公开(公告)号：US20120292804A1

公开(公告)日：2012-11-22

申请号：US13506101

申请日：2012-03-26

申请人： Bruce L. Carvalho ,  Maury D. Cosman

发明人： Bruce L. Carvalho ,  Maury D. Cosman

IPC分类号： B29C59/02

CPC分类号： B29C59/022 ,  B29C2059/023 ,  B29C2791/006

摘要： This invention relates to an apparatus and methods for forming polymeric devices, especially fluidic or microfluidic devices used as conduits for controlling fluid flow. Such devices have important applications in chemistry and biology including immunoassays, enzyme assays and cell separation processes. The invention claims the use of fixed-temperature heating of thermoplastic resin in combination with vacuum and low pressure on the tool in order to rapidly produce good quality devices. The combination of features claimed in the invention is important because it enables simple, lightweight, economical equipment to be constructed to fabricate useful polymeric devices.

摘要翻译： 本发明涉及用于形成聚合物装置的装置和方法，特别是用作控制流体流动的导管的流体或微流体装置。 这些装置在化学和生物学中具有重要的应用，包括免疫测定，酶分析和细胞分离过程。 本发明要求在工具上使用热塑性树脂的固定温度加热与真空和低压结合，以便快速地生产出高品质的装置。 本发明要求保护的特征的组合是重要的，因为它使得能够构造简单，轻便，经济的设备来制造有用的聚合物装置。

公开(公告)号：US06855542B2

公开(公告)日：2005-02-15

申请号：US10325437

申请日：2002-12-19

申请人： Paul A. DiMilla ,  Maury D. Cosman ,  Rachel Halych ,  Lisa Romito ,  Chris Gemmeti ,  Kevin Odlum

发明人： Paul A. DiMilla ,  Maury D. Cosman ,  Rachel Halych ,  Lisa Romito ,  Chris Gemmeti ,  Kevin Odlum

IPC分类号： C12M3/00 ,  A61L31/00 ,  C12M3/04 ,  C12N5/06 ,  C12N5/08

CPC分类号： C12M29/10 ,  C12M41/44

摘要： The invention features modular chambers for culturing cells in which the volume of a chamber can be adjusted without compromising the seal or sterility of the chamber. The invention is based on the principle that the volume of a chamber formed between two plates sandwiching a compressible gasket and a substantially incompressible stop can be adjusted using a gasket that forms a fluid-tight seal between the plates at a plurality of levels of compression. The invention enables the culture of cells between substantially parallel and rigid plates in which a relatively large volume can be used to seed the cells and the holdup volume reduced for perfusion without opening or otherwise disassembling the system to compromise its liquidtightness and sterility. The new closed, modular and scalable cell-culturing chamber can be thus perfused and used to culture cells (e.g., hepatocytes) with high levels of cell function in organ (e.g., liver) assist systems, for production of cells, for production of cell-derived products, such as proteins or viruses, or for systems to treat biological liquids to remove toxins, such as ammonia, add cell-synthesized products, or both.

摘要翻译： 本发明提供了用于培养细胞的模块化室，其中可以调节室的体积而不损害室的密封或不可靠性。 本发明基于这样的原理，即可以使用在多个压缩水平下在板之间形成流体密封的垫圈来调节形成在夹住可压缩垫圈的两个板和基本上不可压缩的止挡件之间的腔室的体积。 本发明使得能够在基本上平行的和刚性的板之间培养细胞，其中可以使用相对较大体积的细胞来种植细胞，并且减少用于灌注的保留体积，而不打开或以其他方式分解系统以损害其液体密度和不育。 因此可以将新的封闭的，模块化和可扩展的细胞培养室灌注并用于培养器官（例如肝）辅助系统中具有高水平细胞功能的细胞（例如肝细胞），用于细胞的产生，用于生产细胞 或衍生的产品，如蛋白质或病毒，或用于处理生物液体以除去毒素（如氨），添加细胞合成产物或两者的系统。

公开(公告)号：US06167710A

公开(公告)日：2001-01-02

申请号：US09117412

申请日：1998-12-17

申请人： Maury D. Cosman

发明人： Maury D. Cosman

IPC分类号： F24F316

CPC分类号： G01N1/42 ,  A01N1/02 ,  A01N1/0257 ,  F25D3/102 ,  F25D25/00 ,  F25D29/001

摘要： An apparatus for ice seeding during cryopreservation of biological samples such as cells, harvested tissues, and cellular biological constructs such as culture tissues equivalents wherein ice seeding is performed by discharging a liquefied or chilled gas from a nozzle to the surface container containing the biological sample in cryopreservative. Inside a freezing chamber, containers are placed on racks that are located proximal to a sprayrail containing nozzles. Ice seeding is performed by discharge of liquefied or chilled gas from the nozzles to the container surface at the solid-liquid equilibrium temperature of the cryopreservative. Localized cooling of the container surface by the discharge results in ice seed formation within the container.

摘要翻译： 一种用于在冷冻保存生物样品例如细胞，收获的组织和细胞生物学构造物例如培养组织当量时进行冰接种的装置，其中通过将来自喷嘴的液化或冷却气体排出到含有生物样品的表面容器进行冰接种 冷冻保存 在冷冻室内，将容器放置在靠近包含喷嘴的喷淋杆的机架上。 通过在冷冻保存剂的固液平衡温度下将液化或冷却的气体从喷嘴排放到容器表面进行冰播种。 容器表面通过排放的局部冷却导致容器内形成冰晶种。

公开(公告)号：US06978815B2

公开(公告)日：2005-12-27

申请号：US10325444

申请日：2002-12-19

申请人： Maury D. Cosman ,  Kristen Billiar ,  Ryan Mercer ,  Bruce Miller

发明人： Maury D. Cosman ,  Kristen Billiar ,  Ryan Mercer ,  Bruce Miller

IPC分类号： A61F2/06 ,  B29C53/56 ,  B65H81/00

CPC分类号： A61F2/062 ,  B29C53/562

摘要： An apparatus for forming a tube construct from a planar sheet matrix includes a stand supporting two opposing mounts and spanning between the opposing mounts are a mandrel, a porous rod, and a spring-loaded roller held in parallel arrangement; a guide for aligning and engaging the mandrel on the opposing mounts; and a means for imparting a tangential force on the planar sheet matrix to prevent wrinkling. The porous rod has a lumen running its length and has pores that communicate between the lumen of the porous rod through to the surface of the rod for water to uniformly pass through. The spring-loaded roller runs along the length of the porous rod creating a line of contact between the roller and the mandrel. The mandrel is contacted with a planar sheet of matrix and is rotated such that successive portions of the matrix contact the porous rod and become lightly moistened by the water passing through the pores of the porous rod and become wrapped around the mandrel to form a tube construct.

摘要翻译： 用于从平面片状基体形成管构造的装置包括支撑两个相对的安装件并跨过相对的安装件的支架是平行布置地保持的心轴，多孔杆和弹簧加载的辊; 用于在相对的安装件上对准和接合心轴的引导件; 以及用于在平面片基体上施加切向力以防止起皱的装置。 多孔棒具有延伸其长度的内腔，并且具有在多孔棒的内腔之间连通到杆的表面以使水均匀通过的孔。 弹簧加载的滚筒沿着多孔棒的长度延伸，在滚筒和心轴之间形成一条接触线。 心轴与平面的基质片材接触并且旋转，使得基质的连续部分接触多孔棒并被穿过多孔棒的孔的水轻轻地润湿，并且缠绕在心轴上以形成管构造 。

公开(公告)号：US06465252B1

公开(公告)日：2002-10-15

申请号：US09599891

申请日：2000-06-21

申请人： Mehmet Toner ,  Arno W. Tilles ,  Ulysses J. Balis ,  Martin L. Yarmush ,  Maury D. Cosman ,  Paul A. Dimilla

发明人： Mehmet Toner ,  Arno W. Tilles ,  Ulysses J. Balis ,  Martin L. Yarmush ,  Maury D. Cosman ,  Paul A. Dimilla

IPC分类号： C12N500

摘要： The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.

公开(公告)号：US07348176B2

公开(公告)日：2008-03-25

申请号：US11057772

申请日：2005-02-14

申请人： Paul A. DiMilla ,  Maury D. Cosman ,  Rachel Halych ,  Lisa Romito ,  Chris Gemmeti ,  Kevin Odlum

发明人： Paul A. DiMilla ,  Maury D. Cosman ,  Rachel Halych ,  Lisa Romito ,  Chris Gemmeti ,  Kevin Odlum

IPC分类号： C12M3/00

CPC分类号： C12M29/10 ,  C12M41/44

摘要： The invention features modular chambers for culturing cells in which the volume of a chamber can be adjusted without compromising the seal or sterility of the chamber. The invention is based on the principle that the volume of a chamber formed between two plates sandwiching a compressible gasket and a substantially incompressible stop can be adjusted using a gasket that forms a fluid-tight seal between the plates at a plurality of levels of compression. The invention enables the culture of cells between substantially parallel and rigid plates in which a relatively large volume can be used to seed the cells and the holdup volume reduced for perfusion without opening or otherwise disassembling the system to compromise its liquidtightness and sterility. The new closed, modular and scalable cell-culturing chamber can be thus perfused and used to culture cells (e.g., hepatocytes) with high levels of cell function in organ (e.g., liver) assist systems, for production of cells, for production of cell-derived products, such as proteins or viruses, or for systems to treat biological liquids to remove toxins, such as ammonia, add cell-synthesized products, or both.

摘要翻译： 本发明提供了用于培养细胞的模块化室，其中可以调节室的体积而不损害室的密封或不可靠性。 本发明基于这样的原理，即可以使用在多个压缩水平下在板之间形成流体密封的垫圈来调节形成在夹住可压缩垫圈的两个板和基本上不可压缩的止挡件之间的腔室的体积。 本发明使得能够在基本上平行的和刚性的板之间培养细胞，其中可以使用相对较大体积的细胞来种植细胞，并且减少用于灌注的保留体积，而不打开或以其他方式分解系统以损害其液体密度和不育。 因此可以将新的封闭的，模块化和可扩展的细胞培养室灌注并用于培养器官（例如肝）辅助系统中具有高水平细胞功能的细胞（例如肝细胞），用于细胞的产生，用于生产细胞 或衍生的产品，如蛋白质或病毒，或用于处理生物液体以除去毒素（如氨），添加细胞合成产物或两者的系统。

公开(公告)号：US06759245B1

公开(公告)日：2004-07-06

申请号：US09599891

申请日：2000-06-21

申请人： Mehmet Toner ,  Arno W. Tilles ,  Ulysses J. Balis ,  Martin L. Yarmush ,  Maury D. Cosman ,  Paul A. Dimilla

发明人： Mehmet Toner ,  Arno W. Tilles ,  Ulysses J. Balis ,  Martin L. Yarmush ,  Maury D. Cosman ,  Paul A. Dimilla

IPC分类号： C12N500

CPC分类号： A61M1/3472 ,  A61F2/022 ,  A61M1/3482 ,  A61M1/3489 ,  A61M1/3633 ,  A61M2210/1071 ,  C12M23/24 ,  C12M29/04 ,  C12M29/10 ,  C12N5/0068 ,  C12N5/0671

摘要： The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.

摘要翻译： 本发明的特征在于包括一个或多个平板模块的模块化细胞培养装置，并且基于如下发现：如果液体介质和氧合流体的流动被透气的液体不可渗透膜分离，并且细胞生长 附着于膜的液体侧，该装置可用于通过膜输送氧气（即，直接氧合）来培养细胞，而不考虑通过该装置的液体介质的流速。 因此，新的流通细胞培养装置可用于培养细胞，例如肝细胞，在器官中具有高水平的细胞功能，例如肝，辅助系统，细胞产生，细胞衍生产品的生产，例如 或蛋白质或病毒，或用于处理生物液体以除去毒素（例如氨）或添加细胞合成产物或两者的系统。

公开(公告)号：US06347525B2

公开(公告)日：2002-02-19

申请号：US09753168

申请日：2001-01-02

申请人： Maury D. Cosman

发明人： Maury D. Cosman

IPC分类号： F25D1304

CPC分类号： G01N1/42 ,  A01N1/02 ,  A01N1/0257 ,  F25D3/102 ,  F25D25/00 ,  F25D29/001

摘要： This invention is directed to a method of ice seeding a biological samples, such as cells, harvested tissues, and cellular biological constructs such as culture tissue equivalents. The method initiates the formation of ice that is controllable to allow for maximal viability of the sample to be cryopreserved after it has been subsequently thawed.

摘要翻译： 本发明涉及一种将生物样品如细胞，收获的组织和细胞生物构建体如培养组织当量冰接种的方法。 该方法开始冰的形成，其可控制以允许样品在其随后解冻之后被冷冻保存的最大生存力。