Title:
Heating and cooling system for biological materials
Kind Code:
A1


Abstract:
A method of cooling a biological material includes providing a vessel. The vessel includes a generally vertical inner wall disposed at an inner radius from a vertically disposed center axis. The generally vertical inner wall defines in part an interior volume. A medium including a biological material is provided. A plurality of heat transfer surfaces is positioned within the interior volume. Each of the plurality of heat transfer surfaces is oriented generally vertically through the interior volume. Each of the heat transfer surfaces is arranged such that it does not extend into the portion of the interior volume defined by a distance from the center axis greater than 90% of the inner radius. The medium is introduced into the vessel. A heat transfer fluid is circulated through the plurality of heat transfer surfaces. The heat transfer surfaces conduct heat out of the medium.



Inventors:
Lam, Philippe (South San Francisco, CA, US)
Sane, Samir U. (Redwood City, CA, US)
Application Number:
11/313248
Publication Date:
06/21/2007
Filing Date:
12/20/2005
Primary Class:
International Classes:
F28D7/10
View Patent Images:
Related US Applications:



Primary Examiner:
FORD, JOHN K
Attorney, Agent or Firm:
BGL (CHICAGO, IL, US)
Claims:
What is claimed is:

1. A system for heating and cooling biological materials comprising: a vessel comprising a generally vertical inner wall defining in part an interior volume; and a first and second plurality of conduit portions disposed in a generally vertical orientation within the interior volume, each conduit portion containing a heat transfer fluid and comprising a heat transfer surface exposed to the interior volume; wherein each conduit portion of the first plurality of conduit portions is disposed at about a first distance from the inner wall and each conduit portion of the second plurality of conduit portions is disposed at about a second distance from the inner wall, wherein the second distance is greater than the first distance.

2. The system of claim 1 wherein the generally vertical inner wall is disposed at an inner radius from a vertically disposed center axis and wherein the first distance is between about 20% and about 50% of the inner radius and the second distance is between about 50% and about 80% of the inner radius.

3. The system of claim 1 wherein the conduit portions of the first plurality of conduit portions are generally distributed symmetrically around a circumference defmed by the first distance and the conduit portions of the second plurality of conduit portions are generally distributed symmetrically around a circumference defined by the second distance.

4. The system of claim 1 further comprising a plurality of fins coupled to at least some of the conduit portions and extending into the interior volume.

5. The system of claim 1 further comprising a plurality of fins coupled to the conduit portions of the first plurality of conduit portions and generally oriented tangentially from a radius of the vessel.

6. The system of claim 1 further comprising a plurality of fins coupled to the conduit portions of the second plurality of conduit portions and generally oriented along a radius of the vessel.

7. The system of claim 1 wherein the generally vertical inner wall is disposed at an inner radius from a vertically disposed center axis and wherein the conduit portions are arranged such that they do not extend into the portion of the interior volume defined by a distance from the center axis greater than 90% of the inner radius.

8. The system of claim 1 wherein the generally vertical inner wall is disposed at an inner radius from a vertically disposed center axis and wherein the conduit portions are arranged such that they do not extend into the portion of the interior volume defined by a distance from the center axis greater than 60% of the inner radius.

9. The system of claim 1 wherein the interior volume of the vessel is between about 10 liters and about 500 liters.

10. The system of claim 9 wherein the conduit portions are arranged such that they do not extend within 2 inches of the inner wall of the vessel.

11. The system of claim 1 wherein the conduit portions are interconnected and convey the heat transfer fluid within.

12. The system of claim 1 wherein the conduit portions of the first plurality of conduit portions are interconnected and the conduit portions of the second plurality of conduit portions are interconnected.

13. The system of claim 1 wherein the first plurality of conduit portions comprises between four and ten vertically extending conduit portions and the second plurality of conduit portions comprises between two and six vertically extending conduit portions.

14. The system of claim 1 wherein the first plurality of conduit portions comprises between six and eight vertically extending conduit portions and the second plurality of conduit portions comprises between four and six vertically extending conduit portions.

15. A method of heating or cooling a biological material comprising: providing a vessel comprising a generally vertical inner wall disposed at an inner radius from a vertically disposed center axis, the inner wall defining in part an interior volume; providing a medium comprising a biological material; positioning a plurality of heat transfer surfaces within the interior volume, the heat transfer surfaces oriented generally vertically through the interior volume and arranged such that they do not extend into the portion of the interior volume defined by a distance from the center axis greater than 90% of the inner radius; introducing the medium into the vessel; and circulating a heat transfer fluid through the plurality of heat transfer surfaces.

16. The method of claim 15 wherein the heat transfer surfaces conduct heat out of the medium to cool the medium.

17. The method of claim 15 wherein the medium is frozen and the heat transfer surfaces conduct heat into the medium to thaw the medium.

18. The method of claim 15 wherein the plurality of heat transfer surfaces are formed on a plurality of conduit portions circulating the heat transfer fluid.

19. The method of claim 18 further comprising a plurality of fins coupled to at least some of the conduit portions and extending into the interior volume.

20. The method of claim 19 wherein the interior volume of the vessel is between about 10 liters and about 500 liters.

21. The method of claim 20 wherein the plurality of fins are arranged such that they do not extend within 2 inches of the inner wall of the vessel.

22. The method of claim 15 wherein thermal bridges are not formed between the heat transfer surfaces and the inner wall of the vessel during the cooling of the biological material.

23. A method of cooling a biological material comprising: providing a vessel comprising a generally vertical inner wall disposed at an inner radius from a vertically disposed center axis, the inner wall defining in part an interior volume; providing a medium comprising a biological material; positioning a first and second plurality of conduit portions in a generally vertical orientation within the interior volume, each conduit portion containing a heat transfer fluid and comprising a heat transfer surface exposed to the interior volume; wherein each conduit portion of the first plurality of conduit portions is disposed at about a first distance from the center axis and each conduit portion of the second plurality of conduit portions is disposed at about a second distance from the center axis, wherein the first distance is greater than the second distance; introducing the medium into the vessel; and circulating a heat transfer fluid through the first and second plurality of conduit portions, wherein the heat transfer surfaces conduct heat out of the medium.

24. The method of claim 23 wherein thermal bridges are not formed between the heat transfer surfaces and the inner wall of the vessel during the cooling of the biological material.

25. The method of claim 23 wherein the first distance is between about 20% and about 50% of the inner radius and the second distance is between about 50% and about 80% of the inner radius.

26. The method of claim 23 wherein the conduit portions of the first plurality of conduit portions are generally distributed symmetrically around a circumference defined by the first distance and the conduit portions of the second plurality of conduit portions are generally distributed symmetrically around a circumference defined by the second distance.

27. The method of claim 23 further comprising a plurality of fins coupled to at least some of the conduit portions and extending into the interior volume.

28. The method of claim 27 wherein the interior volume of the vessel is between about 10 liters and about 500 liters.

29. The method of claim 28 wherein the conduit portions and the fins are arranged such that they do not extend within 2 inches of the inner wall of the vessel.

30. The method of claim 23 further comprising a plurality of fins coupled to the first plurality of conduit portions and generally oriented tangentially from a radius of the vessel.

31. The method of claim 23 further comprising a plurality of fins coupled to the second plurality of conduit portions and generally oriented along a radius of the vessel.

32. The method of claim 23 wherein the plurality of conduit portions are arranged such that it does not extend into the portion of the interior volume defined by a distance from the center axis greater than 90% of the inner radius.

33. The method of claim 23 wherein the first plurality of conduit portions are interconnected and the second plurality of conduit portions are interconnected.

34. The method of claim 23 wherein the first plurality of conduit portions comprises between four and ten vertically extending conduit portions and the second plurality of conduit portions comprises between two and six vertically extending conduit portions.

35. The method of claim 23 wherein the first plurality of conduit portions comprises between six and eight vertically extending conduit portions and the second plurality of conduit portions comprises between four and six vertically extending conduit portions.

36. A method of cooling a biological material comprising: providing a vessel comprising a generally vertical inner wall disposed at an inner radius from a vertically disposed center axis, the inner wall defining in part an interior volume; providing a medium comprising a biological material; positioning a first and second plurality of conduit portions in a generally vertical orientation within the interior volume, each conduit portion containing a heat transfer fluid and comprising a heat transfer surface exposed to the interior volume, wherein a plurality of fins are coupled to at least some of the conduit portions; wherein each conduit portion of the first plurality of conduit portions is disposed at about a first distance from the center axis and each conduit portion of the second plurality of conduit portions is disposed at about a second distance from the center axis, wherein the first distance is between about 20% and about 50% of the inner radius and the second distance is between about 50% and about 80% of the inner radius, and wherein the conduit portions of the first plurality of conduit portions are generally distributed symmetrically around a circumference defined by the first distance and the conduit portions of the second plurality of conduit portions are generally distributed symmetrically around a circumference defined by the second distance; introducing the medium into the vessel; and circulating a heat transfer fluid through the first and second plurality of conduit portions, wherein the heat transfer surfaces conduct heat out of the medium and wherein thermal bridges are not formed between the heat transfer surfaces and the inner wall of the vessel during the cooling of the biological material.

Description:

BACKGROUND

The present invention relates to a system and method for uniformly heating and cooling a material, particularly a biological material such as a biopharmaceutical product.

Biological materials such as biopharmaceutical products are typically frozen for long periods of time for storage and then thawed for later use. The speed and uniformity of the freezing and thawing processes must be controlled properly. If the freezing or thawing is too slow, the active material may be subject to degradation from concentration gradients. These problems can be exacerbated by compartmentalization of the material that is freezing or thawing. Overall, uneven freezing and thawing can lead to less uniformity in the active material and challenges in properly mixing it during the freeze and thaw processes. An additional problem is that the materials best suited for contact with biological materials have relatively poor heat transfer properties.

Typically, vessels used to heat or cool a medium have a heat exchange fluid circulated in tubes placed in the vessel or around the exterior of the vessel. Extensions, such as fins, may be coupled to the vessel or structures in the vessel to increase the surface area of the system that is in contact with the medium to improve the transfer of heat to or from the medium to the heat exchange fluid.

Fins will usually be attached by one end to a portion of the vessel or some other structure in the vessel and the fins will conduct heat to or from that portion of the vessel. However, since a fin is typically attached to the vessel or an internal structure at only one point, all of the heat transferred to or from the fin to the container or an internal structure must enter or leave the fin through the one connection that the fin has with the rest of the system.

Current commercial embodiments of vessels for heating a cooling biopharmaceutical products use a system in which one or more of the fins are rigidly attached to both the container and an internal structure within the container. This configuration allows heat to be transferred to or from a fin through two portions of the fin, increasing the rate at which heat is put into or withdrawn from a medium placed in the container. However, because the fin is rigidly attached between the container and a structure within the container, the structure within the container itself then becomes rigidly attached to the container. The attachment of the structure inside the container can make cleaning and decontaminating the container more difficult. Additionally, it may be more difficult to manufacture the system because, for example, tighter tolerances may be required so that the fin can be attached to two surfaces within the container, and each fin may require two or more welded joints. Furthermore, it may be inconvenient, costly, or impossible for fins made of certain materials to be welded to a container.

Another previous design for freezing and thawing biological materials is disclosed in U.S. Pat. No. 6,196,296 to Wisniewski et al. This design has some difficulties. Analysis of this design (described below in the Examples section) indicates that it is inefficient, particularly toward the later stages of freezing. There are large distances between the active heat transfer surfaces. As freezing proceeds, an ice layer forms on the cooling surfaces and acts as an insulator between the freezing point and the cooling surface. It would be advantageous from a performance standpoint to minimize the thickness of the ice. Additionally, the fins in the design disclosed in U.S. Pat. No. 6,196,296 are very close to the vessel walls, which increases the chance of damaging the vessel or the fins during cleaning or disassembly of the vessel. Further, the fins create compartmentalization of material which can detract from uniform cooling and heating and present challenges in mixing such material.

BRIEF SUMMARY

In one aspect, a system for heating and cooling biological materials includes a vessel and a first and second plurality of conduit portions. The vessel includes a generally vertical inner wall defining in part an interior volume. Each conduit portion of the first and second plurality of conduit portions is disposed in a generally vertical orientation within the interior volume. Each conduit portion contains a heat transfer fluid and includes a heat transfer surface exposed to the interior volume. Each conduit portion of the first plurality of conduit portions is disposed at about a first distance from the inner wall. Each conduit portion of the second plurality of conduit portions is disposed at about a second distance from the inner wall. The second distance is greater than the first distance.

In another aspect, a method of heating or cooling a biological material includes providing a vessel. The vessel includes a generally vertical inner wall disposed at an inner radius from a vertically disposed center axis. The generally vertical inner wall defines in part an interior volume. A medium including a biological material is provided. A plurality of heat transfer surfaces is positioned within the interior volume. Each of the plurality of heat transfer surfaces is oriented generally vertically through the interior volume. Each of the heat transfer surfaces is arranged such that it does not extend into the portion of the interior volume defined by a distance from the center axis greater than 90% of the inner radius. The medium is introduced into the vessel. A heat transfer fluid is circulated through the plurality of heat transfer surfaces. The heat transfer surfaces conduct heat out of the medium during freezing and into the medium during thawing.

The system of the present invention is capable of minimizing the thickness of the ice formed on the cooling surfaces and reducing the compartmentalization of the medium when compared to prior art systems. Additionally, in various embodiments the system of the present invention provides increases distance between the heat transfer surfaces and the inner wall of the vessel compared to prior art systems, thus minimizing the risks of collision damage during removal and insertion of the heat transfer surfaces.

The foregoing paragraphs have been provided by way of general introduction, and are not intended to limit the scope of the following claims. The presently preferred embodiments, together with further advantages, will be best understood by reference to the following detailed description taken in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial cutaway view of a first embodiment of a heating and cooling system.

FIG. 2 is a top view of a first embodiment of a heating and cooling system.

FIG. 3 is a side view of a first embodiment of a heating and cooling system.

FIG. 4 is a partial cutaway view of a second embodiment of a heating and cooling system.

FIG. 5 is a partial cutaway top view of a second embodiment of a heating and cooling system.

FIG. 6 is a top cross-sectional view of a third embodiment of a heating and cooling system.

FIG. 7 is a temperature graph from a computer simulation showing the temperature profile from a prior art heating and cooling system.

FIG. 8 is a temperature graph from a computer simulation showing the temperature profile from a first embodiment of a heating and cooling system.

FIG. 9 is a temperature graph from a computer simulation showing the temperature profile from a second embodiment of a heating and cooling system.

FIG. 10 is a graph showing the liquid fraction remaining in a vessel as a function of time for a prior art heating and cooling system, a first embodiment of a heating and cooling system, and a second embodiment of a heating and cooling system.

FIG. 11 is a graph showing the medium temperature as a function of time during the freezing process.

DETAILED DESCRIPTION

The invention is described with reference to the drawings in which like elements are referred to by like numerals. The relationship and functioning of the various elements of this invention are better understood by the following detailed description. However, the embodiments of this invention as described below are by way of example only, and the invention is not limited to the embodiments illustrated in the drawings.

One embodiment of a system 10 for heating and cooling biological materials is shown in FIGS. 1-3. The system includes a vessel 20 and a plurality of heat transfer surfaces 30 disposed within the vessel 20. The heat transfer surfaces 30 act to add heat to or remove heat from a medium disposed within the vessel 20. The vessel 20 includes a generally vertical inner wall 22 positioned at an inner radius 18 from a vertically extending center axis 24. The inner wall 22 defines in part an interior volume 26. The heat transfer surfaces 30 are oriented generally vertically through the interior volume 26. The heat transfer surfaces may include portions which are not vertically oriented, such as bends and other connections. The heat transfer surfaces may also deviate somewhat from vertical to accommodate the use of a variety of materials to manufacture the heat transfer surfaces. Although the vessel 20 is shown as generally cylindrical in shape and circular in cross-section, other shapes and cross-sections are possible. The vessel 20 includes an inner diameter 28, a bottom inner wall 32, and an outlet 34.

The heat transfer surfaces 30 can assume a variety of configurations. The heat transfer surfaces 30 are preferably formed on conduit portions 40 circulating a heat transfer fluid, as shown in FIG. 1. The heat transfer surfaces 30 include the conduit portions 40. The conduit portions 40 extend generally vertically throughout the inner volume. At least some of the conduit portions 40 may be interconnected and convey the heat transfer fluid within. In one embodiment, adjacent conduit portions 40 are connected by curved, generally semicircular loops 42. Thus, a heat transfer fluid flows down one conduit portion, through a bottom loop, up into an adjacent conduit portion, through a top loop, and so forth. A heat transfer fluid also may flow through the wall of the vessel 20. However, it will be apparent that a variety of configurations for connecting conduit portions is possible.

In one embodiment, as best seen in FIG. 2, the conduit portions 40 includes a first or outer set of conduit portions 50, 52, 54, 56, 58, 60, 62, 64 disposed at about a first distance 68 from the center axis 24 of the vessel 20 and a second or outer set of conduit portions 70, 72, 74, 76 disposed at about a second distance 78 from the center axis 24 of the vessel. The outer set of conduit portions need not be disposed at exactly the first distance 68 from the center axis 24, but is disposed generally about the first distance 68. Similarly, the inner set of conduit portions need not be disposed at exactly the second distance 78 from the center axis 24, but is disposed at generally about the distance 78. The first distance 68 is greater than the second distance 78. This arrangement of the conduit portions allows the heat transfer surfaces 30 to be distributed more evenly throughout the volume 26 of the vessel 20. In the embodiment shown in FIG. 2, conduit portions 50, 52, 54, 56, 58, 60, 62, 64 are distributed along a circle defined by the first distance 68, and the conduit portions 70, 72, 74, 76 are distributed along a circle defmed by the second distance 78. Adjacent conduit portions 40 are preferably connected by curved, generally semicircular loops 42.

The conduit portions 50, 52, 54, 56, 58, 60, 62, 64 are preferably interconnected and conduit portions 70, 72, 74, 76 are preferably interconnected. The first and second set of conduit portions may be interconnected, with the same fluid flowing through both of them, or they may be separate systems.

The first and second sets of conduit portions are preferably arranged so that the heat transfer surfaces 30 are distributed relatively evenly throughout the volume 26. The first distance 68 is preferably between about 50% and about 80% of the inner radius 18 (the distance between the center axis 24 and the inner wall 22 of the vessel). The second distance 78 is preferably between about 20% and about 50% of the inner radius 18. In a preferred embodiment of a 300 liter vessel with a 34 inch inner diameter, the first distance 68 is between about 8.5 inch and about 14 inch, and the second distance 78 is between about 3 inch and 8.5 inch. For a vessel without a circular cross-section, the distance from the center axis may be instead expressed as the equivalent distance away from the inner wall.

The first set of conduit portions 50, 52, 54, 56, 58, 60, 62, 64 are generally distributed symmetrically around a circle or circumference defined by the first distance. The second set of conduit portions 70, 72, 74, 76 is generally distributed symmetrically around a circumference defined by the second distance.

In one embodiment, fins 80 are coupled to at least some of the conduit portions 40 to provide additional heat transfer surfaces. The fins 80 extend a width from the surface of the conduit portions 40 into the interior volume 26. In this context, the width of the fin 80 is the horizontal distance the fin 80 extends from the surface of the conduit portion 40. The fins 80 are thermally coupled to conduit portions 40 to provide additional surface area for heat transfer. The fins 80 preferably extend a relatively short distance from the conduit portions 40, because it is believed that the heat transfer efficiency of the fins 80 decreases rapidly with distance. Each fin 80 preferably has a width of less than twice the diameter of the conduit portion. Alternatively, expressed as a function of the vessel 20 diameter 28, the width of the fin is less than about 10% of the vessel diameter 28. The fins are preferably relatively thin with respect to their width. The term “fin” is used generically to mean any heat exchange surface of the system that extends into the medium from a heat transfer surface or conduit portion, including but not limited to a coil, a flattened protrusion, a tube, or any other structure extending into the vessel.

In one embodiment, each conduit portion 40 includes a pair of fins 80 disposed on opposite sides of the conduit portion 40 and extending radially outwards with respect to the conduit portion 40. In the embodiment shown in FIGS. 1-3, the fins 80 coupled to the first or outer set of conduit portions 50, 52, 54, 56, 58, 60, 62, 64 are generally oriented tangentially from a radius of the vessel 20. The fins 80 coupled to the second or inner set of conduit portions 70, 72, 74, 76 are generally oriented along a radius of the vessel 20. The fins 80 on the first or outer set of conduit portions 50, 52, 54, 56, 58, 60, 62, 64 preferably do not extend toward the vessel wall 22 and are not oriented along a radius of the vessel 20. In another embodiment, none of the fins 80 coupled to the outer set of conduit portions 50, 52, 54, 56, 58, 60, 62, 64 extends toward the inner wall 22 of the vessel 20.

Various arrangements, designs, configurations, and numbers of fins 80 may be used. For example, the fins 80 need not be symmetrically positioned within the vessel, they need not be the same shape, the number of fins per conduit portion can vary, and the fins need not extend the entire length of the conduit portion.

In a second embodiment, shown in FIGS. 4 and 5, the conduit portions 40 do not include any fins 80. Otherwise this second embodiment is identical to the first embodiment in the arrangement of the conduit portions 40.

For both the first embodiment and second embodiment of the heating and cooling system, the number of conduit portions 40 within the vessel 20 may vary. The outer set of conduit portions includes between four and ten, preferably between six and eight, and most preferably eight vertically extending conduit portions. The inner set of conduit portions includes between two and six, preferably between four and six, and most preferably four vertically extending conduit portions. It will be apparent that the heat transfer area increases with increasing number of conduit portions, but with a concurrent increase in equipment cost and complexity and a decrease in available vessel volume.

The heat transfer surfaces 30 are preferably disposed such that they are separated from the inner wall 22 of the vessel 20. In one embodiment, the heat transfer surfaces 30, including both conduit portions 40 and fins 80, are arranged such that they do not extend into the portion of the interior volume defined by a distance from the center axis 24 approximately greater than 90% of the inner radius 18. For a typical vessel 20 size with a 34 inch diameter 28, the heat transfer surfaces do not extend beyond about 15.3 inch from the center axis 24 of the vessel 20. In other embodiments, the distance limitation for the heat transfer surfaces may be 85%, 80%, 75%, 70%, or 60% of the inner radius 18.

The offset of the heat transfer surfaces from the inner wall 22 of the vessel 20 may be expressed as a distance between the heat transfer surface 30 and the inner wall 22 of the vessel 20. In one embodiment, the heat transfer surfaces are arranged such that they do not extend within 2 inches of the inner wall 22 of the vessel 20. In other embodiments, this distance is 3 inches, 4 inches, and 5 inches.

By providing a distance between the heat transfer surfaces and the inner surface of the vessel 20, the chance of contact between the heat transfer surfaces 30 and the vessel 20 is minimized, thus reducing the likelihood of scratching and other damage to the equipment.

A third embodiment of a heating/cooling system is shown in FIG. 6. The conduit portions 40 includes a first set of conduit portions 90 disposed at about a first distance 91 from the center axis 24 of the vessel 20, a second set of conduit portions 92 disposed at about a second distance 93 from the center axis 24 of the vessel, and a third set of conduit portions 94 disposed at about a third distance 95 from the center axis 24 of the vessel. The first distance 91 is greater than the second distance 93, and the second distance 93 is greater than the third distance 95. This arrangement of the conduit portions 40 allows the heat transfer surfaces 30 to be distributed more evenly throughout the volume 26 of the vessel 20. In the embodiment shown in FIG. 6, conduit portions 90 are distributed symmetrically along a circle defined by the first distance 91, conduit portions 92 are distributed symmetrically along a circle defined by the second distance 93, and conduit portions 94 are distributed symmetrically along a circle defined by the third distance 95.

Each set of conduit portions 90, 92, and 94 is preferably interconnected. The three sets of conduit portions may additionally be connected to each other, with the same fluid flowing through both of them, or they may be separate systems. Each conduit portion 90, 92, and 94 includes a pair of fins 80 disposed on opposite sides of the conduit portion and extending radially outwards therefrom. In the embodiment shown in FIG. 6, the fins 80 coupled to the outer set of conduit portions 90 are generally oriented tangentially from a radius of the vessel 20. The fins 80 coupled to the middle and inner sets of conduit portions 92, 94 are generally oriented along a radius of the vessel 20. However, other orientations of the fins 80 are possible.

Turning now to the vessel 20, the interior volume 26 of the vessel 20 may be any size suitable for the proposed task and the system 10 may be scaled up or down to accommodate the vessel size. The volume of the vessel 20 will typically be between about 10 liters and about 500 liters, more typically between about 250 and 350 liters. The components of the system are preferably fashioned from a material suitable for contact with a biological material, such as stainless steel, for example 316L, or higher alloys such as Hastelloy® C-22®.

The vessel 20 also preferably includes a heat transfer fluid circulating therein to promote the heating and/or cooling of the medium therein. The heat transfer fluid is preferably silicone oil and is circulated via an external pump. The vessel 20 used may be of the type disclosed in U.S. Pat. No. 6,196,296. Suitable systems are available from Integrated Biosystems. Vessel 20 has a jacket surrounding its circumference. Between the exterior surface of the vessel and a jacket is a fluid flow path. Spiral baffle corkscrews around the vessel between the exterior surface and the jacket, forcing heat exchange fluid in a fluid flow path to flow in a spiraling path around the exterior surface of the vessel.

The system may be used for both heating and/or cooling a biological material, including thawing a frozen material or otherwise changing the temperature of the material. A method of cooling a biological material includes providing a vessel 20 with an inner wall 22 defining an interior volume 26 and providing a medium including a biological material. A plurality of heat transfer surfaces 30 are positioned within the interior volume. The heat transfer surfaces 30 may be any of the configurations previously described herein. A heat transfer fluid is circulated through the conduit portions or other heat transfer surfaces. The heat transfer surfaces 30 conduct heat out of the medium. The heat transfer fluid may be silicone oil and circulated via an external pump.

In the embodiment shown in FIGS. 1-3, a heat transfer fluid inlet 82 is provided in conduit portion 50 and a heat transfer fluid outlet 84 is provided in conduit portion 70. Thus, the heat transfer fluid flows down through conduit portion 50, through loop 42, up through conduit portion 52, and similarly through conduit portions 54, 56, 58, 60, 62, and 64, and then into conduit portions 76, 74, 72, 70 and exiting through outlet 84. Of course, other configurations of the conduit portions and connections between the conduit portions are possible.

When used for cooling, as the heat transfer fluid flow through the conduit portions, the medium within the vessel begins to cool and then freeze. The spacing of the heat transfer surfaces (including the conduits) distributes the cooling surfaces evenly throughout the vessel. The system of the present invention is capable of minimizing the thickness of the ice formed on the cooling surfaces and reducing the compartmentalization of the medium when compared to prior art systems. Additionally, in various embodiments the system of the present invention increases the distance between the heat transfer surfaces and the inner wall of the vessel compared to prior art systems, thus minimizing the risks of collision damage during removal and insertion of the heat transfer surfaces. Additionally, the present invention does not require thermal bridges to be formed between the inner wall of the vessel and the heat transfer surfaces.

The system may also be used for thawing the frozen medium. As the heat transfer fluid flow through the conduit portions, the frozen medium within the vessel begins to melt. The spacing of the heat transfer surfaces, including the conduits and the fins, distributes the heat evenly throughout the vessel. A recirculation pump may be used to accelerate the thawing of the medium.

Other flow patterns, fin shapes, and fin configurations may be used to heat or cool the medium in any preferred direction, uniformly, and/or at a specified rate. Additionally, parameters of the heat exchange fluid such as flow rate and/or temperature can be used to affect the rate at which the medium is cooled. Furthermore, the heat exchange fluid can be flowed through the system at other points and in a time or process varying manner in order to tailor the timing, direction, and rate of heat flow into or out of the system. Additionally, materials used in, or the shape, or configuration of the system, including the fins, can be used to control parameters of the heating or cooling process such as rate, timing or directionality.

It should be appreciated that there need not be active cooling of both the structure and the vessel. Without departing from the present invention, coolant can be circulated through any part of the system, only one part of the system, or coolant need not be used and the system could be cooled by other means or indirectly or passively.

The present invention can be usefully applied in many fields. For example in the biopharmaceutical industry the present invention can be used to freeze and preserve a variety of biopharmaceutical products, including but not limited to proteins, cells, antibodies, medicines, plasma, blood, buffer solutions, viruses, serum, cell fragments, cellular components, and any other biopharmaceutical product.

EXAMPLES 1-3

The cooling characteristics of several heating/cooling systems designs were analyzed using computer simulations with FLUENT™ computational fluid dynamics software. The simulations were based on a nominal 300 L capacity, 34″ inside diameter vessel called the 300 L Cryovessel available from Integrated Biosystems. The inner wall and heat transfer surface temperature were set at −30° C. The temperature profile of a fluid being cooled was modeled as a function of time. Three systems were modeled: 1) the prior art Integrated Biosystems design (Comparative Example 1); 2) the finned design of the present invention shown in FIGS. 1-3 (Inventive Example 2); and 3) the finless design of the present invention shown in FIGS. 4-5 (Inventive Example 3).

COMPARATIVE EXAMPLE 1

The prior art Integrated Biosystems design was modeled. FIG. 7 shows the temperature profile of the fluid in a horizontal section of the vessel after cooling for approximately 6.5 hours. The coils and fins of the heat transfer surfaces are depicted in white. The temperature of the fluid is indicated by the shading: a light color indicates that the fluid is completely cooled to the temperature of the heat transfer surface, while a dark color indicates the original fluid temperature. The numerical scale is in degrees Kelvin. It can be seen that the prior art design includes large pockets of uncooled fluid in the area between the fins.

INVENTIVE EXAMPLE 2

FIG. 8 shows the temperature profile of the fluid for the finned design after cooling for approximately 6.5 hours. It can be seen that the present invention provides relatively small pockets of uncooled material between the heat transfer surfaces.

INVENTIVE EXAMPLE 3

FIG. 9 shows the temperature profile of the fluid for the finless design after cooling for approximately 6.5 hours. It can be seen that the present invention provides small pockets of uncooled material between the conduit portions.

In comparing the performance of the three systems, it can be seen that the prior art design leaves large pockets of uncooled fluid, and that the present invention provides much smaller pockets of uncooled fluid. It can be seen that the two embodiments of the present invention have better temperature distribution than the prior art design. Although the finless design did not perform as well as the finned design, it still showed superior cooling to the prior art design. The prior art design has large areas that cool slowly due to the distance from the heat transfer surfaces.

The computer simulations were also used to determine the liquid fraction remaining in the vessel as a function of time, to determine how quickly the systems were able to freeze the liquid. FIG. 10 shows the simulation results for the liquid fraction remaining in a vessel as a function of time for the prior art heating and cooling system, the first embodiment (finned design) of the present invention, and the second embodiment (finless design) of the present invention. It can be seen that both embodiments of the present invention were able to freeze the liquid more quickly than the prior art design.

EXAMPLES 4-5

Tests were conducted in a vessel using the prior art design (Comparative Example 4) and the design of the present invention depicted in FIGS. 1-3 (Inventive Example 5). The prior art vessel was a 300 L Cryovessel obtained from Integrated Biosystems. The inlet temperature of the silicone heat transfer fluid was −50° C. The temperature of the medium in the vessel was measured in a spot located near the last part of the vessel to freeze. Tests were conducted for water, a buffer solution, and a HerceptinTM solution. The results for the Herceptin™ solution are show in FIG. 1. It can be seen that the system of the present invention cooled the liquid more quickly than the prior art design.

The embodiments described above and shown herein are illustrative and not restrictive. The scope of the invention is indicated by the claims rather than by the foregoing description and attached drawings. The invention may be embodied in other specific forms without departing from the spirit of the invention. Accordingly, these and any other changes which come within the scope of the claims are intended to be embraced therein.