Stirred-tank reactor system

• US 7,384,783 B2
• Filed: 04/22/2005
• Issued: 06/10/2008
• Est. Priority Date: 04/27/2004
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited, Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Inventors: Kunas, Kurt T., Goodwin, Michael E., Jones, Nephi D., Hasan, Fauad F., Larsen, Jeremy K., Oakley, Robert V.
• Primary Examiner(s): Ketter; James S
• Application Number:
  US11/112,834
• Publication Number:
  US 20050239199A1
• Time in Patent Office: 1,145 Days
• Field of Search: None
• US Class Current: 435/289.1
• CPC Class Codes: B01F 2101/44 Mixing of ingredients for microbiology, enzymology, in vitro culture or genetic manipulation
• CPC Class Codes: B01F 27/071 Fixing of the stirrer to the shaft
• CPC Class Codes: B01F 27/88 with a separate receptacle-stirrer unit that is adapted to be coupled to a drive mechanism
• CPC Class Codes: B01F 27/91 with propellers
• CPC Class Codes: B01F 33/86 Mixing heads comprising a driven stirrer
• CPC Class Codes: B01F 35/51 characterised by their material
• CPC Class Codes: B01F 35/513 Flexible receptacles, e.g. bags supported by rigid containers
• CPC Class Codes: C12M 23/00 Constructional details, e.g. recesses, hinges flow directing inserts in C12M27/18-C12M27/24; apparatus for chemical or physical processes in general B01J, chemical or physical laboratory apparatus in general B01L
• CPC Class Codes: C12M 23/06 Tubular C12M23/08, C12M23/16 take precedence
• CPC Class Codes: C12M 23/14 Bags
• CPC Class Codes: C12M 23/26 flexible flexible containers for laboratory use B01L3/505
• CPC Class Codes: C12M 23/28 disposable or single use
• CPC Class Codes: C12M 27/02 Stirrer or mobile mixing elements
• CPC Class Codes: C12M 29/06 Nozzles; Sprayers; Spargers; Diffusers per se B01F23/231, B01J19/26
• CPC Class Codes: C12M 41/00 Means for regulation, monitoring, measurement or control, e.g. flow regulation controlling or regulating chemical, physical or physicochemical processes B01J19/0006; heating or cooling apparatus for laboratory use B01L7/00; electro optical investigation of individual particles, flow cytometers G01N15/14; automatic analysis G01N35/00; controlling or regulating in general G06N
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

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.

Claims

1. A reactor system, the system comprising:

a container comprising a flexible bag; and

a rotational assembly in sealed cooperation with an opening of the container, the rotational assembly comprising a rotatable hub adapted to receive and releasably couple with a drive shaft such that when the drive shaft is operatively coupled with the rotatable hub, rotation of the drive shaft facilitates a corresponding rotation of the rotatable hub.

2. The reactor system of claim 1, further comprising an impeller coupled with the rotatable hub, the impeller being disposed within the container and adapted to couple with a distal end of the drive shaft.

3. The reactor system of claim 1, wherein the rotational assembly further comprises a casing, the rotational assembly being in sealed cooperation with the opening of the container via the casing.

4. The reactor system of claim 3, further comprising the drive shaft, wherein the rotatable hub and the drive shaft are disposed to rotate relative to the casing.

5. The reactor system of claim 3, wherein the rotational assembly further comprises a bearing assembly disposed between the casing and the rotatable hub.

6. The reactor system of claim 5, wherein the rotational assembly further comprises a sealing arrangement disposed circumferentially to the rotatable hub, between the rotatable hub and the casing.

7. The reactor system of claim 6, wherein the bearing assembly comprises a plurality of race bearings, and the sealing arrangement comprises a rotating disk coupled with the rotatable hub, a wear plate being coupled with the casing, and a dynamic seal being disposed between the rotating disk and the wear plate.

8. The reactor system of claim 7, wherein the dynamic seal comprises two or more seal subunits disposed in co-planar arrangement.

9. The reactor system of claim 6, wherein the bearing assembly comprises a journal bearing, and the sealing arrangement comprises a wear plate coupled with the rotatable hub, a dynamic seal being disposed between the casing and the wear plate.

10. The reactor system of claim 9, wherein the dynamic seal comprises two or more seal subunits disposed in co-planar arrangement.

11. The reactor system of claim 2, wherein the impeller comprises a spline adapted to couple with the drive shaft.

12. The reactor system of claim 2, wherein the rotatable hub is coupled with the impeller via a flexible tube.

13. A bioreactor system, the system comprising:

a frame support coupled with a drive motor;

a flexible bag disposed within a housing of the frame support, the flexible bag comprising one or more ports for introducing a cell culture and a medium into the flexible bag;

a rotational assembly coupled with the frame support and in sealed cooperation with an opening of the flexible bag, the rotational assembly comprising a hub adapted to receive and couple with a drive shaft; and

an impeller coupled with the hub for agitating the cell culture and medium, the impeller being disposed within the flexible bag and adapted to couple with the drive shaft.

14. The bioreactor system of claim 13, the system further comprising a probe assembly, the probe assembly comprising:

a port coupled with the flexible bag;

a connector coupled with the port;

a sleeve coupled with the connector;

a coupler coupled with the sleeve; and

a probe configured to be coupled with the coupler and inserted through the sleeve, connector, and the port, and partially into the flexible bag.

19. The bioreactor system of claim 13, the system further comprising:

a flexible tube extending between the hub and the impeller; and

the drive shaft disposed within the flexible tube and coupled with the impeller and the hub, the drive shaft being selectively rotated by the drive motor.

15. A reactor system, the system comprising:

a container; and

a rotational assembly in sealed cooperation with an opening of the container, the rotational assembly comprising a rotatable hub adapted to receive and releasably couple with a drive shaft such that when the drive shaft is operatively coupled with the rotatable hub, rotation of the drive shaft facilitates a corresponding rotation of the rotatable hub, wherein the rotational assembly further comprises;

a casing, the rotational assembly being in sealed cooperation with the opening of the container via the casing;

a bearing assembly disposed between the casing and the rotatable hub, the bearing assembly comprises a plurality of race bearings; and

a sealing arrangement disposed circumferentially to the rotatable hub between the rotatable hub and the casing, the sealing arrangement comprising a rotating disk coupled with the rotatable hub, a wear plate being coupled with the casing, and a dynamic seal being disposed between the rotating disk and the wear plate.

16. The reactor system of claim 15, wherein the dynamic seal comprises two or more seal subunits disposed in co-planar arrangement.

17. A reactor system, the system comprising:

a container; and

a rotational assembly in sealed cooperation with an opening of the container, the rotational assembly comprising a rotatable hub adapted to receive and releasably couple with a drive shaft such that when the drive shaft is operatively coupled with the rotatable hub, rotation of the drive shaft facilitates a corresponding rotation of the rotatable hub, wherein the rotational assembly further comprises;

a casing, the rotational assembly being in sealed cooperation with the opening of the container via the casing;

a bearing assembly disposed between the casing and the rotatable hub, the bearing assembly comprises a journal bearing; and

a sealing arrangement disposed circumferentially to the rotatable hub between the rotatable hub and the casing, the sealing arrangement comprising a wear plate coupled with the rotatable hub, and a dynamic seal disposed between

the casing and the wear plate, the dynamic seal comprising two or more seal subunits disposed in co-planar arrangement.

18. A reactor system, the system comprising:

a container;

a rotational assembly in sealed cooperation with an opening of the container, the rotational assembly comprising a rotatable hub adapted to receive and releasably couple with a drive shaft such that when the drive shaft is operatively coupled with the rotatable hub, rotation of the drive shaft facilitates a corresponding rotation of the rotatable hub; and

an impeller coupled with the rotatable hub, the impeller being disposed within the container and adapted to couple with a distal end of the drive shaft, wherein the impeller comprises a spline adapted to couple with the drive shaft.