Cell proliferation bioreactor

Abstract

A bioreactor includes a culture medium vessel housing culture medium. The culture medium vessel further includes a first side surface including a first transparent optical window; and a second side surface parallel to the first surface and including one or more sensor adapters to fix optical sensors. A cell retention vessel is disposed underneath and connected to the culture medium vessel, the cell retention vessel housing biological cells and having: a top surface that intersects a base of the culture medium vessel, and a second transparent optical window indented into the top surface at a first corner of the top surface. A semipermeable membrane is disposed at a bottom of the cell retention vessel, and a frame comprising a grid is disposed underneath the semipermeable membrane.

What is claimed is: 
     
         1 . A bioreactor comprising:
 optical sensors, wherein the optical sensors are fixed and determine first conditions or first parameters comprising a pH, a partial pressure of dissolved oxygen (pO 2 ), and a partial pressure of dissolved carbon dioxide (pCO 2 ) within a culture medium vessel, or determine second conditions or second parameters, wherein the second conditions or the second parameters comprise a concentration of viable cells, a diameter, and a morphology of cells;   the culture medium vessel configured to contain culture medium, the culture medium vessel comprising a side surface comprising one or more sensor adapters to fix the optical sensors;   a cell retention vessel disposed underneath and connected to the culture medium vessel, the cell retention vessel configured to contain biological cells;   waste collection interfaces comprising respective first connectors;   culture medium injection interfaces comprising respective second connectors;   a cell harvest interface comprising a third connector;   valves attached to the respective first connectors, the second connectors, or the third connector, wherein the valves are electronically controlled, by a processor, to automatically open and close based on at least a portion of the first conditions or the first parameters, or at least a portion of second conditions or second parameters, wherein the second conditions or the second parameters comprise a concentration of viable cells, a diameter, and a morphology of cells; and   tubes or pipes attached to the valves through which a portion of the culture medium is expelled or injected upon opening of the valves.   
     
     
         2 . The bioreactor of  claim 1 , wherein the valves comprise first valves attached to the respective first connectors, the first valves are electronically controlled, by the processor, to open based on at least the portion of the first conditions or the first parameters. 
     
     
         3 . The bioreactor of  claim 1 , wherein the valves comprise second valves attached to the respective second connectors, the second valves are electronically controlled, by the processor, to open based on at least the portion of the first conditions or the first parameters. 
     
     
         4 . The bioreactor of  claim 3 , wherein at least a portion of the second valves are electronically controlled, by the processor, to open in response to the pO 2  being lower than a first threshold. 
     
     
         5 . The bioreactor of  claim 3 , wherein at least a portion of the second valves are electronically controlled, by the processor, to open in response to the pCO 2  being lower than a second threshold. 
     
     
         6 . The bioreactor of  claim 3 , wherein the optical sensors determine third conditions or third parameters, the third conditions or the third parameters comprising a concentration of glucose, glutamine, glutamate, lactate, ammonium, and ethanol; and
 at least a portion of the second valves are electronically controlled, by the processor, to open and close based on at least a portion of the third conditions or the third parameters.   
     
     
         7 . The bioreactor of  claim 1 , wherein the valves comprise a third valve attached to the third connector, wherein the third valve is electronically controlled, by the processor, to automatically open and close based on at least a portion of the second conditions or the second parameters. 
     
     
         8 . The bioreactor of  claim 1 , further comprising cell injection interfaces comprising respective fourth connectors. 
     
     
         9 . The bioreactor of  claim 8 , wherein the valves comprise respective fourth valves attached to the fourth connectors, wherein the fourth valves are electronically controlled, by the processor, to automatically open and close based on at least a portion of the second conditions or the second parameters. 
     
     
         10 . The bioreactor of  claim 9 , wherein the fourth valves are electronically controlled, by the processor, to automatically open and close based at least on a total cell density within the cell retention vessel. 
     
     
         11 . The bioreactor of  claim 1 , wherein the valves comprise first valves attached to the respective first connectors, and second valves attached to the respective second connectors, and the first valves are electronically controlled, by the processor, to open prior to opening of the second valves. 
     
     
         12 . A method comprising:
 sensing, via fixed optical sensors, first conditions or first parameters comprising a pH, a partial pressure of dissolved oxygen (pO 2 ), and a partial pressure of dissolved carbon dioxide (pCO 2 ) within a culture medium vessel, or sensing, via the fixed optical sensors, second conditions or second parameters, wherein the second conditions or the second parameters comprise a concentration of viable cells, a diameter, and a morphology of cells;   fixing the fixed optical sensors via respective sensor adapters disposed on a side surface of the culture medium vessel;   retaining culture medium within the culture medium vessel;   retaining biological cells within a cell retention vessel disposed underneath and connected to the culture medium vessel;   electronically controlling, by a processor, valves attached to respective first connectors, second connectors, or a third connector, to automatically open and close based on at least a portion of the first conditions or the first parameters, or at least a portion of second conditions or second parameters, wherein the second conditions or the second parameters comprise a concentration of viable cells, a diameter, and a morphology of cells, wherein the first connectors are comprised within waste collection interfaces, the second connectors are comprised within culture medium injection interfaces, and the third connector is comprised within a cell harvest interface; and   expelling or injecting a portion of the culture medium through the culture medium vessel through tubes or pipes attached to the valves.   
     
     
         13 . The method of  claim 12 , wherein the valves comprise first valves attached to the respective first connectors, and the method further comprising:
 opening, by the processor, the first valves based on at least the portion of the first conditions or the first parameters.   
     
     
         14 . The method of  claim 12 , wherein the valves comprise second valves attached to the respective second connectors, and the method further comprising:
 opening, by the processor, the second valves based on at least the portion of the first conditions or the first parameters.   
     
     
         15 . The method of  claim 14 , further comprising:
 opening, by the processor, at least a portion of the second valves in response to the pO 2  being lower than a first threshold.   
     
     
         16 . The method of  claim 14 , further comprising:
 opening, by the processor, at least a portion of the second valves in response to the pCO 2  being lower than a second threshold.   
     
     
         17 . The method of  claim 14 , further comprising:
 sensing, via the fixed optical sensors, third conditions or third parameters, the third conditions or the third parameters comprising a concentration of glucose, glutamine, glutamate, lactate, ammonium, and ethanol; and   opening and closing at least a portion of the second valve, by the processor, based on at least a portion of the third conditions or the third parameters.   
     
     
         18 . The method of  claim 12 , wherein the valves comprise a third valve attached to the third connector, the method further comprising:
 opening and closing, by the processor, the third valve based on at least a portion of the second conditions or the second parameters   
     
     
         19 . The method of  claim 12 , further comprising:
 opening and closing, by the processor, fourth valves attached to fourth connectors comprised within cell injection interfaces, based on at least a portion of the second conditions or the second parameters.   
     
     
         20 . The method of  claim 19 , further comprising:
 opening and closing, by the processor, the fourth valves, to automatically open and close based at least on a total cell density within the cell retention vessel.