Container for biological products requiring cellular stasis

• US 6,773,425 B1
• Filed: 02/11/2003
• Issued: 08/10/2004
• Est. Priority Date: 12/29/2000
• Status: Expired due to Fees

• Current Assignee: Yehuda Tamari
• Original Assignee: Yehuda Tamari
• Inventors: Tamari, Yehuda
• Primary Examiner(s): Michalsky, Gerald A.
• Application Number:
  US10/364,816
• Time in Patent Office: 546 Days
• Field of Search: 604/403, 604/408, 604/410, 383/38
• US Class Current: 604/403
• CPC Class Codes: A01N 1/0236 Mechanical aspects
• CPC Class Codes: A01N 1/0252 Temperature controlling refrigerating apparatus, i.e. devices used to actively control the temperature of a designated internal volume, e.g. refrigerators, freeze-drying apparatus or liquid nitrogen baths
• CPC Class Codes: A01N 1/0263 Non-refrigerated containers specially adapted for transporting or storing living parts whilst preserving, e.g. cool boxes, blood bags or "straws" for cryopreservation
• CPC Class Codes: A61J 1/05 for collecting, storing or administering blood, plasma or medical fluids multiple bags systems for separating or storing blood components A61M1/0209; Infusion or perfusion containers
• CPC Class Codes: A61L 2/26 Accessories or devices or components used for biocidal treatment
• CPC Class Codes: A61L 2202/181 Flexible packaging means, e.g. permeable membranes, paper
• CPC Class Codes: A61L 2202/21 Pharmaceuticals, e.g. medicaments, artificial body parts
• CPC Class Codes: A61L 2202/22 Blood or products thereof
• CPC Class Codes: A61M 1/0277 Frames constraining or supporting bags, e.g. during freezing
• CPC Class Codes: F26B 5/06 the process involving freezing

Abstract

The invention is an improved container for collecting, freeze-drying, storing, reconstituting, and administering biological solutions and, in particular, blood products. The container features a pliable bottom wall providing intimate thermal contact with the cooling/heating shelf of the lyophilizer; a top wall incorporating a hydrophobic membrane providing a path for water vapor and a bacterial barrier; and side walls sufficiently stiff to support the ceiling but preferably also sufficiently flexible to collapse and minimize storage space especially once lyophilization is complete. The walls incorporate sealable ports that can be used to load the solution for processing and/or adding reconstituting liquids and/or administering the reconstituted solution to a patient. The top wall may incorporate a removable cover that protects the membrane before freeze-drying takes place. A secondary pouch encloses the container immediately post-lyophilization and may incorporate means to evacuate its inner space thereby reducing space and limiting the gas volume the final product is exposed to during storage.

Claims

1. A container for drying a biological product to be placed on a shelf of a drying chamber, said container comprising

a) a tray having a product side compatible with said product, said tray defining;

i) a floor having a first inside periphery, an inside surface contacting said product, and an underside surface contacting said shelf;

ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery, said vertical wall and said floor forming at least two wells;

b) a roof having a first area, said roof incorporating a hydrophobic membrane having a second area, said membrane providing vapor communication with said drying chamber while retaining said product within at least two said wells, said at least two wells and roof joined to form at least two sealed pockets for containing said product;

wherein each of said pockets may be filled with said biological product, and wherein once the product is dried, said product in one pocket can be separated, rehydrated, and used without affecting the product in other pockets.

2. A container for drying biological products as claimed in claim 1 wherein said container further incorporates first means for providing efficient thermal transfer between said floor of the container and said shelf of a drying chamber.

3. A container for drying biological products as claimed in claim 2 wherein said first mean for providing efficient thermal transfer between underside of said floor of the container and said shelf, said mean is a thermally conductive plate having a first footprint, said thermal plate interposed between the underside of the floor of the container and the shelf, said thermal plate having a top that conforms to the shape of the underside of the floor of the container, and a bottom side that forms an intimate thermal contact with the shelf.

4. A container for drying biological products as claimed in claim 3 wherein the drying chamber is a lyophilizer and wherein said thermal plate further incorporates second means that assure intimate thermal contact under conditions of lyophilization between the thermal plate and the underside of the floor of the container.

5. A container for lyophilizing biological products as claimed in claim 4 wherein said second means that assure intimate thermal contact between the top of the thermal plate and the underside of the floor of the container under conditions of the lyophilization process are channels incorporated along the surface of the thermal plate, said channels providing a first fluid communication between the top of the thermal plate and the underside of the floor of the container, said fluid communication providing a passage way for air entrapped between the top of the thermal plate and the underside of the floor of the container to escape to the lyophilization chamber.

6. A container for lyophilizing biological products as claimed in claim 5 wherein said second means that assure intimate thermal contact between the top of the thermal plate and the underside of the floor of the container under all the conditions of the lyophilization process wherein the thermal plate further incorporates at least one hole forming a second fluid combination between the top side of the thermal plate and the channels along the bottom surface of the thermal plate, said combination of channels and at least one hole providing a passage way for air, trapped between the top of the thermal plate and the underside of the floor of the container, to escape.

7. A container for drying biological products as claimed in claim 4 wherein further the floor of the container is pliable and said second means that assure intimate thermal contact between the top of the thermal plate and the underside of the floor of the container under conditions of the lyophilization process is allowing the pliable floor of the container to be stretched over the top surface of the thermal plate.

8. A container for drying biological products as claimed in claim 7 wherein said stretching of the pliable floor of the container is improved by further having the top surface of the thermal plate convex.

9. A container for drying biological products as claimed in claim 8 wherein said top surface of the thermal plate is having a center with a first thickness and a third periphery having a second thickness, said first thickness being thicker than second thickness, said difference between the thicknesses defining the convex shape of the top surface of the thermal plate.

10. A container for drying biological products as claimed in claim 3 wherein the thermal plate is made of copper.

11. A container for drying biological products as claimed in claim 3 wherein further the vertical wall is rigid and the second means assuring intimate thermal contact between the top of the thermal plate and the underside of the floor of the container further include a top plate, said top plate having:

a) a second footprint;

b) means to position the top plate over the thermal plate;

c) a first set of holes that ensure that the hydrophobic membrane incorporated in the roof of the container is free to breath when the top plate is placed over the roof of the container;

d) a third means that presses the top plate against the roof of the container thereby pushing the floor of the container against the top of the thermal plate to enhance the intimate thermal contact between the floor of the container and the top of the thermal plate.

12. A container for drying biological products as claimed in claim 11 wherein the second foot print of the top plate is equal to the first footprint of the thermal plate.

13. A container for drying biological products as claimed in claim 11 wherein the second footprint of the top plate is smaller than the first footprint of the thermal plate.

14. A container for drying biological products as claimed in claim 11 wherein the floor of the container is pliable.

15. A container for drying biological products as claimed in claim 11 wherein the top surface of the thermal plate further incorporates at least one groove that accepts the underside of the floor of the container.

16. A container for drying biological products as claimed in claim 11 wherein the third means that presses the top plate against the roof of the container are the combination of threaded studs secured to and extending from the thermal plate, and matching nuts, said nuts when tightened, pushing the top plate against the rigid wall of the container thereby pushing the container against the thermal plate to form intimate thermal contact between the floor of the container and the top of the thermal plate.

17. A container for drying biological products as claimed in claim 11 wherein the third means that presses the top plate against the roof of the container is the weight of the top plate, said weight pushing the container against the thermal plate thereby forming an intimate thermal contact between the floor of the container and the top of the thermal plate.

18. A container for drying biological products as claimed in claim 11 wherein the third means that presses the top plate against the roof of the container is at least one elastic band, said elastic band pushing the container against the thermal plate thereby forming an intimate thermal contact between the floor of the container and the top of the thermal plate.

19. A container for drying biological products as claimed in claim 3 wherein the first footprint of the thermal plate has a third outside perimeter, said outside perimeter being larger than the first inside periphery of the floor of the container.

20. A container for drying biological products as claimed in claim 1 wherein said vertical wall is rigid.

21. A container for drying biological products as claimed in claim 1 wherein said floor of the container is a thin biocompatible film having a thickness between 0.001″

to 0.015″

.

22. A container for drying biological products as claimed in claim 1 wherein the container is further used to store the product and provides a means to rehydrate the product in a controlled manner prior to the use of the product.

23. A container for drying biological products as claimed in claim 22 wherein said means to rehydrate the product in a controlled manner is water vapor transfer across the hydrophobic membrane.

24. A container for drying biological products as claimed in claim 1 wherein said container further incorporates at least one port in fluid communication with at least one of said wells, said port used to introduce said biological product into at least one of said wells.

25. A container for drying biological products as claimed in claim 24 wherein further said port incorporates a screw-on-cap to cover said port.

26. A container for drying biological products as claimed in claim 1 wherein the roof first area is larger than the second area of the hydrophobic membrane, and wherein further, a third area of the roof, defined as the first area less the second area, is sufficiently clear to see the product in the container.

27. A container for drying biological products as claimed in claim 26 wherein the second area of the membrane is between 25% and 75% of the first area of the roof.

28. A container for drying biological products as claimed in claim 26 wherein the second area of the membrane is formed by more than one membrane.

29. A container for drying biological products as claimed in claim 1 wherein the biological product is a product contains cells to be dried.

30. A container for drying biological products as claimed in claim 29 wherein the cells to be dried are stem cells.

31. A container for drying biological products as claimed in claim 1 wherein further includes a barrier that seal and protects said membrane post drying, as well as protect the product from being exposed to water vapor and light.

32. A container for drying biological products as claimed in claim 31 wherein said barrier is a pouch.

33. A container for drying biological products as claimed in claim 32 wherein at least the floor of the container is made of a material that promote cell adhesion and growth.

34. A container for drying biological products as claimed in claim 33 wherein at least the floor of the container is made of polystyrene.

35. A container for drying biological products as claimed in claim 1 wherein the container is further used to grow cells.

36. A container for drying biological products as claimed in claim 1 wherein said container incorporates at least two pockets for drying one or more biological products, wherein each of said pockets may be separately filled with said one or more biological products, and wherein once dried, the product in one pocket can be separated, rehydrated, and used without affecting the product in the other pocket.

37. A container for drying biological products as claimed in claim 36 wherein said container incorporates multiple pockets containing the biological product with each of said pockets having a geometry that allows dispensing of the product in the individual pockets.

38. A container for drying biological products as claimed in claim 37 wherein further the roof is covered with an impermeable cover, said cover protecting the dried product from rehydration, said cover sealed to the roof along said second upper periphery and said cover incorporating tear-seal lines that allow the user to tear open one pocket at a time without affecting the integrity of the product sealed in the other pockets.

39. A container for drying biological products as claimed in claim 37 wherein the multiple pockets of said container is formed as multiwell flasks.

40. A container for drying biological products as claimed in claim 36 wherein the roof of each pocket incorporates a hydrophobic membrane.

41. A container for drying biological products as claimed in claim 36 wherein the pockets are formed from a common chamber to form two or more wells separated by weirs, said weirs forming at least a portion of said second upper periphery of said vertical wall.

42. A container for drying biological products as claimed in claim 41 wherein the roof of the container incorporates means to seal the product side of the roof to the top of the second upper periphery thereby isolating each of the wells to form individual pockets.

43. A container for drying biological products as claimed in claim 42 wherein said means to seal the product side of the roof to the top of the second upper periphery of the wells is adhesion.

44. A container for drying biological products as claimed in claim 42 wherein said means to seal the product side of the roof to the top of the second upper periphery utilizes a supporting tray that provides a structure against which the roof can be forced to mate with the second upper periphery of the individual wells.

45. A container for drying biological products as claimed in claim 42 wherein said means to seal the product side of the roof to the top of the second upper periphery is heat.

46. A container for drying biological products as claimed in claim 45 wherein further the product side of the roof incorporates a thermo-sealant thereby facilitating said heat sealing means.

47. A container for drying biological products as claimed in claim 42 wherein further said container incorporates a port, said port configured to be sealed simultaneously when sealing the product side of the roof to the top of the second upper periphery.

48. A container for drying biological products as claimed in claim 42 wherein further includes an impermeable pouch so that the container may be sealed within said impermeable pouch, said pouch protecting the dried product from rehydration, said pouch sealed simultaneously when the product side of the roof is sealed to the top of the second upper periphery of the vertical wall.

49. A container for drying biological products as claimed in claim 36 wherein the pockets accommodate a specific volume of biological product and wherein the specific volume accommodated by the first pocket is different from the specific volume of the other pockets.

50. A container for drying biological products as claimed in claim 1 wherein said container can be further used to collect, process, dry, store, and reconstitute the biological product.

51. A container for drying biological products as claimed in claim 50 wherein said container further maintains the biological product sterile.

52. A container for drying biological products as claimed in claim 1 wherein said product is red blood cells.

53. A container for drying biological products as claimed in claim 1 wherein said product is mesenchymal cells.

54. A container for drying biological products as claimed in claim 1 wherein said wells are formed as cell culture dishes having at least one rigid wall.

55. A container for drying biological products as claimed in claim 1 wherein said floor and said wall are made of the same material.

56. A multiwell flask system for drying a biological products to be placed on a shelf of a drying chamber, said multiwell flask comprising:

a) a tray having a product side compatible with said product, said tray defining;

(i) a floor having a first inside periphery, an inside surface contacting said product, and an underside surface contacting said shelf;

(ii) a multiplicity of vertical walls extending upward along said first inside periphery, said walls having a second upper periphery, said vertical walls and said floor forming at least two wells;

b) a roof having a first area, said roof incorporating a hydrophobic membrane having a second area, said membrane providing vapor communication with said drying chamber while retaining one or more products within said at least two wells, said at least two wells and roof joined to form at least two sealed pockets for containing said one or more products;

c) at least one port in fluid communication with each well, said port used to introduce said biological product into said wells.

57. A multiwell flask system for drying biological products as claimed in claim 56 wherein said system further includes a thermal plate, said plate having a topside, said top side having multi-cavities, the number of said cavities corresponding to the number of wells of the flask system, said cavities shaped to accept the underside surface of the multiwell flask thereby enhancing thermal contact between said underside of said flask and thermal plate.

58. A culture dish for drying a biological product to be placed on a shelf of a drying chamber, said culture dish comprising:

a) a floor having a first inside periphery, an inside surface contacting said product, and an underside surface contacting said shelf;

b) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery, said vertical wall and said floor forming at least two wells;

c) a roof having a first area, said roof incorporating a hydrophobic membrane having a second area, said membrane providing vapor communication with said drying chamber while retaining said product within said wells, said at least two wells and said roof joined to form at least one sealed pocket for containing said product;

d) at least one port in fluid communication with at least one well, said port used to introduce said biological product into at least one said well;

wherein the first area of the roof is larger than the second area of the hydrophobic membrane, and wherein further, a third area of the roof, defined as the first area less the second area, is sufficiently clear to see the product in at least one of the wells.

59. A container for drying biological products as claimed in claim 58 wherein further the second area of the membrane is composed of at least two membranes incorporated in the first area of the roof.

60. A multiwell flask for drying a biological product to be placed on a shelf of a drying chamber, said multiwell flask comprising:

a) a tray having a product side compatible with said product, said tray defining;

(i) a floor having a first inside periphery, an inside surface contacting said product, and an underside surface contacting said shelf;

(ii) a vertical wall extending upward along said first inside periphery, said walls having a second upper periphery,

(iii) one or more weirs extending from the floor and joining vertical wall to form at least two wells;

b) a roof having a first area, said roof incorporating a hydrophobic membrane having a second area, said membrane providing vapor communication with said drying chamber while retaining one or more products within said at least two wells, said at least two wells and roof joined to form at least two sealed pockets for containing said one or more products;

c) at least one port in fluid communication with each well, said ports used to introduce said biological product into said wells.

61. A multiwell flask for drying a biological product as claimed in claim 60 wherein a said flask contains a single port, said port used to fill all the wells.

62. A multiwell flask for drying a biological product as claimed in claim 60 wherein said flask is formed of pliable material.

63. A multiwell flask for drying a biological product claimed in claim 60 wherein said second area of said membrane equals the first area of said roof.

64. A multiwell flask for drying a biological product as claimed in claim 60 wherein once said product is dried, the product in one pocket can be separated, rehydrated, and used without affecting the product in the other pockets.

65. A multiwell flask for drying a biological product as claimed in claim 60 which further utilizes a thermal plate designed to enhance hear transfer between the shelf of a drying chamber and a product to be dried, said plate having a topside and a bottom side, said topside of said thermal plate making intimate thermal contact with the outer side of the container and said bottom of said thermal plate making intimate thermal contact with the shelf of the drying chamber.

66. A multiwell flask for drying a biological product as claimed in claim 65 which further utilizes wherein further the thermal plate is used to support and handle the multiwell flask with product to be dried.

67. A multiwell flask for drying a biological product as claimed in claim 65 wherein the thermal plate further improves the uniformity of the heat transfer across said floor.

68. A container for drying a biological products in a drying chamber having a shelf to place said container, said container comprising

a) a tray having a solution side compatible with said product, said tray defining;

i) a floor having a first inside periphery, an inside surface contacting said product, and an underside surface contacting said shelf;

said floor formed of a pliable material that easily conforms to said shelf;

ii) a vertical wall extending upward along said first inside periphery, said wall having a second upper periphery, and a landing extending from said second upper periphery, said vertical wall and said floor forming at least two wells;

b) a roof, said roof incorporating a hydrophobic membrane, said membrane providing vapor communication with said drying chamber while retaining said product within at least two said wells, said floor, vertical walls and roof joined to form at least two sealed pockets for containing said product;

c) at least one port in fluid communication with said pocket said port used to introduce into said pocket and or remove from said pocket said product;

d) said floor sufficiently pliable that said floor conforms, by the weight of said product in the container, to the surface of said shelf thereby assuring the intimate contact between the two surfaces necessary for the most efficient thermal transfer between said shelf and said solution via said floor.