Liquid-gas-phase exposure reactor for cell culturing

Abstract

Initiation of growth and cultivation of cells can be performed by introducing the cells into culture compartments of a liquid-gas-phase exposure bioreactor containing a supply chamber in which there are disposed hollow-filament membranes having an inside diameter of no larger than 5 mm, wherein an inner volume of said hollow-filament membranes forms the culture compartments. Approximately one half of the supply chamber is filled with a nutrient medium and a remainder is filled with a gas mixture. Perfusion of medium and gas is turned on simultaneously or separately. The hollow-filament membranes and the cells contained therein are cyclically exposed to the gas or liquid phase.

1 - 8 . (canceled) 
     
     
         9 . A device, comprising:
 a cylindrical two-phase supply chamber which can be charged with gas and a culture medium,   parallel to the longitudinal axis of a shell of said supply chamber, polymeric, cell-retaining, microfiltering, hollow-filament membranes having an inside diameter of not more than 5 mm are fixed in an end plate, wherein the inner volumes of said hollow-filament membranes form culture compartments in which cells to be cultivated are disposed,   wherein the supply chamber contains a gas phase through which a gas mixture can flow and a liquid phase through which said culture medium can flow;   wherein each hollow-filament membrane has a spacing of at least 0.5 mm to the neighboring hollow-filament membrane over the length of the cylinder;   wherein the hollow-filament membranes are symmetrically disposed relative to an imaginary cross section along the longitudinal axis of the cylinder;   wherein no membrane is disposed on the imaginary cross-sectional plane along the longitudinal axis of the cylinder;   wherein said device is capable of being used for initiation of growth and cultivation of cells.   
     
     
         10 . The device according to  claim 9 , wherein, for input and removal of gas, every end plate of the cylinder contains at least two ports, which are respectively disposed above and below the imaginary cross-sectional plane, and so the supply chamber containing the hollow-filament membranes can be rotated around its longitudinal axis during supply of medium and gas. 
     
     
         11 . The device according to  claims 9  or  10 , wherein the ports for the gas supply are mounted on the cylinder shell, above and below the imaginary cross-sectional plane. 
     
     
         12 . The device according to  claim 9 , wherein the hollow-filament membranes have a wall thickness smaller than 300 μm, a water permeability of greater than 6 m3/m2·h·bar and a pore diameter of 0.1 to 1 μm. 
     
     
         13 . The device according to  claim 9 , wherein the membranes are disposed in a hexagonal array in the supply chamber. 
     
     
         14 . The device according to  claim 9 , wherein at least one tubing port for medium perfusion and at least one inlet to the culture chamber are disposed on head faces of said supply chamber. 
     
     
         15 . The device according to  claim 9 , further comprising at least one member selected from the group consisting of tubings, gas humidifiers, a medium trap in a gas line, an ultrafiltration unit in a product-harvesting line, a hardware unit, pumps, compressors, measuring units, control units, a drive motor and a frame to permit mounting and rotation of the device. 
     
     
         16 - 17 . (canceled)