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1. 发明授权

US09557328B2 Magnetic sensor device, method of operating such a device and sample 有权
标题翻译：磁传感器装置，操作这种装置和样品的方法
公开(公告)号：US09557328B2
公开(公告)日：2017-01-31
申请号：US13381115
申请日：2010-06-24
申请人： Wendy Uyen Dittmer , Femke Karina De Theije , Albert Hendrik Jan Immink , Jeroen Hans Nieuwenhuis , Petrus Johannes Wilhelmus Van Lankvelt
发明人： Wendy Uyen Dittmer , Femke Karina De Theije , Albert Hendrik Jan Immink , Jeroen Hans Nieuwenhuis , Petrus Johannes Wilhelmus Van Lankvelt
IPC分类号： G01N33/543 , G01N27/74 , G01N21/552
CPC分类号： G01N33/54326 , G01N21/552 , G01N27/745 , G01N33/54366 , G01N33/54386
摘要： A sensor device (1) for detecting the presence of a target molecule (20) in a sample, is disclosed. The sensor device comprises a measurement sensor (2) comprising a first moiety (16) for forming a binding couple with a first further moiety comprising the target molecule (20) and a detectable label (40) and a reference sensor (3) comprising a second moiety (50) for forming a further binding couple with a second further moiety comprising a further detectable label (40′). The sensor device is adapted to generate a first detection signal (14) from the detection of the detectable label (40) in the first further moiety bound to the first moiety (16) and to generate a second detection signal (14′) from the detection of the further detectable label (40′) in the second further moiety bound to the second moiety (50), wherein at least during operation of the sensor device the second further moiety is expected to be present in a predefined amount such that the value of the second detection signal (14′) falls within an expected signal value window when the binding reaction of the second further moiety to the second moiety takes place as expected. An apparatus comprising such a sensor device, methods of operating the sensor device and apparatus and a sample for use with the sensor device are also disclosed.
摘要翻译：公开了一种用于检测样品中目标分子（20）的存在的传感器装置（1）。所述传感器装置包括测量传感器（2），所述测量传感器（2）包括用于与包含所述目标分子（20）和可检测标记（40）的第一另外部分形成结合对的第一部分（16）和包括用于与包含另外可检测标记物（40'）的第二另外部分形成另外的结合对的第二部分（50）。所述传感器装置适于从与所述第一部分（16）结合的所述第一另外部分中的所述可检测标记（40）的检测产生第一检测信号（14），并且从所述第一检测信号（14'）产生来自所述第一检测信号在第二另外部分结合到第二部分（50）上的另外可检测标记物（40'）的检测，其中至少在传感器装置的操作期间预期第二另外的部分以预定量存在，使得值当第二另外部分与第二部分的结合反应按预期进行时，第二检测信号（14'）落入预期信号值窗口内。还公开了一种包括这种传感器装置的装置，操作传感器装置和装置的方法以及与传感器装置一起使用的样本。

2. 发明申请

US20120107961A1 MAGNETIC SENSOR DEVICE, METHOD OF OPERATING SUCH A DEVICE AND SAMPLE 有权
标题翻译：磁传感器装置，操作这种装置和样品的方法
公开(公告)号：US20120107961A1
公开(公告)日：2012-05-03
申请号：US13381115
申请日：2010-06-24
申请人： Wendy Uyen Dittmer , Femke Karina De Theije , Albert Hendrik Jan Immink , Jeroen Hans Nieuwenhuis , Petrus Johannes Wilhelmus Van Lankvelt
发明人： Wendy Uyen Dittmer , Femke Karina De Theije , Albert Hendrik Jan Immink , Jeroen Hans Nieuwenhuis , Petrus Johannes Wilhelmus Van Lankvelt
IPC分类号： G01N33/566 , G01N30/00
CPC分类号： G01N33/54326 , G01N21/552 , G01N27/745 , G01N33/54366 , G01N33/54386
摘要： A sensor device (1) for detecting the presence of a target molecule (20) in a sample, is disclosed. The sensor device comprises a measurement sensor (2) comprising a first moiety (16) for forming a binding couple with a first further moiety comprising the target molecule (20) and a detectable label (40) and a reference sensor (3) comprising a second moiety (50) for forming a further binding couple with a second further moiety comprising a further detectable label (40′). The sensor device is adapted to generate a first detection signal (14) from the detection of the detectable label (40) in the first further moiety bound to the first moiety (16) and to generate a second detection signal (14′) from the detection of the further detectable label (40′) in the second further moiety bound to the second moiety (50), wherein at least during operation of the sensor device the second further moiety is expected to be present in a predefined amount such that the value of the second detection signal (14′) falls within an expected signal value window when the binding reaction of the second further moiety to the second moiety takes place as expected. An apparatus comprising such a sensor device, methods of operating the sensor device and apparatus and a sample for use with the sensor device are also disclosed.
摘要翻译：公开了一种用于检测样品中目标分子（20）的存在的传感器装置（1）。所述传感器装置包括测量传感器（2），所述测量传感器（2）包括用于与包含所述目标分子（20）和可检测标记（40）的第一另外部分形成结合对的第一部分（16）和包括用于与包含另外可检测标记物（40'）的第二另外部分形成另外的结合对的第二部分（50）。所述传感器装置适于从与所述第一部分（16）结合的所述第一另外部分中的所述可检测标记（40）的检测产生第一检测信号（14），并且从所述第一检测信号（14'）产生来自所述第一检测信号在第二另外部分结合到第二部分（50）上的另外可检测标记物（40'）的检测，其中至少在传感器装置的操作期间预期第二另外的部分以预定量存在，使得值当第二另外部分与第二部分的结合反应按预期进行时，第二检测信号（14'）落入预期信号值窗口内。还公开了一种包括这种传感器装置的装置，操作传感器装置和装置的方法以及与传感器装置一起使用的样本。

3. 发明申请

US20100289483A1 SENSOR CARTRIDGE 审中-公开
标题翻译：传感器盒
公开(公告)号：US20100289483A1
公开(公告)日：2010-11-18
申请号：US12669218
申请日：2008-07-16
申请人： Albert Hendrik Jan Immink , Femke Karina De Theije , Menno Willem Jose Prins , Wendy Uyen Dittmer , Jeroen Hans Nieuwenhuis
发明人： Albert Hendrik Jan Immink , Femke Karina De Theije , Menno Willem Jose Prins , Wendy Uyen Dittmer , Jeroen Hans Nieuwenhuis
IPC分类号： G01N27/74
CPC分类号： G01R33/1269
摘要： The present invention provides a sensor cartridge (10) for distinctively determining at least two different target moieties in a fluid sample. The sensor cartridge (10) comprises a reaction chamber (1) and at least a first and second region (2, 3) distinct from each other. The first region (2) comprises magnetic or magnetizable objects (4a) labelled with a first type of probes for specifically binding a first type of target moieties and the second region (3) comprises magnetic or magnetizable objects (4b) labelled with a second type of probes for specifically binding a second type of target moieties, the magnetic or magnetizable objects (4a, 4b) in the first and second region (2, 3) being directly contactable by the sample fluid. The present invention also provides a method for the manufacturing of such sensor devices (10) and a method for determining the presence and/or amount of at least two different target moieties in a sample fluid using such sensor cartridge (10).
摘要翻译：本发明提供一种用于区别地确定流体样品中至少两个不同靶部分的传感器盒（10）。传感器盒（10）包括反应室（1）和至少彼此不同的第一和第二区域（2,3）。第一区域（2）包括用第一类型的探针标记的磁性或可磁化物体（4a），用于特异性地结合第一类型的靶部分，并且第二区域（3）包括用第二类型标记的磁性或可磁化物体（4b）的用于特异性结合第二类型的靶部分的探针，第一和第二区域（2,3）中的磁性或可磁化物体（4a，4b）可由样品流体直接接触。本发明还提供了用于制造这种传感器装置（10）的方法以及使用这种传感器盒（10）确定样品流体中至少两种不同靶部分的存在和/或量的方法。

4. 发明申请

US20110014719A1 CARTRIDGE FOR ASSAYS WITH MAGNETIC PARTICLES 审中-公开
标题翻译：用于磁性颗粒测定的盒子
公开(公告)号：US20110014719A1
公开(公告)日：2011-01-20
申请号：US12922887
申请日：2009-03-11
申请人： Mara Johanna Jacoba Sijbers , Petrus Johannes Wilhelmus Van Lankvelt , Femke Karina De Theije , Jeroen Hans Nieuwenhuis
发明人： Mara Johanna Jacoba Sijbers , Petrus Johannes Wilhelmus Van Lankvelt , Femke Karina De Theije , Jeroen Hans Nieuwenhuis
IPC分类号： G01N27/00 , G01N21/00 , G01N25/00
CPC分类号： G01N33/54333 , B03C1/282 , B03C1/288 , B03C2201/18 , B03C2201/26 , G01N27/745 , G01N33/54373 , G01N33/946 , G01N33/948 , G01N33/9486
摘要： The invention relates to a cartridge (100) and a corresponding sensor device for the detection of target components in a liquid sample. The cartridge (100) comprises a sample chamber(SC), at least two reservoirs(131, 132) that can be furnished with magnetic particles(MP, MP′), and at least two corresponding sensitive zones (121, 122) in which solved magnetic particles and/or target components can be detected. When a magnetic actuation field(B) of a given configuration is established in the sample chamber, the magnetic particles of different reservoirs migrate predominantly to different sensitive zones. Thus a mixing of magnetic particles can be avoided.
摘要翻译：本发明涉及一种用于检测液体样品中的目标组分的盒（100）和相应的传感器装置。盒（100）包括样品室（SC），至少两个可以配备有磁性颗粒（MP，MP'）和至少两个对应的敏感区域（121,122）的储存器（131,132），其中可以检测到溶解的磁性颗粒和/或目标成分。当在样品室中建立给定构造的磁致动场（B）时，不同储层的磁性颗粒主要迁移到不同的敏感区域。因此，可以避免磁性颗粒的混合。

5. 发明申请

US20100233824A1 MICROFLUIDIC METHODS AND SYSTEMS FOR USE IN DETECTING ANALYTES 审中-公开
标题翻译：用于检测分析的微流感方法和系统
公开(公告)号：US20100233824A1
公开(公告)日：2010-09-16
申请号：US12669213
申请日：2008-07-11
申请人： Godefridus Johannes Verhoeckx , Henkrik Sibolt Van Damme , Jeroen Hans Nieuwenhuis , Sergei Shulepov , Johannes Wilhelmus Weekamp , Mara Johanna Jacoba Sijbers , Harold Johannes Antonius Brans , Femke Karina De Theije , Albert Hendrik Jan Immink
发明人： Godefridus Johannes Verhoeckx , Henkrik Sibolt Van Damme , Jeroen Hans Nieuwenhuis , Sergei Shulepov , Johannes Wilhelmus Weekamp , Mara Johanna Jacoba Sijbers , Harold Johannes Antonius Brans , Femke Karina De Theije , Albert Hendrik Jan Immink
IPC分类号： G01N33/53 , G01N33/00 , B23P17/04
CPC分类号： B01L3/502715 , B01L2200/12 , B01L2200/16 , B01L2300/0627 , B01L2300/0636 , B01L2300/161 , B01L2400/0406 , B01L2400/0487 , Y10T29/49826
摘要： A microfluidic reactor arrangement (100) for use in detecting an analyte in a fluid sample (106) is described. The reactor arrangement is provided with a reagent providing means such that the reagent can be introduced after assembly of the reactor arrangement. The latter can be performed by introducing the reagent in the form of a solution or a dispersion and fixing it on a holding means (118) by removal of the liquid, i.e. by drying, the holding means comprising the reagent in a solid version in the detector chamber. Prior to the introduction of the reagent, components of the reactor arrangement already present, such as the sample inlet can be hydrophilised by a wetting hydrophilising technique. The invention relates to a manufacturing technique as well as to the resulting product. The invention furthermore relates to functionalizing of the reactor arrangement with a particular reagent for particular applications. The latter can be performed well after fabrication and assembly of the major reactor arrangement components.
摘要翻译：描述了用于检测流体样品（106）中的分析物的微流体反应器装置（100）。反应器装置设置有试剂提供装置，使得可以在组装反应器装置之后引入试剂。后者可以通过将试剂以溶液或分散体的形式引入并通过除去液体将其固定在保持装置（118）上来进行，即通过干燥包含试剂的固定装置以固体形式在检测器室。在引入试剂之前，已经存在的反应器装置的组分（例如样品入口）可以通过润湿亲水化技术亲水化。本发明涉及制造技术以及所得到的产品。本发明还涉及用于特定应用的具有特定试剂的反应器装置的功能化。后者可以在主要反应器布置部件的制造和组装之后很好地进行。

6. 发明申请

US20110050215A1 SYSTEM FOR APPLYING MAGNETIC FORCES TO A BIOSENSOR SURFACE BY MECHANICALLY MOVING AT LEAST ONE MAGNET 审中-公开
标题翻译：通过机械移动至少一个磁体将磁力施加到生物传感器表面的系统
公开(公告)号：US20110050215A1
公开(公告)日：2011-03-03
申请号：US12517863
申请日：2007-12-07
申请人： Josephus Arnoldus Henricus Maria Kahlmann , Albert Hendrik Jan Immink , Jeroen Hans Jeroen , Thea Van Der Wijk , Femke Karina De Theije
发明人： Josephus Arnoldus Henricus Maria Kahlmann , Albert Hendrik Jan Immink , Jeroen Hans Jeroen , Thea Van Der Wijk , Femke Karina De Theije
IPC分类号： G01R33/02
CPC分类号： G01N27/745 , G01N33/54333 , G01N35/0098 , H01F7/0273
摘要： A magnetic system for biosensors or a biosystem, wherein magnetic particles that interact with molecules are brought into a magnetic field, in order to be influenced via magnetic attraction or repulsion forces. The external magnetic field is varied by mechanically moving the magnetic poles of at least one magnetic relative to the sensor or at least its surface to allow the magnetic force to be switched between effective attraction towards the sensor surface and effective repulsion away from the sensor surface.
摘要翻译：用于生物传感器或生物系统的磁系统，其中与分子相互作用的磁性颗粒进入磁场，以便通过磁吸引力或排斥力影响。外部磁场通过相对于传感器或至少其表面机械地移动至少一个磁体的磁极来改变，以允许在对传感器表面的有效吸引力和远离传感器表面的有效排斥之间切换磁力。

7. 发明申请

US20100297780A1 METHODS AND SYSTEMS FOR DETECTING 有权
标题翻译：检测方法和系统
公开(公告)号：US20100297780A1
公开(公告)日：2010-11-25
申请号：US12669217
申请日：2008-07-18
申请人： Femke Karina De Theije , Thea Van Der Wijk , Albert Hendrik Jan Immink , Eduard Gerard Marie Pelssers , Wilhelmina Maria Hardeman , Sandra Marlin , Gordon Thomas Jowett
发明人： Femke Karina De Theije , Thea Van Der Wijk , Albert Hendrik Jan Immink , Eduard Gerard Marie Pelssers , Wilhelmina Maria Hardeman , Sandra Marlin , Gordon Thomas Jowett
IPC分类号： G01N33/553 , G01N30/96 , B23P25/00
CPC分类号： G01N33/54366 , G01N27/745 , Y10T29/49885
摘要： A system and method is described wherein components of the reagent (4), e.g. labelled antibodies, are separated from the biologically active sensor surface (5) by depositing the reagent (4) on a carrier surface (3) distinct from the sensor surface (5) in the detection region (2), e.g. detection chamber. In this way, a high assay reproducibility is obtained. By allowing a short, well-defined and controlled, pre-incubation time between the particles of interest, e.g. drugs, in the sample fluid (20) and the reagent (4), the reproducibility will be increased, whereas the speed of the assay is guaranteed by having all components in one detection region (2), e.g. detection chamber.
摘要翻译：描述了一种系统和方法，其中试剂（4）的组分例如。通过将试剂（4）沉积在与检测区域（2）中的传感器表面（5）不同的载体表面（3）上，例如从生物活性传感器表面（5）分离。检测室。以这种方式，获得高的测定重现性。通过在感兴趣的颗粒之间允许短的，明确的和受控的预孵育时间，例如。药物在样品液体（20）和试剂（4）中的重现性将会增加，而测定的速度则通过在一个检测区域（2）中具有所有成分来保证。检测室。

8. 发明申请

US20100092996A1 MICROELECTRONIC SENSOR DEVICE FOR DETECTING LABEL PARTICLES 有权
标题翻译：用于检测标签颗粒的微电子传感器装置
公开(公告)号：US20100092996A1
公开(公告)日：2010-04-15
申请号：US12518164
申请日：2007-12-10
申请人： Coen Adrianus Verschuren , Dominique Maria Bruls , Albert Hendrik Jan Immink , Femke Karina De Theije , Thea Van Der Wijk , Alexander Marc Van Der Lee , Johannes Joseph Hubertina Barbara Schleipen
发明人： Coen Adrianus Verschuren , Dominique Maria Bruls , Albert Hendrik Jan Immink , Femke Karina De Theije , Thea Van Der Wijk , Alexander Marc Van Der Lee , Johannes Joseph Hubertina Barbara Schleipen
IPC分类号： G01N33/53 , C12M1/34
CPC分类号： G01N33/543 , G01N21/552 , G01N21/553 , G01N21/6428 , G01N21/6452 , G01N21/648 , G01N27/745 , G01N33/54306 , G01N33/54386 , Y10S436/00
摘要： The invention relates to a microelectronic sensor device for the detection of target components that comprise label particles, for example magnetic particles (1). The sensor device comprises a carrier (11) with a binding surface (12) at which target components can collect and optionally bind to specific capture elements. An input light beam (L1) is transmitted into the carrier and totally internally reflected at the binding surface (12). The amount of light in the output light beam (L2) and optionally also of fluorescence light emitted by target components at the binding surface is then detected by a light detector (31). Evanescent light generated during the total internal reflection is affected (absorbed, scattered) by target components and/or label particles (1) at the binding surface (12) and will therefore be missing in the output light beam (L2). This can be used to determine the amount of target components at the binding surface (12) from the amount of light in the output light beam (L2, L2a, L2b). A magnetic field generator (41) is optionally used to generate a magnetic field (B) at the binding surface (12) by which magnetic label particles (1) can be manipulated, for example 15 attracted or repelled.
摘要翻译：本发明涉及用于检测包含标签颗粒（例如磁性颗粒（1））的目标组分的微电子传感器装置。传感器装置包括具有结合表面（12）的载体（11），靶组分可以收集并任选地结合到特定的捕获元件。输入光束（L1）被传输到载体中并在结合表面（12）处全反射。由光检测器（31）检测输出光束（L2）中的光量以及可选地由结合表面上的目标成分发出的荧光。在全内反射期间产生的渐消光在目标部件和/或粘合表面（12）处的标签颗粒（1）受到影响（吸收，散射），因此在输出光束（L2）中将被丢失。这可以用于根据输出光束（L2，L2a，L2b）中的光量来确定结合表面（12）处的目标成分的量。可选地使用磁场发生器（41）来在绑定表面（12）处产生磁场（B），通过该磁场可以操纵磁性标签颗粒（1），例如15被吸引或排斥。

9. 发明授权

US09658219B2 Microelectronic sensor device for detecting label particles 有权
公开(公告)号：US09658219B2
公开(公告)日：2017-05-23
申请号：US12518164
申请日：2007-12-10
申请人： Coen Adrianus Verschuren , Dominique Maria Bruls , Albert Hendrik Jan Immink , Femke Karina De Theije , Thea Van Der Wijk , Alexander Marc Van Der Lee , Johannes Joseph Hubertina Barbara Schleipen
发明人： Coen Adrianus Verschuren , Dominique Maria Bruls , Albert Hendrik Jan Immink , Femke Karina De Theije , Thea Van Der Wijk , Alexander Marc Van Der Lee , Johannes Joseph Hubertina Barbara Schleipen
IPC分类号： G01N21/552 , G01N21/64 , G01N33/543 , G01N27/74 , G01N21/39
CPC分类号： G01N33/543 , G01N21/552 , G01N21/553 , G01N21/6428 , G01N21/6452 , G01N21/648 , G01N27/745 , G01N33/54306 , G01N33/54386 , Y10S436/00
摘要： A microelectronic sensor device for the detection of target components with label or magnetic particles includes a carrier with a binding surface at which target components can collect and optionally bind to specific capture elements. An input light beam is transmitted into the carrier and totally internally reflected at the binding surface. The amount of light in the output light beam is detected by a light detector. Evanescent light generated during the total internal reflection is affected by target components and/or label particles at the binding surface and will be missing in the output light beam. This is used to determine the amount of target components at the binding surface from the amount of light in the output light beam. A magnetic field generator is optionally used to generate a magnetic field at the binding surface by which magnetic label particles can be manipulated, such as attracted or repelled.

10. 发明申请

US20100253323A1 MAGNETIC WASHING FOR BIOSENSOR 审中-公开
标题翻译：生物传感器的磁性清洗
公开(公告)号：US20100253323A1
公开(公告)日：2010-10-07
申请号：US12746182
申请日：2008-12-04
申请人： Femke Karina De Theije , Dominique Maria Bruls , Thea Van Der Wijk , Coen Adrianus Verschuren , Albert Hendrik Jan Immink
发明人： Femke Karina De Theije , Dominique Maria Bruls , Thea Van Der Wijk , Coen Adrianus Verschuren , Albert Hendrik Jan Immink
IPC分类号： G01N27/74
CPC分类号： G01N33/54326 , G01N21/552 , G01N21/648 , G01N27/745
摘要： Detecting magnetized or magnetizable target components in a fluid containing the magnetized or magnetizable target components amongst other magnetized or magnetizable components, uses a magnetic field generator (M1, 28) to attract the magnetized or magnetizable components towards a binding surface. A magnetic field controller (C1) applies the magnetic field to concentrate the magnetized or magnetizable components in columns on the binding surface, subsequently reduces the magnetic field to enable the columns to collapse, to allow more components to reach the binding surface, and reapplies the magnetic field so as to cause other components to be pulled off the binding surface to reform columns based on the bound target components. A surface sensitive sensor (S1, 26, 29) detects the bound magnetized or magnetizable target components. The reapplication of the magnetic field acts as a magnetic washing step to release unwanted aspecific adsorption binding, leaving the targets, to improve sensitivity with simplified hardware and a reduction in cost and size.
摘要翻译：检测包含磁化或可磁化的目标部件的流体中的磁化或可磁化的目标部件在其他磁化或可磁化部件之间，使用磁场发生器（M1,28）将磁化或可磁化的部件吸引到装订表面。磁场控制器（C1）施加磁场以将磁化的或可磁化的组件在列中集中在结合表面上，随后减小磁场以使柱能够塌陷，以允许更多的部件到达结合表面，并重新应用磁场，以便使其他组分从结合表面上拉出，以便根据结合的目标组分重新制备柱。表面敏感传感器（S1,26,29）检测结合的磁化或可磁化的目标部件。磁场的重新应用充当磁性洗涤步骤以释放不期望的特异性吸附结合，留下目标，以通过简化的硬件提高灵敏度并降低成本和尺寸。

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