Bioreactor for mammalian cell growth and maintenance

• US 6,048,721 A
• Filed: 09/29/1997
• Issued: 04/11/2000
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: BAE Systems Plc
• Original Assignee: Aastrom Biosciences, Inc.
• Inventors: Armstrong, R. Douglas, Maluta, James, Roecker, David
• Primary Examiner(s): Beisner, William H.
• Application Number:
  US08/939,489
• Time in Patent Office: 925 Days
• Field of Search: 435/293.2, 435/297.2, 435/297.5, 435/372, 435/373, 435/401, 435/286.1, 435/286.5, 435/286.6, 422/48, 210/321.75, 210/321.84
• US Class Current: 435/286.5
• CPC Class Codes: C12M 23/42 Integrated assemblies, e.g. cassettes or cartridges
• CPC Class Codes: C12M 41/14 Incubators; Climatic chambers per se B01L1/00
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00

Abstract

A bioreactor for the ex vivo maintenance and growth of mammalian cells includes a disposable, self contained cell cassette, a system manager, an incubator unit matable with a plurality of the cassettes and a processor unit. The cell cassette includes a substantially circular cell growth chamber defined between a substantially planar cell bed and a gas permeable, liquid impervious membrane. A media inlet enters the cell growth chamber communicates at a radially central portion of the cell bed. A plurality of media outlets are radially outwardly spaced from the media inlet by a distance sufficient for cell growth to occur between the inlet and the outlets. The outlets are substantially equiangularly circumferentially spaced about the cell growth chamber.

Claims

1. A computer program product in a bioreactor system for ex vivo maintenance, and growth of mammalian cells, comprising:

a transportable cassette having a gas chamber and cell growth chamber, environmental conditions in said cell growth chamber being dominated by a media flowing therethrough and environmental conditions in said gas chamber being dominated by a gas flowing therethrough, said transportable cassette having

a computer storage medium encoded with a computer code mechanism that when executed by a processor in the bioreactor system and external to the transportable cassette controls environmental conditions in a bioreactor portion of the system to be suitable for the ex vivo maintenance and growth of the mammalian cells, said computer program code mechanism including,

a media flow code mechanism having a media flow rate parameter embedded therein and being accessible to said processor when maintaining a predetermined media flow rate through the cell growth chamber so as to maintain the environmental conditions to be suitable for the maintenance and growth of the mammalian cells.

2. The computer program product of claim 1, wherein said computer program code mechanism further comprises:

a temperature control mechanism having a temperature paramctcr embedded therein and being accessible to said processor when maintaining a predetermined temperature of said bioreactor portion.

3. The computer program product of claim 1, wherein said computer program code mechanism further comprises:

a gas mixture and gas flowrate code mechanism having at least one of a gas mixture parameter and a gas flowrate parameter embedded therein and being accessible to said processor when maintaining a predetermined gas conditions in said gas chamber.

4. The computer program product of claim 1, wherein said computer program code mechanism further comprises:

a gas concentration code mechanism having at least one of a gas concentration parameter embedded therein and accessible to the processor when maintaining a predetermined gas concentration in said gas chamber.

5. The computer program product of claim 1, wherein said media flow rate parameter, being a time-varying parameter.

6. The computer program product of claim 1, wherein said computer program code mechanism further comprises:

a patient information data field configured to hold patient-specific information regarding a patient that will receive said mammalian cells, said computer program code mechanism being configured to be updated with new information about said patient during an incubation time of said mammalian cells in said computer-controlled bioreactor portion.

7. The computer program product of claim 1, wherein said computer program code mechanism further comprises:

a biological cell data field configured to hold biological cell information pertaining to said mammalian cells, said computer program code mechanism being configured to be updated with new biological cell information about said mammalian cells during an incubation time of said mammalian cells in said bioreactor protion.

8. The computer program product of claim 1, wherein said computer program code mechanism further comprises:

a time period data field configured to hold timing information regarding a period of time that said mammalian cells are incubated in said bioreactor portion.

9. A a bioreactor system for ex vivo maintenance and growth of mammalian cells, comprising:

a central processing unit;

a transportable cassette, separable from said central processing unit having,

a data path to said central processing unit;

a bioreactor having a cell growth chamber and a gas chamber;

a computer storage medium encoded with a computer code mechanism that when executed by the central processing unit through said data path controls environmental conditions in the bioreactor to be suitable for the ex vivo maintenance and growth of the mammalian cells, said computer storage medium being encoded with,

a media flow rate parameter embedded therein and being accessible via said data path to said central processing unit when maintaining a predetermined media flow rate through the cell growth chamber so as to maintain the environmental conditions to be suitable for the maintenance and growth of the mammalian cells; and

means for monitoring process data while said mammalian cells are maintained and grown in said bioreactor.

10. The bioreactor system of claim 9, further comprising:

means for controlling said predetermined media flow rate using said process data monitored by said means for monitoring.

11. The bioreactor system of claim 9, further comprising:

means for inoculating said bioreactor of said transportable cassette with an initial sample of said mammalian cells.

12. The bioreactor system of claim 9, further comprising:

means for harvesting said mammalian cells from said bioreactor.

13. A computer-controlled bioreactor for ex vivo maintenance and growth of mammalian cells, comprising:

a transportable cassette having

a cell growth chamber having a media inlet, a media outlet and an internal volume;

a gas permeable, liquid impervious member disposed within said internal volume so as to divide said internal volume into a gas chamber and a cell growth chamber;

a computer storage medium encoded with a computer code mechanism that when executed by a processor that is external to said transportable cassette controls environmental conditions suitable for the ex vivo maintenance and growth of the mammalian cells, said computer program code mechanism including,

a media flow code mechanism having a media flow rate parameter embedded therein and being accessible to said processor when maintaining a predetermined media flow rate through the cell growth chamber by way of said media inlet.

14. The bioreactor of claim 13, wherein said computer program code mechanism further comprises:

a temperature control mechanism configured to maintain a predetermined temperature within said bioreactor.

15. The bioreactor of claim 13, wherein said computer program code mechanism further comprises:

a gas mixture and gas concentration control mechanism configured to control a mixture of gases and a concentration of the mixture of gases in the gas chamber.

16. The computer-controlled bioreactor of claim 13, wherein said computer program code mechanism further comprises:

an inoculation code mechanism configured to control an inoculation operation in said bioreactor with said mammalian cells while maintaining said bioreactor in said mammalian cells in a sterile environment.

17. The computer-controlled bioreactor of claim 13, wherein said computer program code mechanism further comprises:

a harvesting code mechanism configured to control a cell harvesting operation of said mammalian cells from said cell growth chamber while keeping said mammalian cells in a sterile environment.