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    • 42. 发明授权
    • Method of loading and distributing cells in a bioreactor of a cell expansion system
    • 在细胞扩增系统的生物反应器中负载和分配细胞的方法
    • US09057045B2
    • 2015-06-16
    • US12968483
    • 2010-12-15
    • David M. GibbonsBrian J. Nankervis
    • David M. GibbonsBrian J. Nankervis
    • C12N5/071C12M1/00C12M3/00C12M1/12C12M3/06
    • C12M29/16C12M23/42C12M23/50C12M25/10C12M25/12C12M27/14
    • A method of distributing a plurality of cells in a bioreactor of a cell expansion system includes manipulating an orientation of the bioreactor such that a net impulse due to gravity acting on the plurality cells in the bioreactor is reduced. One method includes (a) rotating the bioreactor at an angular velocity ω about an axis of rotation and through an angular displacement θ, the bioreactor rotating from a first orientation to a second orientation; (b) holding the bioreactor still at the second orientation for a first period of time t1, wherein t1 substantially equals 2/ω; (c) rotating the bioreactor at the angular velocity ω about the axis of rotation and through the angular displacement θ; and (d) holding the bioreactor still for a second period of time t2, wherein t2 substantially equals t1.
    • 在细胞扩增系统的生物反应器中分配多个细胞的方法包括操纵生物反应器的取向,使得由于重力作用在生物反应器中的多个细胞上的净冲击减少。 一种方法包括:(a)以围绕旋转轴线的角速度ω旋转生物反应器并通过角度位移旋转生物反应器;生物反应器从第一取向旋转到第二取向; (b)将所述生物反应器保持在所述第二方向上第一时间段t1,其中t1基本上等于2 /ω; (c)以关于旋转轴线和角位移的角速度ω旋转生物反应器; 和(d)将生物反应器保持第二时间段t2,其中t2基本上等于t1。
    • 44. 发明申请
    • Systems and Methods for Expanding High Density Non-Adherent Cells
    • 用于扩增高密度非粘附细胞的系统和方法
    • US20150011004A1
    • 2015-01-08
    • US14492930
    • 2014-09-22
    • Terumo BCT, Inc.
    • Glen Delbert ANTWILER
    • C12M1/00
    • C12M29/18C12M23/02C12M23/58C12M25/12C12M29/16
    • Embodiments described herein generally relate to systems and methods for promoting the expansion of high density non-adherent cells through the use of a cell growth chamber, a mass transfer device, and a fluid circulation loop. Improved cell growth is achieved in the cell growth chamber by using a chamber having a particular orientation and shape, e.g., conical, to create a media-rich reservoir for growing cells. By placing the chamber in a vertical position, the force of media flow along the chamber walls is substantially equal and opposite to the gravitational force on the cells. The interaction of these forces maintains the non-adherent cells in suspension. The use of the cell growth chamber in conjunction with the mass transfer device and fluid circulation loop(s) creates efficiencies by relying on the cumulative and combined features of the devices.
    • 本文描述的实施方案通常涉及通过使用细胞生长室,质量传递装置和流体循环回路促进高密度非粘附细胞的扩增的系统和方法。 通过使用具有特定取向和形状(例如圆锥形)的室,在细胞生长室中实现改善的细胞生长,以产生用于生长细胞的富含培养基的储存器。 通过将腔室放置在垂直位置,介质沿腔室壁流动的力基本相等并与细胞上的重力相反。 这些力的相互作用使非粘附细胞保持悬浮状态。 与传质装置和流体循环回路结合使用细胞生长室通过依赖于装置的累积和组合特征来产生效率。
    • 50. 发明授权
    • Maintaining cells for an extended time by entrapment in a contracted
matrix
    • 通过在收缩的矩阵中捕获来维持细胞长时间
    • US5981211A
    • 1999-11-09
    • US726652
    • 1996-10-07
    • Wei-Shou HuFrank Bernard CerraScott Lyle NybergMatthew Thomas ScholzRussell A. Shatford
    • Wei-Shou HuFrank Bernard CerraScott Lyle NybergMatthew Thomas ScholzRussell A. Shatford
    • A61F2/02A61K35/12A61M1/16A61M1/34C12M3/06C12N5/071C12P1/00C12M3/00C12N5/00C12N11/04
    • C12N5/0671A61F2/022A61M1/1625A61M1/3475A61M1/3489C12M21/08C12M23/34C12M25/12C12M25/14C12M29/10C12M29/16A61K2035/126C12N2500/02C12N2500/90C12N2510/00C12N2533/30C12N2533/54Y10S435/813
    • Methods of maintaining animal cells for product production, for supporting hepatocyte function and viability to treat a patient suffering from hepatic failure and for preserving tissue-specific function of mammalian cells are carried out with a bioreactor containing a feed and waste chamber and a cell chamber separated by a selectively permeable membrane. Within the cell chamber, a biocompatible contracted three-dimensional gel matrix entraps animal cells or genetic modifications thereof, and a liquid phase contains a concentrated solution of the cell product. The bioreactor uses only two chambers to achieve three distinct zones within the bioreactor. The bioreactor can be of either hollow fiber or flat-bed configuration. In the configuration using hollow fibers, the two fluid paths correspond to the cavity surrounding the hollow fibers (the extracapillary space), and to the lumens of the hollow fibers themselves. Both fluid paths have inlet and outlet ports. Communication between the two fluid paths is across the permeable medium--the hollow fiber material. To prepare a bioartificial liver, hepatocytes are inoculated into the hollow fibers in a solution which quickly forms a highly porous gel. The gel subsequently contracts, leaving an open channel within the hollow fiber adjacent to the gel core entrapped hepatocytes. This channel can be perfused with nutrient media for hepatocytes. The channel can also serve as a waste stream to remove toxins that the hepatocytes have modified to a water soluble form.
    • 维持用于产品生产的动物细胞,用于支持肝细胞功能和用于治疗患有肝衰竭的患者和维持哺乳动物细胞的组织特异性功能的活性的方法是用含有饲料和废物室的细胞室和分离的细胞室进行的 通过选择性渗透膜。 在细胞室内,生物相容的收缩的三维凝胶基质包裹动物细胞或其遗传修饰,液相含有细胞产物的浓缩溶液。 生物反应器仅使用两个室来实现生物反应器内的三个不同区域。 生物反应器可以是中空纤维或平床构型。 在使用中空纤维的构造中,两个流体路径对应于围绕中空纤维(毛细管外空间)的空腔以及中空纤维本身的内腔。 两个流体路径都具有入口和出口。 两个流体路径之间的通信是穿过可渗透介质 - 中空纤维材料。 为了制备生物人造肝,将肝细胞以快速形成高度多孔凝胶的溶液接种到中空纤维中。 凝胶随后收缩,在中空纤维中留下与凝胶芯捕获的肝细胞相邻的开放通道。 该通道可以用肝细胞的营养培养基灌注。 该通道还可用作废物流以除去肝细胞已经修饰成水溶性形式的毒素。