Bioreactor

Abstract

A bioreactor for culturing of cells is described. Screens suitable as a cell growth scaffold may comprise crossed fibers. Screens may be contained loosely in a screen holder, which in turn may be contained inside a manifold assembly. A lower manifold, screen holder and upper manifold may have identical or similar interior open cross-sections. Flow of liquid medium can occur upwardly through the array of screens, then flowing over a weir in the presence of an air pocket, and into a moat and a pump. The screen holder may have slots whose exterior-facing ligaments are rounded, and may have grooves whose interior-facing edges are rounded. These components may be located inside an incubator suitable to maintain desired environmental conditions and cleanliness.

We claim: 
     
         1 . A bioreactor, comprising:
 a reservoir container for holding a liquid medium;   a duct providing a flowpath in a generally vertical direction upward from said reservoir container from a lower end of said duct to an upper end of said duct;   a culture structure located within said duct, a top of said duct being at a higher elevation than a top of said culture structure; and   a circulation system for causing said liquid medium to flow upwardly through said duct past or through said culture structure,   wherein said upper end of said duct comprises an overflow wall surrounded on its outside by a moat, a bottom of said moat being at a lower elevation than said top of said overflow wall, said upper end of said duct and said moat being in contact with a pocket region, said pocket region being bounded by a structure that is connected to said duct, said pocket region being isolated from fluid communication with an exterior of said pocket region,   wherein when said circulation system is operating, said liquid medium flows over said overflow wall within said pocket region and said liquid medium is in contact with gas that is contained in said pocket region, and said liquid medium overflows into said moat and is removed from said moat by said circulation system.   
     
     
         2 . The bioreactor of  claim 1 , further comprising a sump that is in fluid communication with said moat, said sump being at a lower elevation than said bottom of said moat, said circulation system being in fluid communication with said sump so as to withdraw liquid medium from said sump. 
     
     
         3 . The bioreactor of  claim 1 , wherein a lower flow length exists from said lower end of said duct to a lower boundary of said culture structure, and an upper flow length exists from said upper boundary of said culture structure to said upper end of said duct, and wherein said upper flow length is shorter than said lower flow length. 
     
     
         4 . The bioreactor of  claim 1 , wherein said duct has two pairs of parallel walls and said reservoir container has two pairs of parallel walls, and a pair of parallel walls of said duct is parallel to a pair of parallel walls of said reservoir container, and said duct is located midway between one of said pairs of parallel walls of said reservoir container. 
     
     
         5 . The bioreactor of  claim 1 , further comprising an incubator enclosing said reservoir container and said duct, and further comprising a pump that removes gas from a gas space region of said reservoir container and ejects said gas outside said incubator. 
     
     
         6 . A bioreactor, comprising:
 a reservoir container for holding a liquid medium;   a manifold assembly, said manifold assembly comprising an upper manifold and a lower manifold, said lower manifold having a lower end extending into said reservoir container;   a screen holder, said screen holder holding a plurality of screens that are suitable as scaffolds for cells; and   a circulation system for causing said liquid medium to flow through said manifold assembly and through said screen holder,   wherein said manifold assembly and said screen holder provide a flowpath through said lower manifold and said screen holder and said upper manifold,   wherein said screen holder is contained within said manifold assembly, and   wherein said screens are contained within said screen holder but have at least some ability to move with respect to said screen holder in at least one direction.   
     
     
         7 . The bioreactor of  claim 6 , wherein when said screen holder is in place within said manifold assembly, said screen holder has at least one degree of freedom of motion with respect to said lower manifold. 
     
     
         8 . The bioreactor of  claim 6 , wherein said upper manifold and said lower manifold and said screen holder have respective internal cross-sectional flow areas that are substantially identical to each other or are within 10% of each other. 
     
     
         9 . The bioreactor of  claim 6 , wherein a leakage path comprising a gap between an individual one of said screens and said screen holder, has a cross-sectional flow area that is less than 10% of a total flow area through all passageways through said individual one of said screens. 
     
     
         10 . The bioreactor of  claim 6 , wherein said screen comprises a plurality of fibers forming a first layer having fibers parallel o each other and oriented in a first direction and comprises a second layer having a plurality of fibers parallel to each other and oriented in a second direction that is perpendicular to said first direction, said fibers in said second layer being joined to said fibers in said first layer. 
     
     
         11 . The bioreactor of  claim 6 , wherein at least some of said screens comprise a plurality of fibers, and within an individual one of said screens, said fibers are arranged in sequence in at least first, second, third and fourth layers, said fibers within each of said layers being generally parallel to each other, wherein fibers in said first layer are generally parallel to fibers in said third layer and fibers in said second layer are generally parallel to fibers in said fourth layer, and wherein when viewed perpendicular to a flat surface of said screen, fibers of said third layer are located non-aligned with fibers of said first layer and fibers of said fourth layer are located non-aligned with fibers of said second layer. 
     
     
         12 . The bioreactor of  claim 6 , further comprising a compressible seal between said lower manifold and said upper manifold, wherein a surface of said upper manifold bears against a surface of said lower manifold in a vicinity of said seal. 
     
     
         13 . The bioreactor of  claim 6 , further comprising an incubator enclosing said reservoir container and said manifold assembly, wherein said incubator is suitable to maintain a desired value of at least one of a temperature, a humidity, an oxygen concentration, a carbon dioxide concentration, and a gas composition. 
     
     
         14 . The bioreactor of  claim 13 , wherein said circulating system comprises a peristaltic pump that is located outside said incubator. 
     
     
         15 . A bioreactor, comprising:
 a reservoir container for holding a liquid medium;   a manifold assembly, said manifold assembly comprising an upper manifold and a lower manifold, said lower manifold having a lower end extending into said reservoir container;   a screen holder, said screen holder holding a plurality of screens that are suitable as scaffolds for cells; said screen holder being able to be contained within said manifold assembly; and   a circulating system for causing said liquid medium to flow through said manifold assembly and through said screen holder,   wherein said manifold assembly and said screen holder provide a flowpath through said lower manifold and said screen holder and said upper manifold,   wherein said screen holder has grooves on an internal surface thereof, and has slots through an external surface thereof, and wherein said grooves and said slots are configured so that said screens are able to be inserted through said slots and be supported by at least one of said grooves and said slots.   
     
     
         16 . The bioreactor of  claim 15 , wherein said grooves and said slots form a continuous path around a perimeter of said screen holder. 
     
     
         17 . The bioreactor of  claim 15 , wherein said slots comprise rounded edges on an outward-facing surface. 
     
     
         18 . The bioreactor of  claim 17 , wherein said grooves comprise rounded edges on an inward-facing surface that is opposite said slots. 
     
     
         19 . The bioreactor of  claim 15 , a groove-containing surface of said screen holder has openings therethrough to permit a pusher to position said screens. 
     
     
         20 . The bioreactor of  claim 15 , wherein a slot-containing surface of said screen holder has openings therethrough to permit a pusher to position said screens. 
     
     
         21 . The bioreactor of  claim 15 , wherein said screen holder has a cross-sectional shape on either its inside or its outside or both that is rectangular with rounded corners.