Automated cell management system for growth and manipulation of cultured cells

• US 20030040104A1
• Filed: 08/27/2001
• Published: 02/27/2003
• Est. Priority Date: 08/27/2001
• Status: Active Grant

• Current Assignee: BioCrystal, Ltd.
• Original Assignee: BioCrystal, Ltd.
• Inventors: Barbera-Guillem, Emilio
• Granted Patent: US 6,673,595 B2
• Time in Patent Office: Days
• US Class Current: 435/286.2
• CPC Class Codes: C12M 23/24 Gas permeable parts
• CPC Class Codes: C12M 23/48 Holding appliances; Racks; Supports holding devices for laboratory apparatus B01L9/00
• CPC Class Codes: C12M 23/50 Means for positioning or orientating the apparatus C12M41/08 takes precedence
• CPC Class Codes: C12M 41/14 Incubators; Climatic chambers per se B01L1/00
• CPC Class Codes: C12M 41/46 of cellular or enzymatic activity or functionality, e.g. cell viability
• CPC Class Codes: C12M 41/48 Automatic or computerized control automatic analysis G01N35/00

Abstract

An automated cell management system which can be programmed to perform and control various operations of the essential phases of cell culturing, of cell culture manipulation, and of cell culture evaluation. The automated cell management system comprises a housing, a storage array for accommodating a plurality of cell culture devices, a loading station, a means for harvesting one or more components from a cell culture device, and one or more processing stations. The automated cell management system may further comprise mechanism for tracking each cell culture device, a plurality of reservoirs, a centrifuge, a microprocessor, one or more evaluation stations, one or more means for sterilization, and a combination thereof.

Claims

1. An apparatus comprising an automated system for management of cell cultures, the apparatus comprising:

a housing having a biochamber for providing controlled environmental conditions in which cells may be cultured and manipulated;

a storage array for accommodating a plurality of cell culture devices, wherein a cell culture device comprises a housing to which is secured at least one gas permeable, liquid impermeable membrane, and wherein a cell culture device further comprises one or more chambers for culturing cells;

a loading station for introducing cell culture devices into the biochamber;

a handling device for handling and moving one or more cell culture devices within the biochamber;

a means for harvesting a cell culture component from a cell culture device, wherein the cell culture component is selected from the group consisting of cultured cells, cell culture medium, and a combination thereof; and

one or more processing stations for performing a process selected from the group consisting of aspirating a substance from a cell culture device, introducing a substance into the cell culture device, and a combination thereof.

2. The apparatus according to claim 1, further comprising a component selected from the group consisting of

a mechanism for tracking cell culture devices in relation to the apparatus,

a centrifuge,

a plurality of reservoirs which are in fluid communication with one or more stations of the apparatus,

a discharge station for permitting removal of cell culture devices from the apparatus,

a microprocessor for controlling functions and programmable operations of the apparatus,

one or more evaluation stations for measuring one or more cell culture parameters,

one or more means for sterilization of components and surfaces within the biochamber, and

a combination thereof.

3. The apparatus according to claim 1, wherein the housing of the apparatus further comprises one or more sealable accesses which is openable to access the biochamber, and closable to form a closed environment within the biochamber.

4. The apparatus according to claim 3, wherein a sealable access of the one or more sealable accesses comprises a transparent panel.

5. The apparatus according to claim 4, wherein the transparent panel permits a user to view the biochamber from outside the apparatus.

6. The apparatus according to claim 1, wherein the environment conditions are controlled by an environment controlling mechanism that controls a parameter selected from the group consisting of temperature, atmospheric gas content, humidity, pressure, airflow, and a combination thereof.

7. The apparatus according to claim 1, wherein the storage array can accommodate a number of cell culture devices, wherein:

the number comprises at least 50 cell culture devices; and

the number comprises no more than 1000 cell culture devices.

8. The apparatus according to claim 1, wherein the storage array comprises a plurality of positions, and wherein each position is adapted to receive and hold a cell culture device.

9. The apparatus according to claim 8, wherein each position, of the plurality of positions of the storage array, further comprises a coordinate representative of that position for distinguishing between each position of the plurality of positions.

10. The apparatus according to claim 1, wherein the storage array comprises a capability selected from the group consisting of non-rotatable around its axis, rotatable around its axis, and a combination thereof.

11. The apparatus according to claim 10, wherein the storage array is rotatable, and the storage array comprises a mode selected from the group consisting of in a non-rotating position, and rotating partial revolutions about its axis.

12. The apparatus according to claim 11, wherein the storage array comprises a mode in which the storage array is rotated in partial revolutions about its axis in a process of repositioning the storage array.

13. The apparatus according to claim 11, wherein the storage array comprises a mode in which the storage array is rotated in partial revolutions about its axis in a process of agitation.

14. The apparatus according to claim 11, wherein operation of the storage array is controlled by a microprocessor.

15. The apparatus according to claim 1, wherein the handling device comprises a mechanical gripper.

16. The apparatus according to claim 15, wherein the handling device comprises a mechanical gripper and a mechanical arm joined by a translational joint.

17. The apparatus according to claim 1, wherein operation of the handling device is controlled by a microprocessor.

18. The apparatus according to claim 1, wherein the loading device comprises a motorized infeed conveyor, and an access for receiving cell culture devices during a loading process.

19. The apparatus according to claim 18, wherein the loading device further comprises a loading cassette.

20. The apparatus according to claim 1, wherein operation of the loading device is controlled by a microprocessor.

21. The apparatus according to claim 1, wherein a means for harvesting a cell culture component comprises a centrifuge adapted for centrifuging one or more cell culture devices.

22. The apparatus according to claim 1, wherein a processing station comprises the means for harvesting a cell culture component.

23. The apparatus according to claim 1, wherein a means for harvesting a cell culture component comprises a processing station for dilating a membrane of the cell culture device to which cultured cells are adhered in loosening the cells from the dilated membrane.

24. The apparatus according to claim 23, wherein a means for harvesting a cell culture component further comprises a centrifuge for centrifuging the cell culture device.

25. The apparatus according to claim 1, wherein the substance introduced into or aspirated from a cell culture device at the one or more processing stations comprises a substance selected from the group consisting of a fluid, cells, one or more biological substances, air, and a combination thereof.

26. The apparatus according to claim 1, wherein a processing station, of the one or more processing stations, comprises a pipette system;

and wherein a pipette system comprises a plurality of pipettes.

27. The apparatus according to claim 26, wherein the pipette system is in fluid communication with a plurality of reservoirs.

28. The apparatus according to claim 26, wherein each pipette, of the plurality of pipettes, comprises a pipette tip.

29. The apparatus according to claim 1, wherein the process comprises a processing operation selected from the group consisting of initiating a cell culture in a cell culture device, adding tissue culture medium to cells contained in a cell culture device, adding one or more biological substances to cells in a cell culture device, harvesting of a cell culture component from a cell culture device, sampling of a cell culture component from a cell culture device, terminating a cell culture prior to discharge of a cell culture device from the automated system, extracting protein from a cell culture component contained in a cell culture device, extracting nucleic acid from a cell culture component contained in a cell culture device, and a combination thereof.

30. The apparatus according to claim 1, wherein operation of the one or more processing stations is controlled by a microprocessor.

31. The apparatus according to claim 2, wherein the apparatus further comprises a mechanism for tracking cell culture devices in relation to the apparatus;

and wherein the mechanism comprises a mechanism selected from the group consisting of an identification code reader, generating coordinates wherein each coordinate is representative of a specific location relative to the apparatus, and a combination thereof.

32. The apparatus according to claim 2, wherein the apparatus further comprises a mechanism for tracking cell culture devices comprising an identification code reader, wherein the identification code reader comprises a barcode reader, and wherein each cell culture device to be tracked has an identification code comprising a barcode.

33. The apparatus according to claim 31, wherein the mechanism for tracking cell culture devices is operatively connected to a microprocessor.

34. The apparatus according to claim 2, wherein the apparatus further comprises a plurality of reservoirs.

35. The apparatus according to claim 34, wherein each reservoir of the plurality of reservoirs has a fluid pathway that comprises fluid communication between the reservoir and a station of the apparatus.

36. The apparatus according to claim 35, wherein fluid flow, in a fluid pathway comprising fluid communication between a reservoir and a station, is controlled by a microprocessor.

37. The apparatus according to claim 34, wherein one or more reservoirs of the plurality of reservoirs has a fluid level sensor.

38. The apparatus according to claim 2, wherein the apparatus further comprises a discharge station.

39. The apparatus according to claim 38, wherein a microprocessor is used for controlling operation of the discharge station.

40. The apparatus according to claim 2, wherein the apparatus further comprises a microprocessor.

41. The apparatus according to claim 40, wherein the microprocessor controls and coordinates the operation of the apparatus.

42. The apparatus according to claim 41, wherein the microprocessor further provides for data storage for information for a process selected from the group consisting of operation of the apparatus, programming of the apparatus, functioning of the apparatus, and a combination thereof.

43. The apparatus according to claim 2, wherein the apparatus further comprises a centrifuge.

44. The apparatus according to claim 43, wherein the centrifuge comprises an upper cover plate and a support plate which, in operative combination, hold and secure a cell culture device.

45. The apparatus according to claim 43, wherein a microprocessor is used for controlling operation of the centrifuge.

46. The apparatus according to claim 2, wherein the apparatus further comprises one or more evaluation stations.

47. The apparatus according to claim 46, wherein an evaluation station, of the one or more evaluation stations, is selected from the group consisting of an imaging device, a sensor for measuring a parameter of a cell culture component, and a combination thereof.

48. The apparatus according to claim 2, wherein the apparatus further comprises one or more means for sterilization of components and surfaces within the biochamber.

49. The apparatus according to claim 48, wherein the one or more means for sterilization is selected from the group consisting of a source of irradiation, a source comprising a gas for sterilization, a washing and rinsing mechanism, and a combination thereof.

50. An apparatus comprising an automated system for management of cell cultures, the apparatus comprising:

a housing having a biochamber for providing controlled environmental conditions in which cells may be cultured and manipulated, wherein the housing further comprises one or more sealable accesses which is openable to access the biochamber, and closable to form a closed environment within the biochamber;

a storage array for accommodating a plurality of cell culture devices, wherein a cell culture device comprises a housing to which is secured at least one gas permeable, liquid impermeable membrane and further comprises one or more chambers for culturing cells, and wherein the storage array comprises a plurality of positions with each position being adapted to receive and hold a cell culture device;

a loading station for introducing cell culture devices into the biochamber;

a handling device for handling and moving one or more cell culture devices within the biochamber;

a means for harvesting a cell culture component from a cell culture device, wherein the cell culture component is selected from the group consisting of cultured cells, cell culture medium, and a combination thereof;

one or more processing stations for performing a process selected from the group consisting of aspirating a substance from a cell culture device, introducing a substance into the cell culture device, and a combination thereof;

a plurality of reservoirs; and

a microprocessor for controlling functions and programmable operations of the apparatus.

51. The apparatus according to claim 50, further comprising a component selected from the group consisting of:

a mechanism for tracking cell culture devices in relation to the apparatus,

a centrifuge,

a discharge station for permitting removal of cell culture devices from the apparatus,

one or more evaluation stations for measuring one or more cell culture parameters,

one or more means for sterilization of components and surfaces within the biochamber, and

a combination thereof.

52. The apparatus according to claim 50, wherein each position, of the plurality of positions of the storage array, further comprises a coordinate representative of that position for distinguishing between each position of the plurality of positions.

53. The apparatus according to claim 50, wherein the storage array comprises a capability selected from the group consisting of non-rotatable around its axis, rotatable around its axis, and a combination thereof.

54. The apparatus according to claim 50, wherein the handling device comprises a mechanical gripper.

55. The apparatus according to claim 54, wherein the handling device comprises a mechanical gripper and a mechanical arm joined by a translational joint.

56. The apparatus according to claim 50, wherein a processing station comprises the means for harvesting a cell culture component.

57. The apparatus according to claim 50, wherein the substance introduced into or aspirated from a cell culture device at the one or more processing stations comprises a substance selected from the group consisting of a fluid, cells, one or more biological substances, air, and a combination thereof.

58. The apparatus according to claim 50, wherein a processing station, of the one or more processing stations, comprises a pipette system, wherein a pipette system comprises a plurality of pipettes, and wherein the pipette system is in fluid communication with a plurality of reservoirs.

59. The apparatus according to claim 50, wherein the process comprises a processing operation selected from the group consisting of initiating a c ell culture in a cell culture device, adding tissue culture medium to cells contained in a cell culture device, adding one or more biological substances to cells in a cell culture device, harvesting of a cell culture component from a cell culture device, sampling of a cell culture component from a cell culture device, terminating a cell culture prior to discharge of a cell culture device from the automated system, extracting protein from a cell culture component contained in a cell culture device, extracting nucleic acid from a cell culture component contained in a cell culture device, and a combination thereof.

60. The apparatus according to claim 50, wherein each reservoir of the plurality of reservoirs has a fluid pathway that comprises fluid communication between the reservoir and a station of the apparatus.

61. The apparatus according to claim 51, wherein the apparatus further comprises a mechanism for tracking cell culture devices in relation to the apparatus;

and wherein the mechanism comprises a mechanism selected from the group consisting of an identification code reader, generating coordinates wherein each coordinate is representative of a specific location relative to the apparatus, and a combination thereof.

62. The apparatus according to claim 51, wherein the apparatus further comprises a mechanism for tracking cell culture devices comprising an identification code reader, wherein the identification code reader comprises a barcode reader, and wherein each cell culture device to be tracked has an identification code comprising a barcode.

63. The apparatus according to claim 51, wherein the apparatus further comprises a discharge station.

64. The apparatus according to claim 51, wherein the apparatus further comprises one or more evaluation stations.

65. The apparatus according to claim 64, wherein an evaluation station, of the one or more evaluation stations, is selected from the group consisting of an imaging device, a sensor for measuring a parameter of a cell culture component, and a combination thereof.

66. The apparatus according to claim 51, wherein the apparatus further comprises a centrifuge.

67. The apparatus according to claim 66, wherein the centrifuge comprises an upper cover plate and a support plate which, in operative combination, hold and secure a cell culture device.

68. The apparatus according to claim 51, wherein the apparatus further comprises one or more means for sterilization of components and surfaces within the biochamber.