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1. 发明授权

US08797028B2 Sensor device for target particles in a sample 有权
标题翻译：样品中目标颗粒的传感器装置
公开(公告)号：US08797028B2
公开(公告)日：2014-08-05
申请号：US12738317
申请日：2008-10-21
申请人： Coen Adrianus Johannes Verschuren , Josephus Arnoldus Henricus Maria Kahlman , Albert Hendrik Jan Immink , Mischa Megens , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
发明人： Coen Adrianus Johannes Verschuren , Josephus Arnoldus Henricus Maria Kahlman , Albert Hendrik Jan Immink , Mischa Megens , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
IPC分类号： G01R33/02 , G01N33/00 , G01N21/55
CPC分类号： G01N15/06 , G01N15/0656 , G01N2015/0693 , G01R33/1269
摘要： A sensor device and a method for the determination of the amount of target particles at a contact surface adjacent to a sample chamber include detecting, by a detector, the target particles in the sample chamber by a sensor element, and providing at least one corresponding sensor signal. An evaluation unit determines the amount of target particles in a first zone at the contracts surface and in a second zone a distance away from the contact surface based on this sensor signal. In an optical measurement approach, frustrated total internal reflection taking place under different operating conditions, such as wavelength and/or angle of incidence, may be used to extract information about the first and second zones. In a magnetic measurement approach, different magnetic excitation fields may be used to excite magnetic target particles differently in the first and second zone.
摘要翻译：用于确定与样品室相邻的接触表面处的目标颗粒的量的传感器装置和方法包括通过检测器通过传感器元件检测样品室中的目标颗粒，并且提供至少一个相应的传感器信号。评估单元基于该传感器信号确定在合同表面处的第一区域中的目标颗粒的量和距接触表面一定距离的第二区域中的目标颗粒的量。在光学测量方法中，可以使用在诸如波长和/或入射角的不同操作条件下发生的沮丧的全内反射来提取关于第一和第二区域的信息。在磁测量方法中，可以使用不同的磁激励场来在第一和第二区域中不同地激励磁性目标颗粒。

2. 发明申请

US20100259254A1 SENSOR DEVICE FOR TARGET PARTICLES IN A SAMPLE 有权
标题翻译：传感器装置在样品中的目标颗粒
公开(公告)号：US20100259254A1
公开(公告)日：2010-10-14
申请号：US12738317
申请日：2008-10-21
申请人： Coen Adrianus Johannes Verschuren , Josephus Arnoldus Henricus Maria Kahlman , Albert Hendrik Jan Immink , Mischa Megens , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
发明人： Coen Adrianus Johannes Verschuren , Josephus Arnoldus Henricus Maria Kahlman , Albert Hendrik Jan Immink , Mischa Megens , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
IPC分类号： G01R33/02 , G01N33/00 , G01N21/55
CPC分类号： G01N15/06 , G01N15/0656 , G01N2015/0693 , G01R33/1269
摘要： The invention relates to a sensor device (100) and a method for the determination of the amount of target particles (1) at a contact surface (112) adjacent to a sample chamber (2). Target particles (1) in the sample chamber are detected by a sensor element (SE) and at least one corresponding sensor-signal (s, s′) is provided. An evaluation unit (EU) then determines the amount of target particles (1) in a first zone (Z1) immediately at the contracts surface (112) and a second zone (Z2) a distance (z) away from the contact surface based on this sensor-signal. In an optical measurement approach, frustrated total internal reflection taking place under different operating conditions (e.g. wavelength, angle of incidence) may be used to extract information about the first and second zones (Z1, Z2). In a magnetic measurement approach, different magnetic excitation fields may be used to excite magnetic target particles differently in the first and second zone (Z2). Moreover, the temporal course of a sensor-signal (s, s′) can be evaluated, particularly with respect to stochastic movements of the target particles (1).
摘要翻译：本发明涉及一种传感器装置（100）和用于确定在与样品室（2）相邻的接触表面（112）处的目标颗粒（1）的量的方法。通过传感器元件（SE）检测样品室中的目标颗粒（1），并提供至少一个对应的传感器信号（s，s'）。然后，评估单元（EU）基于紧接表面（112）立即确定第一区域（Z1）中的目标颗粒（1）的数量和远离接触表面的距离（z）的第二区域（Z2），基于这个传感器信号。在光学测量方法中，可以使用在不同操作条件（例如波长，入射角）下发生的沮丧的全内反射来提取关于第一和第二区（Z1，Z2）的信息。在磁测量方法中，可以使用不同的磁激励场来在第一和第二区（Z2）中不同地激励磁目标颗粒。此外，可以评估传感器信号（s，s'）的时间过程，特别是关于目标颗粒（1）的随机运动。

3. 发明申请

US20080246471A1 Magnetic Sensor Device With Different Internal Operating Frequencies 审中-公开
标题翻译：具有不同内部工作频率的磁传感器装置
公开(公告)号：US20080246471A1
公开(公告)日：2008-10-09
申请号：US12089947
申请日：2006-09-29
申请人： Josephus Arnoldus Henricus Maria Kahlman , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
发明人： Josephus Arnoldus Henricus Maria Kahlman , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
IPC分类号： G01N15/06
CPC分类号： G01R33/09 , B82Y25/00 , G01N15/0656 , G01N27/745 , G01R33/093 , G01R33/12 , G01R33/1269
摘要： The invention relates to a magnetic sensor device (10) comprising wires (11, 13) for the generation of a magnetic field with a first frequency f1 a GMR sensor (12) operated with an input current of a second frequency f2, and a demodulator (26) operated at a third frequency f3. In order to avoid signal corruption by phase noise and to improve the signal-to-noise ratio, the first, second and third frequencies are derived by a supply unit (121) from a common reference frequency fref. Said derivation may for example be achieved with the help of digital frequency dividers. Furthermore, phase detectors (PD1, PD2) may be used in a feedback control loop to assure predetermined relations between the phases of the three frequencies. In another embodiment of the invention, the phase and/or amplitude of a model signal, which is used to process a desired signal component in the output of the sensor, is tracked by an adaptation algorithm, for example a gradient descent.
摘要翻译：本发明涉及一种磁传感器装置（10），其包括用于产生具有第一频率f 1的磁场的导线（11,13），GMR传感器（12）用输入电流第二频率f 2 2和在第三频率f 3 3处操作的解调器（26）。为了避免相位噪声的信号损坏并提高信噪比，第一，第二和第三频率由供电单元（121）从公共参考频率f ref 。所述推导可以例如在数字分频器的帮助下实现。此外，相位检测器（PD1，PD2）可以用在反馈控制环路中，以确保三个频率的相位之间的预定关系。在本发明的另一个实施例中，用于处理传感器的输出中的期望信号分量的模型信号的相位和/或幅度由适应算法（例如梯度下降）来跟踪。

4. 发明申请

US20100060275A1 MAGNETIC SENSOR DEVICE WITH ROBUST SIGNAL PROCESSING 审中-公开
标题翻译：具有鲁棒信号处理的磁传感器装置
公开(公告)号：US20100060275A1
公开(公告)日：2010-03-11
申请号：US12518897
申请日：2007-12-14
申请人： Jeroen Veen , Theodorus Petrus Henricus Gerardus Jansen , Bart Michiel De Boer , Josephus Arnoldus Henricus Maria Kahlman
发明人： Jeroen Veen , Theodorus Petrus Henricus Gerardus Jansen , Bart Michiel De Boer , Josephus Arnoldus Henricus Maria Kahlman
IPC分类号： G01R33/12
CPC分类号： G01R33/093 , B82Y25/00 , G01R33/1269
摘要： The invention relates to a magnetic sensor device (100) comprising a magnetic field generator (1) driven with an excitation current of a first frequency (f1) and a magnetic sensor element (e.g. a GIVER sensor (2)) driven with a sensor current (I2) of a second frequency (f2) for measuring reaction fields (HB) generated by magnetized particles (3). In an associated evaluation unit (10), a reference component (uQ) of the measurement signal (uGMR) is separated that depends on the excitation current (I1) and the sensor current (I2) but not on the presence of magnetized particles (3). The reference component (uQ) may particularly be produced by a combination of the self-magnetization (H2) of the magnetic sensor element (2) and cross-talk related currents. The reference component (uQ) may be isolated based on its phase with respect to a particle-dependent component of the measurement signal (uGMR) or based on its scaling with one of the current frequencies. Monitoring of the reference component (uQ) reveals variations in operating conditions, for example in the sensor gain, that can be used to calibrate the measurement results.
摘要翻译：本发明涉及一种磁传感器装置（100），其包括用第一频率（f1）的激励电流驱动的磁场发生器（1）和由传感器电流驱动的磁传感器元件（例如GIVER传感器（2））（I2），用于测量由磁化颗粒（3）产生的反应场（HB）的第二频率（f2）。在相关联的评估单元（10）中，测量信号（uGMR）的参考分量（uQ）被分离，其取决于激励电流（I1）和传感器电流（I2），但不依赖于磁化颗粒（3 ）。参考分量（uQ）可以特别地通过磁传感器元件（2）的自磁化（H2）和串扰相关电流的组合来产生。参考分量（uQ）可以基于其相对于测量信号（uGMR）的粒子相关分量的相位或者基于其与当前频率之一的比例来隔离。参考组件（uQ）的监视显示了可用于校准测量结果的操作条件的变化，例如传感器增益。

5. 发明申请

US20100001722A1 MAGNETIC SENSOR DEVICE WITH SUPPRESSION OF SPURIOUS SIGNAL COMPONENTS 审中-公开
标题翻译：具有抑制SPUIOUS信号组件的磁传感器装置
公开(公告)号：US20100001722A1
公开(公告)日：2010-01-07
申请号：US12518890
申请日：2007-12-12
申请人： Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen , Jeroen Veen
发明人： Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen , Jeroen Veen
IPC分类号： G01R33/02
CPC分类号： G01R33/093 , B82Y25/00 , G01R33/1269
摘要： The invention relates to a magnetic sensor device for the determination of magnetized particles (3) which comprises a magnetic field generator (1, 1′)(e.g. a conductor wire) that is driven with an excitation current (I1) of a first frequency (f1), and a magnetic sensor element (2) (e.g. a GMR resistance), that is driven with a sensor current (I2) of a second frequency (f2) for generating measurement signals (UGMR). A preprocessed signal (uf) is then generated from the measurement signal (UGMR) that comprises a predetermined frequency (Δf), and an evaluation unit (10) separates from this preprocessed signal a spurious component that does not depend on the presence of magnetized particles (3) in the sample chamber. The spurious component (UQ) may particularly be caused by self-magnetization (H2) of the magnetic sensor element (2) in combination with parasitic (capacitive or inductive) cross-talk. Furthermore, an unknown, variable phase-shift (φSP) in the preprocessed signal (uf) may be determined by varying the ratio between the spurious component and a particle-dependent target component. This variation may for example be achieved if, in an optimization stage (OS), the excitation current (I1) is conducted through a bypass resistor (R, R′) and/or if an additional capacitor is introduced between the magnetic field generator and the magnetic sensor element. The determined phase shift can then be used to adjust the phase of a demodulation signal (udem) such that the spurious component is suppressed.
摘要翻译：本发明涉及一种用于确定磁化颗粒（3）的磁传感器装置，该磁化颗粒包括由第一频率的激励电流（I1）驱动的磁场发生器（1,1'）（例如导线） f1）和由用于产生测量信号（UGMR）的第二频率（f2）的传感器电流（I2）驱动的磁传感器元件（2）（例如，GMR电阻）。然后从包括预定频率（Deltaf）的测量信号（UGMR）生成预处理信号（uf），并且评估单元（10）从该预处理信号中分离出不依赖于磁化颗粒的存在的杂散分量（3）。杂散分量（UQ）可以特别地由磁传感器元件（2）与寄生（电容或电感）串扰的自磁化（H2）引起。此外，预处理信号（uf）中的未知的可变相移（phiSP）可以通过改变杂散分量和粒子相关目标分量之间的比率来确定。例如，如果在优化级（OS）中通过旁路电阻（R，R'）传导励磁电流（I1）和/或如果在磁场发生器和磁传感元件。然后可以使用所确定的相移来调整解调信号（udem）的相位，使得抑制杂散分量。

6. 发明申请

US20090219012A1 MICROELECTRONIC SENSOR DEVICE FOR CONCENTRATION MEASUREMENTS 审中-公开
标题翻译：用于浓度测量的微电子传感器装置
公开(公告)号：US20090219012A1
公开(公告)日：2009-09-03
申请号：US12299698
申请日：2007-04-24
申请人： Jeroen Hans Nieuwenhuis , Hans Van Zon , Josephus Arnoldus Henricus Maria Kahlman , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
发明人： Jeroen Hans Nieuwenhuis , Hans Van Zon , Josephus Arnoldus Henricus Maria Kahlman , Jeroen Veen , Bart Michiel De Boer , Theodorus Petrus Henricus Gerardus Jansen
IPC分类号： G01N27/74
CPC分类号： G01R33/093 , B82Y25/00 , G01N27/745 , G01R33/1269
摘要： The invention relates to a method and a magnetic sensor device for the determination of the concentration of target particles (2) in a sample fluid, wherein the amount of the target particles (2) in a sensitive region (14) is observed by sampling measurement signals with associated sensor units (10a-10d). The target particles (2) may optionally be bound to binding sites (3) in the sensitive region, and a parametric binding curve, e.g. a Langmuir isotherm, may be fitted to the sampled measurement signals to determine the desired particle concentration in the sample. Moreover, parameters like the sampling rate and the size of the sensitive region (14) can be dynamically fitted during the ongoing sampling process to improve the signal-to-noise ratio. In another embodiment of the invention, single events corresponding to the movement of target particles into, out of, or within the sensitive region are detected and counted.
摘要翻译：本发明涉及一种用于确定样品流体中目标颗粒（2）的浓度的方法和磁传感器装置，其中通过采样测量观察敏感区域（14）中的目标颗粒（2）的量信号与相关联的传感器单元（10a-10d）。目标颗粒（2）可以任选地结合到敏感区域中的结合位点（3），参与结合曲线，例如， Langmuir等温线可以适应于采样的测量信号，以确定样品中所需的颗粒浓度。此外，在持续采样过程中，可以动态拟合诸如采样率和敏感区域（14）的尺寸的参数，以提高信噪比。在本发明的另一个实施例中，检测并计数与目标颗粒移动到敏感区域内部或之内的单个事件。

7. 发明申请

US20080314749A1 Microelectronic Device with Magnetic Excitation Wires 审中-公开
标题翻译：具有励磁线的微电子器件
公开(公告)号：US20080314749A1
公开(公告)日：2008-12-25
申请号：US12159465
申请日：2006-10-25
申请人： Mark Thomas Johnson , Albert Hendrik Jan Immink , Marc Wilhelmus Gijsbert Ponjee , Mirielle Ann Reijme , Josephus Arnoldus Henricus Maria Kahlman , Jeroen Hans Nieuwenhuis , Bart Michiel De Boer
发明人： Mark Thomas Johnson , Albert Hendrik Jan Immink , Marc Wilhelmus Gijsbert Ponjee , Mirielle Ann Reijme , Josephus Arnoldus Henricus Maria Kahlman , Jeroen Hans Nieuwenhuis , Bart Michiel De Boer
IPC分类号： G01N27/26
CPC分类号： G01N33/54326 , B01L3/50273 , B01L3/502761 , B01L2200/0647 , B01L2400/0415 , B01L2400/043 , G01N27/745 , G01N33/5438
摘要： The invention relates to a microelectronic device (200), particularly a magnetic biosensor, comprising B/E-electrodes (21) that can generate a magnetic field (B) in a sample chamber (10). The device further comprises E-electrodes (23, 24) that can generate an electrical field (E) in the sample chamber (10) in cooperation with the B/E-electrodes (21). Thus the B/E-electrodes are used for two purposes. Electrical fields (E) in the sample chamber (10) may particularly be used for pumping and/or mixing of a fluid sample or for a stringency test of particle bindings.
摘要翻译：本发明涉及一种微电子器件（200），特别是包括可在样品室（10）中产生磁场（B））的B / E电极（21）的磁性生物传感器。所述装置还包括可与所述B / E电极（21）配合地在样品室（10）中产生电场（E）的E电极（23,24）。因此，B / E电极用于两个目的。样品室（10）中的电场（E）可特别用于泵送和/或混合流体样品或用于颗粒结合的严格性测试。

8. 发明申请

US20080218165A1 Microsensor Device 审中-公开
标题翻译：微传感器装置
公开(公告)号：US20080218165A1
公开(公告)日：2008-09-11
申请号：US12065612
申请日：2006-09-07
申请人： Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer , Albert Hendrik Jan Immink , Jeroen Hans Nieuwenhuis
发明人： Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer , Albert Hendrik Jan Immink , Jeroen Hans Nieuwenhuis
IPC分类号： G01N27/72
CPC分类号： G01N33/54326 , G01N27/745
摘要： The invention relates to a microsensor device like a magnetic biosensor (100). The microsensor device comprises an array of probe-sensors (10.1, 10.2, 10.3) for the measurement of a physical quantity, for example the concentration of molecules labeled with magnetic beads in a sample chamber. The array further comprises a reference-sensor (10.4) that is disposed close to the probe-sensors (10.1, 10.2, 10.3) but shielded from the physical quantity to be measured. The measuring signal of the reference-sensor (10.4) reflects the influence of environmental conditions like temperature and can therefore be used to correct the measuring signals of the probe-sensors (10.1, 10.2, 10.3). The sensors (10.1, 10.2, 10.3, 10.4) are connected via a multiplexer to the same detector unit for further processing in order to minimize variations and to reduce hardware complexity.
摘要翻译：本发明涉及一种诸如磁性生物传感器（100）的微传感器装置。微传感器装置包括用于测量物理量的探针传感器阵列（10.1,10.2,10.3），例如在样品室中用磁珠标记的分子的浓度。该阵列还包括靠近探头传感器（10.1,10.2,10.3）设置但与被测量的物理量屏蔽的参考传感器（10.4）。参考传感器（10.4）的测量信号反映了诸如温度等环境条件的影响，因此可用于校正探头传感器（10.1,10.2,10.3）的测量信号。传感器（10.1,10.2,10.3,10.4）通过多路复用器连接到相同的检测器单元以进行进一步处理，以便最小化变化并降低硬件复杂度。

9. 发明申请

US20080129286A1 Means and Method for Reducing Magnetic Cross-Talk in Biosensors 失效
标题翻译：减少生物传感器中磁交互的手段和方法
公开(公告)号：US20080129286A1
公开(公告)日：2008-06-05
申请号：US11719955
申请日：2005-11-28
申请人： Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer
发明人： Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer
IPC分类号： G01N27/72
CPC分类号： G01R33/093 , B82Y25/00 , G01R33/1269
摘要： A magnetic sensor (MS) for sensing a magnetic stray field (SF) generated by magnetizable object (SPB) when magnetized and for generating an electrical object signal (UOB) which depends on the sensed magnetic stray field (SF), comprising a magnetic field generator (WR1, WR2) for generating a magnetic main field (H) for magnetizing the magnetizable object (SPB), and cross-talk reduction means for reducing the effect of a cross talk signal component in the electrical object signal (UOB) caused by magnetic cross-talk between the magnetic main field (H) and the magnetic stray field (SF), wherein the cross-talk reduction means is arranged for distinguishing a signal property between the cross-talk signal component and the remaining part of the electrical object signal (UOB) and for generating an electrical output signal (Uo).
摘要翻译：一种磁传感器（MS），用于感测磁化物体（SPB）产生的磁性杂散场（SF），当被磁化并产生取决于感测的磁性杂散场的电气对象信号（U OB OB）时（SF），包括用于产生用于磁化可磁化物体（SPB）的磁性主场（H）的磁场发生器（WR 1，W 2），并且交叉 - 减小装置，用于降低由磁性主场（H）和磁性杂散场（H）和磁性杂散场（H）之间的磁场串扰引起的电气对象信号（U OB OB）中串扰信号分量的影响 SF），其中所述串扰降低装置被布置用于区分串扰信号分量与电对象信号的剩余部分（U OB OB）之间的信号特性，并用于产生电输出信号（U o）。

10. 发明申请

US20100176807A1 MAGNETIC SENSOR DEVICE 审中-公开
标题翻译：磁传感器装置
公开(公告)号：US20100176807A1
公开(公告)日：2010-07-15
申请号：US12377219
申请日：2007-08-07
申请人： Haris Duric , Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer
发明人： Haris Duric , Josephus Arnoldus Henricus Maria Kahlman , Bart Michiel De Boer
IPC分类号： G01R33/12
CPC分类号： G01N33/54366 , G01N27/745 , G01N33/54326 , G01N33/54373 , G01N35/0098
摘要： The present invention provides a magnetic sensor device (20) comprising at least one sensor surface lying in a first plane, a first magnetic field generating means (12) for attracting magnetic or magnetizable objects (15) toward a sensor surface (13), the first magnetic field generating means (12) lying in a second plane different from and substantially parallel to the first plane, and a second magnetic field generating means (14) for magnetizing magnetic or magnetizable objects (15) which are bond to the sensor. The spacing between the first magnetic field generating means (12) and the at least one sensor element (11) is smaller than 2 μm down to optionally overlapping. The present invention furthermore provides a method for determining the presence and/or amount of magnetic or magnetizable objects (15) in a sample fluid using the magnetic sensor device (20) according to embodiments of the invention.
摘要翻译：本发明提供了一种包括位于第一平面中的至少一个传感器表面的磁传感器装置（20），用于将磁性或可磁化物体（15）吸引到传感器表面（13）的第一磁场产生装置（12）第一磁场产生装置（12），其位于与第一平面不同并且基本上平行的第二平面中;以及第二磁场产生装置（14），用于磁化磁性或可磁化物体（15），所述第二磁场产生装置结合到传感器。第一磁场产生装置（12）和至少一个传感器元件（11）之间的间隔小于2μm，直到可选地重叠。本发明还提供一种用于使用根据本发明的实施例的磁传感器装置（20）来确定样品流体中的磁性或可磁化物体（15）的存在和/或量的方法。

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