Materials and reactor systems having humidity and gas control

• US 20040058437A1
• Filed: 06/05/2003
• Published: 03/25/2004
• Est. Priority Date: 04/10/2001
• Status: Abandoned Application

• Current Assignee: BioProcessors Corp.
• Original Assignee: BioProcessors Corp.
• Inventors: Schreyer, Howard B., Zarur, Andrey J., Rodgers, Seth T., Russo, A. Peter
• Application Number:
  US10/457,049
• Publication Number:
  US 20040058437A1
• Time in Patent Office: Days
• US Class Current: 435/297.1
• CPC Class Codes: C12M 23/12 Well or multiwell plates C12M25/04 takes precedence
• CPC Class Codes: C12M 23/24 Gas permeable parts
• CPC Class Codes: C12M 25/02 Membranes; Filters filters or filtration in general B01D24/00-B01D41/00
• CPC Class Codes: C12M 29/04 Filters; Permeable or porous membranes or plates, e.g. dialysis
• CPC Class Codes: C12M 41/34 of gas

Abstract

The present invention is directed to materials and reactor systems having humidity and/or gas control. The material may have high oxygen permeability and/or low water vapor permeability. In some cases, the material may have sufficient permeance and/or permeability to allow cell culture to occur in a chip or other reactor system using the material. In certain embodiments, the material may be positioned adjacent to or abut a reaction site within a chip or reactor; in other embodiments, the material may be positioned such that it is in fluidic communication with the reaction site. The material may also be porous and/or transparent in some cases. In one set of embodiments, the material include a polymer that is branched, and/or contains bulky side groups that allow the polymer to have a more open structure. In some cases, the material may include two or more layers. Each layer may have a desired property, which may include, for example, permeability, transparency, cytophilicity, biophilicity, hydrophilicity, or a structural feature. In some embodiments, the material may be chosen so as to promote cell growth within the chip or reactor.

Claims

1. A membrane comprising a material having a permeability to oxygen greater than about 50 (cm³_STP mm/m² atm day) and a permeability to water vapor lower than about 6×

10⁶ (cm³_STP mm/m² atm day).

2. The membrane of claim 1, wherein the membrane is translucent or substantially translucent.

3. The membrane of claim 1, wherein the membrane is transparent or substantially transparent.

4. The membrane of claim 1, wherein the membrane is between 10 micrometers and 2 millimeters thick.

5. A membrane comprising:

a first layer comprising at least 55% by weight of a first polymer or copolymer;

a second layer comprising no more than 45% by weight of the first polymer or copolymer;

a permeability to oxygen greater than about 1×

10² (cm³_STP mm/m² atm day); and

a permeability to water vapor lower than about 6×

10⁶ (cm³_STP mm/m² atm day).

6. The membrane of claim 5, wherein the permeability to oxygen is greater than about 1×

10³ (cm³_STP mm/m² atm day).

7. The membrane of claim 5, wherein the permeability to water vapor lower than about 1×

10⁵ (cm³_STP mm/m² atm day).

8. The membrane of claim 5, wherein the first and second layers are laminated together.

9. The membrane of claim 5, wherein the first and second layers are at least partially intermixed.

10. The membrane of claim 5, wherein a portion of the first layer is co-polymerized with a portion of the second layer.

11. The membrane of claim 5, wherein the first layer has a higher permeability to oxygen and water vapor than the second layer.

12. The membrane of claim 11, wherein the first layer has a permeability to oxygen between about 1.0×

10¹ (cm³_STP mm/m² atm day) and about 1.0×

10⁴ (cm³_STP mm/m² atm day) and a permeability to water vapor between about 1.0×

10² (cm³_STP mm/m² atm day) and about 5×

10⁴ (cm³_STP mm/m² atm day).

13. The membrane of claim 11, wherein the second layer has a permeability to oxygen between about 1×

10⁴ (cm³_STP mm/m² atm day) and about 1×

10⁵ (cm³_STP mm/m² atm day) and a permeability to water vapor between about 1×

10⁵ (cm³_STP mm/m² atm day) and about 1×

10⁷ (cm³_STP mm/m² atm day).

14. The membrane of claim 11, wherein the first layer has a permeability to oxygen between about 1×

10¹ (cm³_STP mm/m² atm day) and about 1×

10⁴ (cm³_STP mm/m² atm day) and a permeability to water vapor between about 1×

10² (cm³_STP mm/m² atm day) and about 1×

10⁶ (cm³_STP mm/m² atm day) and the second layer has a permeability to oxygen between about 1×

10⁴ (cm³_STP mm/m² atm day) and about 1×

10⁵ (cm³_STP mm/m² atm day) and a permeability to water vapor between about 1×

10⁵ (cm³_STP mm/m² atm day) and about 1×

10⁷ (cm³_STP mm/m² atm day).

15. The membrane of claim 5, wherein the first layer comprises a material selected from the group consisting of polydimethlysiloxane, a polyfluoroorganic material, polystyrene, HDPE, LDPE, LLDPE, ULDPE, poly(4-methyl pentene-1), poly(1-trimethylsilyl-1-propyne), and combinations, analogs, and derivatives thereof.

16. The membrane of claim 5, wherein the first layer comprises poly(4-methyl pentene-1).

17. The membrane of claim 16, wherein the first layer comprises at least 50% poly(4-methyl pentene-1) by weight.

18. The membrane of claim 5, wherein the first layer comprises poly(1-trimethylsilyl-1-propyne).

19. The membrane of claim 16, wherein the first layer comprises at least 50% poly(1-trimethylsilyl-1-propyne) by weight.

20. The membrane of claim 5, wherein the first layer comprises at least 50% polyfluoroorganic material by weight.

21. The membrane of claim 5, wherein the first layer is between about 10 micrometers and 2 millimeters thick.

22. The membrane of claim 21, wherein the second layer is between about 10 micrometers and 2 millimeters thick.

23. The membrane of claim 5, wherein the membrane is translucent or substantially translucent.

24. The membrane of claim 5, wherein the membrane is transparent or substantially transparent.

25. The membrane of claim 5, wherein the membrane is between 10 micrometers and 2 millimeters thick.

26. An apparatus, comprising:

a chip comprising a predetermined reaction site including a membrane comprising a permeability to oxygen greater than about 1×

10² (cm³_STP mm/m² atm day); and

a permeability to water vapor lower than about 6×

10⁶ (cm³_STP mm/m² atm day).

27. The apparatus of claim 26, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

28. The apparatus of claim 26, wherein the membrane includes a cell adhesion layer.

29. The apparatus of claim 28, wherein cell adhesion layer comprises a material selected from the group consisting of polyfluoroorganic materials, polyester, polydimethlysiloxane, polycarbonate, polystyrene, poly(4-methyl pentene-1), poly(1-trimethylsilyl-1-propyne), aluminum oxide, and combinations thereof.

30. The apparatus of claim 28, wherein the cell adhesion layer comprises a modified surface.

31. The apparatus of claim 28, wherein the cell adhesion layer is an inner layer of the membrane and abuts an interior of the predetermined reaction site.

32. The apparatus of claim 26, wherein the membrane comprises a support layer.

33. The apparatus of claim 32, wherein the support layer is one of an outer layer and an intermediate layer.

34. The apparatus of claim 32, wherein the support layer comprises a material selected from a group consisting of polydimethylsiloxane, latex, glass, silicon, polystyrene, polyester, poly(4-methyl pentene-1), poly(1-trimethylsilyl-1-propyne), and combinations thereof.

35. The apparatus of claim 26, further comprising a predetermined reaction site no greater than 1 millimeter in maximum cross section, wherein the membrane abuts the predetermined reaction site.

36. The apparatus of claim 26, further comprising a predetermined reaction site no greater than 20 cm² in maximum cross sectional area, wherein the membrane abuts the predetermined reaction site.

37. The apparatus of claim 26, further comprising at least 7 predetermined reaction sites, and wherein the membrane abuts at least one of the at least 7 predetermined reaction sites.

38. The apparatus of claim 26, further comprising at least 20 predetermined reaction sites, and wherein the membrane abuts at least one of the at least 20 predetermined reaction sites.

39. An apparatus, comprising:

a chip comprising a predetermined reaction site no greater than 1 milliliter in volume; and

a humidity controller positioned adjacent to the predetermined reaction site.

40. The apparatus of claim 39, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

41. The apparatus of claim 39, wherein the humidity controller has high enough oxygen permeability and low enough water vapor permeability to allow cell growth within the predetermined reaction site.

42. The apparatus of claim 39, wherein the cell growth is mammalian cell growth.

43. The apparatus of claim 39, wherein the cell growth is animal cell growth.

44. The apparatus of claim 39, wherein the humidity controller has a permeability to oxygen greater than about 1×

10² (cm³_STP mm/m² μ

m day) and a permeability to water vapor lower than about 6×

10⁶ (cm³_STP mm/m² atm day).

45. The apparatus of claim 39, wherein the humidity controller is positioned in a wall of the predetermined reaction site.

46. The apparatus of claim 39, wherein the humidity controller comprises a membrane.

47. The apparatus of claim 39, wherein the humidity controller comprises a cell adhesion layer.

48. The apparatus of claim 47, wherein the cell adhesion layer is positioned in an inner wall of the predetermined reaction site.

49. A method of culturing cells, comprising:

identifying an oxygen requirement and a humidity requirement of the cells;

selecting a material having an oxygen permeability high enough to meet the oxygen requirement of the cells and a water vapor permeability low enough to meet the humidity requirement of the cells; and

culturing the cells in a chip comprising a predetermined reaction site having a volume of no more than 1 milliliter and at least one wall having at least a portion thereof formed of the material.

50. The method of claim 49, further comprising culturing the cells for at least 24 hours.

51. The method of claim 49, further comprising culturing the cells for at least 48 hours.

52. The method of claim 49, further comprising culturing the cells for at least 1 week.

53. The method of claim 49, further comprising culturing the cells for at least 2 weeks.

54. The method of claim 49, further comprising culturing the cells for at least 4 weeks.

55. The method of claim 49, further comprising culturing the cells for at least 6 weeks.

56. The method of claim 49, further comprising observing the cells through the material.

57. The method of claim 49, wherein, during culturing, the humidity external to the chip is insufficient to meet the humidity requirement of the cells.

58. An apparatus, comprising:

a chip comprising a predetermined reaction site no greater than 1 milliliter in volume; and

a humidity controller having sufficient oxygen permeability and a low water vapor permeability selected to allow cell growth within the predetermined reaction site.

59. The apparatus of claim 58, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

60. The apparatus of claim 58, wherein the humidity controller is a membrane.

61. The apparatus of claim 58, wherein the humidity controller is a thin film.

62. An apparatus, comprising:

a chip comprising a predetermined reaction site no greater than 1 milliliter in volume; and

a humidity controller able to maintain a humidity level and an oxygen concentration in the predetermined reaction site sufficient to allow cell growth within the predetermined reaction site.

63. The apparatus of claim 62, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

64. The apparatus of claim 62, wherein the humidity controller is a membrane.

65. The apparatus of claim 62, wherein the humidity controller is a thin film.

66. An apparatus, comprising:

a chip comprising a predetermined reaction site no greater than 1 milliliter in volume; and

a humidity controller positioned adjacent to the predetermined reaction site.

67. The apparatus of claim 66, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

68. An apparatus, comprising:

a chip comprising a predetermined reaction site no greater than 1 milliliter in volume; and

a humidity controller having sufficient oxygen permeability and a low water vapor permeability selected to allow cell growth within the predetermined reaction site.

69. The apparatus of claim 68, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

70. An apparatus, comprising:

a chip comprising a predetermined reaction site no greater than 1 milliliter in volume; and

a gas-permeable surface positioned adjacent to the predetermined reaction site.

71. The apparatus of claim 70, wherein the chip is constructed and arranged to maintain at least one living cell at the predetermined reaction site.

72. A method, comprising:

diffusing a gas into a predetermined reaction site no greater than 1 milliliter in volume.