Stirred-tank reactor system
The present invention relates to a stirred-tank reactor system and methods of preparing such systems. The present invention further encompasses the use of the stirred-tank reactor system as a disposable bioreactor and in kits with disposable elements.
1 . A stirred-tank reactor system, comprising:
(i) a flexible bag with at least one opening, wherein the bag functions as a sterile container for a fluidic medium;
(ii) a shaft situated within the bag;
(iii) an impeller attachable to said shaft, wherein said impeller is used to agitate the fluidic medium to provide a hydrodynamic environment; and
(iv) a bearing attached to said shaft and to said opening of the bag.
2 . The stirred-tank system of claim 1 , wherein said system is disposable.
3 . The stirred-tank system of claim 1 , wherein said system is pre-sterilized.
4 . The stirred-tank reactor system of claim 1 , wherein said system further comprises a housing on the outside of the bag, wherein said housing includes at least one support that holds the bearing and a motor, and wherein said bag is contained within the housing.
5 . The stirred-tank reactor system of claim 4 , wherein said system further includes a heater selected from the group consisting of a heating pad, a steam jacket, and a circulating fluid or water heater.
6 . The stirred-tank reactor system of claim 5 , wherein said heater is located between the bag and the housing.
7 . The stirred-tank reactor system of claim 5 , wherein said heater is incorporated into the housing.
8 . The stirred-tank reactor system of claim 4 , wherein the housing further includes a plurality of baffles and the bag folds around the baffles.
9 . The stirred-tank reactor system of claim 4 , wherein said system further includes a product loop with flow past a pH sensor and a dissolved-oxygen sensor, wherein said sensors are incorporated into the housing.
10 . The stirred-tank reactor system of claim 4 , wherein said housing is selected from the group consisting of a metal barrel, a plastic barrel, wood barrel, and a glass barrel.
11 . The stirred-tank reactor system of claim 1 , wherein said bag is a disposable, plastic bag.
12 . The stirred-tank reactor system of claim 1 , wherein said fluidic medium is selected from the group consisting of a biological fluid, a cell culture medium, a culture of microorganisms, and a food production.
13 . The stirred-tank reactor system of claim 12 , wherein the fluidic medium is a cell culture medium and the system is operated in batch mode, semi-batch mode, fed-batch mode, or continuous mode.
14 . The stirred-tank reactor system of claim 1 , wherein said impeller agitates the fluidic medium by stirring.
15 . The stirred-tank reactor system of claim 14 , wherein said impeller is selected from the group consisting of Rushton, hydrofoil, pitched blade, and marine.
16 . The stirred-tank reactor system of claim 1 , wherein said bag is affixed to the shaft and the bearing through at least one seal or o-ring such that the inside of the bag remains sterile.
17 . The stirred-tank reactor system of claim 16 , wherein said seals or o-rings are affixed to the bag.
18 . The stirred-tank reactor system of claim 16 , wherein said bag further includes a pH sensor and a dissolved-oxygen sensor, wherein said sensors are incorporated into the bag.
19 . The stirred-tank reactor system of claim 16 , wherein said system further includes at least one internal pouch sealed to the bag, wherein the pouch includes one end that can be opened to the outside of the bag such that a probe can be inserted into the reactor.
20 . The stirred-tank reactor system of claim 19 , wherein said probe is selected from the group consisting of a temperature probe, a pH probe, a dissolved gas sensor, an oxygen sensor, a carbon dioxide sensor, a cell mass sensor, a nutrient sensor, and an osmometer.
21 . The stirred-tank reactor system of claim 16 , wherein said system further includes a least one port in the bag allowing for the connection of a device to the port, wherein said device is selected from the group consisting of a tube, a filter, a sampler, a probe and a connector.
22 . The stirred-tank reactor system of claim 21 , wherein the port allows for gas flow in and out of the bag.
23 . The stirred-tank reactor system of claim 21 , wherein the port allows for media flow in and out of the bag.
24 . The stirred-tank reactor system of claim 21 , wherein the port allows for sampling, inoculation, titration, adding of chemostat reagents, and sparging.
25 . A method for preparing a stirred-tank reactor system, comprising:
(i) providing a flexible bag with at least one opening, wherein the bag functions as a sterile container for a fluidic medium;
(ii) inserting a shaft with an impeller attachable to said shaft into the bag, wherein said impeller is used to agitate the fluidic medium to provide a hydrodynamic environment;
(iii) attaching a bearing to said shaft and to said opening of the bag; and
(iv) sealing the bag to the shaft and the bearing such that the inside of the bag remains sterile.
26 . The method of claim 25 , wherein said stirred-tank reactor system is pre-sterilized.
27 . The method of claim 25 , wherein said stirred-tank reactor system is disposable.
28 . The method of claim 25 , wherein said stirred-tank reactor system includes at least one disposable element selected from the group consisting of the bag, the shaft, the impeller, and the bearing.
29 . A kit comprising:
(i) the stirred-tank reactor system of claim 16; and
(ii) instructions for use.
30 . The kit of claim 29 , wherein said stirred-tank reactor system is disposable.
31 . The kit of claim 29 , wherein said stirred-tank reactor system includes at least one disposable element selected from the group consisting of the bag, the shaft, the impeller, and the bearing.
32 . The kit of claim 29 , wherein said bag is affixed to the shaft and the bearing through at least one seal or o-ring such that the inside of the bag remains sterile.
33 . The kit of claim 29 , wherein said bag further includes a pH sensor and a dissolved-oxygen sensor, wherein said sensors are incorporated into the bag.
34 . The kit of claim 29 , wherein said system further includes at least one internal pouch sealed to the bag, wherein the pouch includes one end that can be opened to the outside of the bag such that a probe can be inserted into the reactor.
35 . The kit of claim 34 , wherein said probe is selected from the group consisting of a temperature probe, a pH probe, a dissolved gas sensor, an oxygen sensor, a carbon dioxide sensor, a cell mass sensor, a nutrient sensor and an osmometer.
36 . The kit of claim 29 , wherein said system further includes a least one port in the bag allowing for the connection of a device to the port, wherein said device is selected from the group consisting of a tube, a filter, a sampler, a probe and a connector.
37 . The kit of claim 36 , wherein the port allows for gas flow in and out of the bag.
38 . The kit of claim 36 , wherein the port allows for media flow in and out of the bag.
39 . The kit of claim 36 , wherein the port allows for sampling, inoculation, titration, adding of chemostat reagents, and sparging.
40 . A bag for use in the stirred-tank reactor system of claim 1 .
41 . The bag of claim 40 , wherein said bag is a disposable plastic bag.
42 . The bag of claim 40 , wherein said bag further includes at least one disposable element selected from the group consisting of a seal, an o-ring, a port, a pouch, a tube, a filter, a sampler, a probe, a sensor and a connector.