公开(公告)号：US06638743B2

公开(公告)日：2003-10-28

申请号：US10119354

申请日：2002-04-09

申请人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jörg Gahle ,  Bernhard Wolf ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

发明人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jörg Gahle ,  Bernhard Wolf ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

IPC分类号： C12N1300

CPC分类号： C12N15/89 ,  C12M35/02 ,  C12M35/04 ,  C12M35/08 ,  C12N13/00

摘要： A method is provided for measuring a state variable of a biological cell (3) located in a nutrient medium (2) and supported on and adhering to a support area (5). Within the support area (5) for the cell (3) and at a distance from the support area edge, an opening is made in the membrane of the cell (3). The edge of the cell membrane that surrounds the opening and adheres to the support area (5) seals off the liquid found inside the cell (3) from the nutrient medium (2). Through the opening the state variable (2) is measured. An apparatus for performing the method is also provided.

公开(公告)号：US06368851B1

公开(公告)日：2002-04-09

申请号：US09321458

申请日：1999-05-27

申请人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jürgen Gahle ,  Bernhard Wolf ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

发明人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jürgen Gahle ,  Bernhard Wolf ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

IPC分类号： C12M142

CPC分类号： C12N15/89 ,  C12M35/02 ,  C12M35/04 ,  C12M35/08 ,  C12N13/00

摘要： A method is provided for measuring a state variable of a biological cell (3) located in a nutrient medium (2) and supported on and adhering to a support area (5). Within the support area (5) for the cell (3) and at a distance from the support area edge, an opening is made in the membrane of the cell (3). The edge of the cell membrane that surrounds the opening and adheres to the support area (5) seals off the liquid found inside the cell (3) from the nutrient medium (2). Through the opening the state variable (2) is measured. An apparatus for performing the method is also provided.

摘要翻译： 提供了一种用于测量位于营养介质（2）中并被支撑并附着到支撑区域（5）上的生物体（3）的状态变量的方法。 在电池（3）的支撑区域（5）内并且距离支撑区域边缘一定距离处，在电池（3）的膜中形成开口。 围绕开口并附着到支撑区域（5）的细胞膜的边缘将从细胞（3）内发现的液体与营养培养基（2）密封。 通过打开状态变量（2）进行测量。 还提供了一种用于执行该方法的装置。

公开(公告)号：US06475760B1

公开(公告)日：2002-11-05

申请号：US09321051

申请日：1999-05-27

申请人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jürgen Gahle ,  Bernhard Wolf ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

发明人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jürgen Gahle ,  Bernhard Wolf ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

IPC分类号： C12N1300

CPC分类号： C12N15/89 ,  C12M35/02 ,  C12M35/04 ,  C12M35/08 ,  C12N13/00

摘要： A process is provided for the intracellular manipulation of a biological cell (3) which is positioned adhering to a support area (5) in a culture medium (2). Inside the support area (5) for the cell (3) an opening into the membrane of the cell (3) is created spaced from its support edge. The edge of the cell membrane surrounding the opening, adhering to the support area (5), thus seals off the cell fluid situated in the interior of the cell (3) from the culture medium (2) and insulates the cell fluid against the culture medium (2). The interior of the cell (3) is manipulated through the opening. An apparatus for implementing the process is also provided, including an object carrier (4) with a support area (5) for adhering the cell and a poration tool (6) for creating the opening in the cell membrane. The poration tool (6) may be any of various chemical, mechanical and/or electrical devices.

摘要翻译： 提供了一种用于细胞内操作生物细胞（3）的方法，所述生物细胞（3）定位为粘附在培养基（2）中的支持区域（5）。 在电池（3）的支撑区域（5）的内部，与电池（3）的隔膜形成的开口与其支撑边缘间隔开。 围绕开口的细胞膜的边缘附着在支撑区域（5）上，从而将位于细胞（3）内部的细胞液体与培养基（2）密封并使细胞液体抵抗培养物 中等（2）。 电池（3）的内部通过开口被操纵。 还提供了一种用于实现该方法的装置，包括具有用于粘附细胞的支撑区域（5）的物体载体（4）和用于在细胞膜中形成开口的引锭工具（6）。 引锭工具（6）可以是各种化学，机械和/或电气装置中的任何一种。

公开(公告)号：US07501276B2

公开(公告)日：2009-03-10

申请号：US10202419

申请日：2002-07-23

申请人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jürgen Gahle ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

发明人： Werner Baumann ,  Ralf Ehret ,  Mirko Lehmann ,  Günter Igel ,  Hans-Jürgen Gahle ,  Ulrich Sieben ,  Ingo Freund ,  Martin Brischwein

IPC分类号： C12M1/42 ,  C12N15/87

CPC分类号： C12N15/89 ,  C12M35/02 ,  C12M35/04 ,  C12M35/08 ,  C12N13/00

摘要： A process is provided for the intracellular manipulation of a biological cell (3) which is positioned adhering to a support area (5) in a culture medium (2). Inside the support area (5) for the cell (3) an opening into the membrane of the cell (3) is created spaced from its support edge. The edge of the cell membrane surrounding the opening, adhering to the support area (5), thus seals off the cell fluid situated in the interior of the cell (3) from the culture medium (2) and insulates the cell fluid against the culture medium (2). The interior of the cell (3) is manipulated through the opening. An apparatus for implementing the process is also provided, including an object carrier (4) with a support area (5) for adhering the cell and a poration tool (6) for creating the opening in the cell membrane. The poration tool (6) may be any of various chemical, mechanical and/or electrical devices.

摘要翻译： 提供了一种用于细胞内操作生物细胞（3）的方法，所述生物细胞（3）定位为粘附在培养基（2）中的支持区域（5）。 在电池（3）的支撑区域（5）的内部，与电池（3）的隔膜形成的开口与其支撑边缘间隔开。 围绕开口的细胞膜的边缘附着在支撑区域（5）上，从而将位于细胞（3）内部的细胞液体与培养基（2）密封在一起，并使细胞液体抵抗培养物 中等（2）。 电池（3）的内部通过开口被操纵。 还提供了一种用于实现该方法的装置，包括具有用于粘附细胞的支撑区域（5）的物体载体（4）和用于在细胞膜中形成开口的引锭工具（6）。 引锭工具（6）可以是各种化学，机械和/或电气装置中的任何一种。

公开(公告)号：US20080145922A1

公开(公告)日：2008-06-19

申请号：US11952219

申请日：2007-12-07

申请人： Mirko Lehmann ,  Martin Brischwein ,  Werner Baumann ,  Ralf Ehret ,  Ingo Freund

发明人： Mirko Lehmann ,  Martin Brischwein ,  Werner Baumann ,  Ralf Ehret ,  Ingo Freund

IPC分类号： C12M1/00

CPC分类号： C12M41/46 ,  C12M27/02 ,  C12M33/04

摘要： A device (1) for the carrying out of investigations on cell cultures (2) which take place in a liquid culture medium (4). The device possesses at least a receptacle (3) to contain the culture medium (4) including the cell culture (2), wherein one or more sensors (6) for measurement of the cell culture activities is provided and wherein the receptacle (3) has at least an opening for the adding and the removal of liquid culture medium (4) and the like. A separating element (7) can be introduced into the open upper part of the receptacle (3) and can be brought within the said receptacle (3) in a position close to the bottom (5), in which the said separating element (7) makes a boundary forming a partial space (8) which has a small volume in relation to the entire volume of the receptacle (3). Further, a flow channel (9) is provided, which first, communicates with the small volume partial space (8), and second, communicates with the said reservoir (14). This flow channel (9) and/or the sensors (6) are placed in the area of the small volume partial space (8). By means of the capability for adjustment of the separating element (7) as to its distance from the bottom of the receptacle (3), in the neighborhood of the cell culture (2) a microreaction volume exactly fitting the current requirements can be adjusted. By means of the flow channel (9), the cell culture (2) in the small volume partial space (8) stands in fluid communication with that in the reservoir. For the regeneration of the cell culture solution in the small volume partial space, the separating element (7) can be elevated and depressed, or it is possible, to inject into the small volume partial space of the receptacle (3) a quantity of liquid and by means of a through-flow channel. In this case, a convective mixing of fresh and spent medium takes place through the flow channel (9) between the small volume partial space and the reservoir (14).

公开(公告)号：US07795012B2

公开(公告)日：2010-09-14

申请号：US11952219

申请日：2007-12-07

申请人： Mirko Lehmann ,  Martin Brischwein ,  Werner Baumann ,  Ralf Ehret ,  Ingo Freund

发明人： Mirko Lehmann ,  Martin Brischwein ,  Werner Baumann ,  Ralf Ehret ,  Ingo Freund

IPC分类号： C12M1/34

CPC分类号： C12M41/46 ,  C12M27/02 ,  C12M33/04

摘要： A device for investigating activities of cell cultures in a liquid culture medium includes a receptacle for the culture medium, and one or more sensors for measurement of cell culture activities. An opening for adding and removing liquid culture medium is provided. A separating element can be placed close to the receptacle bottom, forming a partial space with a small volume relative to the entire volume. A flow channel that communicates with the small volume and the reservoir and/or the sensors are placed in the small volume partial space. By adjustment of the separating element distance from the receptacle bottom, a microreaction volume exactly fitting the current requirements is obtained. For regeneration of the cell culture solution in the small volume partial space, the separating element can be elevated and depressed, or liquid can be injected into the small volume by the through-flow channel, providing convective mixing of fresh and spent medium.

摘要翻译： 用于调查液体培养基中细胞培养物的活性的装置包括用于培养基的容器和用于测量细胞培养活性的一个或多个传感器。 提供了用于添加和除去液体培养基的开口。 分离元件可以靠近容器底部放置，形成相对于整个体积具有小体积的部分空间。 与小容量和储存器和/或传感器连通的流动通道被放置在小体积部分空间中。 通过调节与容器底部的分离元件距离，可以获得与当前要求完全一致的微反应体积。 为了在小体积部分空间中再生细胞培养液，分离元件可以被升高和降低，或者可以通过通流通道将液体注入到小容积中，从而提供新鲜和废弃的介质的对流混合。

公开(公告)号：US07470962B2

公开(公告)日：2008-12-30

申请号：US10591413

申请日：2005-03-01

申请人： Werner Baumann ,  Mirko Lehmann ,  Ingo Freund ,  Hans-Jurgen Gahle

发明人： Werner Baumann ,  Mirko Lehmann ,  Ingo Freund ,  Hans-Jurgen Gahle

IPC分类号： H01L31/00

CPC分类号： G01N33/48728 ,  G01N27/4145

摘要： The invention relates to a device for measuring living cells or similar biocomponents comprising a field effect transistor which is provided with a source, a drain and a channel area placed on a substrate. Said channel area connects said source and drain and is provided with a gate-electrode mounted thereon. The gate electrode has at least two laterally disposed parallel electrode areas which are perpendicular to a direction in which the channel area connects the source to the drain in such a way that they are distant and electrically insulated from each other.

摘要翻译： 本发明涉及用于测量活细胞或类似生物组件的装置，其包括场效应晶体管，该场效应晶体管设置有放置在基板上的源极，漏极和沟道区域。 所述通道区域连接所述源极和漏极，并且设置有安装在其上的栅电极。 栅电极具有至少两个横向设置的平行电极区域，其垂直于沟道区域将源极连接到漏极的方向，使得它们彼此远离并且电绝缘。

公开(公告)号：US20070284630A1

公开(公告)日：2007-12-13

申请号：US10591413

申请日：2005-03-01

申请人： Werner Baumann ,  Mirko Lehmann ,  Ingo Freund ,  Hans-Jurger Gahle

发明人： Werner Baumann ,  Mirko Lehmann ,  Ingo Freund ,  Hans-Jurger Gahle

IPC分类号： H01L29/76 ,  C12Q1/02

CPC分类号： G01N33/48728 ,  G01N27/4145

摘要： The invention relates to a device for measuring living cells or similar biocomponents comprising a field effect transistor which is provided with a source, a drain and a channel area placed on a substrate. Said channel area connects said source and drain and is provided with a gate-electrode mounted thereon. The gate electrode has at least two laterally disposed parallel electrode areas which are perpendicular to a direction in which the channel area connects the source to the drain in such a way that they are distant and electrically insulated from each other.

摘要翻译： 本发明涉及用于测量活细胞或类似生物组件的装置，其包括场效应晶体管，该场效应晶体管设置有放置在基板上的源极，漏极和沟道区域。 所述通道区域连接所述源极和漏极，并且设置有安装在其上的栅电极。 栅电极具有至少两个横向设置的平行电极区域，其垂直于沟道区域将源极连接到漏极的方向，使得它们彼此远离并且电绝缘。

公开(公告)号：US08084792B2

公开(公告)日：2011-12-27

申请号：US12840597

申请日：2010-07-21

申请人： Mirko Lehmann ,  Ingo Freund

发明人： Mirko Lehmann ,  Ingo Freund

IPC分类号： H01L29/78

CPC分类号： G01N27/4148

摘要： An electric component comprising a sensor and/or actuator chip with a substrate on which a passivating layer and a sensor and/or actuator structure consisting of an active surface area is arranged. The chip is surrounded by an encapsulation having an opening which forms an access to the at least one active surface area. A layer stack is arranged on the substrate, said stack of layers comprising from the passivating layer to the substrate at least one first strip conductor layer, a first electric insulating layer, a second strip conductor layer and a second electric insulating layer. The first conductor strip layer is fully arranged outside the area of the chip covered by the opening. At least one conductor strip of the second conductor strip layer is connected to the sensor and/or actuator structure.

摘要翻译： 一种电气部件，包括具有衬底的传感器和/或致动器芯片，其上布置有由活性表面积组成的钝化层和传感器和/或致动器结构。 芯片由具有开口的封装围绕，该开口形成对至少一个有源表面区域的访问。 层叠在衬底上，层叠层包括至少一个第一带状导体层，第一电绝缘层，第二带状导体层和第二电绝缘层，从钝化层到衬底。 第一导体带层完全布置在由开口覆盖的芯片的区域的外部。 第二导体带层的至少一个导体条连接到传感器和/或致动器结构。

公开(公告)号：US07592195B2

公开(公告)日：2009-09-22

申请号：US10504738

申请日：2003-02-07

申请人： Markus Rogalla ,  Ingo Freund ,  Mirko Lehmann

发明人： Markus Rogalla ,  Ingo Freund ,  Mirko Lehmann

IPC分类号： H01L21/00

CPC分类号： B81B7/0061

摘要： In a method for producing a sensor arrangement and the resulting sensor arrangement, a sensor is provided on or in a chip and the chip is covered with a protective cover, the cover being an interface between the sensor and the environment. An adhesive layer is provided between the chip and the protective cover, the adhesive layer alone or together with the protective cover being an interface between the sensor and the environment. The protective cover and/or the adhesive layer may have a channel formed therein, the channel functioning as the reception channel for a sensor. In an alternative embodiment, the protective cover placed on a wafer with several chips, and the wafer is cut up to produce the individual chips with the protective cover. Thus, a sensor arrangement may have the protective cover applied to the individual chip after the chip is cut from the wafer, or the protective cover may be applied to the wafer, and the wafer and cover are then cut up into the individual chips and corresponding covers. The channel leading from one side of the arrangement to the sensor may be taken through the adhesive layer, through the protective cover, or through both. A hole may be formed in the protective cover above the sensor, with the sensor lying loosely in the hole. The reaction volume may be determined by the dimensions of the hole.

摘要翻译： 在用于制造传感器装置和所得到的传感器装置的方法中，传感器设置在芯片上或芯片中，并且芯片被保护盖覆盖，盖是传感器和环境之间的接口。 粘合剂层设置在芯片和保护盖之间，粘合剂层单独或与保护罩一起作为传感器和环境之间的界面。 保护盖和/或粘合剂层可以具有形成在其中的通道，该通道用作传感器的接收通道。 在替代实施例中，将保护盖放置在具有几个芯片的晶片上，并且切割晶片以用保护盖产生单独的芯片。 因此，在从晶片切割芯片之后，传感器装置可以具有施加到单个芯片的保护盖，或者可以将保护盖施加到晶片，然后将晶片和盖切割成各个芯片，并且对应于 盖子。 从布置的一侧引导到传感器的通道可以穿过粘合剂层，通过保护盖，或者通过两者。 可以在传感器上方的保护罩中形成孔，传感器松动地位于孔中。 反应体积可以由孔的尺寸确定。