公开(公告)号：US09841421B2

公开(公告)日：2017-12-12

申请号：US13988833

申请日：2011-11-28

申请人： Wendy Uyen Dittmer ,  Mikhail Mikhaylovich Ovsyanko ,  Toon Hendrik Evers ,  Jeroen Hans Nieuwenhuis ,  Joannes Baptist Adrianus Dionisius Van Zon

发明人： Wendy Uyen Dittmer ,  Mikhail Mikhaylovich Ovsyanko ,  Toon Hendrik Evers ,  Jeroen Hans Nieuwenhuis ,  Joannes Baptist Adrianus Dionisius Van Zon

IPC分类号： G01N33/543 ,  G01N27/82 ,  G01N27/72 ,  G01N27/74 ,  G01N35/00 ,  G01N21/27 ,  G01N21/552

CPC分类号： G01N33/54373 ,  G01N21/274 ,  G01N21/552 ,  G01N27/72 ,  G01N27/745 ,  G01N27/825 ,  G01N33/54326 ,  G01N35/0098

摘要： The invention relates to a sensor device (100) and a method for the detection of magnetic particles (1) in a sample chamber (2) with a contact surface (11). The sensor device (100) comprises a sensor unit (120, 130) for detecting magnetic particles (1) in a target region (TR) and/or in at least one reference region on the contact surface. Moreover, it comprises a magnetic field generator (140) for generating a magnetic field that shall guide magnetic particles to the contact surface. With the help of these components, an “auxiliary parameter” is determined that is related to the magnetic particles (1) and/or their movement but that is independent of binding processes taking place in the target region between magnetic particles and the contact surface. The auxiliary parameter may for example be related to the degree of mismatch between the positions reached by the magnetic particles (1) under the influence of a magnetic field and the target region (TR). The evaluation results can be used to validate and/or correct the measurements obtained in the target region (TR).

公开(公告)号：US20130088221A1

公开(公告)日：2013-04-11

申请号：US13705000

申请日：2010-11-30

申请人： Joannes Baptist Adrianus Dionisius Van Zon ,  Mkhail Mikhaylovich Ovsyanko ,  Toon Hendrik Evers ,  Mara Johanna Jacoba Sijbers

发明人： Joannes Baptist Adrianus Dionisius Van Zon ,  Mkhail Mikhaylovich Ovsyanko ,  Toon Hendrik Evers ,  Mara Johanna Jacoba Sijbers

IPC分类号： G01N27/72

CPC分类号： G01N27/72 ,  B01L3/502761 ,  B82Y25/00 ,  G01N15/06 ,  G01N15/0656 ,  G01N2015/0693 ,  G01R33/1276 ,  H01F1/0036

摘要： The invention relates to a method and associated apparatuses (100) for the detection of magnetic particles (MP) in a sample chamber (111). The method comprises the determination of a “particle-parameter” that is related to the amount of magnetic particles (MP) in a first detection region (P, C), the determination of a “cluster-parameter” that is related to the degree of clustering of magnetic particles (MP) in a second detection region (P, C), and the evaluation of the particle-parameter based on the cluster-parameter. Various apparatuses are disclosed that can be applied in said method. In one apparatus (100), a magnetic field (B) is generated in the sample chamber (111) in such a way that it has different inclinations in a first and second field region (P, C) and/or that it is oblique to the binding surface (112) in at least one field region. Magnetic particles (MP) are then detected in said first and second field region and/or in said at least one field region before and after a permanent switch-off of the inclined magnetic field. The resulting detection signals are related to each other to determine a cluster-parameter. In other embodiments, a cluster-parameter may be determined from light transmission measurements during the application of a magnetic field that is switched on and off.

摘要翻译： 本发明涉及一种用于检测样品室（111）中的磁性颗粒（MP）的方法和相关装置（100）。 该方法包括确定与第一检测区域（P，C）中的磁性粒子（MP）的量相关的粒子参数，确定与磁性聚类程度相关的聚类参数 颗粒（MP）在第二检测区域（P，C）中，以及基于聚类参数的粒子参数的评估。 公开了可以应用于所述方法的各种装置。 在一个装置（100）中，在样品室（111）中产生磁场（B），使得其在第一和第二场区域（P，C）中具有不同的倾斜度和/或倾斜 到达至少一个场区域中的结合表面（112）。 然后在永久关闭倾斜磁场之前和之后，在所述第一和第二场区和/或所述至少一个场区中检测磁性颗粒（MP）。 所得到的检测信号彼此相关，以确定簇参数。 在其他实施例中，可以在施加接通和关断的磁场期间的光透射测量来确定簇参数。

公开(公告)号：US09804089B2

公开(公告)日：2017-10-31

申请号：US13201927

申请日：2010-02-08

申请人： Dominique Maria Bruls ,  Toon Hendrik Evers ,  Johannes Joseph Hubertina Barbara Schleipen

发明人： Dominique Maria Bruls ,  Toon Hendrik Evers ,  Johannes Joseph Hubertina Barbara Schleipen

IPC分类号： G01N21/552 ,  G01N33/543 ,  G01N21/27

CPC分类号： G01N21/552 ,  G01N21/274 ,  G01N33/54373

摘要： A sensing device (100) detects a target substance (2) in an investigation region (113). The sensing device (100) includes a sensing surface (112) with an investigation region (113) and a reference region (120). The sensing device (100) further includes a reference element (121) located at the reference region (120). The reference element (121) is adapted to shield the reference region (120) from the target substance (2) such that light reflected at the reference region (120) under total internal reflection conditions remains unaffected by the presence or absence of the target substance (2). This allows measuring a property, typically the intensity, of light reflected at the reference region (120) independent of the presence or absence of the target substance (2). This measured property of the reflected light can be used for performing a correction of light reflected at the investigation region (113).

公开(公告)号：US20120040475A1

公开(公告)日：2012-02-16

申请号：US13201927

申请日：2010-02-08

申请人： Dominique Maria Bruls ,  Toon Hendrik Evers ,  Johannes Joseph Hubertina Barbara Schleipen

发明人： Dominique Maria Bruls ,  Toon Hendrik Evers ,  Johannes Joseph Hubertina Barbara Schleipen

IPC分类号： G01N21/55

CPC分类号： G01N21/552 ,  G01N21/274 ,  G01N33/54373

摘要： The present invention relates to a sensing device (100) for detecting a target substance (2) in an investigation region (113). The sensing device (100) comprises a sensing surface (112) with an investigation region (113) and a reference region (120) thereon. The sensing device (100) further comprises a reference element (121) located at the reference region (120). The reference element (121) is adapted to shield the reference region (120) from the target substance (2) such that light reflected at the reference region (120) under total internal reflection conditions remains unaffected by the presence or absence of the target substance (2). This allows measuring a property, typically the intensity, of light reflected at the reference region (120) independent of the presence or absence of the target substance (2). This measured property of the reflected light can be used for performing an improved correction of light reflected at the investigation region (113).

摘要翻译： 本发明涉及一种用于在调查区域（113）中检测目标物质（2）的感测装置（100）。 感测装置（100）包括其上具有调查区域（113）和参考区域（120）的感测表面（112）。 感测装置（100）还包括位于参考区域（120）处的参考元件（121）。 参考元件（121）适于屏蔽参考区域（120）与目标物质（2），使得在全内反射条件下在参考区域（120）处反射的光线不会受到目标物质的存在或不存在的影响 （2）。 这允许独立于目标物质（2）的存在或不存在来测量在参考区域（120）处反射的光的特性（通常为强度）。 反射光的测量特性可用于对在调查区域（113）反射的光进行改进的校正。

公开(公告)号：US20130109106A1

公开(公告)日：2013-05-02

申请号：US13808522

申请日：2011-07-04

申请人： Derk Jan Wilfred Klunder ,  Jeroen Hans Nieuwehuis ,  Menno Willem Jose Prins ,  Toon Hendrik Evers

发明人： Derk Jan Wilfred Klunder ,  Jeroen Hans Nieuwehuis ,  Menno Willem Jose Prins ,  Toon Hendrik Evers

IPC分类号： G01N1/10

CPC分类号： G01N1/10 ,  B01L3/0275 ,  B01L3/527 ,  B01L7/52 ,  B01L2200/04 ,  B01L2200/0684 ,  B01L2200/16 ,  B01L2300/027 ,  B01L2300/044 ,  B01L2300/0627 ,  B01L2300/0654 ,  B01L2300/087 ,  B01L2400/043 ,  G01N35/00029 ,  G01N35/0098 ,  G01N35/1002 ,  G01N2035/00158 ,  G01N2035/0436 ,  Y10T436/2575

摘要： The invention relates to a method and a system (100) for selectively processing a sample (130) according to one of a plurality of different assays, for example for detecting a certain target component in the sample. The system comprises a plurality of “specific reagent reservoirs” (120) that contain different sets of reagents, wherein each set is required for one of the assays. Moreover, the system (100) comprises a “universal reagent reservoir” in which reagents for several assays are provided, preferably reagents for all assays. The universal reagent reservoir may preferably be a cartridge (110) in which the processing of a sample (130) can take place and which comprises a plurality of binding sites that are selective for different target components. Depending on the assay to be performed with a sample (130) at hand, the appropriate specific reagent reservoir (121b) is chosen and processed in the universal cartridge (110). This can particularly be done by a manipulator (140) in a high-throughput automated laboratory system.

摘要翻译： 本发明涉及用于根据多种不同测定中的一种选择性处理样品（130）的方法和系统（100），例如用于检测样品中某一目标成分。 该系统包括多个含有不同试剂组的“特异性试剂储存器”（120），其中每种试剂均需要每组。 此外，系统（100）包括“通用试剂储库”，其中提供用于几种测定的试剂，优选用于所有测定的试剂。 通用试剂储存器可以优选地是其中样品（130）的处理可以发生并且包括对不同目标组分具有选择性的多个结合位点的盒（110）。 根据将要用手的样品（130）进行的测定，在通用盒（110）中选择并处理适当的特定试剂储存器（121b）。 这可以通过高通量自动化实验室系统中的机械手（140）来进行。

公开(公告)号：US20140051187A1

公开(公告)日：2014-02-20

申请号：US14113964

申请日：2012-04-23

申请人： Toon Hendrik Evers ,  Derk Jan Wilfred Klunder ,  Jeroen Hans Nieuwenhuis ,  Joannes Baptist Adianus Dionisius Van Zon

发明人： Toon Hendrik Evers ,  Derk Jan Wilfred Klunder ,  Jeroen Hans Nieuwenhuis ,  Joannes Baptist Adianus Dionisius Van Zon

IPC分类号： G01N21/00

摘要： The invention relates to a method and a sensor device (100) for evaluating an assay with a sample. During the assay, optical measurements are made at a sensing surface (112), and at least one “homogeneity-image” of the sensing surface (112) is generated. From this image, an “homogeneity-indicator” is determined for at least one region of interest, and the optical measurements are then evaluated in dependence on said indicator. The homogeneity-indicator may for example be a binary value which indicates if an inhomogeneity was detected or not. If an inhomogeneity was detected, all optical measurements may be rejected, only measurements for the involved region of interest may be rejected, or measurements for a selected sub-area of the involved region of interest(ROI) may be rejected.

摘要翻译： 本发明涉及用于评价样品的测定方法和传感器装置（100）。 在测定期间，在感测表面（112）处进行光学测量，并且产生感测表面（112）的至少一个“均匀性图像”。 从该图像中，对于至少一个感兴趣的区域确定“均匀度指标”，然后根据所述指标来评估光学测量。 均匀度指示符可以例如是二进制值，其指示是否检测到不均匀性。 如果检测到不均匀性，则所有光学测量可能被拒绝，只有感兴趣区域的测量可能被拒绝，或者所涉及的感兴趣区域（ROI）的选定子区域的测量可能被拒绝。

公开(公告)号：US10041939B2

公开(公告)日：2018-08-07

申请号：US13497813

申请日：2010-09-10

申请人： Jeroen Hans Nieuwennhuis ,  Toon Hendrik Evers

发明人： Jeroen Hans Nieuwennhuis ,  Toon Hendrik Evers

IPC分类号： G01N33/553 ,  G01N33/543 ,  G01N27/74

摘要： The present invention relates to a cartridge (1) for the detection of an analyte (2) in a binding assay with magnetic labels (3), the cartridge comprising at least one capture binding agent (4) against a binding site on the analyte and comprising at least two magnetically labelled tracer binding agents (51 and 52) against further different binding sites on the analyte, characterized in that the cartridge comprises at least two regions (61 and 62) wherein a first region (61) comprises the at least one capture binding agent (4) and a first magnetically labelled tracer binding agent (51) and wherein a second region (62) comprises at least one capture binding agent (4) and a second magnetically labelled tracer binding agent (52). Herein the first region (61) does not comprise a magnetically labelled tracer binding agent other than the first magnetically labelled tracer bind agent (51) and wherein the second region (62) does not comprise a magnetically labelled tracer binding agent other than the second magnetically labelled tracer binding agent (52).

公开(公告)号：US09588112B2

公开(公告)日：2017-03-07

申请号：US12863219

申请日：2009-01-19

申请人： Toon Hendrik Evers

发明人： Toon Hendrik Evers

IPC分类号： G01N33/543 ,  B82Y25/00 ,  B82Y30/00 ,  G01N27/74 ,  G01N33/542 ,  G01N21/552

CPC分类号： G01N33/54373 ,  B82Y25/00 ,  B82Y30/00 ,  G01N21/552 ,  G01N27/745 ,  G01N33/542 ,  G01N33/54326

摘要： The invention relates to a system and a method for the detection of target components (102) in a sample with the help of indicator particles (101) distributed in said sample. The distance (d) between indicator particles (101) and a contact surface (112) is determined after the target components could bind to the contact surface and/or the indicator particles. Thus it is possible to detect how many target components (102) are bound without a need for a binding between indicator particles (101) and contact surface (112). Optionally the indicator particles (101) can be affected by a modulated force, e.g. via an electromagnet (141). The determination of the distance (d) between indicator particles (101) and contact surface (112) may for example be achieved by frustrated total internal reflection, measurement of magnetic fields, or FRET.

摘要翻译： 本发明涉及借助于分布在所述样品中的指示剂颗粒（101）来检测样品中的目标组分（102）的系统和方法。 在目标组分可以结合到接触表面和/或指示剂颗粒之后，确定指示剂颗粒（101）和接触表面（112）之间的距离（d）。 因此，可以检测多少目标部件（102）被绑定，而不需要指示剂颗粒（101）和接触表面（112）之间的结合。 任选地，指示剂颗粒（101）可以受到调制的力，例如， 经由电磁体（141）。 指示剂颗粒（101）和接触表面（112）之间的距离（d）的确定可以例如通过沮丧的全内反射，磁场测量或FRET来实现。

公开(公告)号：US20110207229A1

公开(公告)日：2011-08-25

申请号：US13124407

申请日：2009-10-06

申请人： Toon Hendrik Evers ,  Wendy Uyen Dittmer

发明人： Toon Hendrik Evers ,  Wendy Uyen Dittmer

IPC分类号： G01N33/00

CPC分类号： G01N33/54326 ,  B82Y25/00 ,  G01N27/745 ,  G01N35/0098 ,  G01R33/093 ,  G01R33/1269

摘要： The invention relates to a method and a device (100) for determining the amount of a target component (2) in a sample, wherein magnetic particles (2) can bind to a contact surface (4) with kinetics that depend on the sample-amount of the target component. The method comprises at least two washing steps during which magnetic particles (2) are magnetically moved away from the contact surface (4) and corresponding measurements of the remaining amount of magnetic particles (2) at the contact surface (4). The amount of target component in the sample is estimated from at least one of such measurement results. The measurement allows to determine also high concentrations of target component for which the sensor surface (4) is saturated in a steady-state.

摘要翻译： 本发明涉及一种用于确定样品中目标组分（2）的量的方法和装置（100），其中磁性颗粒（2）可以结合取决于样品的动力学的接触表面（4） 目标成分的数量。 该方法包括至少两个洗涤步骤，在此过程中，磁性颗粒（2）被磁性地远离接触表面（4）移动，并且在接触表面（4）处磁性颗粒（2）剩余量的相应测量值。 从这些测量结果中的至少一个估计样品中的目标组分的量。 该测量允许确定传感器表面（4）在稳定状态下饱和的目标部件的高浓度。

公开(公告)号：US20120178186A1

公开(公告)日：2012-07-12

申请号：US13497813

申请日：2010-09-10

申请人： Jeroen Hans Nieuwennhuis ,  Toon Hendrik Evers

发明人： Jeroen Hans Nieuwennhuis ,  Toon Hendrik Evers

IPC分类号： G01N27/72

CPC分类号： G01N33/54326 ,  G01N27/745

摘要： The present invention relates to a cartridge (1) for the detection of an analyte (2) in a binding assay with magnetic labels (3), the cartridge comprising at least one capture binding agent (4) against a binding site on the analyte and comprising at least two magnetically labelled tracer binding agents (51 and 52) against further different binding sites on the analyte, characterised in that the cartridge comprises at least two regions (61 and 62) wherein a first region (61) comprises the at least one capture binding agent (4) and a first magnetically labelled tracer binding agent (51) and wherein a second region (62) comprises at least one capture binding agent (4) and a second magnetically labelled tracer binding agent (52). Herein the first region (61) does not comprise a magnetically labelled tracer binding agent other than the first magnetically labelled tracer bind agent (51) and wherein the second region (62) does not comprise a magnetically labelled tracer binding agent other than the second magnetically labelled tracer binding agent (52).

摘要翻译： 本发明涉及一种用于在具有磁性标签（3）的结合测定中检测分析物（2）的盒（1），所述盒包含针对分析物上的结合位点的至少一种捕获结合剂（4） 包括至少两个磁性标记的示踪剂结合剂（51和52），其抵抗所述分析物上的另外不同的结合位点，其特征在于，所述盒包括至少两个区域（61和62），其中第一区域（61）包括所述至少一个 捕获结合剂（4）和第一磁性标记的示踪剂结合剂（51），并且其中第二区域（62）包含至少一种捕获结合剂（4）和第二磁性标记示踪剂结合剂（52）。 本文中，第一区域（61）不包含除了第一磁性标记的示踪剂结合剂（51）之外的磁性标记的示踪剂结合剂，并且其中第二区域（62）不包括除了第二磁性标记的磁性标记的示踪剂结合剂 标记示踪剂结合剂（52）。