Automated bioculture and bioculture experiments system

Abstract

The present invention provides a feedback controlled bioculture platform for use as a precision cell biology research tool and for clinical cell growth and maintenance applications. The system provides individual closed-loop flowpath cartridges, with integrated, aseptic sampling and routing to collection vials or analysis systems. The system can operate in a standard laboratory or other incubator for provision of requisite gas and thermal environment. System cartridges are modular and can be operated independently or under a unified system controlling architecture, and provide for scale-up production of cell and cell products for research and clinical applications. Multiple replicates of the flowpath cartridges allow for individual, yet replicate cell culture growth and multiples of the experiment models that can be varied according to the experiment design, or modulated to desired cell development of cell culture end-points. The integral flowpath cartridge aseptic sampling system provides for dynamic analysis of metabolic products or representative cells from the culture.

1 . An incubator rack for supporting a plurality of cell culture perfusion flowpath assembly cartridges, comprising: 
 a horizontal base having a surface with a plurality of grooves each adapted to support a flowpath assembly cartridge;    a plurality of data interface connections for transmitting data between said rack and said plurality of cartridges; and    at least one control interface for communication between said rack and an external computer.    
   
   
       2 . The incubator rack of  claim 1 , further comprising a vertical wall connectable to said horizontal base, wherein said vertical wall is perpendicular to said plurality of grooves.  
   
   
       3 . The incubator rack of  claim 1 , wherein said rack further comprises a means for preventing a specific cartridge from being inserted into more than one location on said rack.  
   
   
       4 . The incubator rack of  claim 1 , wherein the rack further comprises a fan.  
   
   
       5 . The incubator rack of  claim 1 , wherein the rack further comprises a vibration dampening system.  
   
   
       6 . A biochamber convertible for use in static cell culture or in a cell perfusion apparatus, said biochamber comprising: 
 a first chamber;    a cover;    a sealing means for rendering said first chamber removably connectable to said cover and for sealing said cell culture within said biochamber from biologic contaminants;    at least one insert positioned between the first chamber and the cover, thereby forming a second chamber; and    wherein said first chamber and said second chamber are each in fluid communication with a media stream during perfusion.    
   
   
       7 . The biochamber of  claim 6 , wherein said seal means comprises a means for verifying seal integrity.  
   
   
       8 . The biochamber of  claim 6 , wherein said insert comprises a material selected from the group consisting of: 
 a hollow fiber bundle;    a plastic surface;    a three dimensional matrix; and    an optically reflective surface.    
   
   
       9 . The apparatus of  claim 8 , wherein said seal means comprises two or more sealing interfaces.  
   
   
       10 . The apparatus of  claim 8 , wherein said biochamber further comprises at least one air gap between said two or more sealing interfaces.  
   
   
       11 . The apparatus of  claim 8 , wherein said two or more sealing interfaces are capable of indicating seating of said interfaces by a color change.  
   
   
       12 . The biochamber of  claim 6 , further comprising at least one means for diffusing media flow within said biochamber.  
   
   
       13 . The biochamber of  claim 6 , further comprising a sampling port.  
   
   
       14 . The biochamber of  claim 6 , further comprising a n injection port.  
   
   
       15 . The biochamber of  claim 6 , further comprising a sampling interface.  
   
   
       16 . A sampling device for use with a cell culture perfusion loop, said sampling device comprising: 
 a fluidic pump for transporting a routing fluid;    a one way flow valve;    a valve for diverting an aliquot of sample from said perfusion loop to said one way flow valve;    wherein said fluidic pump and one way flow valve are connected for transporting said routing fluid to said one way valve; and    a means for transporting said aliquot of sample and said routing fluid from said one way flow valve to a collection device or analysis instrument.    
   
   
       17 . The automated sampling apparatus of  claim 16 , wherein said routing fluid is air.  
   
   
       18 . The automated sampling apparatus of  claim 16 , further comprises at least one filter.  
   
   
       19 . A sampling device for obtaining a sample from a cell culture perfusion loop having: 
 a pump means for causing a routing fluid to be transported through tubing;    a means for releasing an aliquot of sample from said perfusion loop;    a valve means,    wherein said pump means and said valve means are connected for transporting said routing fluid; and    a means for transporting said sample within said routing fluid from said valve means to a sample collection device or analysis instrument.    
   
   
       20 . A method of culturing cells comprising: 
 providing a biochamber convertible for use in static cell culture or in a cell perfusion apparatus, said biochamber comprising:    a first chamber;    a cover;    a seal rendering said first chamber removably connectable to said cover; and    at least one insert positioned between the first chamber and the disposable cover, thereby forming a second chamber;    providing a biological cell;    introducing said biological cell into said biochamber;    placing said biochamber in an incubator under gas and temperature conditions permitting said cell to propagate to achieve a desired cell density within said biochamber;    inserting said biochamber containing said desired density of cells into a cell perfusion apparatus, such that said first chamber and said second chamber are in fluid communication with medium flowing through said cell perfusion apparatus; and    operating said cell perfusion apparatus under conditions permitting said cell to propagate.    
   
   
       21 . The method of  claim 20 , further comprising: 
 removing said biochamber from said cell perfusion apparatus;    disconnecting said first chamber from said cover; and    harvesting said propagated cells or a cell product from said biochamber.    
   
   
       22 . The method of  claim 21 , wherein said cell product is removably anchored to said insert.  
   
   
       23 . The method of  claim 21 , wherein said cell product is in suspension.