Method for Using a Disposable Bioreactor

Abstract

In one embodiment, a disposable bioreactor including a headplate and a stirrer. The headplate has at least one inlet port aperture and one outlet port aperture formed therein and is adapted to couple sealingly with a bag capable of receiving a culture medium. The stirrer is coupled to and extends from the headplate and is adapted to stir the culture medium when the headplate is coupled to the bag. The bioreactor is adapted to fit within the upper opening of the stand of an existing conventional glass bioreactor, so that the bag is suspended within the vessel.

1 . A method for performing bioreactor operations, the method comprising:
 providing a support structure of an existing bioreactor system;   mounting a disposable bioreactor onto the support structure; and   performing the bioreactor operations using the disposable bioreactor mounted onto the support structure.   
     
     
         2 . The method of  claim 1 , wherein:
 the disposable bioreactor defines an interior volume having a circular top surface, a cylindrical side wall, and a bottom surface;   the disposable bioreactor comprises:
 a rigid headplate comprising a circular headplate disk defining a headplate disk plane and having a headplate disk diameter; and 
 a flexible, cylindrical bag (a) having a circular bag opening and a cylindrical side wall having a bag diameter and (b) receiving a culture medium, wherein:
 the headplate disk diameter is larger than the bag diameter; 
 a circular portion of the headplate having a diameter substantially equal to the bag diameter, forms the circular top surface of the bioreactor's interior volume; 
 an extended portion of the headplate disk extends beyond the top surface of the bioreactor's interior volume in the headplate disk plane; and 
 the extended portion of the headplate disk enables the bioreactor to be supported by the support structure having a diameter larger than the bag diameter, but smaller than the headplate disk diameter. 
 
   
     
     
         3 . The method of  claim 2 , wherein:
 the headplate further comprises a cylindrical headplate collar formed on an inner side of the headplate disk, defining a collar aperture, and having a cylindrical side wall having a headplate collar diameter smaller than the headplate disk diameter, wherein the collar fits within the upper opening of the support structure of the existing bioreactor;   the bag diameter is substantially equal to the outer diameter of the headplate collar;   the side wall of the bag is parallel to the side wall of the headplate collar; and   the inner surface of the headplate collar forms a portion of the interior surface of the cylindrical side wall of the bioreactor's interior volume with the bag forming the remainder of the interior surface of the cylindrical side wall of the bioreactor's interior volume.   
     
     
         4 . The method of  claim 3 , wherein the bag is sealingly and permanently coupled to the headplate collar. 
     
     
         5 . The method of  claim 2 , wherein the bag is welded to the headplate to provide a permanent coupling seal of the bag to the headplate. 
     
     
         6 . The method of  claim 2 , wherein the bag is heat sealed to the headplate to provide a permanent coupling seal of the bag to the headplate. 
     
     
         7 . The method of  claim 2 , wherein the bag is a flexible vessel liner that is fit within a rigid structure of the existing bioreactor. 
     
     
         8 . The method of  claim 7 , wherein the rigid structure is a glass vessel of the existing bioreactor. 
     
     
         9 . The method of  claim 2 , wherein the bioreactor is suspended from above without the bag being contained within any other structure. 
     
     
         10 . The method of  claim 9 , wherein:
 the bag forms the bottom surface and at least a portion of the cylindrical side wall of the bioreactor's interior volume; and   the side wall of the bag is sealingly and permanently coupled at the bag opening to the headplate such that the side wall of the bag is perpendicular to the headplate disk plane.   
     
     
         11 . The method of  claim 10 , wherein:
 the rigid headplate has a plurality of disk apertures formed therein; and   the disposable bioreactor further comprises:
 tubing, for one or more of the disk apertures, extending from an outer side of the headplate disk through the corresponding disk aperture into the bioreactor's interior volume; 
 an impeller shaft extending from the outer side of the headplate disk through a corresponding disk aperture into the bioreactor's interior volume; 
 an impeller connected to an end of the impeller shaft inside the bioreactor's interior volume; and 
 a drive assembly connected to the headplate disk on the outer side of the headplate disk and rotating the impeller shaft and the impeller. 
   
     
     
         12 . The method of  claim 11 , wherein the tubing comprises at least one inlet tube passing through an inlet port aperture and at least one outlet tube passing through an output port aperture, wherein:
 the inlet tube provides matter to the culture medium; and   the outlet tube extracts matter from the culture medium.   
     
     
         13 . The method of  claim 11 , wherein the drive assembly comprises an extended portion and a permanent magnet disposed within the extended portion and coupled to the impeller shaft, wherein, when a motor-driven magnet rotates around the extended portion, the permanent magnet is caused to rotate, thereby rotating the impeller shaft. 
     
     
         14 . The method of  claim 11 , wherein at least one tubing comprises a coiled portion that extends on the outer side of the headplate disk. 
     
     
         15 . The method of  claim 11 , wherein:
 the only access to the bioreactor's interior volume is through the disk apertures in the rigid headplate;   other than the bag's circular opening which is sealingly and permanently coupled to the headplate, the bag has no apertures that provide access to the bioreactor's interior volume; and   the cylindrical side wall and the bottom of the bioreactor's interior volume have no apertures that provide access to the bioreactor's interior volume.   
     
     
         16 . The method of  claim 15 , wherein the bioreactor further comprises:
 a dissolved oxygen sensor coupled to and extending from the headplate, wherein the dissolved oxygen sensor detects dissolved oxygen in the culture medium;   a temperature sensor coupled to and extending from the headplate, wherein the temperature sensor detects temperature in the culture medium;   an exhaust port coupled to a filter extending from the headplate, wherein the exhaust port permits ventilation through the filter of gas from inside the bag; and   a sparger port coupled to a filter extending from the headplate and to a sparger tube, wherein the sparger tube receives a gas through the filter and injects the gas into the culture medium, wherein:
 the bioreactor is suspended from above without the bag being contained within any other structure; 
 the tubing comprises at least one inlet tube passing through an inlet port aperture and at least one outlet tube passing through an output port aperture; 
 the inlet tube provides matter to the culture medium; 
 the outlet tube extracts matter from the culture medium; 
 the headplate further comprises a cylindrical headplate collar formed on an inner side of the headplate disk, defining a collar aperture, and having a cylindrical side wall having headplate collar diameter smaller than the headplate disk diameter, wherein the collar fits within the upper opening of the support structure of the existing bioreactor; 
 the bag diameter is substantially equal to the outer diameter of the headplate collar; 
 the side wall of the bag is parallel to the side wall of the headplate collar; 
 the inner surface of the headplate collar forms a portion of the interior surface of the cylindrical side wall of the bioreactor's interior volume with the bag forming the remainder of the interior surface of the cylindrical side wall of the bioreactor's interior volume; 
 the impeller shaft and each tubing extends through the collar aperture on the inner side of the headplate disk; 
 the bag is sealingly and permanently coupled to the headplate collar; 
 the drive assembly comprises an extended portion and a permanent magnet disposed within the extended portion and coupled to the impeller shaft, wherein, when a motor-driven magnet rotates around the extended portion, the permanent magnet is caused to rotate, thereby rotating the impeller shaft; and 
 the bag is welded or heat sealed to the headplate to provide a permanent coupling seal of the bag to the headplate.