Gas delivery configurations, foam control systems, and bag molding methods and articles for collapsible bag vessels and bioreactors

Abstract

Systems for containing and manipulating fluids including systems and methods involving supported collapsible bags that may be used as reactors for performing chemical, biochemical and/or biological reactions contained therein are provided. Generally, a series of improvements and features for fluid containment systems such as gas delivery configurations, foam control systems and bag molding methods and articles for supported collapsible bag vessels and bioreactors are provided. For instance, in one aspect, fluids contained in a vessel can be sparged, e.g., such that a fluid is directed into a container of the vessel, and in some cases, the sparging can be controlled by rapidly activating or altering the degree of sparging as needed. Multiple spargers may be used in some cases. In another aspect, the vessel includes a seamless collapsible bag. In some cases, the collapsible bag may be injected, blown, or spin cast molded. In yet another aspect, the vessel includes a device which can reduce the foam produced or contained within the vessel. Sensors and/or controllers may optionally be used to monitor and/or control foaming.

1 . A vessel configured to contain a volume of liquid, the vessel comprising: 
 a collapsible bag for containing the volume of liquid, the collapsible bag having a volume of at least 2 liters;    a support structure surrounding and containing the collapsible bag;    a first sparger connected to the collapsible bag, the first sparger being in fluid communication with a source of a first gas composition; and    a second sparger connected to the collapsible bag, the second sparger being in fluid communication with a source of a second gas composition different from the first gas composition.    
   
   
       2 - 4 . (canceled)  
   
   
       5 . A vessel as in  claim 1 , wherein the vessel further comprises a mixing system including an impeller and a base plate, wherein the first and/or second spargers is associated with the base plate.  
   
   
       6 - 17 . (canceled)  
   
   
       18 . A vessel configured to contain a volume of liquid, the vessel comprising: 
 a collapsible bag able to contain the volume of liquid;    a support structure surrounding and containing the collapsible bag;    a first sparger connected to the collapsible bag, the first sparger having a first aperture size, wherein at least a portion of the first sparger is dimensioned to be connected to a source of a first gas; and    a second sparger connected to the collapsible bag, the second sparger having a second aperture size, wherein at least a portion of the second sparger is dimensioned to be connected to a source of a second gas.    
   
   
       19 . (canceled)  
   
   
       20 . A vessel as in  claim 18 , wherein the vessel further comprises a control system operatively associated with the first and second spargers and configured to operate the first and second spargers independently of each other.  
   
   
       21 - 29 . (canceled)  
   
   
       30 . A vessel configured to contain a volume of liquid comprising: 
 a container able to contain the volume of liquid; and    a magnetically-driven antifoaming device, at least a portion of which is positioned in a head space of the container when the container contains the volume of liquid, the antifoaming device being configured and arranged to break up foam in the head space during rotation of at least a portion of the antifoaming device.    
   
   
       31 . A vessel as in  claim 30 , wherein the container is a collapsible bag.  
   
   
       32 . A vessel as in  claim 30 , further comprising a reusable support structure surrounding and containing the collapsible bag.  
   
   
       33 - 34 . (canceled)  
   
   
       35 . A vessel as in claim  34 , wherein the impeller is connected to a top portion of the container.  
   
   
       36 - 46 . (canceled)  
   
   
       47 . A vessel as in claim  46 , wherein the antifoaming device is regulated by the control system via detection of electrical current flow between the probe and the wall.  
   
   
       48 - 57 . (canceled)  
   
   
       58 . A vessel configured to contain a volume of liquid, the vessel comprising: 
 a collapsible bag able to contain the liquid;    a reusable support structure surrounding and containing the collapsible bag;    a pressure sensor for determining a pressure in the collapsible bag, the pressure sensor in fluid communication with the collapsible bag;    an antifoaming device associated with the collapsible bag and configured to break up foam in the collapsible bag; and    a control system operatively associated with the pressure sensor and the antifoaming device, wherein the control system regulates the antifoaming device upon receipt of a signal from the pressure sensor.    
   
   
       59 - 63 . (canceled)  
   
   
       64 . A collapsible bag configured to contain a volume of at least 2 liters, the collapsible bag comprising: 
 a first rotatable impeller positioned at a bottom portion of the collapsible bag, the first impeller able to be magnetically rotated; and    a second impeller positioned at a top portion of the collapsible bag, the second impeller able to be magnetically rotated.    
   
   
       65 - 70 . (canceled)  
   
   
       71 . A collapsible bag as in  claim 64 , wherein the sparger is positioned below a bottom impeller and an outlet is positioned above a top impeller.  
   
   
       72 . A container able to contain a volume of liquid, the container comprising: 
 a collapsible bag having a volume of at least 40 liters, wherein the collapsible bag does not include any seams joining two or more flexible wall portions of the collapsible bag; and    a reusable support structure surrounding and containing the collapsible bag.    
   
   
       73 - 77 . (canceled)  
   
   
       78 . A container as in  claim 72 , wherein the collapsible bag comprises an impeller.  
   
   
       79 . (canceled)  
   
   
       80 . A method comprising: 
 positioning a rigid component in a mold having a shape configured to mold a container having a volume of at least 10 mL;    introducing a first polymer precursor into the mold; and    forming a seamless container within the mold by solidifying the polymer precursor to form the container, wherein the component is incorporated in the container.    
   
   
       81 - 100 . (canceled)  
   
   
       101 . A method, comprising: 
 introducing a first polymer precursor into a mold, the mold having a shape configured to mold a container having a volume of at least 10 mL, the mold further comprising at least one mandrel for forming a functional component of a liquid containment system;    forming a container within the mold;    forming a component within the mold utilizing the mandrel; and    joining the functional component and the container without welding.    
   
   
       102 - 107 . (canceled)  
   
   
       108 . A method as in claim  107 , wherein the wall portion of the container having a first thickness and the portion of the functional component having a second thickness which are joined together have thicknesses within 20% of each other, relative to the larger of the first and second thicknesses.  
   
   
       109 - 111 . (canceled)  
   
   
       112 . An article comprising: 
 a collapsible bag comprising a flexible wall portion and a rigid portion comprising a base including a shaft configured to support a magnetic impeller, wherein the rigid portion is embedded with the flexible wall portion.    
   
   
       113 - 124 . (canceled)  
   
   
       125 . A method, comprising: 
 introducing a first polymer precursor into a mold, the mold having a shape configured to mold a collapsible bag having a volume of at least 10 mL and also configured to mold a base including a shaft configured to support a magnetic impeller;    forming a collapsible bag within the mold;    introducing a second polymer precursor into the mold;    forming a component of the mixing system by solidifying the second polymer precursor; and    joining the component of the mixing system and the collapsible bag without welding.    
   
   
       126 . A method as in  claim 125 , wherein the first and second polymers are introduced into the mold simultaneously.  
   
   
       127 - 133 . (canceled)