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1. 发明申请

WO2012127413A1 METHOD FOR PERFORMING MOLECULAR REACTIONS BY USING IMMISCIBLE INTERMEDIATE FLUIDS 审中-公开
标题翻译：通过使用可疑中间流体进行分子反应的方法
公开(公告)号：WO2012127413A1
公开(公告)日：2012-09-27
申请号：PCT/IB2012/051319
申请日：2012-03-20
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , WIMBERGER-FRIEDL, Reinhold , VAN DER ZAAG, Pieter, Jan , SERVOLI, Eva
发明人： WIMBERGER-FRIEDL, Reinhold , VAN DER ZAAG, Pieter, Jan , SERVOLI, Eva
IPC分类号： B01L3/00 , C12Q1/68 , B01J19/00 , G01N35/08
CPC分类号： C12Q1/6869 , B01L3/502784 , B01L7/52 , B01L2200/0673 , B01L2200/16 , B01L2300/0636 , B01L2300/088 , B01L2400/0487 , G01N35/08
摘要： The present invention relates to a method for performing molecular reactions in a device comprising the steps of (a) introducing one or more reagent solution(s) and an immiscible intermediate fluid into the device, wherein the device comprises a substrate, on which chemically or biochemically recognizable entities are immobilized; (b) performing molecular reactions between the immobilized chemically or biochemically recognizable entities and the reagent solution(s); or on the immobilized chemically or biochemically recognizable entities in the presence of the reagent solution(s); (c) displacing the reagent solution(s) present on the substrate by the immiscible intermediate fluid; (d) separating the immiscible intermediate fluid and the reagent solution(s); and reusing the reagent solution(s) and/or immiscible intermediate fluid for one or more repetitions of steps (a) to (e). The invention further relates to a device for performing a molecular reaction, comprising a reaction zone, reservoirs and liquid connections and a collection and regeneration zone wherein the immiscible intermediate fluid and the reagent solution(s) are separable by gravitational separation; or a redirection and distribution module, wherein the immiscible intermediate fluid and reagent solution(s) are separated. The invention also relates to the use of an immiscible intermediate fluid for displacing a reagent solution present in a reaction zone in a microfluidic device, as well as the use of a corresponding device for performing a sequencing reaction or a nucleic acid synthesis reaction.
摘要翻译：本发明涉及一种在器件中进行分子反应的方法，包括以下步骤：（a）将一种或多种试剂溶液和不混溶的中间体流体引入该装置，其中该装置包括基底，化学或生化鉴定实体被固定化; （b）在固定的化学或生化学可识别的实体和试剂溶液之间进行分子反应; 或在试剂溶液存在下在固定的化学或生物化学可识别的实体上; （c）通过不混溶的中间流体置换存在于基板上的试剂溶液; （d）分离不混溶的中间体液体和试剂溶液; 以及重复使用所述试剂溶液和/或不混溶的中间体流体以进行一个或多个重复的步骤（a）至（e）。本发明还涉及一种用于进行分子反应的装置，包括反应区，储存器和液体连接以及收集和再生区，其中不混溶的中间流体和试剂溶液可通过重力分离而分离; 或重定向和分配模块，其中不混溶的中间流体和试剂溶液被分离。本发明还涉及不混溶中间体液体用于置换微流体装置中反应区中存在的试剂溶液的用途，以及使用相应的装置进行测序反应或核酸合成反应。

2. 发明申请

WO2012059839A3 IN VITRO DIAGNOSTIC TESTING INCLUDING AUTOMATED BROKERING OF ROYALTY PAYMENTS FOR PROPRIETARY TESTS 审中-公开
标题翻译：体外诊断试验包括自动处理专利测试的专利费用
公开(公告)号：WO2012059839A3
公开(公告)日：2012-09-07
申请号：PCT/IB2011054735
申请日：2011-10-24
申请人： KONINKL PHILIPS ELECTRONICS NV , VAN DER ZAAG PIETER JAN , DIMITROVA NEVENKA , VAN DE STOLPE ANJA , VAN HOUTEN HENDRIK
发明人： VAN DER ZAAG PIETER JAN , DIMITROVA NEVENKA , VAN DE STOLPE ANJA , VAN HOUTEN HENDRIK
IPC分类号： G06Q10/00 , C12Q1/68 , G06F19/00
CPC分类号： G06Q20/10 , G06F19/18 , G06Q10/00 , G06Q50/22
摘要： A method comprises: recording an electronic record of diagnostic events including the performing of in- vitro diagnostic tests; during the recording, identifying the performing of a licensed in- vitro diagnostic test for which license information is stored in a licenses database; and computing license compensation due to a licensor for the performing of the licensed in- vitro diagnostic test based on royalty calculation information stored in the licenses database. The recording, identifying, and computing operations are performed by one or more computers. The method may further include remitting the computed license compensation to the licensor, the remitting also being performed by one or more computers. The licensed in- vitro diagnostic test may comprise a licensed biomarker test, for example one obtained by DNA or RNA sequencing, and the method may further comprise: performing the licensed biomarker test using a genome sequencer, wherein the performing of the licensed biomarker test and the computing of license compensation are both performed at a single medical facility.
摘要翻译：一种方法包括：记录诊断事件的电子记录，包括进行体外诊断测试; 在记录期间，识别许可证信息存储在许可证数据库中的执行的体外诊断测试的执行; 以及基于许可证数据库中存储的使用费计算信息，计算许可人对执行许可的体外诊断测试的许可证补偿。记录，识别和计算操作由一台或多台计算机执行。该方法可以进一步包括将计算出的许可证补偿汇出给许可人，汇款也由一个或多个计算机执行。许可的体外诊断测试可以包括许可的生物标志物测试，例如通过DNA或RNA测序获得的测试，并且该方法可以进一步包括：使用基因组测序仪执行许可的生物标志物测试，其中执行许可的生物标志物测试和许可证补偿的计算都是在单一的医疗机构进行的。

3. 发明申请

WO2011027268A2 DEVICES AND METHODS FOR MICROARRAY SELECTION 审中-公开
标题翻译：用于微阵列选择的装置和方法
公开(公告)号：WO2011027268A2
公开(公告)日：2011-03-10
申请号：PCT/IB2010/053839
申请日：2010-08-26
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , VAN DER ZAAG, Pieter, Jan , FEITSMA, Harma, Martine , DEN TOONDER, Jacob, Marinus, Jan , WIMBERGER-FRIEDL, Reinhold
发明人： VAN DER ZAAG, Pieter, Jan , FEITSMA, Harma, Martine , DEN TOONDER, Jacob, Marinus, Jan , WIMBERGER-FRIEDL, Reinhold
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6834 , C12Q2537/149 , C12Q2527/107
摘要： The present invention relates to a device for the specific selection of target molecules, comprising: (a) at least one reaction zone comprising a microarray, wherein the microarray comprises a substrate, on which one or more species of capture molecules are immobilized, comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the zone; (b) at least one non-reaction zone comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the zone, which is in fluid connection with the reaction zone; and (c) at least one transportation means capable of generating and/or regulating a fluid flow between said reaction zone (a) and said non-reaction zone comprising one or more temperature control and/or regulating units (b). The present invention further relates to a device for the specific selection of target molecules wherein the immobilized capture molecules are organized in the microarray in the form of spots, elongated spots and/or lines. In a further aspect the present invention relates to a method of specifically selecting target molecules, comprising the introducing a medium to such a device, performing interaction reactions in a reaction zone, transporting not interacted or not bound target molecules to a zone allowing reactivation of the target molecules and performing additional interaction reactions with the reactivated target molecules at the reaction zone, as well as the use of such a device for specifically selecting target molecules, e.g. for target enrichment also referred to as microarray based genome selection (MGS) in the literature.
摘要翻译：本发明涉及用于特异性选择靶分子的装置，其包含：（a）至少一个包含微阵列的反应区，其中所述微阵列包含底物，一种或多种物质捕捉分子被固定，包括一个或多个温度控制和/或调节单元，用于控制和/或调节区域内的温度; （b）至少一个非反应区，其包含一个或多个温度控制和/或调节单元，用于控制和/或调节与反应区流体连通的区域内的温度; 和（c）至少一个能够产生和/或调节所述反应区（a）和包含一个或多个温度控制和/或调节单元（b）的所述非反应区之间的流体流动的运输工具。本发明进一步涉及用于特异性选择靶分子的装置，其中固定的捕获分子以点，细长点和/或线的形式在微阵列中组织。在另一方面，本发明涉及特异性选择靶分子的方法，包括将介质引入这样的装置，在反应区中进行相互作用反应，将未相互作用或未结合的靶分子转运至允许再激活靶分子并且在反应区与再活化的靶分子进行另外的相互作用反应，以及使用这样的装置用于特异性选择靶分子，例如目标富集在文献中也被称为基于微阵列的基因组选择（MGS）。

4. 发明申请

WO2011027268A3 DEVICES AND METHODS FOR MICROARRAY SELECTION 审中-公开
标题翻译： MICROARRAY选择的设备和方法
公开(公告)号：WO2011027268A3
公开(公告)日：2011-06-16
申请号：PCT/IB2010053839
申请日：2010-08-26
申请人： KONINKL PHILIPS ELECTRONICS NV , VAN DER ZAAG PIETER JAN , FEITSMA HARMA MARTINE , DEN TOONDER JACOB MARINUS JAN , WIMBERGER-FRIEDL REINHOLD
发明人： VAN DER ZAAG PIETER JAN , FEITSMA HARMA MARTINE , DEN TOONDER JACOB MARINUS JAN , WIMBERGER-FRIEDL REINHOLD
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6834 , C12Q2537/149 , C12Q2527/107
摘要： The present invention relates to a device for the specific selection of target molecules, comprising: (a) at least one reaction zone comprising a microarray, wherein the microarray comprises a substrate, on which one or more species of capture molecules are immobilized, comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the zone; (b) at least one non-reaction zone comprising one or more temperature control and/or regulating units for controlling and/or regulating the temperature within the zone, which is in fluid connection with the reaction zone; and (c) at least one transportation means capable of generating and/or regulating a fluid flow between said reaction zone (a) and said non-reaction zone comprising one or more temperature control and/or regulating units (b). The present invention further relates to a device for the specific selection of target molecules wherein the immobilized capture molecules are organized in the microarray in the form of spots, elongated spots and/or lines. In a further aspect the present invention relates to a method of specifically selecting target molecules, comprising the introducing a medium to such a device, performing interaction reactions in a reaction zone, transporting not interacted or not bound target molecules to a zone allowing reactivation of the target molecules and performing additional interaction reactions with the reactivated target molecules at the reaction zone, as well as the use of such a device for specifically selecting target molecules, e.g. for target enrichment also referred to as microarray based genome selection (MGS) in the literature.
摘要翻译：本发明涉及用于特异性选择靶分子的装置，其包括：（a）包含微阵列的至少一个反应区，其中所述微阵列包含其上固定有一种或多种捕获分子的底物，其包含一个或更多温度控制和/或调节单元，用于控制和/或调节该区域内的温度; （b）至少一个非反应区，包括一个或多个温度控制和/或调节单元，用于控制和/或调节与反应区流体连通的区域内的温度; 和（c）能够产生和/或调节所述反应区（a）和包括一个或多个温度控制和/或调节单元（b）的所述非反应区之间的流体流动的至少一个输送装置。本发明还涉及用于特异性选择靶分子的装置，其中固定的捕获分子以斑点，细长斑点和/或线的形式组织在微阵列中。在另一方面，本发明涉及一种特异性选择靶分子的方法，包括向这种装置中引入培养基，在反应区中进行相互作用反应，将不相互作用或不结合的靶分子传输到允许重新激活目标分子，并在反应区域与再活化的靶分子进行额外的相互作用反应，以及使用这种用于特异性选择靶分子的装置，例如对于目标富集，文献中也称为基于微阵列的基因组选择（MGS）。

5. 发明申请

WO2012168803A3 PROVIDING NUCLEOTIDE SEQUENCE DATA 审中-公开
标题翻译：提供核苷酸序列数据
公开(公告)号：WO2012168803A3
公开(公告)日：2013-07-04
申请号：PCT/IB2012051920
申请日：2012-04-17
申请人： KONINKL PHILIPS ELECTRONICS NV , PHILIPS INTELLECTUAL PROPERTY , VAN DER ZAAG PIETER JAN , AMBERG RONNY , VERHAEGH WILHELMUS FRANCISCUS JOHANNES , BEYERLEIN PETER , BOETTCHER RENE
发明人： VAN DER ZAAG PIETER JAN , AMBERG RONNY , VERHAEGH WILHELMUS FRANCISCUS JOHANNES , BEYERLEIN PETER , BOETTCHER RENE
IPC分类号： G06F19/22 , C12Q1/68 , G06F19/20
CPC分类号： G06F19/22 , C12Q1/6874 , G06F19/20
摘要： A sequencer device generates basic nucleotide sequence data 30 comprising probe data 34 of a capture probe in the sequencer device 10 and a determined sequence of identifiers 32 of a fragment of nucleic acids captured by the probe. The sequencer device outputs enriched nucleotide sequence data 36 that is enriched with data comprising a reference to a sequence 38 that is expected for the fragment of nucleic acids.
摘要翻译：定序器装置产生包括序列发生器装置10中的捕获探针的探针数据34的基本核苷酸序列数据30以及由探针俘获的核酸片段的确定序列32。定序器装置输出富集的核苷酸序列数据36，其富含数据，该数据包括对核酸片段预期的序列38的引用。

6. 发明申请

WO2012168803A2 PROVIDING NUCLEOTIDE SEQUENCE DATA 审中-公开
标题翻译：提供核苷酸序列数据
公开(公告)号：WO2012168803A2
公开(公告)日：2012-12-13
申请号：PCT/IB2012/051920
申请日：2012-04-17
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , PHILIPS INTELLECTUAL PROPERTY & STANDARDS GMBH , VAN DER ZAAG, Pieter, Jan , AMBERG, Ronny , VERHAEGH, Wilhelmus, Franciscus, Johannes , BEYERLEIN, Peter , BOETTCHER, Rene
发明人： VAN DER ZAAG, Pieter, Jan , AMBERG, Ronny , VERHAEGH, Wilhelmus, Franciscus, Johannes , BEYERLEIN, Peter , BOETTCHER, Rene
IPC分类号： G06F19/20 , G06F19/22 , C12Q1/68
CPC分类号： G06F19/22 , C12Q1/6874 , G06F19/20
摘要： A sequencer device generates basic nucleotide sequence data 30 comprising probe data 34 of a capture probe in the sequencer device 10 and a determined sequence of identifiers 32 of a fragment of nucleic acids captured by the probe. The sequencer device outputs enriched nucleotide sequence data 36 that is enriched with data comprising a reference to a sequence 38 that is expected for the fragment of nucleic acids.
摘要翻译：定序器装置产生包括序列发生器装置10中的捕获探针的探针数据34的基本核苷酸序列数据30以及由探针俘获的核酸片段的确定序列32。定序器装置输出富集的核苷酸序列数据36，其富含数据，该数据包括对核酸片段预期的序列38的引用。

7. 发明申请

WO2007060591A3 LUMINESCENT PARTICLE AND METHOD OF DETECTING A BIOLOGICAL ENTITY USING A LUMINESCENT PARTICLE 审中-公开
标题翻译：发光颗粒和使用发光颗粒检测生物实体的方法
公开(公告)号：WO2007060591A3
公开(公告)日：2007-11-01
申请号：PCT/IB2006054330
申请日：2006-11-20
申请人： KONINKL PHILIPS ELECTRONICS NV , VAN DER ZAAG PIETER JAN , BAKKERS ERIK PETRUS ANTONIUS M , VAN DER MARK MARTINUS BERNARDU
发明人： VAN DER ZAAG PIETER JAN , BAKKERS ERIK PETRUS ANTONIUS M , VAN DER MARK MARTINUS BERNARDU
IPC分类号： G01N33/58
CPC分类号： G01N33/588 , B82Y15/00 , G01N33/533
摘要： The invention provides a luminescent particle (10) and a method of detecting a biological entity using a luminescent particle, the luminescent particle comprising a core area (20) and a shell area (30), the core area (20) being covered by the shell area (30), the core area (20) conferring a luminescent behavior on the luminescent particle (10) for at least one excitation wavelength and for at least one emission wavelength by means of a nanocrystal material (21), and the shell area (30) being provided such that it realizes an antireflective coating (31) of the core area (20).
摘要翻译：本发明提供一种发光粒子（10）和使用发光粒子检测生物实体的方法，所述发光粒子包括核心区域（20）和壳体区域（30），所述核心区域（20）由壳体区域（30），通过纳米晶体材料（21）赋予发光粒子（10）上至少一个激发波长和至少一个发射波长的发光特性的核心区域（20），并且壳区域（30）被设置成使得其实现所述芯部区域（20）的抗反射涂层（31）。

8. 发明申请

WO2012168853A1 DEVICE FOR FRAGMENTING MOLECULES IN A SAMPLE BY ULTRASOUND 审中-公开
标题翻译：用于通过超声波在样品中分离分子的装置
公开(公告)号：WO2012168853A1
公开(公告)日：2012-12-13
申请号：PCT/IB2012/052812
申请日：2012-06-05
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , CRAUS, Cristian Bogdan , DEN TOONDER, Jacob Marinus Jan , PENTERMAN, Roel , VAN DER ZAAG, Pieter Jan
发明人： CRAUS, Cristian Bogdan , DEN TOONDER, Jacob Marinus Jan , PENTERMAN, Roel , VAN DER ZAAG, Pieter Jan
IPC分类号： B02C19/18 , C12M1/33 , C12M3/08 , C12N1/06
CPC分类号： B06B3/00 , B02C19/18 , C12M47/06 , G01N1/286 , Y10T29/49826
摘要： According to an aspect of the present invention, a device for fragmenting molecules in a sample by ultrasound is provided. The device comprises a planar-shaped cartridge and a fragmentation instrument that has a vessel-like shape. By means of applying under-pressure in the fragmentation instrument the cartridge is pulled towards the fragmentation instrument and therefore spatially closes a fluid compartment that is comprised by the fragmentation instrument. Afterwards, an ultrasound treatment of the sample, which is comprised in a sample compartment of the cartridge, may be processed. A sealing layer is provided in between the cartridge and the fragmentation instrument in order to hold the fixation of the cartridge tightly and in order to provide for leakage prevention out of the fluid compartment.
摘要翻译：根据本发明的一个方面，提供了一种通过超声将碎片分子分解的装置。该装置包括具有容器状形状的平面形状的盒和碎片装置。通过在破碎仪器中施加低压力，将药筒拉向碎裂仪器，因此空间上封闭由碎裂仪器组成的流体隔室。之后，可以处理包含在药筒的样品室中的样品的超声处理。密封层设置在药筒和碎裂仪器之间，以便牢固地保持药筒的固定，以便防止流体隔室泄漏。

9. 发明申请

WO2012059839A2 IN VITRO DIAGNOSTIC TESTING INCLUDING AUTOMATED BROKERING OF ROYALTY PAYMENTS FOR PROPRIETARY TESTS 审中-公开
标题翻译：在体外诊断测试中，包括自动检测专有费用的专有费用
公开(公告)号：WO2012059839A2
公开(公告)日：2012-05-10
申请号：PCT/IB2011/054735
申请日：2011-10-24
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , VAN DER ZAAG, Pieter, Jan , DIMITROVA, Nevenka , VAN DE STOLPE, Anja , VAN HOUTEN, Hendrik
发明人： VAN DER ZAAG, Pieter, Jan , DIMITROVA, Nevenka , VAN DE STOLPE, Anja , VAN HOUTEN, Hendrik
IPC分类号： G06Q10/00 , C12Q1/68 , G06F19/00
CPC分类号： G06Q20/10 , G06F19/00 , G06F19/18 , G06Q10/00 , G06Q50/22
摘要： A method comprises: recording an electronic record of diagnostic events including the performing of in- vitro diagnostic tests; during the recording, identifying the performing of a licensed in- vitro diagnostic test for which license information is stored in a licenses database; and computing license compensation due to a licensor for the performing of the licensed in- vitro diagnostic test based on royalty calculation information stored in the licenses database. The recording, identifying, and computing operations are performed by one or more computers. The method may further include remitting the computed license compensation to the licensor, the remitting also being performed by one or more computers. The licensed in- vitro diagnostic test may comprise a licensed biomarker test, for example one obtained by DNA or RNA sequencing, and the method may further comprise: performing the licensed biomarker test using a genome sequencer, wherein the performing of the licensed biomarker test and the computing of license compensation are both performed at a single medical facility.
摘要翻译：一种方法包括：记录诊断事件的电子记录，包括进行体外诊断测试; 在记录期间，识别许可证信息被存储在许可证数据库中的许可的体外诊断测试的执行; 以及由许可人根据许可证数据库中存储的使用费计算信息执行许可的体外诊断测试的计算许可证补偿。记录，识别和计算操作由一个或多个计算机执行。该方法还可以包括将所计算的许可证补偿递交给许可方，还由一个或多个计算机执行。许可的体外诊断测试可以包括许可的生物标志物测试，例如通过DNA或RNA测序获得的测试，并且该方法可以进一步包括：使用基因组测序仪进行许可的生物标志物测试，其中执行许可的生物标志物测试和许可证补偿的计算都在单一医疗机构进行。

10. 发明申请

WO2012029037A1 METHOD FOR AMPLIFYING NUCLEIC ACIDS 审中-公开
标题翻译：放大核酸的方法
公开(公告)号：WO2012029037A1
公开(公告)日：2012-03-08
申请号：PCT/IB2011/053817
申请日：2011-08-31
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , FEITSMA, Harma, Martine , OVERDIJK, Marlieke, Joan , VAN DE STOLPE, Anja , VAN DER ZAAG, Pieter, Jan
发明人： FEITSMA, Harma, Martine , OVERDIJK, Marlieke, Joan , VAN DE STOLPE, Anja , VAN DER ZAAG, Pieter, Jan
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6869 , C12Q1/6837 , C12Q1/6874 , C12Q2565/543 , C12Q2525/301
摘要： The present invention describes methods for amplifying a target nucleic acid wherein target nucleic acids hybridise to capture probe nucleic acids which are immobilized to a support via their 5 ' end. The hybridization product is further extended with a polymerase to form a double stranded nucleic acid. To this double stranded nucleic acid, a hairpin nucleic acid is ligated. This ligation product is further amplified and sequenced.
摘要翻译：本发明描述了用于扩增目标核酸的方法，其中靶核酸与通过其5'末端固定在载体上的探针核酸杂交。进一步用聚合酶扩增杂交产物以形成双链核酸。向该双链核酸中连接发夹核酸。该连接产物进一步扩增和测序。

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