Portable cassette for use in maintaining and growing biological cells

• US 5,994,129 A
• Filed: 07/08/1997
• Issued: 11/30/1999
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Aastrom Biosciences, Inc.
• Original Assignee: Aastrom Biosciences, Inc.
• Inventors: Roecker, David W., Armstrong, R. Douglas, Maluta, James
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): GRASER, JENNIFER E
• Application Number:
  US08/889,848
• Time in Patent Office: 875 Days
• Field of Search: 435/325, 435/289.1, 435/303.1, 435/287.3, 435/286.1, 435/286.2, 435/284, 435/290, 435/383
• US Class Current: 435/325
• CPC Class Codes: C12M 23/42 Integrated assemblies, e.g. cassettes or cartridges
• CPC Class Codes: C12M 23/54 hand portable
• 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

Abstract

A portable cassette is disclosed, for use in receiving, maintaining and growing biological cells ex vivo without exposing the cells to the external environment. The portable cassette is used in combination with a processor instrument that facilitates an initial inoculation of the cassette with cells of the kind to be grown and to distribute those cells in a predetermined pattern (e.g., uniformly) throughout a cell growth chamber. Thereafter, the portable cassette is used in combination with an incubator instrument that incubates the cell growth chamber so that the cells are optimally expanded. The same processor instrument then is used to harvest the expanded cells from the portable cassette. Both instruments are configured to condition the portable cassette during stages of the cell growth process, without disturbing the cassette'"'"'s sterile system.

Claims

1. A portable cell growth apparatus for maintaining and growing biological cells, comprising:

a first casing that defines a cell growth chamber configured to carry a quantity of biological cells and growth media;

a media container connected to the cell growth chamber and configured to carry growth media;

a waste container connected to the cell growth chamber and configured to carry media discharged from the growth chamber;

wherein the cell growth chamber, the media container, and the waste container are connected together to form a closed system configured to be sterilizable as a unit; and

a flow control device that is mechanically engageable with an external mechanical control system, for transporting growth media through the cell growth chamber, from the media container to the waste container, without exposing the closed, sterile system to the external environment;

and wherein the cell growth chamber is configured to be inoculated with biological cells, and thereafter to maintain and grow the inoculated biological cells while the flow control device, in response to the external mechanical control system transports growth media through the cell growth chamber, from the media container to the waste container, without exposing the closed, sterile system to the external environment.

2. A portable cell growth apparatus as defined in claim 1 and further including an updatable memory device that stores data indicating information about the cell growth chamber and the biological cells and growth media it carries and further indicating information about the condition of the cell growth chamber over time.

3. A portable cell growth apparatus as defined in claim 2, wherein:

the first casing includes an external panel; and

the updatable memory device is located on the rear panel of the first casing.

4. A portable cell growth apparatus as defined in claim 1 wherein:

the first casing includes an external panel, a gas-permeable/liquid-impermeable membrane defining a portion of the cell growth chamber, and a gas chamber located on the side of the membrane opposite the cell growth chamber; and

the portable cell growth apparatus further includes a gas supply fitting carried on the external panel of the first casing, a gas supply line connecting the gas supply fitting with the gas chamber, and a sterile filter associated with the gas supply line, to deliver a sterile gas to the gas chamber for permeation through the membrane to the cell growth chamber.

5. A portable cell growth apparatus as defined in claim 1, and further including a second casing, separable from the first casing, that houses the media container.

6. A portable cell growth apparatus as defined in claim 5, wherein the second casing includes a port that receives a gas for pressurizing the growth media contained within the media container, without disturbing the closed, sterile system formed by the cell growth chamber, the media container, and the waste container.

7. A portable cell growth apparatus as defined in claim 1, wherein:

the first casing further includes an external panel;

the portable cell growth apparatus further includes a media flow path communicating with the cell growth chamber; and

at least a portion of the media flow path is located adjacent to the external panel of the first casing.

8. A portable cell growth apparatus as defined in claim 7, wherein:

the media flow path includes a first resilient tube interconnecting the media container with the cell growth chamber and a second resilient tube interconnecting the cell growth chamber with the waste container; and

the flow control device is configured to engage at least one of the first and second resilient tubes, so as to control the flow of growth media through the growth chamber.

9. A portable cell growth apparatus as defined in claim 8, wherein the flow control device includes:

a plunger that is spring-biased to constrict the tube; and

a plate mounted adjacent to the external panel of the first casing and operatively connected to the plunger such that, when the plate is depressed, the plunger releases its constriction of the tube.

17. A portable cell growth apparatus as defined in claim 1, and further comprising a harvest container connected to the cell growth chamber and configured to carry growth media and biological cells harvested from the cell growth chamber, wherein the harvest container is part of the same closed, sterilizable system as are the cell growth chamber and the media container.

18. A portable cell growth apparatus as defined in claim 17, and further comprising means for selectively directing fluid from the cell growth chamber either to the waste container or to the harvest container.

19. A portable cell growth apparatus as defined in claim 1, wherein the flow control device is part of an interface configured to be engageable individually with a succession of instruments and to be controlled by each instrument such that the apparatus implements a predetermined stage of a cell maintenance and growth process, without exposing the closed, sterile system to the external environment.

20. A portable cell growth apparatus as defined in claim 1, wherein:

the closed system defined by the cell growth chamber, the media container, and the waste container forms a continuous media flow path; and

the continuous media flow path is interrupted by a pressure break located between the cell growth chamber and the waste container.

21. A portable cell growth apparatus as defined in claim 20, wherein the pressure break located between the cell growth chamber and the waste container is a drip chamber.

22. A portable cell growth apparatus as defined in claim 1, wherein:

the apparatus further includes a port that receives a fluid for pressurizing the growth media contained within the media container;

pressurization of the growth media contained within the media container transports the media through the cell growth chamber to the waste container, under the control of the flow control device; and

the apparatus is configured such that growth media is transported through the cell growth chamber, from the media container to the waste container, solely by the pressurization provided at the media container.

23. A portable cell growth apparatus as defined in claim 1, wherein:

the closed system defined by the cell growth chamber, the media container, and the waste container forms a continuous media flow path; and

the continuous media flow path is configured to allow an external device to monitor the flow of growth media from the media container to the waste container.

24. A portable cell growth apparatus as defined in claim 23, wherein the continuous media flow path includes a drip chamber configured to allow an external device to monitor the flow of growth media from the media container to the waste container.

10. A portable cell growth apparatus operable in a succession of process stages to maintain and grow biological cells, comprising:

a first casing that defines a cell growth chamber configured to carry a quantity of biological cells and growth media;

a media container connected to the cell growth chamber and configured to carry growth media for delivery to the growth chamber;

a waste container connected to the cell growth chamber and configured to carry media discharged from the growth chamber;

wherein the cell growth chamber, the media container, and the waste container are connected together to form a sterile system, closed to the external environment; and

an interface configured to be engageable individually with a succession of instruments and to be controlled by each instrument such that the apparatus implements a predetermined stage of a cell maintenance and growth process, without exposing the closed, sterile system to the external environment, wherein the interface includes a flow control device that is mechanically engageable with a mechanical control system of each instrument, for controllably transporting growth media through the cell growth chamber, from the media container to the waste container.

11. A portable cell growth apparatus as defined in claim 10, wherein the interface includes an updatable memory device that stores information about the cell growth chamber and the biological cells and growth media it carries and further storing information about the condition of the cell growth chamber over time.

12. A portable cell growth apparatus as defined in claim 10, wherein:

the apparatus further includes a gas-permeable/liquid-impermeable membrane defining a portion of the cell growth chamber and a gas chamber located on the side of the membrane opposite the cell growth chamber; and

the interface includes a gas supply fitting and a gas supply line connecting the gas supply fitting with the gas chamber, to deliver gas to the gas chamber for permeation through the membrane to the cell growth chamber.

13. A portable cell growth apparatus as defined in claim 10, and further including a second casing, separable from the first casing, that defines the media container.

14. A portable cell growth apparatus as defined in claim 13, wherein the second casing includes a port that receives a gas for pressurizing the growth media contained within the media container, without disturbing the closed, sterile system formed by the cell growth chamber, the media container, and the waste container.

15. A portable cell growth apparatus as defined in claim 10, wherein:

the portable cell growth apparatus further includes a media flow path communicating with the cell growth chamber; and

the flow control device of the interface is engageable with at least a portion of the media flow path, to control the flow of growth media through the cell growth chamber.

16. A portable cell growth apparatus as defined in claim 10, and further including a harvest container connected to the cell growth chamber and configured to carry growth media and biological cells harvested from the cell growth chamber, wherein the harvest container is part of the same closed, sterile system as are the cell growth chamber, the media container, and the waste container.

25. A portable cell growth apparatus as defined in claim 16, and further comprising means for selectively directing fluid from the cell growth chamber either to the waste container or to the harvest container.

26. A portable cell growth apparatus as defined in claim 10, wherein:

the first casing further includes an external panel;

the portable cell growth apparatus further includes a media flow path communicating with the cell growth chamber; and

at least a portion of the media flow path is located adjacent to the external panel of the first casing.

27. A portable cell growth apparatus as defined in claim 26, wherein:

the media flow path includes a first resilient tube interconnecting the media container with the cell growth chamber and a second resilient tube interconnecting the cell growth chamber with the waste container; and

the flow control device is configured to engage at least one of the first and second resilient tubes, so as to control the flow of growth media through the growth chamber.

28. A portable cell growth apparatus as defined in claim 27, wherein the flow control device includes:

a plunger that is spring-biased to constrict the tube; and

a plate mounted adjacent to the external panel of the first casing and operatively connected to the plunger such that, when the plate is depressed, the plunger releases its constriction of the tube.

29. A portable cell growth apparatus as defined in claim 10, wherein:

the closed system defined by the cell growth chamber, the media container, and the waste container forms a continuous media flow path; and

the continuous media flow path is interrupted by a pressure break located between the cell growth chamber and the waste container.

30. A portable cell growth apparatus as defined in claim 29, wherein the pressure break located between the cell growth chamber and the waste container is a drip chamber.

31. A portable cell growth apparatus as defined in claim 10, wherein:

the interface includes a port that receives a fluid for pressurizing the growth media contained within the media container;

pressurization of the growth media contained within the media container transports the media through the cell growth chamber to the waste container, under the control of the flow control device; and

the apparatus is configured such that growth media is transported through the cell growth chamber, from the media container to the waste container, solely by the pressurization provided at the media container.

32. A portable cell growth apparatus as defined in claim 10, wherein:

the closed system defined by the cell growth chamber, the media container, and the waste container forms a continuous media flow path; and

the continuous media flow path is configured to allow an external device to monitor the flow of growth media from the media container to the waste container.

33. A portable cell growth apparatus as defined in claim 32, wherein the continuous media flow path includes a drip chamber configured to allow an external device to monitor the flow of growth media from the media container to the waste container.

34. A portable cell growth apparatus for maintaining and growing biological cells, comprising:

means for defining a cell growth chamber configured to carry a quantity of biological cells and growth media, such means including a gas-permeable/liquid-impermeable membrane defining a portion of the cell growth chamber;

means for defining a gas chamber located on the side of the membrane opposite the cell growth chamber and for supplying a predetermined gas to the gas chamber;

a media container connected by a first media flow path to the cell growth chamber and configured to carry growth media;

a waste container connected to the cell growth chamber by a second media flow path and configured to carry media discharged from the growth chamber;

a harvest container connected to the cell growth chamber by a third media flow path and configured to carry growth media and biological cells harvested from the cell growth chamber;

wherein the cell growth chamber, the media container, the waste container, the harvest container, and the first, second, and third media flow paths are connected together to form a closed, sterile system configured to be sterilizable as a unit;

means for pressurizing the growth media contained within the media container, without disturbing the closed, sterile system; and

an interface configured to be engageable individually with a succession of instruments and to be controlled by each instrument such that the apparatus implements a predetermined stage of a cell maintenance and growth process, without exposing the closed sterile system to the external environment, wherein the interface includes a flow control device that is mechanically engageable with a mechanical control system of each instrument, for controllably transporting growth media through the cell growth chamber, from the media container to the waste container;

wherein, in a first stage, the apparatus is conditioned to prime the cell growth chamber with growth media from the media container, without exposing the closed, sterile system to the external environment;

wherein, in a second stage, the apparatus is conditioned to allow the cell growth chamber to be inoculated with biological cells;

wherein, in a third stage, the apparatus is conditioned to maintain and grow inoculated cells in the cell growth chamber while growth media is transported through the cell growth chamber, from the media container to the waste container, without exposing the closed, sterile system to the external environment;

and wherein, in a fourth stage, the apparatus is conditioned such that biological cells are transported from the cell growth chamber to the harvest container, without exposing the closed, sterile system to the external environment.