Apparatus for the large scale growth and packaging of cell suspensions and three-dimensional tissue cultures

• US 5,763,267 A
• Filed: 04/16/1996
• Issued: 06/09/1998
• Est. Priority Date: 04/16/1996
• Status: Expired due to Term

• Current Assignee: Shire Regenerative Medicine Incorporated (Shire plc)
• Original Assignee: Advanced Tissue Sciences, Inc.
• Inventors: Baumgartner, Mark, Bloom, Nicole, Applegate, Dawn Orton, Kurjan, Christine, Flatt, James H., Applegate, Mark A.
• Primary Examiner(s): Smith, Lynette F.
• Assistant Examiner(s): NELSON, BRETT L
• Application Number:
  US08/632,972
• Time in Patent Office: 784 Days
• Field of Search: 210/456, 210/321.86, 210/321.75, 435/293.1, 435/297.2, 435/304.1, 435/304.2, 435/240.2, 435/325, 435/399
• US Class Current: 435/293.1
• CPC Class Codes: C12M 23/26 flexible flexible containers for laboratory use B01L3/505
• CPC Class Codes: C12M 23/34 Internal compartments or partitions
• CPC Class Codes: C12M 23/40 Manifolds; Distribution pieces fluid transfer means B01L3/563
• CPC Class Codes: C12M 45/22 Means for packing or storing viable microorganisms casings for storing cell samples A61B10/0096, preservation of living parts of the human or animal body A01N1/02

Abstract

An apparatus for the large scale culturing and packaging of cell suspensions, three dimensional tissue, and other biological systems is disclosed. The apparatus includes a plurality of flexible or semi-flexible treatment chambers comprising one or more individual culture pockets, a plurality of rigid spacers, an inlet fluid manifold, an outlet fluid manifold, a fluid reservoir, and a means for transporting fluid within the system. During treatment, liquid media is transported from the fluid reservoir to the inlet manifold, which will in turn evenly distribute the media to each of the connected treatment chambers and internal culture pockets. An outlet fluid manifold is also provided to ensure that each treatment chamber is evenly filled and to ensure that any air bubbles formed during treatment are removed from the treatment chambers. The treatment chambers are flexible or semi-flexible so as to provide for easy end-user handling during rinsing and application of the cultured transplants. Due to the flexibility of the treatment chambers, rigid spacers are also provided which ensure even fluid distribution within the chambers during treatment.

Claims

1. An apparatus, comprising

a plurality of growth chambers comprising flexible front and back sheets bonded together along predetermined boundaries to delimit a first port for the inflow of fluid into said growth chambers, a second port for the outflow of fluid from said growth chambers, and at least one compartment for growth of tissue;

at least one substrate disposed within each of said plurality of growth chambers designed to facilitate three-dimensional tissue growth on said substrate;

a plurality of spacer members adapted to contact the flexible growth chambers in a manner which maintains even fluid distribution within the chambers, thereby promoting even growth of tissue;

an inlet manifold with an inlet port and a plurality of outlet ports for uniformly providing fluid to the growth chambers, said outlet ports adapted to mate with the first ports of the growth chambers;

an outlet manifold with a plurality of inlet ports, each of said inlet ports adapted to mate with the second ports of the growth chambers; and

a support member for connecting said plurality of spacer members to said inlet and outlet manifolds.

2. The apparatus of claim 1, wherein said growth chambers comprise:

a plurality of growth compartments within said growth chambers, said growth compartments each configured and dimensioned to house a substrate; and

an internal passageway fluidly connecting said plurality of growth compartments to said first and second ports.

3. The apparatus of claim 1, further comprising:

a supply of fluid in fluid communication with the inlet port of the inlet manifold; and

fluid transportation means for supplying the fluid to the inlet port of said inlet manifold.

4. The apparatus of claim 3, wherein the fluid transportation means comprises a fluid pump.

5. The apparatus of claim 1, further comprising a second support member configured and dimensioned to support and maintain a predetermined distance between said spacer members.

6. The apparatus of claim 1, wherein said spacer members are configured and dimensioned to support and maintain a predetermined distance between said members.

7. The apparatus of claim 1, wherein said inlet and outlet manifolds are configured and dimensioned to support and maintain a predetermined distance between said spacer members.

8. The apparatus of claim 1, wherein said support member comprises the spacer members and the inlet and outlet manifolds.

9. The apparatus of claim 1, wherein said support member is a rod for connecting said spacers to said inlet and outlet manifolds.

10. The apparatus of claim 1, wherein said outlet manifold further includes an air filter for removal of air from the apparatus during treatment.

11. The apparatus of claim 1, wherein said outlet manifold further includes an outlet port, said outlet port in fluid communication with an overflow container for accepting excess fluid entering said outlet manifold.

12. The apparatus of claim 3, wherein said outlet manifold includes an outlet port, said outlet port in fluid communication with said supply of fluid so as to create a closed fluid loop within the apparatus.

13. An apparatus for promoting the growth of tissue, comprising:

a plurality of growth chambers defined by flexible front and back walls, said chambers each having a first port and a second port for flow of fluid therethrough;

at least one substrate disposed within each of said plurality of growth chambers designed to facilitate three-dimensional tissue growth on said substrate;

an inlet manifold with an inlet port and a plurality of outlet ports, each of said outlet ports in fluid communication with one of said first ports of said growth chambers;

a supply of fluid in fluid communication with the inlet port of said inlet manifold;

fluid transportation means for supplying fluid to the inlet port of said inlet manifold; and

an outlet manifold with a plurality of inlet ports, each of said inlet ports in fluid communication with one of said second ports of said growth chambers.

14. The apparatus of claim 13, wherein each of said growth chambers further comprises:

a plurality of growth compartments defined by said flexible front and back walls bonded together along predetermined boundaries; and

an internal passageway fluidly connecting said plurality of growth cells, said passageway further connecting said plurality of growth compartments to said first and second ports.

15. The apparatus of claim 13, further comprising a plurality of spacer members positioned to contact the front and back walls of each of said plurality of chambers so that even fluid distribution within said growth chambers is maintained.

16. The apparatus of claim 13, wherein said outlet manifold includes an air filter for aseptic removal of air from the apparatus during treatment.

17. The apparatus of claim 13, wherein closed fluid connections are provided between the supply of fluid and the fluid transportation means, between the fluid transportation means and the inlet manifold, between each outlet port of said inlet manifold and one of said first ports of said chambers, and between each second port of said chambers and one of said inlet ports of said outlet manifold.

18. The apparatus of claim 13, wherein said outlet manifold further comprises an outlet port, said outlet port in fluid communication with an overflow container for accepting excess fluid entering said outlet manifold.

19. The apparatus of claim 13, wherein said outlet manifold further comprises an outlet port, said outlet port in fluid communication with said supply of fluid so as to create a closed fluid loop within the apparatus.

20. The apparatus of claim 15, further comprising a support member for connecting said plurality of spacer members to said inlet and outlet manifolds.

21. The apparatus of claim 20, wherein said support member comprises the spacer members and the inlet and outlet manifolds.

22. An apparatus for promoting growth of cells and tissue, comprising a flexible front and back sheet bonded together along predetermined boundaries wherein:

a plurality of growth chambers are defined by said flexible front and back sheets bonded together along predetermined boundaries, said growth chambers each configured and dimensioned to house cells or tissue substrates;

at least one internal passageway is defined by said flexible front and back sheets bonded together along predetermined boundaries, said passageway fluidly connecting said plurality of growth chambers; and

an inlet port and an outlet port are defined by said flexible front and back sheets bonded together along predetermined boundaries, said inlet and outlet ports fluidly connected to each of said growth chambers by said at least one internal passageway.

23. The apparatus of claim 22, further comprising a frame configured and dimensioned to fit within said bonded front and back sheets, said frame configured in a predetermined pattern so as to further define said growth chambers.

24. The apparatus of claim 22, further comprising a substrate disposed within each of said plurality of growth chambers, wherein each of said substrates is designed to facilitate three-dimensional tissue growth on said substrate.