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1. 发明授权

US09108220B2 Device for franmenting molecules in a sample by ultrasound 有权
标题翻译：用于通过超声波使样品中的分子残留的装置
公开(公告)号：US09108220B2
公开(公告)日：2015-08-18
申请号：US14117378
申请日：2012-06-05
申请人： Cristian Bogdan Craus , Jacob Marinus Jan Den Toonder , Roel Penterman , Pieter Jan Van Der Zaag
发明人： Cristian Bogdan Craus , Jacob Marinus Jan Den Toonder , Roel Penterman , Pieter Jan Van Der Zaag
IPC分类号： G01N15/06 , G01N33/00 , G01N33/48 , B06B3/00 , B02C19/18 , C12M1/00 , G01N1/28
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。

2. 发明申请

US20140193305A1 DEVICE FOR FRANMENTING MOLECULES IN A SAMPLE BY ULTRASOUND 有权
标题翻译：用超声波法分离样品中的分子的装置
公开(公告)号：US20140193305A1
公开(公告)日：2014-07-10
申请号：US14117378
申请日：2012-06-05
申请人： Cristian Bogdan Craus , Jacob Marinus Jan Den Toonder , Roel Penterman , Pieter Jan Van Der Zaag
发明人： Cristian Bogdan Craus , Jacob Marinus Jan Den Toonder , Roel Penterman , Pieter Jan Van Der Zaag
IPC分类号： B06B3/00
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，将药筒拉向破碎仪器，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。

3. 发明授权

US08932540B2 Device and method for transporting magnetic or magnetisable beads 有权
标题翻译：用于运输磁性或可磁化珠粒的装置和方法
公开(公告)号：US08932540B2
公开(公告)日：2015-01-13
申请号：US13395321
申请日：2010-09-06
申请人： Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag , Hao Chieh Chao
发明人： Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag , Hao Chieh Chao
IPC分类号： B01L99/00 , B03C1/034 , B01L3/00 , B03C1/033 , B03C1/24
CPC分类号： B03C1/034 , B01L3/502761 , B01L2200/0668 , B01L2400/043 , B03C1/0335 , B03C1/24 , B03C2201/18
摘要： A device for transporting magnetic or magnetizable beads over a transport surface includes a chamber holding magnetic or magnetizable beads in a fluid, a transport element including the transport surface within the chamber, and a current wire structure including at least two sets of meandering current wires arranged on a side of the transport element opposite to the transport surface. The at least two sets are displaced with respect to each other in at least two directions. A switching unit switches currents individually applied to the sets of current wires according to a current driving scheme resulting in a transport of the beads over the transport surface.
摘要翻译：用于在输送表面上传送磁性或可磁化珠的装置包括在流体中容纳磁性或可磁化珠粒的腔室，包括腔室内的输送表面的输送元件，以及包括至少两组曲折的电流布线的电流线结构，在运输元件的与运输表面相对的一侧。至少两组相对于彼此在至少两个方向上移位。开关单元根据当前的驱动方案来切换单独施加到电流线组的电流，从而导致小珠在输送表面上的传送。

4. 发明申请

US20120165219A1 DEVICES AND METHODS FOR MICROARRAY SELECTION 有权
标题翻译： MICROARRAY选择的设备和方法
公开(公告)号：US20120165219A1
公开(公告)日：2012-06-28
申请号：US13393255
申请日：2010-08-26
申请人： Pieter Jan Van Der Zaag , Harma Feitsma , Jacob Marinus Jan Den Toonder , Reinhold Wimberger-Friedl
发明人： Pieter Jan Van Der Zaag , Harma Feitsma , Jacob Marinus Jan Den Toonder , Reinhold Wimberger-Friedl
IPC分类号： C40B30/04 , C40B60/12
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. 发明授权

US08932811B2 Genomic selection and sequencing using encoded microcarriers 有权
标题翻译：使用编码的微载体的基因组选择和测序
公开(公告)号：US08932811B2
公开(公告)日：2015-01-13
申请号：US13203637
申请日：2010-02-26
申请人： Anja Van De Stolpe , Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag
发明人： Anja Van De Stolpe , Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag
IPC分类号： C12Q1/68 , C12P19/34 , C12M1/00 , C12M1/34 , B32B5/16 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6869 , Y10T428/2982 , C12Q2565/519 , C12Q2563/149 , C12Q2537/143
摘要： The present invention relates to a method for determining the sequence of a nucleic molecule. Herein a capture oligonucleotide probe is attached to an encoded microcarrier, wherein the code of said microcarrier identifies the sequence of said oligonucleotide probe. The capture oligonucleotide probe is hybridized with a sample comprising nucleic acids molecules, wherein said DNA fragment comprises a sequence which is complementary to the sequence of the capture oligonucleotide probe. The sequence of the DNA molecule is determined, wherein the capture oligonucleotide probe serves as a primer for a DNA polymerase, in the case of single molecule sequencing this is a sequencing primer. After the sequence determination, the nucleotide sequence of the capture oligonucleotide probe is identified by determining the code on the microcarrier, which corresponds with the capture oligonucleotide probe. This sequence information directly identifies the location of the sequenced DNA fragment on the genome, allowing direct comparison.
摘要翻译：本发明涉及确定核酸分子序列的方法。本文中，捕获寡核苷酸探针连接到编码的微载体上，其中所述微载体的编码识别所述寡核苷酸探针的序列。捕获寡核苷酸探针与包含核酸分子的样品杂交，其中所述DNA片段包含与捕获寡核苷酸探针的序列互补的序列。确定DNA分子的序列，其中捕获寡核苷酸探针用作DNA聚合酶的引物，在单分子测序的情况下，这是测序引物。序列测定后，通过测定与捕获寡核苷酸探针对应的微载体上的编码来鉴定捕获寡核苷酸探针的核苷酸序列。该序列信息直接识别基因组上测序的DNA片段的位置，从而直接比较。

6. 发明申请

US20120171085A1 DEVICE AND METHOD FOR TRANSPORTING MAGNETIC OR MAGNETISABLE BEADS 有权
标题翻译：用于运输磁性或可磁化珠的装置和方法
公开(公告)号：US20120171085A1
公开(公告)日：2012-07-05
申请号：US13395321
申请日：2010-09-06
申请人： Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag , Hao Chieh Chao
发明人： Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag , Hao Chieh Chao
IPC分类号： B65G53/04 , B01L3/00 , H03K3/00
CPC分类号： B03C1/034 , B01L3/502761 , B01L2200/0668 , B01L2400/043 , B03C1/0335 , B03C1/24 , B03C2201/18
摘要： The present invention relates to a device (24) for transporting magnetic or magnetizable beads (10) over a transport surface (12). It comprises a chamber (26) comprising magnetic or magnetizable beads (10) in a fluid (28), a transport element (14) including said transport surface (12) within said chamber (26) over which said beads (10) shall be transported, a current wire structure (20) comprising at least two sets (20a, 20b, 20c) of meandering current wires arranged on a side of said transport element (14) opposite to said transport surface (12), said at least two sets (20a, 20b, 20c) being displaced with respect to each other in at least two directions, and a switching unit (32) for individually switching currents (1a, 1b, 1c) individually applied to said sets of current wires according to a current driving scheme resulting in a transport of said beads (10) over said transport surface (12). In preferred embodiments a stationary substantially uniform magnetic field (30) in a direction substantially parallel to the transport surface (12) is additionally provided.
摘要翻译：本发明涉及一种用于在输送表面（12）上输送磁性或可磁化珠（10）的装置（24）。其包括在流体（28）中包括磁性或可磁化珠（10）的腔室（26），包括所述腔室（26）内的所述输送表面（12）的输送元件（14），所述珠子传送的电流线结构（20）包括至少两组布置在与所述传输表面（12）相对的所述传输元件（14）侧上的曲折电流线（20a，20b，20c），所述至少两组（20a，20b，20c）在至少两个方向相对于彼此移位;以及开关单元（32），用于根据电流单独地切换电流（1a，1b，1c），分别施加到所述电流线组驱动方案导致所述珠（10）在所述输送表面（12）上的运输。在优选实施例中，附加地提供了在基本上平行于输送表面（12）的方向上的固定的基本均匀的磁场（30）。

7. 发明授权

US09493822B2 Devices and methods for microarray selection 有权
标题翻译：用于微阵列选择的设备和方法
公开(公告)号：US09493822B2
公开(公告)日：2016-11-15
申请号：US13393255
申请日：2010-08-26
申请人： Pieter Jan Van Der Zaag , Harma Feitsma , Jacob Marinus Jan Den Toonder , Reinhold Wimberger-Friedl
发明人： Pieter Jan Van Der Zaag , Harma Feitsma , Jacob Marinus Jan Den Toonder , Reinhold Wimberger-Friedl
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, wherein immobilized capture molecules can be organized in a microarray in the form of spots or lines. In a further aspect the present invention relates to a method of specifically selecting target molecules in a reaction zone, as well as the use of such a device for specifically selecting target molecules, e.g. for target enrichment, or microarray based genome selection (MGS).
摘要翻译：本发明涉及用于特异性选择靶分子的装置，其中固定的捕获分子可以以点或线的形式组织在微阵列中。在另一方面，本发明涉及在反应区中特异性选择靶分子的方法，以及这种用于特异性选择靶分子的装置的使用，例如，用于靶标富集或基于微阵列的基因组选择（MGS）。

8. 发明申请

US20110311975A1 GENOMIC SELECTION AND SEQUENCING USING ENCODED MICROCARRIERS 有权
标题翻译：使用编码微控制器的基因选择和序列
公开(公告)号：US20110311975A1
公开(公告)日：2011-12-22
申请号：US13203637
申请日：2010-02-26
申请人： Anja Van De Stolpe , Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag
发明人： Anja Van De Stolpe , Jacob Marinus Jan Den Toonder , Pieter Jan Van Der Zaag
IPC分类号： C12Q1/68 , C12M1/34
CPC分类号： C12Q1/6869 , Y10T428/2982 , C12Q2565/519 , C12Q2563/149 , C12Q2537/143
摘要： The present invention relates to a method for determining the sequence of a nucleic molecule. Herein a capture oligonucleotide probe is attached to an encoded microcarrier, wherein the code of said microcarrier identifies the sequence of said oligonucleotide probe. The capture oligonucleotide probe is hybridized with a sample comprising nucleic acids molecules, wherein said DNA fragment comprises a sequence which is complementary to the sequence of the capture oligonucleotide probe. The sequence of the DNA molecule is determined, wherein the capture oligonucleotide probe serves as a primer for a DNA polymerase, in the case of single molecule sequencing this is a sequencing primer. After the sequence determination, the nucleotide sequence of the capture oligonucleotide probe is identified by determining the code on the microcarrier, which corresponds with the capture oligonucleotide probe. This sequence information directly identifies the location of the sequenced DNA fragment on the genome, allowing direct comparison.
摘要翻译：本发明涉及确定核酸分子序列的方法。本文中，捕获寡核苷酸探针连接到编码的微载体上，其中所述微载体的编码识别所述寡核苷酸探针的序列。捕获寡核苷酸探针与包含核酸分子的样品杂交，其中所述DNA片段包含与捕获寡核苷酸探针的序列互补的序列。确定DNA分子的序列，其中捕获寡核苷酸探针用作DNA聚合酶的引物，在单分子测序的情况下，这是测序引物。序列测定后，通过测定与捕获寡核苷酸探针对应的微载体上的编码来鉴定捕获寡核苷酸探针的核苷酸序列。该序列信息直接识别基因组上测序的DNA片段的位置，从而直接比较。

9. 发明申请

US20140017687A1 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：US20140017687A1
公开(公告)日：2014-01-16
申请号：US14004439
申请日：2012-03-20
申请人： Reinhold Wimberger-Friedl , Pieter Jan Van Der Zaag , Eva Servoli
发明人： Reinhold Wimberger-Friedl , Pieter Jan Van Der Zaag , Eva Servoli
IPC分类号： C12Q1/68
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 col lection 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; 并重复使用试剂溶液和/或不混溶的中间体液体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。

10. 发明申请

US20110171086A1 MICROFLUIDIC DEVICE 有权
标题翻译：微流体装置
公开(公告)号：US20110171086A1
公开(公告)日：2011-07-14
申请号：US13120456
申请日：2009-10-01
申请人： Menno Willem Jose Prins , Pieter Jan Van Der Zaag , Remco Christiaan Den Dulk
发明人： Menno Willem Jose Prins , Pieter Jan Van Der Zaag , Remco Christiaan Den Dulk
IPC分类号： B01L3/00
CPC分类号： B01L3/50273 , B01L3/502738 , B01L3/502761 , B01L2200/0668 , B01L2200/10 , B01L2300/0816 , B01L2300/087 , B01L2400/043 , B01L2400/086
摘要： A microfluidic device is provided, the microfluidic device comprising: a plurality of chambers (3, 4, 5, 6) adapted for performing chemical, biochemical, or physical processes and a flow path (9) connecting the plurality of chambers (3, 4, 5, 6) adapted for accommodating at least one magnetic particle (7) subsequently moving through the plurality of chambers The plurality of chambers (3, 4, 5, 6) are separated by at least one valve-like structure (10) adapted to enable passing-through of the at least one magnetic particle (7) from one of the plurality of chambers to another one of the plurality of chambers. At least one delaying structure (11, 111) adapted to delay movement of the at least one magnetic particle (7) along the flow path is provided.
摘要翻译：提供了一种微流体装置，所述微流体装置包括：适于进行化学，生物化学或物理过程的多个腔室（3,4,5,6）和连接所述多个腔室（3,4）的流路（9），5,6），其适于容纳随后移动通过所述多个室的至少一个磁性颗粒（7）。所述多个室（3,4,5,6）由至少一个阀状结构（10）分隔，所述阀状结构（10）适于以使所述至少一个磁性颗粒（7）从所述多个室中的一个到达所述多个室中的另一个。提供了适于延迟至少一个磁性颗粒（7）沿流动路径移动的至少一个延迟结构（11,111）。

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