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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

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）。

3. 发明申请

WO2009156942A1 MICROARRAY CHARACTERIZATION SYSTEM AND METHOD 审中-公开
标题翻译：微阵列特征系统和方法
公开(公告)号：WO2009156942A1
公开(公告)日：2009-12-30
申请号：PCT/IB2009/052683
申请日：2009-06-23
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , WIMBERGER-FRIEDL, Reinhold , DIRKSEN, Peter , BOAMFA, Marius, I. , VAN DIJK, Erik, M., H., P.
发明人： WIMBERGER-FRIEDL, Reinhold , DIRKSEN, Peter , BOAMFA, Marius, I. , VAN DIJK, Erik, M., H., P.
IPC分类号： G01N21/64
CPC分类号： G01N21/6452 , B01L3/5027 , G02B21/0028
摘要： A system and method is described for detecting a plurality of analytes in a sample. The characterization system (100) comprises an aperture array (108) and a lens array (110) for generating and focusing a plurality of excitation sub-beams on different sub-regions of a substrate. These sub-regions can be provided with different binding sites for binding different analytes in the sample. By detecting the different luminescent responses in a detector, the presence or amount of different analytes can be determined simultaneously. Alternatively or in addition thereto collection of the luminescence radiation can be performed using the lens array for directly collecting the luminescence response and for guiding the collected luminescence response to corresponding apertures. In a preferred embodiment, the excitation sub-beams are focused at the side of the substrate opposite of the lens array and an immersion fluid is provided between the lens array and the substrate to increase the collection efficiency of the luminescence radiation.
摘要翻译：描述了用于检测样品中多个分析物的系统和方法。表征系统（100）包括孔径阵列（108）和透镜阵列（110），用于在衬底的不同子区域上产生和聚焦多个激励子束。这些子区域可以具有不同的结合位点，用于结合样品中的不同分析物。通过检测检测器中的不同发光响应，可以同时测定不同分析物的存在或量。或者或另外，可以使用透镜阵列来进行发光辐射的收集，用于直接收集发光响应并且用于将所收集的发光响应引导到相应的孔。在优选实施例中，激发子光束在与透镜阵列相对的一侧聚焦，并且在透镜阵列和基板之间提供浸没流体，以增加发光辐射的收集效率。

4. 发明申请

WO2008012706A2 MULTI-COLOR BIOSENSOR 审中-公开
标题翻译：多色生物传感器
公开(公告)号：WO2008012706A2
公开(公告)日：2008-01-31
申请号：PCT/IB2007/052634
申请日：2007-07-05
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , VAN DIJK, Erik, M., H., P. , BOAMFA, Marius, I. , WIMBERGER-FRIEDL, Reinhold
发明人： VAN DIJK, Erik, M., H., P. , BOAMFA, Marius, I. , WIMBERGER-FRIEDL, Reinhold
IPC分类号： G01N21/64
CPC分类号： G01N21/6428 , G01J3/02 , G01J3/021 , G01J3/10 , G01J3/36 , G01J3/4406 , G01N21/645 , G01N2021/6419 , G01N2021/6421 , G01N2021/6441 , G01N2021/6463
摘要： A detection system is described (100) for detecting luminescence sites on a substrate (6). The detection system (100) typically comprises an irradiation unit (102) for generating at least one excitation irradiation beam for exciting luminescence sites on the substrate (6). The at least one excitation irradiation beam may be a plurality of excitation irradiation beams. The detection system (100) also comprises a first optical element, e.g. refractive element (25), adapted for receiving at least two irradiation beams of different wavelengths or wavelength ranges, the at least two irradiation beams being excitation irradiation beam(s) to be focused on a substrate and/or luminescence irradiation beam(s) to be collected from the excited luminescence sites on the substrate (6). The detection system (100) also comprises an optical compensator for adjusting at least one of the at least two irradiation beams of different wavelengths or wavelength ranges so as to reduce or compensate for optical aberrations. The present invention also relates to a corresponding method for detecting, a phase plate and a method for designing such a phase plate.
摘要翻译：描述了用于检测衬底（6）上的发光位点的检测系统（100）。检测系统（100）通常包括用于产生至少一个用于激发衬底（6）上的发光位置的激发照射束的照射单元（102）。该至少一个激励照射束可以是多个激励照射束。检测系统（100）还包括第一光学元件，例如第二光学元件。（25），适于接收不同波长或波长范围的至少两个照射光束，所述至少两个照射光束是激发照射光束以聚焦在衬底上和/或发光照射光束到从衬底（6）上的激发发光位点收集。检测系统（100）还包括光学补偿器，用于调节不同波长或波长范围的至少两个照射光束中的至少一个，以减少或补偿光学像差。本发明还涉及用于检测的相应方法，相位板和用于设计这种相位板的方法。

5. 发明申请

WO2007043005A1 ALL POLYMER OPTICAL WAVEGUIDE SENSOR 审中-公开
标题翻译：所有聚合物光波导传感器
公开(公告)号：WO2007043005A1
公开(公告)日：2007-04-19
申请号：PCT/IB2006/053710
申请日：2006-10-10
申请人： KONINKLIJKE PHILIPS ELECTRONICS N. V. , WIMBERGER-FRIEDL, Reinhold , 'T HOOFT, Gert , DE WITZ, Christiane
发明人： WIMBERGER-FRIEDL, Reinhold , 'T HOOFT, Gert , DE WITZ, Christiane
IPC分类号： G01N21/00
CPC分类号： G01N21/7703 , G01N21/648
摘要： The present invention is directed to an evanescent field induced optical sensor of a transparent polymer substrate coated with a thin transparent polymer waveguide for use as biosensor for detecting biological molecules, wherein the transparent polymer waveguide has a refractive index n of 1.4 to 1.79, said transparent polymer waveguide has a coupling grating recess structure for the coupling of the light wave into said transparent polymer waveguide, the lower surface of said transparent polymer waveguide contacts a transparent polymer substrate, said transparent polymer substrate has a refractive index n of 1.29 to 1.69 and the outer upper surface of said polymer waveguide or optical sensor possess specific binding compounds to detect at least one specific chemical.
摘要翻译：本发明涉及涂覆有用作检测生物分子的生物传感器的薄透明聚合物波导的透明聚合物基质的消逝场感应光学传感器，其中透明聚合物波导的折射率n为1.4至1.79，所述透明聚合物波导具有用于将光波耦合到所述透明聚合物波导中的耦合光栅凹槽结构，所述透明聚合物波导的下表面接触透明聚合物基底，所述透明聚合物基底的折射率n为1.29至1.69，并且所述聚合物波导或光学传感器的外部上表面具有特异性结合化合物以检测至少一种特定化学物质。

6. 发明申请

WO2007034404A2 A MICROFLUIDIC REGULATING DEVICE 审中-公开
标题翻译：微流控制器件
公开(公告)号：WO2007034404A2
公开(公告)日：2007-03-29
申请号：PCT/IB2006053357
申请日：2006-09-19
申请人： KONINKL PHILIPS ELECTRONICS NV , WIMBERGER-FRIEDL REINHOLD , HIKMET RIFAT ATA MUSTAFA , VAN BOMMEL TIES , DEN TOONDER JACOB MARINUS JAN , YAVUZ MEIKE
发明人： WIMBERGER-FRIEDL REINHOLD , HIKMET RIFAT ATA MUSTAFA , VAN BOMMEL TIES , DEN TOONDER JACOB MARINUS JAN , YAVUZ MEIKE
IPC分类号： B01L3/00
CPC分类号： F15C3/04 , B01L3/502738 , B01L2200/12 , B01L2400/0487 , B01L2400/0633 , B01L2400/0638 , Y10T137/2191 , Y10T137/2202 , Y10T137/2213
摘要： The invention relates to a microfluidic regulating device, comprising a first layer having a first microfluidic channel defined therein, a second layer having a second microfluidic channel defined therein, a fluid flow regulating layer disposed between the first and the second microfluidic channel, which layer comprises a movable valve member which in open position allows fluid communication between the first and second channel and in closed position seals against a valve seat, whereby at least part of the valve member and of the valve seat is magnetic. The device is able to store small quantities of liquids at microfluidic cartridges and access these on demand in a well controlled and simple way.
摘要翻译：本发明涉及一种微流体调节装置，其包括具有限定在其中的第一微流体通道的第一层，其中限定有第二微流体通道的第二层，设置在第一和第二微流体通道之间的流体流动调节层，该层包括处于打开位置的可移动阀构件允许第一和第二通道之间的流体连通并且在关闭位置中密封抵靠阀座，由此阀构件和阀座的至少一部分是磁性的。该设备能够在微流控盒中储存少量液体，并以良好控制和简单的方式随时访问。

7. 发明申请

WO2006067715A3 METHOD FOR CONTROLLING THE FLOW OF LIQUIDS CONTAINING BIOLOGICAL MATERIAL BY INDUCING ELECTRO- OR MAGNETO-RHEOLOGICAL EFFECT 审中-公开
标题翻译：通过诱导电磁流变效应来控制含有生物材料的液体的流动方法
公开(公告)号：WO2006067715A3
公开(公告)日：2006-09-14
申请号：PCT/IB2005054283
申请日：2005-12-16
申请人： KONINKL PHILIPS ELECTRONICS NV , HIKMET RIFAT , WIMBERGER-FRIEDL REINHOLD
发明人： HIKMET RIFAT , WIMBERGER-FRIEDL REINHOLD
IPC分类号： B01L3/00 , F15C5/00
CPC分类号： F15B21/001 , B01L3/50273 , B01L3/502738 , B01L3/502746 , B01L2300/0816 , B01L2400/0677 , B01L2400/082 , F16K99/0001 , F16K99/0021 , F16K99/0046 , F16K99/0051 , F16K99/0053 , F16K2099/0073 , F16K2099/0074 , F16K2099/008 , F16K2099/0084 , G01N35/1097 , Y10T436/25
摘要： The invention provides a method for controlling or manipulating the flow of a solution or liquid comprising biological material or biomolecules. Therefore, particles are added to the solution or liquid for providing the solution or liquid with rheological properties. The solution or liquid comprising the particles is provided in a microchannel and by applying an electric and/or magnetic field to the microchannel, the flow of the liquid or solution can be controlled.
摘要翻译：本发明提供了一种用于控制或操纵包含生物材料或生物分子的溶液或液体的流动的方法。因此，将颗粒加入溶液或液体中以提供具有流变性质的溶液或液体。包含颗粒的溶液或液体设置在微通道中并通过向微通道施加电场和/或磁场，可以控制液体或溶液的流动。

8. 发明申请

WO2006079998A1 RAPID AND SENSITIVE BIOSENSING 审中-公开
标题翻译：快速敏感的生物传感
公开(公告)号：WO2006079998A1
公开(公告)日：2006-08-03
申请号：PCT/IB2006/050322
申请日：2006-01-30
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , KAHLMAN, Josephus, A., H., M. , THILWIND, Rachel, E. , PRINS, Menno, W., J. , MEGENS, Mischa , WIMBERGER-FRIEDL, Reinhold
发明人： KAHLMAN, Josephus, A., H., M. , THILWIND, Rachel, E. , PRINS, Menno, W., J. , MEGENS, Mischa , WIMBERGER-FRIEDL, Reinhold
IPC分类号： G01N33/553 , G01N33/543
CPC分类号： G01N27/745 , G01N33/54333 , G01N33/553
摘要： A sensor device (15) for detecting magnetic particles (13) has a binding surface (40) with binding sites thereon and comprises: at least one sensor element (23) for detecting the presence of magnetic particles (13), means for attracting magnetic structures comprising at least one magnetic particle (13) toward and onto the binding surface (40) of the sensor device (15), and means for re-arranging and randomizing the position of individual magnetic particles (13) with respect to the binding sites on the binding surface (40) to give binding sites on all individual particles (13) a substantial probability to have a contact time with binding sites on the binding surface (40). With such sensor device (15), the speed of detection of target molecules in a fluid is enhanced.
摘要翻译：用于检测磁性颗粒（13）的传感器装置（15）具有在其上具有结合位置的结合表面（40），并包括：用于检测磁性颗粒（13）的存在的至少一个传感器元件（23），用于吸引磁性颗粒包括朝向和传递到传感器装置（15）的结合表面（40）上的至少一个磁性颗粒（13）的结构，以及用于重新排列和随机化各个磁性颗粒（13）相对于结合位点在结合表面（40）上以在所有单独的颗粒（13）上产生与结合表面（40）上的结合位点具有接触时间的可能性。利用这种传感器装置（15），提高了流体中目标分子的检测速度。

9. 发明申请

WO2006025014A1 MICRO-FLUIDIC SYSTEM 审中-公开
标题翻译：微流体系统
公开(公告)号：WO2006025014A1
公开(公告)日：2006-03-09
申请号：PCT/IB2005/052825
申请日：2005-08-30
申请人： KONINKLIJKE PHILIPS ELECTRONICS N. V. , WIMBERGER-FRIEDL, Reinhold , WEEKAMP, Johannus Wilhelmus
发明人： WIMBERGER-FRIEDL, Reinhold , WEEKAMP, Johannus Wilhelmus
IPC分类号： B01L3/00 , B81B7/00 , G06K19/077 , G06K7/00
CPC分类号： B01L3/502715 , B01L3/502707 , B01L2200/0689 , B01L2200/12
摘要： Micro-fluidic systems comprise components (4), for instance sensors or pump units, which are intended to measure properties of a fluid or exert influence on this fluid, which is conducted in a channel (7). In the present invention, a micro-fluidic system is proposed in which a component (4) is embedded in cast jacket material (5), such that a component structure (49) is formed, parallel to which a channel structure (8) is arranged, wherein a channel (7) is incorporated in the channel structure (8). In such a micro-fluidic system, the component can be positioned in relation to the channel in such a manner that a fluid flow with very good flow properties through the channel can be realized.
摘要翻译：微流体系统包括组件（4），例如用于测量流体性质或对通道（7）中进行的这种流体的影响的传感器或泵单元。在本发明中，提出了一种微流体系统，其中组件（4）嵌入在铸造外壳材料（5）中，使得形成部件结构（49），平行于通道结构（8）布置，其中通道（7）被并入所述通道结构（8）中。在这种微流体系统中，组件可以相对于通道定位，使得可以实现通过通道具有非常好的流动特性的流体流动。

10. 发明申请

WO2010049883A1 BIOSENSOR WITH MULTI-CHAMBER CARTRIDGE 审中-公开
标题翻译：生物传感器与多个盒子
公开(公告)号：WO2010049883A1
公开(公告)日：2010-05-06
申请号：PCT/IB2009/054740
申请日：2009-10-27
申请人： KONINKLIJKE PHILIPS ELECTRONICS N.V. , NEIJZEN, Jacobus, H., M. , WIMBERGER-FRIEDL, Reinhold , MAAS, Joost, H. , NIEUWENHUIS, Jeroen, H. , BRULS, Dominique, M. , IMMINK, Albert, H., J. , OVSYANKO, Mikhail, M.
发明人： NEIJZEN, Jacobus, H., M. , WIMBERGER-FRIEDL, Reinhold , MAAS, Joost, H. , NIEUWENHUIS, Jeroen, H. , BRULS, Dominique, M. , IMMINK, Albert, H., J. , OVSYANKO, Mikhail, M.
IPC分类号： G01N33/543 , G01N35/00 , G01R33/00
CPC分类号： G01N33/54326 , B01L3/502761 , B82Y25/00 , G01N27/745 , G01R33/093 , G01R33/1269
摘要： The present invention provides a biosensor comprising a cartridge for accommodating a fluid sample, the cartridge comprising at least two chambers, wherein each chamber comprises a sensor surface with one or more binding sites. The biosensor further comprises means for generating a magnetic field at the binding sites of the sensor surfaces of the at least two chambers. The biosensor also comprises means for detecting particles accumulated at/and or proximate the binding sites of the sensor surfaces of the at least two chambers. Therein, the magnetic field at the binding sites has a sufficiently large gradient to actuate magnetic label particles towards the binding sites.
摘要翻译：本发明提供了一种生物传感器，其包括用于容纳流体样品的盒，所述盒包括至少两个室，其中每个室包括具有一个或多个结合位点的传感器表面。生物传感器还包括用于在至少两个室的传感器表面的结合位置处产生磁场的装置。生物传感器还包括用于检测在至少两个室的传感器表面的结合位点处和/或附近堆积的颗粒的装置。其中，结合位点处的磁场具有足够大的梯度以朝向结合位点致动磁性标记颗粒。

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