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1. 发明授权

US09181521B2 Bioreactor with upward flowing impeller system for use in a mammalian cell culture process 有权
标题翻译：具有向上流动的叶轮系统的生物反应器用于哺乳动物细胞培养过程
公开(公告)号：US09181521B2
公开(公告)日：2015-11-10
申请号：US13559957
申请日：2012-07-27
申请人： Alan T. Y. Cheng , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
发明人： Alan T. Y. Cheng , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
IPC分类号： C12M1/06 , C12M1/00 , C12N1/38 , C12M1/08 , C12M1/34 , C12M1/36
CPC分类号： C12M27/20 , C12M27/02 , C12M27/24 , C12M29/06 , C12M41/12 , C12M41/26 , C12M41/32 , C12M41/48 , C12N1/38
摘要： A bioreactor with an upward flowing impeller system for controlling a mammalian cell culture process is provided. The disclosed system enables control of the cell culture process by controlling the level of dissolved carbon dioxide in the cell culture media and prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide via surface gas exchange with little or no damage to the mammalian cells. The use of an upward flow impeller combined with vertical baffles converts the swirling motions of the cell culture media into a largely vertical flow and promotes the removal of dissolved carbon dioxide via surface gas exchange with a sweep gas flowing over the top surface of the cell culture media within the bioreactor vessel.
摘要翻译：提供了一种具有向上流动的叶轮系统用于控制哺乳动物细胞培养过程的生物反应器。所公开的系统能够通过控制细胞培养基中溶解的二氧化碳的水平来控制细胞培养过程，并且通过经由表面气体交换增强汽提二氧化碳来实现渗透压浓度的增加，对哺乳动物几乎没有或没有损伤细胞。使用与垂直挡板结合的向上流动叶轮将细胞培养基的旋转运动转化为大体垂直的流动，并通过与流过细胞培养物顶表面的吹扫气体的表面气体交换促进去除溶解的二氧化碳生物反应器容器内的介质。

2. 发明申请

US20130189767A1 BIOREACTOR WITH UPWARD FLOWING IMPELLER SYSTEM FOR USE IN A MAMMALIAN CELL CULTURE PROCESS 有权
标题翻译：具有向上流动的叶轮系统的生物反应器在马马里细胞培养过程中使用
公开(公告)号：US20130189767A1
公开(公告)日：2013-07-25
申请号：US13559957
申请日：2012-07-27
申请人： Alan T. Y. Cheng , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
发明人： Alan T. Y. Cheng , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
IPC分类号： C12M1/00
CPC分类号： C12M27/20 , C12M27/02 , C12M27/24 , C12M29/06 , C12M41/12 , C12M41/26 , C12M41/32 , C12M41/48 , C12N1/38
摘要： A bioreactor with an upward flowing impeller system for controlling a mammalian cell culture process is provided. The disclosed system enables control of the cell culture process by controlling the level of dissolved carbon dioxide in the cell culture media and prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide via surface gas exchange with little or no damage to the mammalian cells. The use of an upward flow impeller combined with vertical baffles converts the swirling motions of the cell culture media into a largely vertical flow and promotes the removal of dissolved carbon dioxide via surface gas exchange with a sweep gas flowing over the top surface of the cell culture media within the bioreactor vessel.
摘要翻译：提供了一种具有向上流动的叶轮系统用于控制哺乳动物细胞培养过程的生物反应器。所公开的系统能够通过控制细胞培养基中溶解的二氧化碳的水平来控制细胞培养过程，并且通过经由表面气体交换增强汽提二氧化碳来实现渗透压浓度的增加，对哺乳动物几乎没有或没有损伤细胞。使用与垂直挡板结合的向上流动叶轮将细胞培养基的旋转运动转化为大体垂直的流动，并通过与流过细胞培养物顶表面的吹扫气体的表面气体交换促进去除溶解的二氧化碳生物反应器容器内的介质。

3. 发明授权

US08241904B2 System and method for controlling a mammalian cell culture process 有权
标题翻译：用于控制哺乳动物细胞培养过程的系统和方法
公开(公告)号：US08241904B2
公开(公告)日：2012-08-14
申请号：US12536559
申请日：2009-08-06
申请人： Alan T. Y. Cheng , Ying Zhou , Balazs Hunek , Amitabh Gupta , Nigel Grinter
发明人： Alan T. Y. Cheng , Ying Zhou , Balazs Hunek , Amitabh Gupta , Nigel Grinter
IPC分类号： C12N5/02
CPC分类号： C12N1/38 , C12M27/02 , C12M29/22
摘要： A system and method for controlling a mammalian cell culture process are provided. Such control of the cell culture process involves control of the level of dissolved carbon dioxide in the cell culture media and the resulting ability to prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide with little or no damage to the mammalian cells. The disclosed methods and systems of dissolved carbon dioxide stripping include enhanced surface gas exchange mechanisms within the bioreactor vessel through the use of an upward flow impeller combined with vertical baffles to convert swirling motions of the liquid into a largely vertical flow.
摘要翻译：提供了一种用于控制哺乳动物细胞培养方法的系统和方法。细胞培养过程的这种控制涉及控制细胞培养基中溶解的二氧化碳的水平，并且通过增强对二氧化碳的去除而对哺乳动物细胞几乎没有或没有损伤来实现所产生的渗透压浓度增加的能力。所公开的溶解二氧化碳汽提方法和系统包括通过使用与垂直挡板结合的向上流动叶轮将生物反应器容器内的表面气体交换机制改进为将液体的旋转运动转化成大体垂直的流动。

4. 发明授权

US08178318B2 Method for controlling pH, osmolality and dissolved carbon dioxide levels in a mammalian cell culture process to enhance cell viability and biologic product yield 有权
标题翻译：用于在哺乳动物细胞培养过程中控制pH，重量摩尔渗透压浓度和溶解二氧化碳水平以增强细胞活力和生物产物产率的方法
公开(公告)号：US08178318B2
公开(公告)日：2012-05-15
申请号：US12702428
申请日：2010-02-09
申请人： Alan T. Y. Cheng , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
发明人： Alan T. Y. Cheng , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
IPC分类号： C12P21/02
CPC分类号： C12N5/0018 , C12N1/38 , C12N2500/02 , C12N2500/60
摘要： Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.
摘要翻译：提供了用于在哺乳动物细胞培养过程中控制溶解二氧化碳水平和限制重量克分子渗透浓度以增强细胞生长，活力和密度以及提高生物产物浓度和产量的方法。通过在哺乳动物细胞培养过程中采用替代的pH控制策略和CO 2汽提技术来实现对哺乳动物细胞培养过程中溶解的二氧化碳和pH的水平的控制以及所产生的限制重量克分子渗透浓度的能力。这种pH控制技术和二氧化碳汽提不发生泡沫，对哺乳动物细胞几乎没有或没有损害。

5. 发明申请

US20100035343A1 SYSTEM AND METHOD FOR CONTROLLING A MAMMALIAN CELL CULTURE PROCESS 有权
标题翻译：用于控制MAMMALIAN细胞培养方法的系统和方法
公开(公告)号：US20100035343A1
公开(公告)日：2010-02-11
申请号：US12536559
申请日：2009-08-06
申请人： Alan T.Y. Cheng , Ying Zhou , Balazs Hunek , Amitabh Gupta , Nigel Grinter
发明人： Alan T.Y. Cheng , Ying Zhou , Balazs Hunek , Amitabh Gupta , Nigel Grinter
IPC分类号： C12N5/02 , C12M1/02 , C12M1/34 , C12M1/36 , C12M1/00
CPC分类号： C12N1/38 , C12M27/02 , C12M29/22
摘要： A system and method for controlling a mammalian cell culture process are provided. Such control of the cell culture process involves control of the level of dissolved carbon dioxide in the cell culture media and the resulting ability to prevent increases in the osmolality level is achieved by enhanced stripping of carbon dioxide with little or no damage to the mammalian cells. The disclosed methods and systems of dissolved carbon dioxide stripping include enhanced surface gas exchange mechanisms within the bioreactor vessel through the use of an upward flow impeller combined with vertical baffles to convert swirling motions of the liquid into a largely vertical flow.
摘要翻译：提供了一种用于控制哺乳动物细胞培养方法的系统和方法。细胞培养过程的这种控制涉及控制细胞培养基中溶解的二氧化碳的水平，并且通过增强对二氧化碳的去除而对哺乳动物细胞几乎没有或没有损伤来实现所产生的渗透压浓度增加的能力。所公开的溶解二氧化碳汽提方法和系统包括通过使用与垂直挡板结合的向上流动叶轮将生物反应器容器内的表面气体交换机制改进为将液体的旋转运动转化成大体垂直的流动。

6. 发明申请

US20100184147A1 METHOD FOR CONTROLLING pH, OSMOLALITY AND DISSOLVED CARBON DIOXIDE LEVELS IN A MAMMALIAN CELL CULTURE PROCESS TO ENHANCE CELL VIABILITY AND BIOLOGIC PRODUCT YIELD 有权
标题翻译：用于控制马萨诸塞细胞培养过程中pH，OSMALALITY和溶解二氧化碳水平的方法，以增强细胞毒性和生物产品含量
公开(公告)号：US20100184147A1
公开(公告)日：2010-07-22
申请号：US12702428
申请日：2010-02-09
申请人： ALAN T.Y. CHENG , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
发明人： ALAN T.Y. CHENG , Ying Zhou , Amitabh Gupta , Balazs Hunek , Nigel Grinter
IPC分类号： C12P21/06 , C12N5/02
CPC分类号： C12N5/0018 , C12N1/38 , C12N2500/02 , C12N2500/60
摘要： Methods for controlling the level of dissolved carbon dioxide and limiting osmolality in a mammalian cell culture process to enhance cell growth, viability and density, and increase biologic product concentration and yield are provided. Such control of the level of dissolved carbon dioxide and pH as well as the resulting ability to limit osmolality in a mammalian cell culture process is achieved by adopting alternative pH control strategies and CO2 stripping techniques during a mammalian cell culture process. Such pH control techniques and carbon dioxide stripping occur without foam and with little or no damage to the mammalian cells.
摘要翻译：提供了用于在哺乳动物细胞培养过程中控制溶解二氧化碳水平和限制重量克分子渗透浓度以增强细胞生长，活力和密度以及提高生物产物浓度和产量的方法。通过在哺乳动物细胞培养过程中采用替代的pH控制策略和CO 2汽提技术来实现对哺乳动物细胞培养过程中溶解的二氧化碳和pH的水平的控制以及所产生的限制重量克分子渗透浓度的能力。这种pH控制技术和二氧化碳汽提不发生泡沫，对哺乳动物细胞几乎没有或没有损害。

7. 发明申请

US20140047851A1 BULK FREEZING OF BIOPHARMACEUTICALS 审中-公开
标题翻译：生物吸收的大容量冷冻
公开(公告)号：US20140047851A1
公开(公告)日：2014-02-20
申请号：US14008455
申请日：2012-03-27
申请人： Ying Zhou , Alan Cheng , Nigel Grinter , Zachary Fowler , Robert Sever , Ranko Bursac
发明人： Ying Zhou , Alan Cheng , Nigel Grinter , Zachary Fowler , Robert Sever , Ranko Bursac
IPC分类号： F25D3/10
CPC分类号： F25D3/10 , A01N1/0252 , A23L3/364 , F25D15/00 , F25D17/06 , F25D2400/38
摘要： A system and method for bulk freezing is provided. In one embodiment, the system and method for bulk freezing includes a bulk freezing container adapted to hold at least one and preferably a plurality of bags holding a biopharmaceutical liquid. The bulk freezing container includes at least a first and second shelf having corrugations wherein the second shelf is vertically arranged above the first shelf with the bags disposed between the shelves. The bags and the corrugations of the first and second shelves define a plurality of substantially parallel flow channels through which a cryogenic cold fluid or a warming fluid is passed to freeze and/or thaw the biopharmaceutical fluid. In another embodiment, the bulk freezing system and method includes a bulk freezing container with a plurality of adjacent elongated chambers adapted for holding the biopharmaceutical fluid. The adjacent elongated chambers have side walls defining a plurality of substantially parallel flow channels between the plurality of adjacent elongated chambers through which a heat transfer medium is passed for heat exchange through the side walls of the elongated chambers to the fluid within the elongated chambers.
摘要翻译：提供一种用于大容量冷冻的系统和方法。在一个实施例中，用于体积冷冻的系统和方法包括适于容纳至少一个并且优选地多个保持生物药物液体的袋的体积冷冻容器。散装冷冻容器至少包括具有波纹的第一和第二搁架，其中第二搁板垂直地布置在第一搁板的上方，袋子设置在搁架之间。第一和第二搁架的袋和波纹限定了多个基本平行的流动通道，低温冷流体或加温流体通过该流动通道冷冻和/或解冻生物药物流体。在另一个实施方案中，本体冷冻系统和方法包括具有适于保持生物药物流体的多个相邻细长室的体积冷冻容器。相邻的细长室具有在多个相邻的细长室之间限定多个基本平行的流动通道的侧壁，通过该多个相邻的细长室之间传热介质通过细长室的侧壁进行热交换，使其在细长室内的流体。

8. 发明授权

US09043172B2 Estimating virtual machine energy consumption 有权
标题翻译：估计虚拟机能耗
公开(公告)号：US09043172B2
公开(公告)日：2015-05-26
申请号：US13596612
申请日：2012-08-28
申请人： Ying Chen , Li Li , Liang Liu , Hao Wang , Ying Zhou
发明人： Ying Chen , Li Li , Liang Liu , Hao Wang , Ying Zhou
IPC分类号： G01R21/00 , G06F9/455 , G06F1/00 , G06F1/28 , G06F19/00
CPC分类号： G06F1/28 , G06F19/00 , Y02D10/26 , Y02D10/28
摘要： A method and apparatus for estimating virtual machine energy consumption, and in particular, a method and apparatus for estimating virtual machine energy consumption in a computer system. The method includes: obtaining system energy consumption of the system hardware resources; obtaining event information of a plurality of functional units into which the system hardware resources are divided, and mapping the event information to the respective virtual machines; and calculating energy consumption of the virtual machines according to a plurality of energy consumption coefficients corresponding to the plurality of functional units and according to the event information mapped to the functional units of the respective virtual machines.
摘要翻译：一种用于估计虚拟机能量消耗的方法和装置，特别是一种用于估计计算机系统中的虚拟机能量消耗的方法和装置。该方法包括：获取系统硬件资源的系统能耗; 获取所述系统硬件资源划分到的多个功能单元的事件信息，并将所述事件信息映射到各个虚拟机; 以及根据与所述多个功能单元对应的多个能量消耗系数并根据映射到各个虚拟机的功能单元的事件信息来计算虚拟机的能量消耗。

9. 发明授权

US08794013B2 Method and system for nucleation control in a controlled rate freezer (CRF) 有权
标题翻译：控制率冷冻机（CRF）中成核控制的方法和系统
公开(公告)号：US08794013B2
公开(公告)日：2014-08-05
申请号：US13097724
申请日：2011-04-29
申请人： Ying Zhou , Theodore H. Gasteyer, III , Nigel J. Grinter , Alan T. Cheng , Yeu-Chuan Simon Ho , Robert R. Sever
发明人： Ying Zhou , Theodore H. Gasteyer, III , Nigel J. Grinter , Alan T. Cheng , Yeu-Chuan Simon Ho , Robert R. Sever
IPC分类号： F25D25/00 , G01N1/22 , C12M3/00 , A01N1/02 , F25D3/10 , F25D29/00
CPC分类号： A01N1/0289 , A01N1/0257 , A01N1/0284 , F25D3/102 , F25D29/001
摘要： A method and system for controlled rate freezing and nucleation of materials is provided. The presently disclosed system and method provides the ability to rapidly cool the materials contained in vials or other containers within a cooling unit via forced convective cooling using a laminar and uniform flow of cryogen in proximity to the plurality of vials disposed within the cooling unit. The rapid cooling of the biological materials is achieved by precisely controlling and adjusting the temperature of the cryogen being introduced to the system as a function of time. The presently disclosed methods to systems also provide nucleation control via temperature quench and depressurized nucleation control.
摘要翻译：提供了控制速率冷冻和成核的方法和系统。本公开的系统和方法提供了通过强制对流冷却来快速冷却包含在冷却单元内的小瓶或其他容器中的材料的能力，其中使用层流和均匀流动的冷冻剂靠近设置在冷却单元内的多个小瓶。生物材料的快速冷却是通过精确地控制和调节作为时间的函数引入到系统中的冷冻剂的温度来实现的。目前公开的系统方法还通过温度骤冷和减压成核控制提供成核控制。

10. 发明申请

US20130323714A1 SYSTEM AND METHOD FOR MICRO-AERATION BASED FERMENTATION 审中-公开
标题翻译：基于微生物发酵的系统和方法
公开(公告)号：US20130323714A1
公开(公告)日：2013-12-05
申请号：US13908462
申请日：2013-06-03
申请人： Alan T. Cheng , Ying Zhou , Paul W. Belanger , Jennifer G. Bugayong
发明人： Alan T. Cheng , Ying Zhou , Paul W. Belanger , Jennifer G. Bugayong
IPC分类号： C12M1/00
CPC分类号： C12M41/48 , C12M21/12 , C12M27/00 , C12M29/06 , C12M29/24 , C12M41/32 , C12M41/34
摘要： A method and apparatus for micro-aeration of large scale fermentation systems is provided. The micro-aeration system includes a fermentation reactor, a sparging apparatus, and a micro-aeration gas mixture delivered to the fermentation reactor via the sparging apparatus. The micro-aeration gas mixture is a very low oxygen concentration mixture comprising an oxygen containing gas and an inert carrier gas that is preferably recycled through the fermentation reactor. The inert carrier gas is preferably nitrogen whereas the oxygen containing gas is oxygen or and is introduced to the fermentation reactor at a minimum superficial velocity of about 0.02 m/sec to produce a uniform dispersion of the oxygen/air throughout the fermentation broth while concurrently mixing the entire fermentation broth. The micro-aeration method and apparatus further comprises a controller operatively coupled to one or more control valves for regulating the micro-aeration conditions in the fermentation reactor.
摘要翻译：提供了一种用于大规模发酵系统微通气的方法和装置。微曝气系统包括通过喷射装置输送到发酵反应器的发酵反应器，喷射装置和微通气气体混合物。微通气气体混合物是包含含氧气体和惰性载气的非常低的氧浓度混合物，其优选通过发酵反应器再循环。惰性载气优选为氮气，而含氧气体为氧气，或以约0.02m / sec的最小表观速度引入发酵反应器，以产生氧气/空气在整个发酵液中的均匀分散，同时混合整个发酵液。微曝气方法和装置还包括操作地耦合到一个或多个控制阀的控制器，用于调节发酵反应器中的微通气条件。

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