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1. 发明授权

US09500584B2 Multiple examinations of a sample 有权
标题翻译：样本的多次检查
公开(公告)号：US09500584B2
公开(公告)日：2016-11-22
申请号：US14125093
申请日：2012-06-25
申请人： Jacobus Hermanus Maria Neijzen , Wendy Uyen Dittmer , Mikhail Mikhaylovich Ovsyanko
发明人： Jacobus Hermanus Maria Neijzen , Wendy Uyen Dittmer , Mikhail Mikhaylovich Ovsyanko
IPC分类号： G01N21/00 , G01N21/59 , G01N21/03 , G01N21/31 , G01N21/552 , G01N33/543 , G01N21/17
CPC分类号： G01N21/59 , G01N21/0303 , G01N21/31 , G01N21/3151 , G01N21/552 , G01N33/54326 , G01N2021/0325 , G01N2021/1738 , G01N2021/1742 , G01N2201/024 , G01N2201/066
摘要： An apparatus for examination of a sample includes at least one sample chamber in which the sample can be provided, where the sample chamber has a detection surface; at least one light source for emitting a first input light beam which is totally internally reflected at the detection surface of the sample chamber into a first output light beam, and for emitting a second input light beam which is at least partially transmitted through the sample chamber into a second output light beam. The apparatus further includes at least one light detector for detecting the first and the second output light beams. The sample chamber is elongated and traversed in longitudinal direction by light of the second input light beam.
摘要翻译：用于检查样品的装置包括至少一个样品室，其中可以提供样品，其中样品室具有检测表面; 至少一个光源，用于发射在样品室的检测表面处完全内部反射到第一输出光束中的第一输入光束，并且用于发射至少部分透射通过样品室的第二输入光束进入第二输出光束。该装置还包括至少一个用于检测第一和第二输出光束的光检测器。样品室通过第二输入光束的光线在纵向方向上被细长并横越。

2. 发明申请

US20140118745A1 MULTIPLE EXAMINATIONS OF A SAMPLE 有权
标题翻译：样品的多次检验
公开(公告)号：US20140118745A1
公开(公告)日：2014-05-01
申请号：US14125093
申请日：2012-06-25
申请人： Jacobus Hermanus Maria Neijzen , Wendy Uyen Dittmer , Mikhail Mikhaylovich Ovsyanko
发明人： Jacobus Hermanus Maria Neijzen , Wendy Uyen Dittmer , Mikhail Mikhaylovich Ovsyanko
IPC分类号： G01N21/59
CPC分类号： G01N21/59 , G01N21/0303 , G01N21/31 , G01N21/3151 , G01N21/552 , G01N33/54326 , G01N2021/0325 , G01N2021/1738 , G01N2021/1742 , G01N2201/024 , G01N2201/066
摘要： The invention relates to means for the examination of a sample, wherein a first input light beam (L1) is totally internally reflected at a detection surface of a sample chamber (111), while a second input light beam (L1′) is transmitted through the sample chamber (111). The resulting first and second output light beams (L2, L2′) are detected and can be evaluated with respect to frustrated total internal reflection and optical absorbance, respectively. Preferably, both output light beams (L2, L2′) are detected by a single image sensor (155).
摘要翻译：本发明涉及一种用于检查样品的装置，其中第一输入光束（L1）在样品室（111）的检测表面处被全内反射，而第二输入光束（L1'）被透射样品室（111）。检测所得到的第一和第二输出光束（L2，L2'），并且可以分别对沮丧的全内反射和光吸收率进行评估。优选地，两个输出光束（L2，L2'）由单个图像传感器（155）检测。

3. 发明授权

US09841421B2 Sensor device for magnetically actuated particles 有权
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).

4. 发明申请

US20140057366A1 SENSOR DEVICE FOR MAGNETICALLY ACTUATED PARTICLES 有权
标题翻译：用于磁力驱动颗粒的传感器装置
公开(公告)号：US20140057366A1
公开(公告)日：2014-02-27
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
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).
摘要翻译：本发明涉及一种传感器装置（100）和用于在具有接触表面（11））的样品室（2）中检测磁性颗粒（1）的方法。传感器装置（100）包括用于检测目标区域（TR）中和/或接触表面上的至少一个参考区域中的磁性颗粒（1）的传感器单元（120,130）。此外，它包括用于产生磁场的磁场发生器（140），该磁场将磁性颗粒引导到接触表面。在这些组件的帮助下，确定与磁性颗粒（1）和/或它们的运动相关的“辅助参数”，但是与磁性颗粒和接触表面之间的目标区域中发生的结合过程无关。辅助参数可以例如与在磁场和目标区域（TR）的影响下由磁性颗粒（1）达到的位置之间的失配程度相关。评估结果可用于验证和/或校正在目标区域（TR）中获得的测量结果。

5. 发明授权

US08981772B2 Rotating magnetic field for improved detection in cluster assays 有权
标题翻译：旋转磁场用于集群测定中的改进检测
公开(公告)号：US08981772B2
公开(公告)日：2015-03-17
申请号：US13060804
申请日：2009-09-04
申请人： Andrea Ranzoni , Menno Willem Jose Prins , Mikhail Mikhaylovich Ovsyanko
发明人： Andrea Ranzoni , Menno Willem Jose Prins , Mikhail Mikhaylovich Ovsyanko
IPC分类号： G01R33/02 , G01N33/553 , G01N33/543 , G01N27/74
CPC分类号： G01N33/54333 , G01N27/745
摘要： In a method of performing a cluster assay, a suspension (14) of superparamagnetic particles in a fluid to be analyzed is provided, wherein the superparamagnetic particles are coated with a bioactive agent. The particles are then allowed to form clusters due to an analyte present within the fluid. Subsequently, clusters of superparamagnetic particles are selectively actuated by applying a rotating magnetic field, wherein the amplitude of the magnetic field varies over time. Finally, the selectively actuated clusters are detected. An apparatus for performing a cluster assay comprises means for accommodating a sample (12) and means for applying a rotating magnetic field (11), the magnetic field being adapted for selectively actuating clusters of superparamagnetic particles. The apparatus further comprises means for detecting the selectively actuated clusters.
摘要翻译：在进行聚集测定的方法中，提供了待分析流体中超顺磁性颗粒的悬浮液（14），其中超顺磁性颗粒用生物活性剂涂覆。然后由于存在于流体内的分析物，使颗粒形成簇。随后，通过施加旋转磁场来选择性地致动超顺磁性颗粒簇，其中磁场的振幅随时间而变化。最后，检测到选择性地致动的簇。用于进行聚集测定的装置包括用于容纳样品（12）的装置和用于施加旋转磁场（11）的装置，所述磁场适于选择性地致动超顺磁颗粒簇。该装置还包括用于检测选择性地致动的簇的装置。

6. 发明申请

US20100291710A1 BIOSENSOR SYSTEM FOR EXTERNAL ACTUATION OF MAGNETIC PARTICLES IN A BIOSENSOR CARTRIDGE 审中-公开
标题翻译：用于生物传感器盒中磁性颗粒外部致动的生物传感器系统
公开(公告)号：US20100291710A1
公开(公告)日：2010-11-18
申请号：US12863818
申请日：2009-01-22
申请人： Mikhail Mikhaylovich Ovsyanko , Petrus Johannes Wilhelmus Van Lankvelt
发明人： Mikhail Mikhaylovich Ovsyanko , Petrus Johannes Wilhelmus Van Lankvelt
IPC分类号： G01N33/543 , G01N35/00
CPC分类号： G01N33/54373 , G01N27/745 , G01R33/1269
摘要： The invention provides for a biosensor system (1), wherein the system comprises a biosensor magnet assembly (10) with at least three electromagnetic subunits (20a, 20b, 20c). The magnetic field strength of each electromagnetic subunit is separately changeable by electrical control. Further, the system comprises a detachable biosensor cartridge (30) having a sensor surface and adapted to be arranged with the sensor surface adjacent to the biosensor magnet assembly (10). The invention further provides a method for steering the movement of magnetic particles in a biosensor cartridge (30). The method comprises the steps (a) and (b): in step (a), a sensor surface of a detachable biosensor cartridge (30) is arranged adjacent to a biosensor magnet assembly (10). The biosensor magnet assembly comprises three electromagnetic subunits (20a, 20b, 20c), wherein the magnetic field strength of each subunit is separately changeable by electrical control. In step (b), the magnetic field strength of each subunit is separately changed by electrical control to obtain a magnetic field gradient in the biosensor cartridge (30).
摘要翻译：本发明提供了一种生物传感器系统（1），其中该系统包括具有至少三个电磁子单元（20a，20b，20c）的生物传感器磁体组件（10）。每个电磁子单元的磁场强度可以通过电气控制单独更改。此外，该系统包括具有传感器表面并且适于布置有传感器表面邻近生物传感器磁体组件（10）的可拆卸的生物传感器盒（30）。本发明还提供了一种用于转向生物传感器盒（30）中的磁性颗粒运动的方法。该方法包括步骤（a）和（b）：在步骤（a）中，可拆卸的生物传感器盒（30）的传感器表面布置成与生物传感器磁体组件（10）相邻。生物传感器磁体组件包括三个电磁子单元（20a，20b，20c），其中每个子单元的磁场强度可通过电气控制单独改变。在步骤（b）中，通过电气控制单独地改变每个子单元的磁场强度，以在生物传感器盒（30）中获得磁场梯度。

7. 发明申请

US20140147883A1 FILTER SUPPORT WITH A PHASE-CHANGING MEDIUM 有权
标题翻译：过滤器支持与相位变化中
公开(公告)号：US20140147883A1
公开(公告)日：2014-05-29
申请号：US14131757
申请日：2012-07-04
申请人： Menno Willem Jose Prins , Mikhail Mikhaylovich Ovsyanko , Freek Van Hemert , Arie Rombertus Van Doorn
发明人： Menno Willem Jose Prins , Mikhail Mikhaylovich Ovsyanko , Freek Van Hemert , Arie Rombertus Van Doorn
IPC分类号： G01N1/30
CPC分类号： G01N1/30 , G01N1/2813 , G01N1/36 , G01N33/48 , G01N33/569 , G02B21/34
摘要： The present invention relates to a method for processing isolated cells, in particular rare cells such as circulating tumor cells, to render them suitable for optical imaging, comprising the steps of (a) depositing filter material comprising captured cells on a phase-change medium; (b) melting said phase-change medium until the medium is spread out below said filter material; and (c) lowering the temperature of said phase-change medium until the medium solidifies, resulting in an optically flat filter comprising said cells at a fixed position. The method may additionally comprise an initial step of capturing a cell on a filter material. The phase-change medium, preferably paraffin wax, may comprise a porous, or mesh-like structure allowing the passage of a fluid through the medium. The phase-change medium may further be mounted on a carrier such as a glass carrier or a polymer material carrier. The present invention further relates to processed filter material comprising isolated cells suitable for optical imaging, which is obtainable by the method; the use of such filter material for diagnostic, histological, microbiological, biochemical, oncologic, or hematologic analysis, as well as a device for isolating cells or processing cells to render them suitable for optical imaging.
摘要翻译：本发明涉及一种用于处理分离的细胞，特别是稀有细胞例如循环肿瘤细胞以使其适合于光学成像的方法，包括以下步骤：（a）将包含捕获的细胞的过滤材料沉积在相变介质上; （b）熔化所述相变介质，直到介质在所述过滤材料之下展开; 和（c）降低所述相变介质的温度，直到介质凝固，得到包含所述电池在固定位置的光学平面滤光器。该方法可以另外包括在过滤材料上捕获细胞的初始步骤。相变介质，优选石蜡，可以包括允许流体通过介质的多孔或网状结构。相变介质还可以安装在诸如玻璃载体或聚合物材料载体的载体上。本发明还涉及包含可通过该方法获得的适于光学成像的分离的细胞的经处理的过滤材料; 使用这种过滤材料进行诊断，组织学，微生物学，生物化学，肿瘤学或血液学分析，以及用于分离细胞或处理细胞以使其适合于光学成像的装置。

8. 发明申请

US20120250005A1 BIOSENSOR SYSTEM FOR SINGLE PARTICLE DETECTION 有权
标题翻译：用于单颗粒检测的生物传感器系统
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。

9. 发明授权

US09291533B2 Filter support with a phase-changing medium 有权
标题翻译：过滤器支持与相变介质
公开(公告)号：US09291533B2
公开(公告)日：2016-03-22
申请号：US14131757
申请日：2012-07-04
申请人： Menno Willem Jose Prins , Mikhail Mikhaylovich Ovsyanko , Freek Van Hemert , Arie Rombertus Van Doorn
发明人： Menno Willem Jose Prins , Mikhail Mikhaylovich Ovsyanko , Freek Van Hemert , Arie Rombertus Van Doorn
IPC分类号： G02B21/34 , G01N1/28 , G01N1/30 , G01N1/36 , G01N33/569 , G01N33/48
CPC分类号： G01N1/30 , G01N1/2813 , G01N1/36 , G01N33/48 , G01N33/569 , G02B21/34
摘要： The present invention relates to a method for processing isolated cells, in particular rare cells such as circulating tumor cells, to render them suitable for optical imaging, comprising the steps of (a) depositing filter material comprising captured cells on a phase-change medium; (b) melting said phase-change medium until the medium is spread out below said filter material; and (c) lowering the temperature of said phase-change medium until the medium solidifies, resulting in an optically flat filter comprising said cells at a fixed position. The method may additionally comprise an initial step of capturing a cell on a filter material. The phase-change medium, preferably paraffin wax, may comprise a porous, or mesh-like structure allowing the passage of a fluid through the medium. The phase-change medium may further be mounted on a carrier such as a glass carrier or a polymer material carrier. The present invention further relates to processed filter material comprising isolated cells suitable for optical imaging, which is obtainable by the method; the use of such filter material for diagnostic, histological, microbiological, biochemical, oncologic, or hematologic analysis, as well as a device for isolating cells or processing cells to render them suitable for optical imaging.
摘要翻译：本发明涉及一种用于处理分离的细胞，特别是稀有细胞例如循环肿瘤细胞以使其适合于光学成像的方法，包括以下步骤：（a）将包含捕获的细胞的过滤材料沉积在相变介质上; （b）熔化所述相变介质，直到介质在所述过滤材料之下展开; 和（c）降低所述相变介质的温度，直到介质凝固，得到包含所述电池在固定位置的光学平面滤光器。该方法可以另外包括在过滤材料上捕获细胞的初始步骤。相变介质，优选石蜡，可以包括允许流体通过介质的多孔或网状结构。相变介质还可以安装在诸如玻璃载体或聚合物材料载体的载体上。本发明还涉及包含可通过该方法获得的适于光学成像的分离的细胞的经处理的过滤材料; 使用这种过滤材料进行诊断，组织学，微生物学，生物化学，肿瘤学或血液学分析，以及用于分离细胞或处理细胞以使其适合于光学成像的装置。

10. 发明授权

US09207210B2 Method and a device for attracting magnetic particles to a surface 有权
标题翻译：方法和用于将磁性颗粒吸引到表面的装置
公开(公告)号：US09207210B2
公开(公告)日：2015-12-08
申请号：US13821022
申请日：2011-09-07
申请人： Mikhail Mikhaylovich Ovsyanko
发明人： Mikhail Mikhaylovich Ovsyanko
IPC分类号： G01N27/74 , H01F7/06 , G01N33/543 , G01R33/12 , G01N21/552 , G01N35/00
CPC分类号： G01N27/745 , G01N21/552 , G01N33/54366 , G01N35/0098 , G01R33/1269
摘要： Magnetic particles (1) are attracted to a contact surface (11) in an associated sensor device (100) by generating a pulsed magnetic field (B) according to an actuation protocol. The protocol includes a “local attraction phase” during which the duty cycle of the pulsations is smaller than about 10%, preferably ranging between 2% and 5%. These small duty cycles are advantageous in bringing magnetic particles (1) into actual contact with the contact surface (11).
摘要翻译：通过根据致动协议生成脉冲磁场（B），磁性颗粒（1）被吸引到相关传感器装置（100）中的接触表面（11）。该方案包括“局部吸引相”，在此期间脉动的占空比小于约10％，优选在2％和5％之间。这些小的占空比有利于使磁性颗粒（1）与接触表面（11）实际接触。

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