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1. 发明申请

WO2022112475A1 DIFFRACTOMETRIC SENSOR FOR THE DETECTION OF BINDING AFFINITIES 审中-公开
公开(公告)号：WO2022112475A1
公开(公告)日：2022-06-02
申请号：PCT/EP2021/083109
申请日：2021-11-26
申请人： F. HOFFMANN-LA ROCHE AG , EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH , HOFFMANN-LA ROCHE INC.
发明人： FATTINGER, Christof , FRUTIGER, Andreas , REICHMUTH, Andreas Michael , BLICKENSTORFER, Yves Lukas , VÖRÖS, Janos , POPOV, Roman
IPC分类号： G01N21/47 , G01N21/77 , G01N33/50
摘要： A diffractometric sensor (1), comprises:- a substrate (3);- two interdigitated affinity gratings (2), a first affinity grating (20) comprising first unit cells (200) with affinity elements (201) and a second affinity grating (21) comprising second unit cells (210) with affinity elements (211),wherein the first unit cells (200) and second unit cells (210) are configured and arranged such that coherent light of a predetermined wavelength generated at a predetermined beam generation location (40) and diffracted by target molecules (204, 214)) bound to the affinity elements (201, 211) constructively interferes at a predetermined detection location (50) with an inverse phase, and wherein the first and second affinity gratings (20, 21) are balanced to generate a bias signal at the predetermined detection location (50) that corresponds to a difference (∆m) in the scattering mass of the first and second affinity gratings (20, 21) which is in the range of 0.001 pg/mm2 to 30000 pg/mm2.

2. 发明申请

WO2021074161A1 ARTIFICIAL TRANSMEMBRANE PROTEINS FOR DETECTING INTRACELLULAR OR INTRAVESICULAR BIOMOLECULAR INTERACTIONS 审中-公开
公开(公告)号：WO2021074161A1
公开(公告)日：2021-04-22
申请号：PCT/EP2020/078797
申请日：2020-10-13
申请人： ETH ZÜRICH , F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： VOEROES, Janos , REICHMUTH, Andreas, Michael , LUECHTEFELD, Ines , INCAVIGLIA, Ilaria , BLICKENSTORFER, Yves, Lukas , FRUTIGER, Andreas , FATTINGER, Christof
IPC分类号： G01N33/68 , C07K14/705 , C07K14/47 , C07K14/71 , C12N15/62
摘要： Disclosed herein is an artificial transmembrane protein for use in a biomolecular detection device for detecting intracellular or intravesicular biomolecular interactions, the artificial transmembrane protein comprising an extracellular or extravesicular binder structure, a hydrophobic transmembrane domain and an intracellular or intravesicular domain with an intracellular or intravesicular receptor structure, wherein the receptor structure is configured to interact with an intracellular or intravesicular component of the biomolecular interaction to be detected and wherein the extracellular or extravesicular binder structure is configured to bind to membrane recognition elements arranged along a plurality of predetermined lines of the biomolecular detection device.

3. 发明申请

WO2015004264A1 DEVICE FOR USE IN THE DETECTION OF BINDING AFFINITIES 审中-公开
标题翻译：用于检测绑定关系的设备
公开(公告)号：WO2015004264A1
公开(公告)日：2015-01-15
申请号：PCT/EP2014/064884
申请日：2014-07-11
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： FATTINGER, Christof
IPC分类号： G01N21/77
CPC分类号： G01N33/54386 , G01N21/7743 , G01N33/54373
摘要： A device (1) for use in the detection of binding affinities comprises a planar waveguide (2) arranged on a substrate (22). The waveguide (2) has an outer surface (21) and a plurality of incoupling lines (31) for coupling a beam of coherent light into the waveguide (2) such that a parallel beam of coherent light (62) propagates along the waveguide (2). The incoupling lines (31) are curved and have an increasing distance between adjacent incoupling lines (31). A divergent beam of coherent light (61) of a predetermined wavelength is coupled into the waveguide (2) such that it propagates along the waveguide (2). A plurality of binding sites (51) is attached to the outer surface (21) along at least one further plurality of diffraction lines arranged in an outcoupling section of the waveguide (2). These diffraction lines comprise a plurality of curved outcoupling lines (41) having a decreasing distance between adjacent outcoupling lines. They decouple a diffracted portion of coherent light from the planar waveguide (2), and the decoupled portion of coherent light (63) converges into a predetermined second focal location (631).
摘要翻译：用于检测结合亲和力的装置（1）包括布置在基底（22）上的平面波导（2）。波导（2）具有外表面（21）和多个入射线（31），用于将相干光束耦合到波导（2）中，使得平行的相干光束（62）沿着波导（ 2）。连接线（31）是弯曲的并且在相邻的连接线（31）之间具有增加的距离。将预定波长的相干光（61）的发散光束耦合到波导（2）中，使得其沿着波导（2）传播。沿着布置在波导管（2）的外耦合部分中的至少一个其它多个衍射线，多个结合位置（51）附接到外表面（21）。这些衍射线包括多个弯曲的输出耦合线（41），其相邻的输出耦合线之间的距离减小。它们将来自平面波导（2）的相干光的衍射部分分离，并且相干光（63）的解耦部分会聚到预定的第二焦点位置（631）。

4. 发明申请

WO2011076705A1 UNIT AND DEVICE FOR THE PREPARATION OF CELLS AND/OR PARTICLES IN A LIQUID AND METHOD FOR MICROSCOPIC ANALYSIS 审中-公开
标题翻译：用于制备液体中的细胞和/或颗粒的装置和装置以及用于微观分析的方法
公开(公告)号：WO2011076705A1
公开(公告)日：2011-06-30
申请号：PCT/EP2010/070185
申请日：2010-12-20
申请人： F. HOFFMANN-LA ROCHE AG , FATTINGER, Christof , RIETMANN, René , VOEGELIN, Dieter
发明人： FATTINGER, Christof , RIETMANN, René , VOEGELIN, Dieter
IPC分类号： B01L3/00 , G01N1/28
CPC分类号： B01L3/5025 , B01L2200/0647 , B01L2300/069 , B01L2300/0822 , B01L2300/0829 , B01L2400/0409 , B01L2400/0688 , G01N1/2813
摘要： A unit (10) for the preparation of cells contained in a liquid comprises a storage chamber (20) configured to store the liquid containing the cells and to release the stored liquid via an exit opening (22) upon the application of a predetermined external force, in particular a centrifugal force. A passage (30) adjacently arranged to the exit opening (22) has a cross-section larger than that of the exit opening (22). The wall at the transition from the exit opening (22) to the passage (30) forms an edge (32). The unit further comprises an observation member (50) for receiving the released liquid and an absorbing means (40) arranged adjacent to the observation member (50) between the passage (30) and the observation member (50). The absorbing means (40) has an aperture (42) allowing the released liquid to travel onto the observation member (50), and removes the liquid so as to leave the cells on the observation member (50) for observation.
摘要翻译：用于制备包含在液体中的细胞的单元（10）包括储存室（20），其被配置为储存含有细胞的液体，并且在施加预定的外力时通过出口（22）释放所储存的液体，特别是离心力。相邻地布置在出口开口（22）上的通道（30）的横截面大于出口开口（22）的横截面。从出口（22）到通道（30）的过渡处的壁形成边缘（32）。该单元还包括用于接收释放液体的观察构件（50）和在通道（30）和观察构件（50）之间邻近观察构件（50）布置的吸收装置（40）。吸收装置（40）具有允许释放的液体行进到观察构件（50）上的孔（42），并且除去液体以使细胞留在观察构件（50）上观察。

5. 发明申请

WO2021053042A1 BIOMOLECULAR DETECTION DEVICE 审中-公开
公开(公告)号：WO2021053042A1
公开(公告)日：2021-03-25
申请号：PCT/EP2020/075914
申请日：2020-09-16
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC. , ETH ZÜRICH
发明人： BLICKENSTORFER, Yves , FATTINGER, Christof , FRUTIGER, Andreas , REICHMUTH, Andreas, Michael , VOEROES, Janos
IPC分类号： G01N33/543 , G01N21/552 , G01N21/77
摘要： Disclosed herein is a biomolecular detection device (1) for analyzing a cell, vesicle or a cellular or vesicular component, comprising an evanescent illuminator with an optical coupling unit configured for generating an evanescent field from coherent light (L) with a predefined wavelength on a first surface of the evanescent illuminator. The first surface of evanescent illuminator comprises a template nanopattern (5), containing a coherent arrangement of a plurality of predetermined lines along which membrane recognition elements for a binder structure (82) of a transmembrane protein (81), preferably a laterally diffusible transmembrane protein, of the cell, vesicle or the cellular or vesicular component (8) are arranged. The membrane recognition elements (53) are configured to bind the binder structure (82) of the transmembrane protein (81) for forming a transmembrane nanopattern within the cell, vesicle or the cellular or vesicular component (8) based on the template nanopattern (5) of the evanescent illuminator, such that light of the evanescent field is scattered by the cell, vesicle or the cellular or vesicular component (8) bound to the membrane recognition elements (53). The predetermined lines are arranged such that light scattered by the cell, vesicle or cellular or vesicular components (8) bound to the membrane recognition elements (53) constructively interferes at a predefined detection site (7) with a difference in optical path length that is an integer multiple of the predefined wavelength of the coherent light (L).

6. 发明申请

WO2019166562A1 DEVICE FOR USE IN THE DETECTION OF BINDING AFFINITIES 审中-公开
公开(公告)号：WO2019166562A1
公开(公告)日：2019-09-06
申请号：PCT/EP2019/055008
申请日：2019-02-28
申请人： F. HOFFMANN-LA ROCHE AG
发明人： FATTINGER, Christof
IPC分类号： G01N21/77 , G01N21/47
摘要： A device for use in the detection of binding affinities comprises a substrate (3), a planar waveguide (2) arranged thereon and having an outer surface (7). The device further comprises a grating (4) for coupling coherent light of a predetermined wavelength into the planar waveguide (2) such that the coherent light (5) coupled into the planar waveguide (2) propagates through the planar waveguide in a predetermined propagation direction. An evanescent field (6) of the coherent light (5) propagates along the outer surface (7) of the planar waveguide (2). The outer surface (7) of the planar waveguide (2) has receptor molecules (8) arranged thereon capable of binding target samples (9) to the receptor molecules (8) such that light of the evanescent field (6) is diffracted by the target samples (9) bound to the receptor molecules (8). The receptor molecules (8) are arranged along a plurality of straight parallel lines (11) which are spaced from each other such that a portion of the light of the evanescent field is diffracted by the target samples (9) bound to the receptor molecules (8) and forms a collimated beam (12) of diffracted coherent light propagating away from the planar waveguide (2) in a predetermined detection direction (13).

7. 发明申请

WO2014111521A1 METHOD FOR PREPARING AN OUTER SURFACE OF A PLANAR WAVEGUIDE TO BE CAPABLE OF BINDING TARGET SAMPLES ALONG A PLURALITY OF PREDETERMINED LINES AND A PLANAR WAVEGUIDE 审中-公开
标题翻译：用于制备平面波导的外表面的方法可用于在预测线和平面波导的多重条件下的绑定目标样本
公开(公告)号：WO2014111521A1
公开(公告)日：2014-07-24
申请号：PCT/EP2014/050902
申请日：2014-01-17
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： FATTINGER, Christof
IPC分类号： G01N33/543
CPC分类号： G02B6/26 , G01N33/54353 , G01N33/54373 , G01N33/54393
摘要： According to the invention there is provided a method for preparing the outer surface (11) of the planar waveguide (1) for binding target samples along the plurality of predetermined lines (4). The method comprises the following steps. Providing a planar waveguide (1) with an outer surface (11) adapted for attachment of a head group (21) of a linker molecule (2) to the outer surface (11). Sequentially applying at least one plurality of linker molecules (2, 5) to the outer surface (11). Each plurality of the at least one plurality of linker molecules (2, 5) assembles to form an individual layer of linker molecules (2, 5) with individual layers formed one above the other starting from the outer surface (11) of the planar waveguide (1). Each linker molecule (2, 5) comprises a functional group (22, 52) and the head group (21, 51) which is capable of attaching to the outer surface (11) of the planar waveguide (1) or to the functional groups (22) of the preceding layer of linker molecules (2). The functional groups (52) of the plurality of linker molecules (5; 2) of the uppermost layer are bound to photo-labile protecting groups (3) so that each functional group (52) bound to a said photo-labile protecting group (3) is incapable of attaching a complementary functional group of a further molecule. Exposing those photo-labile protecting groups (3) of the uppermost layer arranged along a plurality of predetermined lines (4) to light of a predetermined wavelength to remove the exposed photo-labile protecting groups (3) from the functional groups (52) to make these functional groups (52) capable of attaching a complementary functional group of a further molecule. (Fig. 1)
摘要翻译：根据本发明，提供了一种用于制备平面波导（1）的外表面（11）的方法，用于沿着多条预定线（4）结合目标样本。该方法包括以下步骤。提供具有适于将连接分子（2）的头基（21）附接到外表面（11）的外表面（11）的平面波导（1）。将至少一个多个接头分子（2,5）顺序施加到外表面（11）上。每个多个至少一个多个连接分子（2,5）组装形成一个单独的连接分子层（2,5），其中各层从平面波导的外表面（11）一个层叠在一起（1）。每个连接体分子（2,5）包括能够连接到平面波导（1）的外表面（11）的官能团（22,52）和头基（21,51）或官能团（22）连接分子（2）的前一层。最上层的多个连接分子（5; 2）中的官能团（52）与光不稳定保护基（3）结合，使得每个官能团（52）与所述光不稳定保护基（ 3）不能连接另外分子的互补官能团。将沿着多个预定线（4）布置的最上层的那些光不稳定保护基（3）暴露于预定波长的光以将暴露的光不稳定保护基（3）从官能团（52）移除到使得能够附着另外分子的互补官能团的这些官能团（52）。（图。1）

8. 发明申请

WO2013107811A1 DEVICE FOR USE IN THE DETECTION OF BINDING AFFINITIES 审中-公开
标题翻译：用于检测绑定关系的设备
公开(公告)号：WO2013107811A1
公开(公告)日：2013-07-25
申请号：PCT/EP2013/050825
申请日：2013-01-17
申请人： F. HOFFMANN-LA ROCHE AG
发明人： FATTINGER, Christof
IPC分类号： G01N21/55 , G01N21/77 , G01N33/543
CPC分类号： G01N21/75 , G01N21/552 , G01N21/7743 , G01N33/54373
摘要： A device for use in the detection of binding affinities comprises a planar waveguide (2) arranged on a substrate (3), and an optical coupler (4) for coupling coherent light (1) of a predetermined wavelength into the planar waveguide. The coherent light propagates through the planar waveguide (2) with an evanescent field (6) propagating along an outer surface (5) of the planar waveguide. The outer surface (5) of the planar waveguide comprises binding sites (7) thereon capable of binding target samples (8) to the binding sites (7) such that light of the evanescent field (6) is scattered by target samples (8) bound to the binding sites (7). The binding sites (7) are arranged along a plurality of predetermined lines (9) which are arranged such that the scattered light constructively interferes at a predetermined detection location with a difference in optical path length which is an integer multiple of the predetermined wavelength.
摘要翻译：用于检测结合亲和力的装置包括布置在基板（3）上的平面波导（2）和用于将预定波长的相干光（1）耦合到平面波导中的光耦合器（4）。相干光通过平面波导（2）传播，沿着平面波导的外表面（5）传播的渐逝场（6）。平面波导的外表面（5）包括其上能够将目标样品（8）结合到结合位点（7）的结合位点（7），使得消逝场（6）的光被目标样品（8）散射，结合位点（7）。绑定位置（7）沿着多条预定线（9）布置，这些线被布置为使得散射光以预定波长的整数倍的光路长度的差异在预定的检测位置建设性地干扰。

9. 发明申请

WO2015007674A1 DEVICE FOR USE IN THE DETECTION OF BINDING AFFINITIES 审中-公开
标题翻译：用于检测绑定关系的设备
公开(公告)号：WO2015007674A1
公开(公告)日：2015-01-22
申请号：PCT/EP2014/065013
申请日：2014-07-14
申请人： F. HOFFMANN-LA ROCHE AG , HOFFMANN-LA ROCHE INC.
发明人： FATTINGER, Christof
IPC分类号： G01N21/64 , G01N33/543 , G01N33/551 , G01N21/47
CPC分类号： G01N33/54373 , G01N21/47 , G01N21/648
摘要： A device (1) for use in the detection of binding affinities comprises a substrate (2) devoid of a waveguide. The substrate (2) has a planar surface (21) having arranged thereon a plurality of binding sites (31) capable of binding with a target molecule (32). The binding sites (31) are arranged along a plurality of adjacently arranged curved lines (4). The lines are spaced from one another by a distance to in operation cause a beam of coherent light (51) of a predetermined wavelength incident on the binding sites (31) with the bound target molecule (32) to be diffracted in a manner such that diffracted portions (61) interfere at a predetermined detection location (62) with a difference in optical path length which is a multiple integer of the predetermined wavelength of the coherent light. The device further comprises a beam stop (7) arranged to prevent propagation of non-diffracted portions (63) of the incident beam of coherent light (51) to the detection location (62).
摘要翻译：用于检测结合亲和力的装置（1）包括没有波导的基板（2）。衬底（2）具有在其上布置有能够与靶分子（32）结合的多个结合位点（31）的平面（21）。结合位置（31）沿着多个相邻排列的曲线（4）排列。这些线彼此间隔开一段距离，使入射到结合位点（31）上的预定波长的相干光束（51）与结合的靶分子（32）被衍射，使得衍射部分（61）在相干光的预定波长的多个整数的光程长度差处于预定检测位置（62）。该装置还包括一个光束停止器（7），其布置成防止相干光（51）的入射光束的非衍射部分（63）传播到检测位置（62）。

10. 发明申请

WO2014086789A1 DEVICE FOR USE IN THE DETECTION OF BINDING AFFINITIES 审中-公开
标题翻译：用于检测绑定关系的设备
公开(公告)号：WO2014086789A1
公开(公告)日：2014-06-12
申请号：PCT/EP2013/075408
申请日：2013-12-03
申请人： F. HOFFMANN-LA ROCHE AG
发明人： FATTINGER, Christof
IPC分类号： G01N21/77
CPC分类号： G01N21/75 , G01N21/7703 , G01N21/774 , G01N2021/752 , G01N2021/7776 , G01N2021/7793 , G01N2201/0438
摘要： A device for use in the detection of binding affinities, the device comprising a planar waveguide (2) arranged on a substrate (3), and further comprising an optical coupler (41) having a predetermined length for coupling coherent light (1) of a predetermined wavelength into the planar waveguide (2) such that a parallel beam of coherent light propagates through the planar waveguide (2) with an evanescent field (11) of the coherent light propagating along an outer surface (21) of the planar waveguide (2). The outer surface (21) of the planar waveguide (2) comprises binding sites thereon capable of binding target samples to the binding sites such that light of the evanescent field (11) is diffracted by target samples bound to the binding sites. The binding sites are arranged along a plurality of predetermined straight lines (7) running parallel to one another with a constant distance between adjacent straight lines. The predetermined straight lines (7) are arranged at an angle relative to the direction of propagation of the evanescent field (11) such that the coherent light (12) diffracted by the target samples bound to the binding sites impinges under a diffraction angle relative to the straight lines onto a further optical coupler (8) arranged in a portion (10) of the planar waveguide (2) outside the beam of coherent light propagating through the planar waveguide. The further optical coupler (8) couples the diffracted coherent light (13) out of the planar waveguide (2) such as to interfere at a predetermined detection location (9) with a difference in optical path length which is an integer multiple of the predetermined wavelength.
摘要翻译：一种用于检测结合亲和力的装置，该装置包括布置在基板（3）上的平面波导（2），并且还包括具有预定长度的光耦合器（41），用于耦合相干光（1）预定波长进入平面波导（2），使得相干光的平行光通过平面波导（2）的外表面（21）的相干光的消逝场（11）传播通过平面波导（2））。平面波导（2）的外表面（21）包括其上能够将目标样品结合到结合位点的结合位点，使得消逝场（11）的光被与结合位点结合的靶标样物衍射。结合位置沿着彼此平行延伸的多条预定直线（7）布置，在相邻直线之间具有恒定的距离。预定的直线（7）相对于ev逝场（11）的传播方向以一定角度排列，使得被绑定位置的目标样本衍射的相干光（12）相对于布置在平面波导（2）的部分（10）中的另外的光耦合器（8）的直线延伸穿过平面波导传播的相干光束外部。另外的光耦合器（8）将衍射的相干光（13）耦合到平面波导（2）之外，以便以预定的检测位置（9）干涉光路长度的差异，该光程长度是预定的波长。

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