的固体支持物。 将共价结合的寡核苷酸与桥寡核苷酸退火,其中桥还与形成靶多核苷酸的一部分的第一寡核苷酸退火。 在合成靶多核苷酸之后,可以在变性条件下将其从固体支持物上除去,并且固体支持物再次用于制备另外的靶多核苷酸。 当剪切力施加到与生长的寡核苷酸连接的固体支持物上时,靶多核苷酸的产量增加。 认为这种剪切力使得寡核苷酸的生长末端远离与与固体支持物结合的其它寡核苷酸的接触,并使得该结果更容易用溶液寡核苷酸退火。 合成方便地在多孔玻璃料上完成,其中试剂和洗涤溶液通过玻璃料泵送。
    • 6. 发明申请
    • Automated polymer-synthesis system
    • 自动聚合物合成系统
    • US20110256031A1
    • 2011-10-20
    • US12932334
    • 2011-02-22
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • B01J19/00
    • B01J19/0046B01J2219/00286B01J2219/00315B01J2219/0036B01J2219/00414B01J2219/00423B01J2219/00722
    • Embodiments of the present invention are directed to automated-polymer-synthesis systems that include discrete reagent-solution-addition, wait-time, and reagent-solution-draining sub-systems which together significantly increase throughput and decrease sub-system idle time. The automated-polymer-synthesis systems that represent embodiments of the present invention additionally include switches at points in which carriers can be received from multiple input paths or output to multiple different output paths. The automated-polymer-synthesis systems that represent embodiments of the present invention generally include an input spur and output spur in addition to a main loop, allowing carriers containing only completed polymers to be removed and new carriers input, so that carriers traverse the automated-polymer-synthesis systems independently from one another.
    • 本发明的实施方案涉及自动聚合物合成系统,其包括离散的试剂 - 溶液添加,等待时间和试剂 - 溶液 - 排出子系统,这些子系统共同显着增加生产量并减少子系统空闲时间。 代表本发明实施例的自动化 - 聚合物合成系统另外包括在多个输入路径上可以接收载波或输出到多个不同输出路径的点处的交换机。 代表本发明实施例的自动化 - 聚合物 - 合成系统通常包括除了主回路之外的输入支线和输出支线,允许仅去除已完成的聚合物的载流子和新的载流子输入,使得载流子穿过自动化 - 聚合物合成系统彼此独立。
    • 7. 发明申请
    • Wicking-based reagent-solution draining in an automated system
    • 基于芯片的试剂溶液在自动化系统中排水
    • US20110236270A1
    • 2011-09-29
    • US12932337
    • 2011-02-22
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • Hsing-Yeh ParkerJohn C. TaboneJohn Mulligan
    • B01J19/00
    • B01J19/0046B01J2219/00286B01J2219/00315B01J2219/0036B01J2219/00414B01J2219/00423B01J2219/00722
    • Embodiments of the present invention include processing steps and subsystems, within automated-biopolymer-synthesis systems and within other automated systems for organic-chemistry-based processing, for removing reagent solutions and solvents from reaction chambers following various synthetic reaction steps and washing steps undertaken during biopolymer synthesis. Embodiments of the present invention employ any of various different types of liquid-absorbing materials to wick, or remove by capillary action, liquids from reaction chambers. Wicking-based methods and subcomponents of the present invention remove significantly greater fractions of solutions from reaction chambers than conventional methods and subsystems and, in addition, are mechanically simpler and produce fewer deleterious side effects than currently used methods and subsystems.
    • 本发明的实施方案包括在自动生物聚合物 - 合成系统内和在用于基于有机化学的处理的其他自动化系统内的处理步骤和子系统,用于在各种合成反应步骤之后从反应室中除去试剂溶液和溶剂,并在 生物聚合物合成。 本发明的实施例使用各种不同类型的液体吸收材料中的任何一种来吸收或者通过毛细管作用从反应室中除去液体。 与常规方法和子系统相比,本发明的基于芯吸的方法和子部件从常规方法和子系统中除去反应室的溶液的显着更多的部分,此外,与目前使用的方法和子系统相比,机械上更简单并且产生较少有害的副作用。
    • 8. 发明申请
    • SOLID PHASE METHODS FOR POLYNUCLEOTIDE PRODUCTION
    • 用于多核苷酸生产的固相方法
    • US20090137027A1
    • 2009-05-28
    • US12336412
    • 2008-12-16
    • Hsing-Yeh ParkerJohn T. Mulligan
    • Hsing-Yeh ParkerJohn T. Mulligan
    • C12M1/36C12M1/00
    • C12P19/34B01J19/0046B01J2219/00286B01J2219/00308B01J2219/00351B01J2219/00353B01J2219/00389B01J2219/00495B01J2219/00547B01J2219/00585B01J2219/00596B01J2219/00689B01J2219/00698B01J2219/00722C07H21/00
    • Polynucleotides having in excess of 1,000 nucleotides can be prepared using a solid phase synthesis technique. A feature of the technique is the use of a reusable solid support that contains covalently bound oligonucleotide. This covalently bound oligonucleotide is annealed to a bridge oligonucleotide, where the bridge is also annealed to a first oligonucleotide that forms a portion of the target polynucleotide. After the target polynucleotide is synthesized, it can be removed from the solid support under denaturing conditions, and the solid support re-used to prepare additional target polynucleotides. The yield of the target polynucleotide increases when shearing force is applied to the solid support that is linked to the growing oligonucleotide. This shearing force is thought to extend the growing end of the oligonucleotide away from contact with other oligonucleotide bound to the solid support and make that end more accessible to annealing with solution oligonucleotide. The synthesis is conveniently accomplished on a porous frit, where reagents and washing solutions are pumped through the frit.
    • 具有超过1,000个核苷酸的多核苷酸可以使用固相合成技术制备。 该技术的特征是使用含有共价结合的寡核苷酸的可重复使用的固体支持物。 将共价结合的寡核苷酸与桥寡核苷酸退火,其中桥还与形成靶多核苷酸的一部分的第一寡核苷酸退火。 在合成靶多核苷酸之后,可以在变性条件下将其从固体支持物上除去,并且固体支持物再次用于制备另外的靶多核苷酸。 当剪切力施加到与生长的寡核苷酸连接的固体支持物上时,靶多核苷酸的产量增加。 认为这种剪切力使得寡核苷酸的生长末端远离与与固体支持物结合的其它寡核苷酸的接触,并使得该结果更容易用溶液寡核苷酸退火。 合成方便地在多孔玻璃料上完成,其中试剂和洗涤溶液通过玻璃料泵送。