公开(公告)号：US08486689B2

公开(公告)日：2013-07-16

申请号：US12747529

申请日：2008-10-31

申请人： Dominique Maria Bruls ,  Johannes Joseph Hubertina Barbara Schleipen ,  Josephus Arnoldus Henricus Maria Kahlman ,  Menno Willem Jose Prins

发明人： Dominique Maria Bruls ,  Johannes Joseph Hubertina Barbara Schleipen ,  Josephus Arnoldus Henricus Maria Kahlman ,  Menno Willem Jose Prins

IPC分类号： C12M1/00

CPC分类号： G01N21/1717 ,  G01N21/552 ,  G01N21/648 ,  G01N2021/1721 ,  G01N2021/1727 ,  G01N2201/0691

摘要： The invention relates to a microelectronic sensor device for the examination of target particles (1) that are bound to binding sites (3) at the binding surface (12) of a carrier (11). In a preferred embodiment, an input light beam (L1) is transmitted into the carrier (11), where a frustrated total internal reflection (FTIR) takes place at the binding surface (12). The amount of light in a resulting output light beam (L2) is detected by a light detector (31) and provides information about the presence of target particles at the binding surface. Moreover, an actuation unit (50) induces movements of the bound target particles (1) by an interaction with a magnetic field (B) or an electric field, particularly with a given modulation frequency (COIn), such that by a demodulation of the detector signal (S) effects of the target particles can be distinguished from background.

摘要翻译： 本发明涉及一种用于检查在载体（11）的结合表面（12）处结合到结合位点（3）的靶颗粒（1）的微电子传感器装置。 在优选实施例中，输入光束（L1）被传输到载体（11）中，其中在结合表面（12）处发生挫败的全内反射（FTIR）。 通过光检测器（31）检测所得到的输出光束（L2）中的光量，并提供关于在结合表面处存在目标颗粒的信息。 此外，致动单元（50）通过与磁场（B）或电场的相互作用（特别是给定的调制频率（COIn））的相互作用来诱导结合的目标颗粒（1）的运动，使得通过解调 目标颗粒的检测器信号（S）效应可以与背景区分开。

公开(公告)号：US20100267165A1

公开(公告)日：2010-10-21

申请号：US12747529

申请日：2008-10-31

申请人： Dominique Maria Bruls ,  Johannes Joseph Hubertina Barbara Schleipen ,  Josephus Arnoldus Henricus Maria Kahlman ,  Menno Willem Jose Prins

发明人： Dominique Maria Bruls ,  Johannes Joseph Hubertina Barbara Schleipen ,  Josephus Arnoldus Henricus Maria Kahlman ,  Menno Willem Jose Prins

IPC分类号： G01N33/53

CPC分类号： G01N21/1717 ,  G01N21/552 ,  G01N21/648 ,  G01N2021/1721 ,  G01N2021/1727 ,  G01N2201/0691

摘要： The invention relates to a microelectronic sensor device for the examination of target particles (1) that are bound to binding sites (3) at the binding surface (12) of a carrier (11). In a preferred embodiment, an input light beam (L1) is transmitted into the carrier (11), where a frustrated total internal reflection (FTIR) takes place at the binding surface (12). The amount of light in a resulting output light beam (L2) is detected by a light detector (31) and provides information about the presence of target particles at the binding surface. Moreover, an actuation unit (50) induces movements of the bound target particles (1) by an interaction with a magnetic field (B) or an electric field, particularly with a given modulation frequency (COIn), such that by a demodulation of the detector signal (S) effects of the target particles can be distinguished from background.

摘要翻译： 本发明涉及一种用于检查在载体（11）的结合表面（12）处结合到结合位点（3）的靶颗粒（1）的微电子传感器装置。 在优选实施例中，输入光束（L1）被传输到载体（11）中，其中在结合表面（12）处发生挫败的全内反射（FTIR）。 通过光检测器（31）检测所得到的输出光束（L2）中的光量，并提供关于在结合表面处存在目标颗粒的信息。 此外，致动单元（50）通过与磁场（B）或电场的相互作用（特别是给定的调制频率（COIn））的相互作用来诱导结合的目标颗粒（1）的运动，使得通过解调 目标颗粒的检测器信号（S）效应可以与背景区分开。

公开(公告)号：US20100290052A1

公开(公告)日：2010-11-18

申请号：US12810867

申请日：2008-12-18

申请人： Johannes Joseph Hubertina Barbara Schleipen ,  Dominique Maria Bruls ,  Josephus Arnoldus Henricus Maria Kahlman

发明人： Johannes Joseph Hubertina Barbara Schleipen ,  Dominique Maria Bruls ,  Josephus Arnoldus Henricus Maria Kahlman

IPC分类号： G01N21/55

CPC分类号： G01N21/552

摘要： The present invention provides an FTIR system comprising a first light source emitting light of a first wavelength, a sample volume with an adjacent sensor surface, a detector for detecting light reflected at said sensor surface. The sensor surface is illuminated by said first light source fulfilling the condition of total internal reflection and generating an evanescent field with a decay length within the sample volume. The system further comprises means for changing the decay length of the evanescent field and means for correlating the detected signals with the change of the decay length of the evanescent field.

摘要翻译： 本发明提供了一种FTIR系统，包括发射第一波长的光的第一光源，具有相邻传感器表面的样品体积，用于检测在所述传感器表面反射的光的检测器。 所述传感器表面由满足全内反射条件的所述第一光源照射，并产生具有在样品体积内的衰减长度的ev逝场。 该系统还包括用于改变ev逝场的衰减长度的装置和用于使检测到的信号与ev逝场的衰减长度变化相关联的装置。

公开(公告)号：US09075052B2

公开(公告)日：2015-07-07

申请号：US13498482

申请日：2010-09-23

申请人： Johannes Joseph Hubertina Barbara Schleipen ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Josephus Arnoldus Henricus Maria Kahlman ,  Ron Martinus Laurentius Van Lieshout ,  Mikhail Mikhaylovich Ovsyanko

发明人： Johannes Joseph Hubertina Barbara Schleipen ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Josephus Arnoldus Henricus Maria Kahlman ,  Ron Martinus Laurentius Van Lieshout ,  Mikhail Mikhaylovich Ovsyanko

IPC分类号： G01N21/00 ,  G01N33/543 ,  G01N21/47 ,  G01N21/552 ,  G01N21/64 ,  G01R33/12 ,  G01N21/51 ,  G01N21/49 ,  G01N27/72 ,  G01N15/10 ,  G01N15/00

CPC分类号： G01N33/54373 ,  G01N15/10 ,  G01N15/1031 ,  G01N21/47 ,  G01N21/49 ,  G01N21/51 ,  G01N21/552 ,  G01N21/6458 ,  G01N27/72 ,  G01N33/54313 ,  G01N2015/0065 ,  G01N2201/12 ,  G01R33/1269

摘要： A biosensor system for the detection of particles includes a biosensor cartridge having a sensor surface. A biosensor magnet assembly is disposed on one side of the cartridge for generating a magnetic field effective at the cartridge and the sensor surface. The biosensor magnet assembly includes at least two magnetic sub-units separated by a gap. A first optical detection system detects the particles arranged at the same side of the cartridge as the magnet assembly. The magnet assembly and the first optical sensor are disposed such that the optical detection is accomplished through the gap of the magnet assembly.

摘要翻译： 用于检测颗粒的生物传感器系统包括具有传感器表面的生物传感器盒。 生物传感器磁体组件设置在盒的一侧，用于在盒和传感器表面产生有效的磁场。 生物传感器磁体组件包括由间隙分开的至少两个磁性子单元。 第一光学检测系统检测与磁体组件布置在盒的同一侧的颗粒。 磁体组件和第一光学传感器被布置成使得通过磁体组件的间隙实现光学检测。

公开(公告)号：US20120250005A1

公开(公告)日：2012-10-04

申请号：US13498482

申请日：2010-09-23

申请人： Johannes Joseph Hubertina Barbara Schleipen ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Josephus Arnoldus Henricus Maria Kahlman ,  Ron Martinus Laurentius Van Lieshout ,  Mikhail Mikhaylovich Ovsyanko

发明人： Johannes Joseph Hubertina Barbara Schleipen ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Josephus Arnoldus Henricus Maria Kahlman ,  Ron Martinus Laurentius Van Lieshout ,  Mikhail Mikhaylovich Ovsyanko

IPC分类号： G01N21/49 ,  G01R33/12

CPC分类号： G01N33/54373 ,  G01N15/10 ,  G01N15/1031 ,  G01N21/47 ,  G01N21/49 ,  G01N21/51 ,  G01N21/552 ,  G01N21/6458 ,  G01N27/72 ,  G01N33/54313 ,  G01N2015/0065 ,  G01N2201/12 ,  G01R33/1269

摘要： The present invention is related to a biosensor system for the detection of particles comprising: a biosensor cartridge comprising a sensor surface, a biosensor magnet assembly on one side of the cartridge for generating a magnetic field effective at the cartridge and the sensor surface, the first biosensor magnet assembly comprising at least two magnetic sub-units separated by a gap, a first optical detection system for detecting the particles arranged at the same side of the cartridge as the magnet assembly, whereas the magnet assembly is designed in a way that the optical detection is accomplished through the gap of the magnet assembly.

摘要翻译： 本发明涉及一种用于检测颗粒的生物传感器系统，包括：生物传感器盒，包括传感器表面，在盒的一侧上的生物传感器磁体组件，用于产生在盒和感测器表面有效的磁场;第一 生物传感器磁体组件，其包括由间隙分隔开的至少两个磁性子单元;第一光学检测系统，用于检测与磁体组件位于盒的同一侧的颗粒，而磁体组件设计成使得光学 通过磁体组件的间隙实现检测。

公开(公告)号：US09339813B2

公开(公告)日：2016-05-17

申请号：US13516060

申请日：2010-12-10

申请人： Josephus Arnoldus Henricus Maria Kahlman ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Johannes Joseph Hubertina Barbara Schleipen ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Ron Martinus Laurentius Van Lieshout

发明人： Josephus Arnoldus Henricus Maria Kahlman ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Johannes Joseph Hubertina Barbara Schleipen ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Ron Martinus Laurentius Van Lieshout

IPC分类号： G01N21/17 ,  B01L3/00 ,  G01N21/552 ,  G01N21/84 ,  G01N33/543

CPC分类号： B01L3/5027 ,  B01L2200/0605 ,  B01L2300/0636 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2400/0406 ,  G01N21/552 ,  G01N21/8483 ,  G01N33/54373

摘要： The invention relates to a substance determining apparatus for determining a substance within a fluid. Particles attach the substance and bind to a binding surface (30), wherein a sensing signal is generated depending on the bound particles. Binding events indicating a binding of a particle on the binding surface (30) are determined from the generated sensing signal, and the substance within the fluid is determined based on the determined binding events. During a procedure of determining a substance within a fluid, particles may bind to the binding surface and may leave the binding surface. Therefore, during this procedure a number of binding events can be determined being much larger than the number of bound particles. The determination of the substance within the fluid can therefore be based on a very large amount of data, thereby increasing the accuracy of determining the substance within the fluid.

摘要翻译： 本发明涉及一种用于确定流体内物质的物质确定装置。 颗粒附着物质并结合到结合表面（30），其中根据结合的颗粒产生感测信号。 根据产生的感测信号确定指示结合表面（30）上的颗粒结合的结合事件，并且基于所确定的结合事件确定流体内的物质。 在确定流体内的物质的过程中，颗粒可能结合到结合表面并且可能离开结合表面。 因此，在此过程中，可以确定许多结合事件比结合粒子的数量大得多。 因此，流体内的物质的测定可以基于非常大量的数据，从而提高确定流体内物质的准确性。

公开(公告)号：US20120329039A1

公开(公告)日：2012-12-27

申请号：US13516060

申请日：2010-12-10

申请人： Josephus Arnoldus Henricus Maria Kahlman ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Johannes Joseph Hubertina Barbara Schleipen ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Ron Martinus Laurentius Van Lieshout

发明人： Josephus Arnoldus Henricus Maria Kahlman ,  Joannes Baptist Adrianus Dionisius Van Zon ,  Johannes Joseph Hubertina Barbara Schleipen ,  Derk Jan Wilfred Klunder ,  Toon Hendrik Evers ,  Ron Martinus Laurentius Van Lieshout

IPC分类号： G01N33/566 ,  C12M1/34 ,  C12Q1/70 ,  G01N30/00 ,  G01N33/53

CPC分类号： B01L3/5027 ,  B01L2200/0605 ,  B01L2300/0636 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2400/0406 ,  G01N21/552 ,  G01N21/8483 ,  G01N33/54373

摘要： The invention relates to a substance determining apparatus for determining a substance within a fluid. Particles attach the substance and bind to a binding surface (30), wherein a sensing signal is generated depending on the bound particles. Binding events indicating a binding of a particle on the binding surface (30) are determined from the generated sensing signal, and the substance within the fluid is determined based on the determined binding events. During a procedure of determining a substance within a fluid, particles may bind to the binding surface and may leave the binding surface. Therefore, during this procedure a number of binding events can be determined being much larger than the number of bound particles. The determination of the substance within the fluid can therefore be based on a very large amount of data, thereby increasing the accuracy of determining the substance within the fluid.

摘要翻译： 本发明涉及一种用于确定流体内物质的物质确定装置。 颗粒附着物质并结合到结合表面（30），其中根据结合的颗粒产生感测信号。 根据产生的感测信号确定指示结合表面（30）上的颗粒结合的结合事件，并且基于所确定的结合事件确定流体内的物质。 在确定流体内的物质的过程中，颗粒可能结合到结合表面并且可能离开结合表面。 因此，在此过程中，可以确定许多结合事件比结合粒子的数量大得多。 因此，流体内的物质的测定可以基于非常大量的数据，从而提高确定流体内物质的准确性。

公开(公告)号：US07892817B2

公开(公告)日：2011-02-22

申请号：US11569084

申请日：2005-05-13

申请人： Menno Willem Jose Prins ,  Martinus Barnardus Van Der Mark ,  Paulus Cornelis Duineveld ,  Mischa Megens ,  Josephus Arnoldus Henricus Maria Kahlman

发明人： Menno Willem Jose Prins ,  Martinus Barnardus Van Der Mark ,  Paulus Cornelis Duineveld ,  Mischa Megens ,  Josephus Arnoldus Henricus Maria Kahlman

IPC分类号： C12M3/00

CPC分类号： G01N33/54373 ,  B82Y5/00 ,  B82Y25/00 ,  G01N27/745

摘要： A method and a device are provided for distinguishing a specific binding from a less specific binding between at least one magnetic nanoparticle and a surface of another entity by applying a magnetic field and detecting a physical parameter relating to magnetic nanoparticle rotational or motional freedom while the magnetic nanoparticle is attached to the surface. The method and device may be applied to in-vivo and in-vitro biomolecular diagnostics. The sensor combines in one sensor the detection of magnetic particles or labels and determination of the binding quality and the properties of magnetic particles or labels which are bound to the surface of another entity.

摘要翻译： 提供了一种方法和装置，用于通过施加磁场和检测与磁性纳米颗粒旋转或运动自由相关的物理参数来区分特定结合与至少一个磁性纳米颗粒与另一个实体的表面之间的较小特异性结合，同时磁性 纳米颗粒附着在表面。 该方法和装置可以应用于体内和体外生物分子诊断。 该传感器将一个传感器结合在一起，检测磁性颗粒或标签，并确定结合质量以及结合到另一个实体表面的磁性颗粒或标签的性质。

公开(公告)号：US20090251136A1

公开(公告)日：2009-10-08

申请号：US12373740

申请日：2007-06-06

申请人： Menno Willem Jose Prins ,  Josephus Arnoldus Henricus Maria Kahlman

发明人： Menno Willem Jose Prins ,  Josephus Arnoldus Henricus Maria Kahlman

IPC分类号： G01R33/12 ,  H01H47/00

CPC分类号： G01N15/0656 ,  B82Y25/00 ,  G01N27/745 ,  G01R33/093 ,  G01R33/12 ,  G01R33/1269

摘要： The present invention provides a magnetic sensor device a first magnetic field generating means (21a, 21b) for attracting magnetic or magnetizable objects (22), e.g. magnetic particles, to a sensor surface (23) and a second magnetic field generating means (25) for, in combination with the first magnetic field, repelling magnetic or magnetizable objects (22), e.g. magnetic particles, from the sensor surface (23). The magnetic fields generated by the first and second magnetic field generating means have substantially anti-parallel directions. The present invention furthermore provides a method for attracting and repelling magnetic or magnetizable objects (22), e.g. magnetic particles, to and from a sensor surface (23).

摘要翻译： 本发明提供一种磁传感器装置，用于吸引磁性或可磁化物体（22）的第一磁场产生装置（21a，21b） 传感器表面（23）和第二磁场产生装置（25），用于与第一磁场结合，排斥磁性或可磁化物体（22），例如磁性颗粒。 磁性颗粒，来自传感器表面（23）。 由第一和第二磁场产生装置产生的磁场具有大致反平行的方向。 本发明还提供了一种用于吸引和排斥磁性或可磁化物体（22）的方法，例如， 磁性颗粒，传送到传感器表面（23）。

公开(公告)号：US20080309329A1

公开(公告)日：2008-12-18

申请号：US10597639

申请日：2004-07-29

申请人： Josephus Arnoldus Henricus Maria Kahlman ,  Bart Michiel De Boer ,  Menno Willem Jose Prins

发明人： Josephus Arnoldus Henricus Maria Kahlman ,  Bart Michiel De Boer ,  Menno Willem Jose Prins

IPC分类号： G01R33/12

CPC分类号： G01R33/12 ,  G01N27/745 ,  G01R33/1269

摘要： A magnetic sensor device is disclosed for the detection or determination of a magnetic field, such as for example, but not limited to, the presence of magnetic particles (15). In particular it relates to an integrated or on-chip magnetic sensor element (11) for the detection of magnetic nano-particles functioning as a label to biological molecules. The device of the present invention offers reduced cross-talk between the magnetic sensor element (11) and a magnetic field generator (12) by compensating capacitive and/or magnetic coupling for instance by using an electrostatic shield and/or modulation and demodulation techniques. The device may be used for magnetic detection of binding of biological molecules on a micro-array or biochip.

摘要翻译： 公开了用于检测或确定磁场的磁传感器装置，例如但不限于存在磁性颗粒（15）。 特别地，其涉及用于检测用作生物分子的标记的磁性纳米颗粒的集成或片上磁传感器元件（11）。 本发明的装置通过例如通过使用静电屏蔽和/或调制和解调技术来补偿电容和/或磁耦合来减小磁传感器元件（11）和磁场发生器（12）之间的串扰。 该装置可用于磁性检测微阵列或生物芯片上生物分子的结合。