Disposable culture bag

• US 6,673,598 B1
• Filed: 10/29/2002
• Issued: 01/06/2004
• Est. Priority Date: 10/29/2002
• Status: Active Grant

• Current Assignee: Synthecon, Inc.
• Original Assignee: Synthecon, Inc.
• Inventors: Akers, Roger, Dinges, Adrian F. Jr., Navran, Stephen S. Jr., Anderson, William J.
• Primary Examiner(s): Redding, David A.
• Application Number:
  US10/283,000
• Time in Patent Office: 434 Days
• Field of Search: 435/289.1, 435/297.1, 435/297.2, 435/297.3, 435/298.2, 435/297.5, 383/33, 383/36, 383/66, 383/67, 383/78, 383/88, 383/100, 383/109, 383/116
• US Class Current: 435/298.2
• CPC Class Codes: C12M 23/14 Bags
• CPC Class Codes: C12M 23/28 disposable or single use
• CPC Class Codes: C12M 29/10 Perfusion

Abstract

A cell culture bag for culturing cells, cellular aggregates, particles, tissues and organoids is disclosed. The cell culture bag is a flexible and disposable culture bag that fits within a bag support chamber of a bioreactor. The cell culture bag has an inlet means and an outlet means for the introduction and removal of media. Certain embodiments of the culture bag have an inlet and outlet fluid coupling swivel joint and/or perforated perfusion tubes extending from the inlet means into the interior of the bag to assist in mass transfer and mixing the media to maintain an even temperature throughout the culture bag.

Claims

1. A culture bag comprising:

at least one sheet having a first end, a second end, an internal side, and an external side, wherein the internal side of said sheet is positioned to face an interior of the culture bag;

a seam formed by fusing overlapped sections of one or more sheets;

an inlet means fused to the first end of one or more sheet;

an outlet means fused to the second end of one or more sheet; and

at least one outer perfusion tube, wherein a proximal end of the outer perfusion tube is in fluid communication with the inlet means, a central section of an external surface of the outer perfusion tube is fused to an interior-surface of the seam, and a distal end of the outer perfusion tube is closed.

2. The culture bag of claim 1, wherein the sheet is made of a biocompatible material.

3. The culture bag of claim 1, wherein the sheet is made of a substantially gas impermeable material.

4. The culture bag of claim 1, wherein the sheet is made of a gas permeable material.

5. The culture bag of claim 1, wherein the sheet is made of a multilayered material.

6. The culture bag of claim 1, wherein the sheet is made of a flexible material.

7. The culture bag of claim 1, wherein said inlet means comprises an inlet end piece and an inlet fluid coupling swivel joint.

8. The culture bag of claim 1, wherein said inlet end piece includes an inlet manifold and a branch port.

9. The culture bag of claim 8, wherein an external surface of the proximal end of the outer perfusion tube is fused to the branch port and a lumen of the outer perfusion tube is in fluid communication with the inlet manifold and the interior of the culture bag.

10. The culture bag of claim 1, wherein said inlet means comprises:

an inlet fluid coupling swivel joint;

an inlet manifold;

a branch port, wherein an external surface of the proximal end of the outer perfusion tube is fused to the branch port and a lumen of the outer perfusion tube is in fluid communication with the inlet manifold and the interior of the culture bag; and

a plurality of inlets, said inlets in fluid communication with the inlet manifold and the lumen of the outer perfusion tube.

11. The culture bag of claim 1, wherein said inlet means includes a plurality of inlets, each inlet introducing an independent fluid stream into the culture bag.

12. The culture bag of claim 1, wherein said outlet means comprises an outlet end piece and an outlet fluid coupling swivel joint.

13. The culture bag of claim 1, wherein said outlet means includes an outlet filter.

14. The culture bag of claim 13, wherein said outlet filter has a predetermined porosity.

15. The culture bag of claim 1, wherein the inlet means and the outlet means are coaxial.

16. The culture bag of claim 1, wherein the inlet means and the outlet means are configured to fit within concentric apertures on opposed ends of a rotating bioreactor chamber.

17. The culture bag of claim 1, further comprising an internal perfusion tube extending from an interior side of the inlet means into the interior of the culture bag.

18. The culture bag of claim 1, further comprising a plurality of internal perfusion tubes extending from an interior side of the inlet means into the interior of the culture bag.

19. The culture bag of claim 1, further comprising a plurality of internal perfusion tubes extending from an interior side of the inlet means into the interior of the culture bag, wherein the internal perfusion tubes have different lengths.

20. The culture bag of claim 1, further comprising a plurality of internal perfusion tubes extending from an interior side of the inlet means into the interior of the culture bag, wherein at least one internal perfusion tube has a distal end attached to the seam.

21. The culture bag of claim 1, further comprising an internal perfusion tube extending from an interior side of the inlet means into the interior of the culture bag, wherein the internal perfusion tube is branched.

22. The culture bag of claim 1, further comprising a plurality of internal perfusion tubes extending from an interior side of the inlet means into the interior of the culture bag, wherein the internal perfusion tubes are branched and at least one branch of at least one internal perfusion tube is attached to the seam.

23. The culture bag of claim 1, further comprising an internal perfusion tube extending from an interior side of the inlet means into the interior of the culture bag, wherein the internal perfusion tube has multiple perforations.

24. The culture bag of claim 1, further comprising an internal perfusion tube extending from an interior side of the inlet means into the interior of the culture bag, wherein the internal perfusion tube is designed to float in a media having a predetermined specific gravity.

25. The culture bag of claim 1, further comprising a gas removal means.

26. The culture bag of claim 1, further comprising a fill port.

27. The culture bag of claim 1, further comprising a gas removal means and a fill port.

28. The culture bag of claim 1, further comprising a patient identifier.

29. The culture bag of claim 28, wherein the patient identifier is a bar code.

30. The culture bag of claim 1, further comprising an internal tubular filter element extending from an interior end of the inlet means to the outlet means, wherein a lumen of said filter element is in fluid communication with said outlet means.

31. A culture bag comprising:

a plurality of sheets having a first end, a second end, an internal side, an external side and two opposed edges, wherein one edge of each sheet is fused with one edge of an adjacent sheet to form a seam, and wherein the internal sides of said fused sheets are positioned within an interior of the bag;

an inlet means fused to the first end of at least one sheet, wherein the inlet means includes an inlet end piece and an inlet fluid coupling swivel joint; and

an outlet means fused to the second end of at least one sheet, wherein the outlet means comprises an outlet end pierce and an outlet fluid coupling swivel joint.

32. The culture bag of claim 31, said inlet means further comprising an inlet manifold and a plurality of inlets, said inlets in communication with the inlet manifold and the interior of the culture bag.

33. The culture bag of claim 31, wherein said outlet means includes an outlet filter.

34. The culture bag of claim 31, further comprising an internal tubular filter element extending from an interior end of the inlet means to the outlet means, wherein a lumen of said filter element is in fluid communication with said outlet means.

35. The culture bag of claim 31, further comprising a gas removal means.

36. The culture bag of claim 31, further comprising a fill port.

37. The culture bag of claim 31, further comprising a patient identifier.

38. The culture bag of claim 31, further comprising an outer perfusion tube, wherein a proximal end of the perfusion tube is in fluid communication with the inlet means, a section of an external surface of the perfusion tube is fused to an interior surface of one seam, and a distal end of the perfusion tube is closed.

39. The culture bag of claim 31, wherein the inlet means further comprises a manifold and a plurality of branch ports.

40. The culture bag of claim 39, further comprising a plurality of perfusion tubes extending from the inlet means into the interior of the culture bag, said perfusion tubes in fluid communication with the manifold and the interior of the culture bag.

41. The culture bag of claim 40, wherein the inlet means further comprises a plurality of inlets, each inlet introducing an independent fluid stream into the interior of the culture bag.

42. The culture bag of claim 41, wherein each inlet is in communication with at least one perfusion tube.

43. A culture bag comprising:

at least one sheet having a first end, a second end, an internal side, and an external side, wherein the internal side of said sheet is positioned to face an interior of the culture bag;

a seam formed by fusing overlapped sections of one or more sheets;

an inlet means fused to the first end of one or more sheet;

an outlet means fused to the second end of one or more sheet; and

at least one outer perfusion tube having a proximal end, a central section and a distal end, wherein the proximal end is in fluid communication with the inlet means, a portion of an external surface of the central section is fused to an interior surface of the seam, and the distal end is closed, and further wherein the central section of the outer perfusion tube is perforated to allow fluid communication between a lumen of the outer perfusion tube and the interior of the culture bag; and

at least one perforated internal perfusion tube, said internal perfusion tube in fluid communication with the inlet means and the interior of the culture bag.

44. The culture bag of claim 43, wherein the inlet means comprises:

an inlet fluid coupling swivel joint;

an inlet manifold;

a plurality of branch ports extending from the inlet manifold, wherein the proximal end of one outer or internal perfusion tube is fused to a side of each branch port; and

a plurality of inlets, wherein each inlet introduces an independent fluid stream into one outer or internal perfusion tube.

45. The culture bag of claim 43, wherein the inlet means comprises:

an inlet fluid coupling swivel joint;

an inlet manifold;

a plurality of branch ports extending from the inlet manifold, wherein the proximal end of one outer or internal perfusion tube is fused to a side of each branch port; and

a plurality of inlets, said inlets in fluid communication with the inlet manifold and the lumen of the outer or internal perfusion tubes.

46. The culture bag of claim 43, wherein said inlet means comprises an inlet end piece and an inlet fluid coupling swivel joint.

47. The culture bag of claim 43, wherein said outlet means comprises an outlet end piece and an outlet fluid coupling swivel joint.

48. The culture bag of claim 43, further comprising a patient identification means.

49. The culture bag of claim 43, further comprising an internal filter element, the filter element extends from an interior end of the inlet means to the outlet means, wherein a lumen of the filter element is in fluid communication with the outlet means.

50. A culture bag of claim 43, further comprising inlet tubing and outlet tubing.

51. A culture bag comprising:

at least one sheet having a first end, a second end, an internal side, and an external side, wherein the internal side of said sheet is positioned to face an interior of the culture bag;

a seam formed by fusing overlapped sections of one or more sheets;

an inlet means fused to the first end of one or more sheet, wherein the inlet means includes an inlet end piece, an inlet fluid coupling swivel joint, a manifold and a branch port;

an outlet means fused to the second end of one or more sheet, wherein the outlet means includes an outlet end piece and an outlet fluid coupling swivel joint; and

a perforated perfusion tube, an external surface of a proximal end of the perfusion tube fused to the branch port and a lumen of the perfusion tube in communication with the manifold and the interior of the culture bag.