公开(公告)号：US06407437B1

公开(公告)日：2002-06-18

申请号：US09044735

申请日：1998-03-19

申请人： Jürgen Burger ,  Felix Baader ,  Rudolf Buser ,  Olivier Elsenhans ,  Nicolas Szita

发明人： Jürgen Burger ,  Felix Baader ,  Rudolf Buser ,  Olivier Elsenhans ,  Nicolas Szita

IPC分类号： H01L2984

CPC分类号： B01L3/0268 ,  B01L3/021 ,  B01L2200/146 ,  B01L2400/0481 ,  G01N2035/1039

摘要： A micromechanical pipetting device comprising an integrally built pipetting module which has an inlet/outlet which may be connected to a removable pipetting tip or integrally built with a pipetting tip. The pipetting module comprises a micromechanical structure which is integrally built on a silicon wafer. In order to improve the accuracy of the pipetted volume the device is characterized in that it comprises a) a first chamber located within said pipetting module, the volume comprised within said first chamber being alterable by displacement of a membrane which is a portion of a wall of said chamber, said first chamber having an opening, said opening being permanently open and allowing fluid flow into and from the interior of said first chamber, b) a channel located within said pipetting module, said channel establishing a direct, valveless and permanent fluidical connection between said opening of the first chamber and the inlet/outlet of the pipetting module, c) actuator means for displacing said membrane, and thereby aspiring or expelling a volume of air or of a liquid into or from said first chamber, which in turn causes aspiring or expelling a volume of a liquid sample into respectively from said pipetting tip, and d) first sensor means for generating a first output signal related to the displacement of the membrane.

摘要翻译： 一种微机械移液装置，其包括一体式构造的移液模块，其具有可连接到可移动移液末端或与移液头一体构建的入口/出口。 移液模块包括一体地构建在硅晶片上的微机械结构。 为了提高吸移体积的精度，该装置的特征在于它包括：a）位于所述移液模块内的第一腔室，包含在所述第一腔室内的体积可以通过膜的位移而变化，所述膜是壁的一部分 所述腔室，所述第一腔室具有开口，所述开口永久地打开并允许流体流入和流出所述第一腔室的内部，b）位于所述移液模块内的通道，所述通道建立直接，无阀和永久的流体连接 在所述第一室的所述开口和所述移液模块的入口/出口之间，c）用于移动所述膜的致动器装置，从而将一定体积的空气或液体向所述第一室吸入或排出， 分别从所述移液头吸取或排出体积的液体样品，以及d）用于产生与t相关的第一输出信号的第一传感器装置 他的膜的位移。

公开(公告)号：US07125519B1

公开(公告)日：2006-10-24

申请号：US10148149

申请日：2000-11-21

申请人： Nicolas Szita ,  Rudolf Buser ,  Olivier Elsenhans

发明人： Nicolas Szita ,  Rudolf Buser ,  Olivier Elsenhans

IPC分类号： B01L3/00

CPC分类号： B01L3/0268 ,  B01L9/54 ,  B01L2200/146 ,  B01L2300/0809 ,  B01L2400/0439 ,  B01L2400/0481 ,  G01N35/10 ,  G01N2035/00237 ,  Y10T436/2575

摘要： The present invention is directed a system for coupling a macroactuator to a movable element of a micromachined device. The system includes a micromachined device, a first body for holding a macroactuator, a macroactuator mechanically mounted on the first body, a second body having a bore for receiving the first body, a screw arrangement for fixing the axial position of the first body within the bore of the second body, and a plate arrangement for mounting the micromachined device on the second body. The plate arrangement is mounted in such a way that the macroactuator exerts a predetermined force or pressure on a movable element of the micromachined device. The present invention further is directed to a pipetting module that includes the micromachined device and the macroactuator.

摘要翻译： 本发明涉及一种将大型致动器耦合到微加工装置的可移动元件的系统。 该系统包括微加工装置，用于保持大致动器的第一主体，机械地安装在第一主体上的大致动器，具有用于容纳第一主体的孔的第二主体，用于将第一主体的轴向位置固定在第一主体内的螺钉装置 第二主体的孔，以及用于将微加工装置安装在第二主体上的板装置。 板装置以这样的方式安装，使得大致动器对微加工装置的可移动元件施加预定的力或压力。 本发明还涉及一种包括微加工装置和大型致动器的移液模块。

公开(公告)号：US20060281213A1

公开(公告)日：2006-12-14

申请号：US11466336

申请日：2006-08-22

申请人： Nicolas Szita ,  Rudolf Buser ,  Olivier Elsenhans

发明人： Nicolas Szita ,  Rudolf Buser ,  Olivier Elsenhans

IPC分类号： H01L21/00 ,  H01L29/82

CPC分类号： B01L3/0268 ,  B01L9/54 ,  B01L2200/146 ,  B01L2300/0809 ,  B01L2400/0439 ,  B01L2400/0481 ,  G01N35/10 ,  G01N2035/00237 ,  Y10T436/2575

摘要： The present invention is directed a system for coupling a macroactuator to a movable element of a micromachined device. The system includes a micromachined device, a first body for holding a macroactuator, a macroactuator mechanically mounted on the first body, a second body having a bore for receiving the first body, a screw arrangement for fixing the axial position of the first body within the bore of the second body, and a plate arrangement for mounting the micromachined device on the second body. The plate arrangement is mounted in such a way that the macroactuator exerts a predetermined force or pressure on a movable element of the micromachined device. The present invention further is directed to a pipetting module that includes the micromachined device and the macroactuator.

摘要翻译： 本发明涉及一种将大型致动器耦合到微加工装置的可移动元件的系统。 该系统包括微加工装置，用于保持大致动器的第一主体，机械地安装在第一主体上的大致动器，具有用于容纳第一主体的孔的第二主体，用于将第一主体的轴向位置固定在第一主体内的螺钉装置 第二主体的孔，以及用于将微加工装置安装在第二主体上的板装置。 板装置以这样的方式安装，使得大致动器对微加工装置的可移动元件施加预定的力或压力。 本发明还涉及一种包括微加工装置和大型致动器的移液模块。

公开(公告)号：US20050089993A1

公开(公告)日：2005-04-28

申请号：US10816046

申请日：2004-04-01

申请人： Paolo Boccazzi ,  Angela Chen ,  Klavs Jensen ,  Nicolas Szita ,  Andrea Zanzotto ,  Zhiyu Zhang

发明人： Paolo Boccazzi ,  Angela Chen ,  Klavs Jensen ,  Nicolas Szita ,  Andrea Zanzotto ,  Zhiyu Zhang

IPC分类号： B01L3/00 ,  B01L9/00 ,  C12M1/34 ,  C12M1/36 ,  C12M3/00 ,  G01N35/00

CPC分类号： C12M1/12 ,  B01F13/0059 ,  B01F13/0827 ,  B01J2219/00283 ,  B01J2219/00317 ,  B01J2219/00479 ,  B01J2219/00481 ,  B01J2219/00484 ,  B01J2219/00495 ,  B01J2219/00585 ,  B01J2219/00599 ,  B01J2219/00691 ,  B01J2219/00743 ,  B01L3/5027 ,  B01L3/502715 ,  B01L3/502723 ,  B01L9/527 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/0867 ,  B01L2300/0877 ,  B01L2300/10 ,  B01L2400/0466 ,  B01L2400/0487 ,  C12M23/16 ,  C12M35/08 ,  C12M41/48 ,  G01N2035/00326 ,  Y10S435/808 ,  Y10S435/809

摘要： The present invention provides a variety of microscale bioreactors (microfermentors) and microscale bioreactor arrays for use in culturing cells. The microfermentors include a vessel for culturing cells and means for providing oxygen to the interior of the vessel at a concentration sufficient to support cell growth, e.g., growth of bacterial cells. Depending on the embodiment, the microfermentor vessel may have various interior volumes less than approximately 1 ml. The microfermentors may include an aeration membrane and optionally a variety of sensing devices. The invention further provides a chamber to contain the microfermentors and microfermentor arrays and to provide environmental control. Certain of the microfermentors include a second chamber that may be used, e.g., to provide oxygen, nutrients, pH control, etc., to the culture vessel and/or to remove metabolites, etc. Various methods of using the microfermentors, e.g., to select optimum cell strains or bioprocess parameters are provided. The invention provides microreactors having a variety of different designs, some of which incorporate active stirring and/or have the capability to operate in batch or fed-batch mode. The invention further provides an apparatus and methods for simultaneous operation of a plurality of microreactors, with monitoring of the individual microreactors during a run. The invention further provides methods of performing gene expression analysis on cells cultured in microreactors.

摘要翻译： 本发明提供用于培养细胞的各种微量生物反应器（微发酵器）和微生物生物反应器阵列。 微发酵器包括用于培养细胞的容器和用于以足以支持细胞生长（例如细菌细胞生长）的浓度向容器内部提供氧气的装置。 根据实施方案，微发酵罐容器可以具有小于约1ml的各种内部容积。 微发酵器可以包括曝气膜和任选的各种感测装置。 本发明进一步提供了容纳微发射体和微发光体阵列并提供环境控制的腔室。 某些微发酵器包括第二室，其可以用于例如向培养容器提供氧气，营养物质，pH控制等，和/或去除代谢物等。使用微发酵器的各种方法，例如， 选择最佳细胞株或生物过程参数。 本发明提供具有各种不同设计的微反应器，其中一些具有主动搅拌和/或具有以分批或分批模式操作的能力。 本发明还提供了一种用于同时操作多个微反应器的装置和方法，其中在运行期间监测各个微反应器。 本发明还提供了对在微反应器中培养的细胞进行基因表达分析的方法。

公开(公告)号：US20110306081A1

公开(公告)日：2011-12-15

申请号：US13116577

申请日：2011-05-26

申请人： Nicolas Szita ,  Marcel Reichen

发明人： Nicolas Szita ,  Marcel Reichen

IPC分类号： C12Q1/02 ,  B32B37/16 ,  C12N5/02 ,  F16L13/14 ,  C12M1/00 ,  B23C3/00

CPC分类号： B01L3/502715 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2200/0689 ,  B01L2300/0627 ,  B01L2300/0816 ,  B01L2300/0874 ,  B01L2300/10 ,  B01L2300/12 ,  B01L2400/086 ,  C12M23/16 ,  C12M23/26 ,  C12M29/10 ,  Y10T409/303752

摘要： The invention relates to a microfluidic device including a chamber having a fluid inlet, a fluid outlet and a sealable port. In some embodiments, the fluid inlet and the fluid outlet may be positioned to direct fluid flowing from the fluid inlet to the fluid outlet through the chamber. Various embodiments may include a sealable port which may be aligned with the chamber to allow material to be placed directly into, or removed from, the chamber from the exterior of the device when the sealable port is open, and to inhibit and/or prevent fluid escaping through the sealable port when the port is sealed.

摘要翻译： 本发明涉及一种微流体装置，其包括具有流体入口，流体出口和可密封端口的室。 在一些实施例中，流体入口和流体出口可以被定位成将从流体入口流出的流体引导通过腔室流体出口。 各种实施例可以包括可密封的端口，其可以与腔室对准，以允许当可密封端口打开时材料被直接放置在设备外部或从设备的外部移除，并且抑制和/或防止流体 当港口密封时，通过可密封的端口排出。

公开(公告)号：US07507579B2

公开(公告)日：2009-03-24

申请号：US10816046

申请日：2004-04-01

申请人： Paolo Boccazzi ,  Angela Y. Chen ,  Klavs F. Jensen ,  Nicolas Szita ,  Andrea Zanzotto ,  Zhiyu Zhang

发明人： Paolo Boccazzi ,  Angela Y. Chen ,  Klavs F. Jensen ,  Nicolas Szita ,  Andrea Zanzotto ,  Zhiyu Zhang

IPC分类号： C12M1/12 ,  C12M1/34 ,  C12M3/00 ,  C12M1/00 ,  G06K9/00

CPC分类号： C12M1/12 ,  B01F13/0059 ,  B01F13/0827 ,  B01J2219/00283 ,  B01J2219/00317 ,  B01J2219/00479 ,  B01J2219/00481 ,  B01J2219/00484 ,  B01J2219/00495 ,  B01J2219/00585 ,  B01J2219/00599 ,  B01J2219/00691 ,  B01J2219/00743 ,  B01L3/5027 ,  B01L3/502715 ,  B01L3/502723 ,  B01L9/527 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/0867 ,  B01L2300/0877 ,  B01L2300/10 ,  B01L2400/0466 ,  B01L2400/0487 ,  C12M23/16 ,  C12M35/08 ,  C12M41/48 ,  G01N2035/00326 ,  Y10S435/808 ,  Y10S435/809

摘要： The present invention provides a variety of microscale bioreactors (microfermentors) and microscale bioreactor arrays for use in culturing cells. The microfermentors include a vessel for culturing cells and means for providing oxygen to the interior of the vessel at a concentration sufficient to support cell growth, e.g., growth of bacterial cells. Depending on the embodiment, the microfermentor vessel may have various interior volumes less than approximately 1 ml. The microfermentors may include an aeration membrane and optionally a variety of sensing devices. The invention further provides a chamber to contain the microfermentors and microfermentor arrays and to provide environmental control. Certain of the microfermentors include a second chamber that may be used, e.g., to provide oxygen, nutrients, pH control, etc., to the culture vessel and/or to remove metabolites, etc. Various methods of using the microfermentors, e.g., to select optimum cell strains or bioprocess parameters are provided. The invention provides microreactors having a variety of different designs, some of which incorporate active stirring and/or have the capability to operate in batch or fed-batch mode. The invention further provides an apparatus and methods for simultaneous operation of a plurality of microreactors, with monitoring of the individual microreactors during a run. The invention further provides methods of performing gene expression analysis on cells cultured in microreactors.

摘要翻译： 本发明提供用于培养细胞的各种微量生物反应器（微发酵器）和微生物生物反应器阵列。 微发酵器包括用于培养细胞的容器和用于以足以支持细胞生长（例如细菌细胞生长）的浓度向容器内部提供氧气的装置。 根据实施方案，微发酵罐容器可以具有小于约1ml的各种内部容积。 微发酵器可以包括曝气膜和任选的各种感测装置。 本发明进一步提供了容纳微发射体和微发光体阵列并提供环境控制的腔室。 某些微发酵器包括第二室，其可以用于例如向培养容器提供氧气，营养物质，pH控制等，和/或去除代谢物等。使用微发酵器的各种方法，例如， 选择最佳细胞株或生物过程参数。 本发明提供具有各种不同设计的微反应器，其中一些具有主动搅拌和/或具有以分批或分批模式操作的能力。 本发明还提供了一种用于同时操作多个微反应器的装置和方法，其中在运行期间监测各个微反应器。 本发明还提供了对在微反应器中培养的细胞进行基因表达分析的方法。

公开(公告)号：US20060249441A1

公开(公告)日：2006-11-09

申请号：US11412991

申请日：2006-04-28

申请人： Jeffery Baur ,  Corey Fucetola ,  Nicolas Szita

发明人： Jeffery Baur ,  Corey Fucetola ,  Nicolas Szita

IPC分类号： B01D63/04

CPC分类号： B01D63/02 ,  B01D63/021 ,  B01D63/022 ,  B01J2219/00813 ,  B01L3/502707 ,  B01L3/502715 ,  B01L3/502746 ,  B01L3/565 ,  B01L2200/027 ,  B01L2300/0896 ,  B81B2201/058 ,  B81B2201/13 ,  B81C1/00071 ,  B82Y30/00

摘要： An apparatus to hold hollow fibers for transporting fluid may include a channel such as a connecting channel, for example formed in a substrate, including extensions or ridges to hold a hollow fiber. The pullout force for the hollow fiber may exceed the mechanical strength of the hollow fiber. A method for making such a device, or for making a nanofluidic connector, may include forming or drilling holes on a substrate along a line, where the holes are generally perpendicular to the substrate and have a desired depth.

摘要翻译： 用于保持用于输送流体的中空纤维的装置可以包括诸如连接通道的通道，例如形成在基板中，包括用于保持中空纤维的延伸部或脊。 中空纤维的拉拔力可能会超过中空纤维的机械强度。 用于制造这种装置或用于制造纳米流体连接器的方法可以包括沿着一条线在基底上形成或钻孔，其中孔通常垂直于基底并且具有期望的深度。