Devices, systems and methods for automated cell culturing

Patent metadata

Field	Value
Publication number	US-9550972-B2
Application number	US-201414499709-A
Country	US
Kind code	B2
Filing date	Sep 29, 2014
Priority date	Sep 29, 2014
Publication date	Jan 24, 2017
Grant date	Jan 24, 2017

Abstract

A bioreactor is provided. The bioreactor is a multi-scalable bioreactor, which comprises a culture vessel for seeding and culturing cells by adding a cell-culture media, wherein the culture vessel comprises at least a side wall and a bottom surface, a specific heat transfer area and a specific gas transfer area; wherein the culture vessel is configured to accommodate the cell-culture media volume up to 10 liters, and wherein the specific heat transfer area and the specific gas transfer area are independent of cell-culture media volume. A kit for culturing cells in a large scale is also provided which further comprises disposable tubings, culture bag or combinations thereof. A method for culturing cells is also provided.

First claim

The invention claimed is:

1. A bioreactor, comprising:
a culture vessel for seeding and culturing cells by adding a cell-culture medium,
wherein the culture vessel comprises at least a side wall and a bottom surface;
wherein the culture vessel is configured such that a specific heat transfer area (sHTA) and a specific gas transfer area (sGTA) of the culture vessel are constant with respect to a change in a volume of the cell-culture medium in the culture vessel, and
wherein the specific heat transfer area at a height h of the cell-culture medium in the culture vessel is defined by equation (1) and the specific gas transfer area at a height h of the cell-culture medium in the culture vessel is defined by equation (2):
sHTA( h )=HTA( h )/ V ( h )  equation (1), and

sGTA( h )=GTA( h )/ V ( h )  equation (2),

wherein sHTA(h) is a specific heat transfer area for a height h of the cell-culture medium in the culture vessel, HTA(h) is a heat transfer area for the height h of the cell-culture medium in the culture vessel, V(h) is a volume of the cell-culture medium for the height h of the cell-culture medium in the culture vessel, sGTA(h) is a specific gas transfer area at the height h of the cell-culture medium in the culture vessel, and GTA(h) is an area of a top surface of the cell-culture medium at the height h of the cell-culture medium in the culture vessel.

2. The bioreactor of claim 1 , wherein the culture vessel is configured to accommodate the volume of cell-culture medium between 15 ml to 10 liters.

3. The bioreactor of claim 1 , wherein the culture vessel is configured to accommodate an expandable cell-culture medium volume.

4. The bioreactor of claim 1 , wherein the bioreactor is a multi scale bioreactor.

5. The bioreactor of claim 1 , wherein the bioreactor system is configured to maintain a set point for constant temperature, pH, dissolved oxygen or combinations thereof during operation.

6. The bioreactor of claim 1 , further comprising a controller for controlling a gas mixing ratio, gas flow rate, heating, agitating or combinations thereof within the culture vessel.

7. The bioreactor of claim 1 , further comprising one or more impellers for agitating the culture medium.

8. The bioreactor of claim 7 , wherein the impellers are operably coupled to a motor by one or more of magnetic coupling, mechanical coupling, electrical coupling and electromagnetic coupling.

9. The bioreactor of claim 7 , wherein the impellers are operably coupled to a motor by magnetic coupling.

10. The bioreactor of claim 1 , further comprising one or more heating units for heating the culture medium.

11. The bioreactor of claim 10 , wherein at least one of the heating units is used to heat the side-walls.

12. The bioreactor of claim 10 , wherein the heating unit comprises an IR source, a heating blanket, a water jacket or combinations thereof.

13. The bioreactor of claim 1 , further comprising one or more temperature controllers for maintaining the temperature of the culture medium.

14. The bioreactor of claim 1 , further comprising a bioreactor lid.

15. The bioreactor of claim 14 , further comprising one or more heating units for heating the bioreactor lid.

16. The bioreactor of claim 14 , further comprising one or more temperature controllers to control a temperature of the bioreactor lid.

17. The bioreactor of claim 1 , further comprising one or more temperature sensors for providing a temperature feedback control of the culture medium.

18. The bioreactor of claim 1 , further comprising one or more pH sensors and/or dissolved oxygen sensors.

19. The bioreactor of claim 1 , wherein the culture vessel has a length in a range of 1 to 500 cm, a width in a range of 1 to 500 cm and a height in a range of 1 to 100 cm.

20. The bioreactor of claim 1 , wherein the culture vessel has an aspect ratio in a range from about 0.3 to about 3.

21. The bioreactor of claim 1 , wherein the culture vessel is made of glass, polymer, ceramic, metal, or a combination thereof.

22. The bioreactor of claim 1 , wherein the culture vessel is made of thermoplastic.

23. The bioreactor of claim 1 , wherein the culture vessel has a perimeter that is triangular, rectangular, square planar, pentagonal, hexagonal, polygonal, circular, elliptical, or irregular.

24. The bioreactor of claim 1 , further comprising a biocompatible coating on an inner wall of the culture vessel, wherein the biocompatible coating comprises notch ligands, anti-CD3 antibody and anti-CD28 antibody.

25. The bioreactor of claim 1 is a stirred tank bioreactor, a reactor with a rocking or rolling motion, a reactor with a one dimensional shaking, a reactor with two dimensional shaking, a reactor with three dimensional shaking, or combinations thereof.

26. The bioreactor of claim 1 is configured to seed and culture cells selected from bacterial cells, animal cells, plant cells, fungi, insect cells, microbes, virus cells, stem cells, or combinations thereof.

27. The bioreactor of claim 1 , further comprising one or more conduits.

28. The bioreactor of claim 27 , wherein the conduits are used for adding culture medium, nutrients, cells, gases, acid, base, or combinations thereof to the vessel, and/or the conduits are used for withdrawing the culture media from the vessel for sampling, transferring the cell culture media with cells to a cell-harvester or combinations thereof under sterile conditions.

29. The bioreactor of claim 1 , wherein the bioreactor further comprises one or more gas inlet ports and/or gas outlet ports.

30. The bioreactor of claim 1 , wherein the gas inlet ports and/or gas outlet ports comprise a sterile filter.

31. The bioreactor of claim 30 , wherein the gas outlet ports comprise an off-gas condenser.

32. The bioreactor of claim 31 , wherein the gas inlet ports comprise a heater.

33. A kit comprising:
one or more disposable tubings; and
a bioreactor comprising:
a culture vessel for seeding and culturing cells by adding a cell-culture medium, wherein the culture vessel comprises at least a side wall and a bottom surface, wherein the culture vessel is configured to accommodate the cell-culture medium without introducing a significant change in bioreactor dynamics by maintaining a specific heat transfer area and a specific gas transfer area,
wherein the culture vessel is configured such that a specific heat transfer area (sHTA) and a specific gas transfer area (sGTA) of the culture vessel are constant with respect to a change in a volume of the cell-culture medium in the culture vessel; and the specific heat transfer area and a specific gas transfer area at a height h of the cell-culture medium in the culture vessel are defined by equations (1) and (2), respectively:
sHTA ( h )=HTA ( h )/ V ( h )  equation (1)

sGTA ( h )=GTA ( h )/ V ( h )  equation (2),

wherein sHTA(h) is a specific heat transfer area for a height h of the cell-culture medium in the culture vessel, HTA(h) is a heat transfer area for the height h of the cell-culture medium in the culture vessel, V(h) is a volume of the cell-culture medium for the height h of the cell-culture medium in the culture vessel, sGTA(h) is a specific gas transfer area at the height h of the cell-culture medium in the culture vessel, and GTA(h) is an area of a to

Assignees

• Gen Electric

Inventors

• Jeong Younkoo
• Griffin Weston Blaine
• Keskar Vandana
• Zhang Zhipeng

Classifications

• C12M23/24

  Gas permeable parts · CPC title

• C12M41/22 Primary

  in contact with the bioreactor walls · CPC title

• C12M41/34

  of gas · CPC title

• C12M41/14 Primary

  Incubators; Climatic chambers (per se B01L1/00) · CPC title

• C12M23/02 Primary

  Form or structure of the vessel (large containers B65D88/00) · CPC title