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1. 发明授权

US10323223B2 Homogeneous cell dispensing mixer 有权
公开(公告)号：US10323223B2
公开(公告)日：2019-06-18
申请号：US15413077
申请日：2017-01-23
申请人： PBS Biotech, Inc.
发明人： Chanyong Brian Lee , Yasunori Hashimura , Oscar Garza , Gary Evans
IPC分类号： C12M1/00 , C12M1/06 , C12N5/071 , C12M1/26 , C12M1/12
摘要： A vessel having a mixer that ensures a homogeneous cell distribution in dispensed quantities. The vessel has a mixer therein for stirring contents of the vessel and an orifice in a lower wall to which a cell dispenser is attached. The cell dispenser dispenses quantities of suspended cells having a homogeneous cell distribution.

2. 发明授权

US09637717B2 Method and apparatus for the use of micro-carriers in a disposable bioreactor system 有权
公开(公告)号：US09637717B2
公开(公告)日：2017-05-02
申请号：US14153679
申请日：2014-01-13
申请人： PBS BIOTECH, Inc.
发明人： Chanyong Brian Lee , Yasunori Hashimura
IPC分类号： C12M3/00 , C12M1/12 , C12M1/06 , C12M1/00 , C12M1/34
CPC分类号： C12M25/16 , C12M27/04 , C12M27/06 , C12M29/04 , C12M29/06 , C12M33/14 , C12M37/00 , C12M41/00 , C12N1/00 , Y10T137/0318
摘要： A system and method for compartmentalizing micro-carriers in a bioreactor includes a container configured to store micro-carriers and a vessel configured to contain a fluid so as to prevent the micro-carriers from entering the vessel during sterilization, shipping, storage, or other pre-use handling of the system. One or more addition lines connect the container and the vessel such that the vessel is in fluid communication with the vessel. The one or more addition lines are contactable by at least one blocking element configured to reversibly block fluid flow between the container and the vessel. The container, addition lines, and vessel are configured to allow the micro-carriers to be injected into the vessel at any point during a cell culture run. The vessel may also include a rotatable wheel, a harvest port configured to allow for the removal of the micro-carriers from the vessel, and a media removal port comprising a retention screen for removing spent medium.

3. 发明授权

US08790913B2 Methods of using pneumatic bioreactors 有权
标题翻译：使用气动生物反应器的方法
公开(公告)号：US08790913B2
公开(公告)日：2014-07-29
申请号：US12884431
申请日：2010-09-17
申请人： J. Gregory Zeikus
发明人： J. Gregory Zeikus
IPC分类号： C12N1/12 , A01G7/00 , C12M1/02 , B01F7/04 , C12M1/00 , B01F7/22 , C12M1/12 , B01F7/00 , C12M1/09 , C12M1/06 , C12M1/34 , B01F3/04
CPC分类号： C12M27/06 , B01F3/04531 , B01F7/00183 , B01F7/00308 , B01F7/00916 , B01F7/04 , B01F7/22 , B01F2003/04631 , B01F2003/04673 , C12M23/28 , C12M23/56 , C12M27/00 , C12M37/00 , C12M41/12 , C12M41/42
摘要： A pneumatic bioreactor includes a vessel containing a fluid to be mixed and at least one mixing device driven by gas pressure. A first embodiment includes a floating impeller that rises and falls in the fluid as gas bubbles carry it upward to the surface where the gas is then vented, permitting the impeller to sink in the fluid. The floating impeller may be tethered to a second impeller with a flexible member and pulley. The mixing speed is controlled with electromagnets in the vessel acting upon magnetic material in the impeller or its guides. In another embodiment, floating pistons mix the fluid, pushing it through a mixing plate with one or more apertures. In a third embodiment, the mixing device is a rotating drum with bubble-catching blades and rotating mixing plates with apertures. The top of the vessel for these mixers may include a closed top and sterile filters.
摘要翻译：气动生物反应器包括容纳待混合的流体的容器和由气体压力驱动的至少一个混合装置。第一实施例包括浮动叶轮，其随着气泡将其向上运送到气体然后被排出的表面而上升和下降，允许叶轮沉入流体中。浮动叶轮可以用柔性构件和滑轮系在第二叶轮上。混合速度由容器中的电磁体控制，作用在叶轮或其引导件中的磁性材料上。在另一个实施例中，浮动活塞将流体混合，将其推入具有一个或多个孔的混合板。在第三实施例中，混合装置是具有吸泡叶片的旋转鼓和具有孔的旋转混合板。用于这些混合器的容器的顶部可以包括封闭的顶部和无菌过滤器。

4. 发明授权

US07819576B2 Pneumatic bioreactor 有权
标题翻译：气动生物反应器
公开(公告)号：US07819576B2
公开(公告)日：2010-10-26
申请号：US12606519
申请日：2009-10-27
申请人： J. Gregory Zeikus
发明人： J. Gregory Zeikus
IPC分类号： B26D7/06
CPC分类号： B01F3/04113 , B01F3/04602 , B01F7/00483 , B01F11/0082 , B01F15/005 , B01F15/00525 , C12M23/56 , C12M27/02 , C12M27/06
摘要： A pneumatic bioreactor includes a vessel containing a fluid to be mixed and at least one mixing device driven by gas pressure. A first embodiment includes a floating impeller that rises and falls in the fluid as gas bubbles carry it upward to the surface where the gas is then vented, permitting the impeller to sink in the fluid. The floating impeller may be tethered to a second impeller with a flexible member and pulley. The mixing speed is controlled with electromagnets in the vessel acting upon magnetic material in the impeller or its guides. In another embodiment, floating pistons mix the fluid, pushing it through a mixing plate with one or more apertures. In a third embodiment, the mixing device is a rotating drum with bubble-catching blades and rotating mixing plates with apertures. The top of the vessel for these mixers may include a closed top and sterile filters.
摘要翻译：气动生物反应器包括容纳待混合的流体的容器和由气体压力驱动的至少一个混合装置。第一实施例包括浮动叶轮，其随着气泡将其向上运送到气体然后被排出的表面而上升和下降，允许叶轮沉入流体中。浮动叶轮可以用柔性构件和滑轮系在第二叶轮上。混合速度由容器中的电磁体控制，作用在叶轮或其引导件中的磁性材料上。在另一个实施例中，浮动活塞将流体混合，将其推入具有一个或多个孔的混合板。在第三实施例中，混合装置是具有吸泡叶片的旋转鼓和具有孔的旋转混合板。用于这些混合器的容器的顶部可以包括封闭的顶部和无菌过滤器。

5. 发明授权

US07713730B2 Pneumatic bioreactor 有权
标题翻译：气动生物反应器
公开(公告)号：US07713730B2
公开(公告)日：2010-05-11
申请号：US11739659
申请日：2007-04-24
申请人： J. Gregory Zeikus , Kyungnam Kim , Thomas A. Post , Keith E. Johnson
发明人： J. Gregory Zeikus , Kyungnam Kim , Thomas A. Post , Keith E. Johnson
IPC分类号： C12M1/06
CPC分类号： C12M27/06 , B01F3/04588 , B01F7/00308 , B01F7/00916 , B01F7/04 , B01F15/005 , B01F15/00545 , C12M27/20
摘要： A pneumatic bioreactor having a containment vessel which includes a semi-cylindrical concavity defined by the vessel bottom. A mixing apparatus includes a rotational mixer rotatably mounted within the containment vessel about a horizontal axis. The rotational mixer has buoyancy-driven mixing cavities which are fed by a gas supply beneath the rotational mixer. The mixing apparatus extends into the semi-cylindrical concavity to substantially fill that concavity. The rotational mixer is divided into two wheels with outer paddles extending axially outwardly and inner paddles extending axially inwardly on either side of each wheel. Blades between the outer and inner paddles form impellers in the wheels to induce axial flow through the wheels in opposite directions. Stationary baffles fixed relative to the containment vessel are inclined toward the rotational mixer in the direction of rotation. The containment vessel may be of film and supported by a structural housing also having a semi-cylindrical concavity defined by the housing bottom.
摘要翻译：一种具有容纳容器的气动生物反应器，其包括由容器底部限定的半圆柱形凹面。混合装置包括旋转混合器，其围绕水平轴可旋转地安装在容纳容器内。旋转混合器具有浮力驱动的混合腔，其通过旋转混合器下面的气体供给。混合装置延伸到半圆柱形凹部中以基本上填充该凹部。旋转混合器被分成两个轮子，其外侧叶片沿轴向向外延伸，内部桨叶在每个轮的任一侧上轴向向内延伸。外桨叶和内桨叶之间的叶片在车轮中形成叶轮，以引起相反方向的轴向流动。相对于安全壳固定的固定挡板在旋转方向上朝向旋转混合器倾斜。安全壳可以是薄膜，并由具有由壳体底部限定的半圆柱形凹面的结构外壳支撑。

6. 发明申请

US20210230532A1 SYSTEMS AND METHODS FOR SCALABLE MANUFACTURING OF THERAPEUTIC CELLS IN BIOREACTORS 有权
公开(公告)号：US20210230532A1
公开(公告)日：2021-07-29
申请号：US17160139
申请日：2021-01-27
申请人： PBS Biotech, Inc.
发明人： Chanyong Brian Lee , Breanna Shalyn Borys
IPC分类号： C12M1/34 , C12N5/0775 , C12N5/0735 , C12N5/074 , C12M1/06 , C12M1/42
摘要： Systems and methods for scalable manufacturing of therapeutic cells in bioreactors are disclosed. Fluid dynamic considerations for scale in accordance with an implementation include a method of production of therapeutic cells grown on microcarriers or as cell aggregates in a suspension-based bioreactor includes depositing a suspension comprising cells suspended in a volume of culture fluid into a bioreactor and setting an agitation rate of a mixer disposed in the bioreactor. The method includes actuating the mixer at the set agitation rate to mix the suspension in the bioreactor. The suspension includes a plurality of turbulent eddies generated by the mixer. A magnitude of an energy dissipation rate (EDR) of at least approximately 60% of the turbulent eddies can be less than approximately 0.0015 m2/s3.

7. 发明授权

US10059915B2 Cell culture method in a bioreactor system using micro-carriers 有权
公开(公告)号：US10059915B2
公开(公告)日：2018-08-28
申请号：US15496753
申请日：2017-04-25
申请人： PBS Biotech, Inc.
发明人： Chanyong Brian Lee , Yasunori Hashimura
IPC分类号： C12M3/00 , C12M1/12 , C12N1/00 , C12M1/26 , C12M1/04 , C12M1/00
CPC分类号： C12M25/16 , C12M27/04 , C12M27/06 , C12M29/04 , C12M29/06 , C12M33/14 , C12M37/00 , C12M41/00 , C12N1/00 , Y10T137/0318
摘要： A system and method for compartmentalizing micro-carriers in a bioreactor includes a container configured to store micro-carriers and a vessel configured to contain a fluid so as to prevent the micro-carriers from entering the vessel during sterilization, shipping, storage, or other pre-use handling of the system. One or more addition lines connect the container and the vessel such that the vessel is in fluid communication with the vessel. The one or more addition lines are contactable by at least one blocking element configured to reversibly block fluid flow between the container and the vessel. The container, addition lines, and vessel are configured to allow the micro-carriers to be injected into the vessel at any point during a cell culture run. The vessel may also include a rotatable wheel, a harvest port configured to allow for the removal of the micro-carriers from the vessel, and a media removal port comprising a retention screen for removing spent medium.

8. 发明申请

US20140196791A1 METHOD AND APPARATUS FOR THE USE OF MICRO-CARRIERS IN A DISPOSABLE BIOREACTOR SYSTEM 有权
标题翻译：使用微载体在可处理的生物反应器系统中的方法和装置
公开(公告)号：US20140196791A1
公开(公告)日：2014-07-17
申请号：US14153679
申请日：2014-01-13
申请人： PBS BIOTECH, Inc.
发明人： Chanyong Brian LEE , Yasunori HASHIMURA
IPC分类号： C12M1/12
CPC分类号： C12M25/16 , C12M27/04 , C12M27/06 , C12M29/04 , C12M29/06 , C12M33/14 , C12M37/00 , C12M41/00 , C12N1/00 , Y10T137/0318
摘要： A system and method for compartmentalizing micro-carriers in a bioreactor includes a container configured to store micro-carriers and a vessel configured to contain a fluid so as to prevent the micro-carriers from entering the vessel during sterilization, shipping, storage, or other pre-use handling of the system. One or more addition lines connect the container and the vessel such that the vessel is in fluid communication with the vessel. The one or more addition lines are contactable by at least one blocking element configured to reversibly block fluid flow between the container and the vessel. The container, addition lines, and vessel are configured to allow the micro-carriers to be injected into the vessel at any point during a cell culture run. The vessel may also include a rotatable wheel, a harvest port configured to allow for the removal of the micro-carriers from the vessel, and a media removal port comprising a retention screen for removing spent medium.
摘要翻译：用于在生物反应器中分隔微载体的系统和方法包括：构造成存储微载体的容器和构造成容纳流体的容器，以便在灭菌，运输，储存或其它过程中防止微载体进入容器系统的预先使用处理。一个或多个添加管线连接容器和容器，使得容器与容器流体连通。一个或多个添加管线可被至少一个阻挡元件接触，该阻挡元件被构造成可逆地阻止容器和容器之间的流体流动。容器，添加管线和容器构造成允许微细载体在细胞培养运行期间的任何点注入血管。容器还可以包括可旋转轮，收集口构造成允许从容器移除微载体，以及介质移除端口，其包括用于移除废介质的保留屏。

9. 发明授权

US08281672B2 Automatable aseptic sample withdrawal system 有权
标题翻译：自动无菌取样系统
公开(公告)号：US08281672B2
公开(公告)日：2012-10-09
申请号：US12727719
申请日：2010-03-19
申请人： Chanyong Brian Lee , Daniel Giroux
发明人： Chanyong Brian Lee , Daniel Giroux
IPC分类号： G01N1/00
CPC分类号： G01N1/14 , C12M33/06 , C12M37/02 , C12M41/00 , G01N2001/1427
摘要： An aseptic sampling system includes substantially sealed sampling lines connecting one or more sample container to a vessel containing the fluid to be sampled. A flow control system includes valves and/or clamps placed strategically along the sampling lines and filtered vent lines are provided at strategic locations relative to a reversible fluid pump in communication with the sampling lines. The clamps are selectively actuated, the vent lines are selectively opened or closed, and the pump is operated in a forward or reverse direction to permit a volume of sample fluid to be drawn from the vessel and into a sample container and to permit fluid to be purged from the sampling lines either into the sample container or back into the vessel. Thus, sampling and purging can be accomplished without opening the system to potentially contaminating agents and without wasting or having to properly dispose the fluid.
摘要翻译：无菌采样系统包括将一个或多个样品容器连接到容纳待采样流体的容器的基本上密封的采样管线。流量控制系统包括沿采样管道策略地放置的阀和/或夹具，并且在与采样管路连通的可逆流体泵的相关战略位置提供过滤的排气管线。选择性地启动夹具，排气管线被选择性地打开或关闭，并且泵在正向或反向方向上操作，以允许一定体积的样品流体从容器中抽出并进入样品容器并允许流体为从采样管线中清除或进入样品容器或回到容器中。因此，可以在不将系统打开到潜在的污染剂的情况下完成取样和清洗，而不会浪费或不必适当地处理流体。

10. 发明申请

US20110003366A1 METHODS OF USING PNEUMATIC BIOREACTORS 有权
标题翻译：使用气动生物反应器的方法
公开(公告)号：US20110003366A1
公开(公告)日：2011-01-06
申请号：US12884431
申请日：2010-09-17
申请人： J. Gregory ZEIKUS
发明人： J. Gregory ZEIKUS
IPC分类号： C12N1/00
CPC分类号： C12M27/06 , B01F3/04531 , B01F7/00183 , B01F7/00308 , B01F7/00916 , B01F7/04 , B01F7/22 , B01F2003/04631 , B01F2003/04673 , C12M23/28 , C12M23/56 , C12M27/00 , C12M37/00 , C12M41/12 , C12M41/42
摘要： A pneumatic bioreactor includes a vessel containing a fluid to be mixed and at least one mixing device driven by gas pressure. A first embodiment includes a floating impeller that rises and falls in the fluid as gas bubbles carry it upward to the surface where the gas is then vented, permitting the impeller to sink in the fluid. The floating impeller may be tethered to a second impeller with a flexible member and pulley. The mixing speed is controlled with electromagnets in the vessel acting upon magnetic material in the impeller or its guides. In another embodiment, floating pistons mix the fluid, pushing it through a mixing plate with one or more apertures. In a third embodiment, the mixing device is a rotating drum with bubble-catching blades and rotating mixing plates with apertures. The top of the vessel for these mixers may include a closed top and sterile filters.
摘要翻译：气动生物反应器包括容纳待混合的流体的容器和由气体压力驱动的至少一个混合装置。第一实施例包括浮动叶轮，其随着气泡将其向上运送到气体然后被排出的表面而上升和下降，允许叶轮沉入流体中。浮动叶轮可以用柔性构件和滑轮系在第二叶轮上。混合速度由容器中的电磁体控制，作用在叶轮或其引导件中的磁性材料上。在另一个实施例中，浮动活塞将流体混合，将其推入具有一个或多个孔的混合板。在第三实施例中，混合装置是具有吸泡叶片的旋转鼓和具有孔的旋转混合板。用于这些混合器的容器的顶部可以包括封闭的顶部和无菌过滤器。

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