Device and method for controlling a bioreactor

Abstract

Bioreactor systems and controlled operation of bioreactor systems are disclosed herein. The bioreactor systems can include at least one bioreactor chamber, at least one reservoir, a plurality of sensors, and a fluid circuit. The operational methods disclosed herein are directed towards growing cells or tissue while measuring various parameters, and a controlled operation of the various parameters during the operation of the bioreactor systems. The controlled operation of the parameters includes, for example, cell concentration; a rate of flow; a volume; a pH; a temperature; a level of oxygen; a level of carbon dioxide; a level of bicarbonate ion; nutrient compound; and any combination thereof.

What is claimed is: 
     
         1 . A method, comprising:
 operating a bioreactor system,   wherein the bioreactor system comprises:
 a bioreactor chamber, 
 at least one reservoir, 
 a plurality of sensors, and 
 a fluid circuit, 
 wherein the fluid circuit comprises:
 a first section of the fluid circuit,
 wherein the first section fluidly connects the bioreactor chamber to the at least one reservoir, and is configured to flow a first fluid contained in the bioreactor chamber to the at least one reservoir, and 
 
 a second section of the fluid circuit,
 wherein the second section fluidly connects the at least one reservoir to the bioreactor chamber, and is configured to flow a second fluid contained in the at least one reservoir to the bioreactor chamber; 
 
 
   wherein the operating the bioreactor system comprises:
 obtaining sensor measured values for at least three parameters via the plurality of sensors; 
 providing a predetermined setpoint for each of the at least three parameters; 
 comparing the sensor measured values to the predetermined setpoint for the at least three parameters; and 
 controlling the fluid circuit to:
 remove some of the first fluid from the bioreactor chamber, 
 add some of the second fluid to the bioreactor chamber, or a combination thereof, 
 until each of the sensor measured values substantially matches the predetermined setpoint of the at least three parameters. 
 
   
     
     
         2 . The method of  claim 1 , wherein the at least three parameters are selected from:
 a level of cell concentration contained in the bioreactor chamber;   a rate of flow of a first fluid into the at least one reservoir;   a rate of flow of a second fluid into the bioreactor chamber;   a volume of the first fluid;   a pH of the first fluid;   a temperature of the first fluid;   a level of dissolved oxygen of the first fluid;   a level of dissolved CO 2  in the first fluid;   a level of HCO 3  in the first fluid; and   a level of nutrient in the first fluid.   
     
     
         3 . A method, comprising:
 operating a bioreactor system,   wherein the bioreactor system comprises:
 a bioreactor chamber, 
 a plurality of reservoirs, 
 wherein the plurality of reservoirs comprises:
 a first reservoir, and 
 a second reservoir, 
 
 a plurality of sensors, and 
 a fluid circuit, 
 wherein the fluid circuit comprises:
 a first section of the fluid circuit,
 wherein the first section fluidly connects the bioreactor chamber to the first reservoir, and is configured to flow a first fluid contained in the bioreactor chamber to the first reservoir, and 
 
 a second section of the fluid circuit,
 wherein the second section fluidly connects the second reservoir to the bioreactor chamber, and is configured to flow a second fluid contained in the second reservoir to the bioreactor chamber; 
 
 
   wherein the operating comprises:
 obtaining sensor measured values for at least three parameters via the plurality of sensors; 
 providing a predetermined setpoint for each of the at least three parameters; 
 comparing the sensor measured values to the predetermined setpoint for the at least three parameters; and 
 controlling the fluid circuit to:
 remove some of the first fluid from the bioreactor chamber, 
 add some of the second fluid to the bioreactor chamber, or a combination thereof, 
 until each of the sensor measured values substantially matches the predetermined setpoint of the at least three parameters. 
 
   
     
     
         4 . The method of  claim 3 , wherein the at least three parameters are selected from:
 a level of cell concentration contained in the bioreactor chamber;   a rate of flow of a first fluid into the at least one reservoir;   a rate of flow of a second fluid into the bioreactor chamber;   a volume of the first fluid;   a pH of the first fluid;   a temperature of the first fluid;   a level of dissolved oxygen of the first fluid;   a level of dissolved CO 2  in the first fluid;   a level of HCO 3  in the first fluid; and   a level of nutrient in the first fluid.   
     
     
         5 . The method of  claim 3 , wherein the bioreactor system comprises a plurality of cells contained in the bioreactor chamber. 
     
     
         6 . The method of  claim 3 , wherein the first fluid is a liquid, a gas, a nutrient, a medium, or a combination there of. 
     
     
         7 . The method of  claim 3 , wherein the second fluid is a liquid, a gas, a nutrient, a medium, or a combination there of. 
     
     
         8 . The method of  claim 3 , wherein the controlling the fluid circuit comprises:
 adjusting one to three of the at least three parameters, wherein the fluid circuit adjusts automatically to the adjusting of the one to three of the at least three parameters.   
     
     
         9 . The method of  claim 3 , wherein the controlling the fluid circuit comprises:
 adjusting all of the at least three parameters, wherein the fluid circuit adjusts automatically to the adjusting all of the at least three parameters.   
     
     
         10 . The method of  claim 9 , wherein the adjusting is simultaneous. 
     
     
         11 . The method of  claim 3 , wherein the operating the bioreactor system is performed for a sufficient amount of time, to obtain a fold expansion of a plurality of cells of 1.5 to 10,000. 
     
     
         12 . The method of  claim 3 , wherein the operating the bioreactor system is performed for a sufficient amount of time, to obtain a fold expansion of a plurality of cells of 100 to 7,500. 
     
     
         13 . The method of  claim 3 , wherein the operating the bioreactor system is performed for a sufficient amount of time, to obtain a fold expansion of a plurality of cells of 500 to 2,500. 
     
     
         14 . The method of  claim 3 , wherein the operating the bioreactor system is performed for a sufficient amount of time, to obtain a fold expansion of a plurality of cells of 50 to 1,000. 
     
     
         15 . The method of  claim 3 ,
 wherein the bioreactor system is configured to have at least two culturing modes selected from:
 a recirculation culturing mode, 
 a perfusion culturing mode, 
 a batch culturing mode, and 
 a fed batch culturing mode; and 
   the operating the bioreactor system further comprises:
 changing, from one to another, of the at least two culturing modes. 
   
     
     
         16 . A bioreactor system, comprising:
 a bioreactor chamber;   at least one reservoir;   a plurality of sensors,   a first controlled fluid flow path,
 wherein the first controlled fluid flow path is connected to the bioreactor chamber and to the at least one reservoir, and 
 wherein the first controlled fluid flow path being configured for flowing fluid from the at least one reservoir to the bioreactor chamber; 
   a second controlled fluid flow path,
 wherein the second controlled fluid flow path is connected to the bioreactor chamber and to the at least one reservoir, and 
 wherein the second controlled fluid flow path being configured for flowing fluid from the bioreactor chamber to the at least one reservoir; and 
   a control device
 wherein the control device is in communication with the plurality of sensors, and is configured to receive a plurality of parameters from the plurality of sensors, 
 wherein the control device is configured to control the first controlled fluid flow path, the second controlled fluid flow path, or both based on the plurality of parameters received from the plurality of sensors. 
   
     
     
         17 . The bioreactor system of  claim 16 , wherein the plurality of parameters includes at least three selected from:
 a level of cell concentration contained in the bioreactor chamber;   a rate of flow of a first fluid into the at least one reservoir;   a rate of flow of a second fluid into the bioreactor chamber;   a volume of the first fluid;   a pH of the first fluid;   a temperature of the first fluid;   a level of dissolved oxygen of the first fluid;   a level of dissolved CO 2  in the first fluid;   a level of HCO 3  in the first fluid; and   a level of nutrient in the first fluid.   
     
     
         18 . The bioreactor system of  claim 16 ,
 wherein the first fluid is a liquid, a gas, a nutrient, or a combination there of, and   wherein the second fluid is a liquid, a gas, a nutrient, or a combination there of.   
     
     
         19 . The bioreactor system of  claim 16 , wherein the bioreactor system is configured to operate for a sufficient amount of time, to obtain a fold expansion of cells of 1.5 to 10,000. 
     
     
         20 . The bioreactor system of  claim 16 , wherein the bioreactor system is configured to have at least two culturing modes selected from:
 a recirculation culturing mode;   a perfusion culturing mode;   a batch culturing mode; and   a fed batch culturing mode,   wherein the control device is configured to change modes from one of the at least two culturing modes to another of the at least two culturing modes while in operation.