Plug for insulating containers and cooling method

Abstract

Disclosed herein is a device in the form of a plug for insulating the interior of a container from the ambient environment, the plug comprising multiple insulating sections and one or more shields for reflecting infrared radiation. Disclosed are a method of preparing a transport system for holding cryopreserved samples, the method including loading the cryopreserved samples into a container, such as a vacuum flask, and attaching a plug to the container to insulate the interior of the container from the ambient environment, and a method for cooling a container, such as a vacuum flask, for maintaining a cryopreserved sample at a desired temperature, the method including cooling the interior of the container by pouring a cryogenic fluid, such as liquid nitrogen, into the container and emptying the cryogenic fluid from the container once cooling is at least partially achieved.

Description

[Technical Field]

[0001] SUMMARY The present disclosure relates to a closure device for insulating the interior of a container apparatus from the surrounding environment and a method for cooling such a container. [Background technology]

[0002] Novel cell and gene therapies are successfully treating a variety of cancers. There is a global demand for these therapies. Often, patients are in a different country from the site of cell production, which means that biological materials such as tissues and cells are often cryogenically frozen (e.g., at temperatures below -120°C) so that they can be stored and transported. Cryogenic freezing is used because cells do not survive long enough when refrigerated to be suitable for therapy. The biological material must be maintained at cryogenic temperatures during transport.

[0003] Therefore, it is necessary to transport cell samples at cryogenic temperatures. An existing method for transporting cell samples at cryogenic temperatures uses a "dry shipper." A dry shipper is a vacuum-insulated storage vessel (or "Dewar") containing zeolite material. The zeolite material absorbs liquid nitrogen (-196 °C), which provides a cooling source for cell samples transported within the dry shipper. The absorption of liquid nitrogen by the zeolite prevents the liquid nitrogen from spilling or splashing out of the vessel. Dry shippers maintain a constant temperature of -196 °C for many days as nitrogen constantly evaporates from the zeolite. Dry shippers typically provide a cryogenic standby time of 4 to 10 days before warming to ambient temperature.

[0004] Existing dry shippers pose hygiene and safety challenges for couriers, airlines, and clinics that handle them. For example, the constant evaporation of liquid nitrogen from zeolites poses a suffocation risk to users because the evaporated nitrogen displaces oxygen from the surrounding environment. The suffocation risk means that dry shippers must be stored and transported carefully. Biological specimens must remain free of contaminants during transport. However, there is a risk that biological specimens may become contaminated with bacteria, viruses, fungi, and other microorganisms, as well as DNA, RNA, and cellular debris from biological specimens previously transported in the same transport device. Biological specimens may also become contaminated by contamination of the cooling medium (e.g., dry ice or liquid nitrogen) or by contamination from the surrounding environment. To minimize the risk of contamination, existing dry shippers are often warmed to ambient temperature and cleaned between uses. Cleaning may involve covering the surface of the dry shipper with a liquid cleaning product such as water, ethanol, methanol, or detergent, a gaseous cleaning agent such as hydrogen peroxide, or a combination of these methods.

[0005] A transport container for cryopreserved biological samples is described in WO 2018 / 115833, which is incorporated by reference in its entirety. One implementation of the transport container described in WO 2018 / 115833 comprises a thermal mass shaped to at least partially contain, hold, or surround one or more cryopreserved samples. The thermal mass is used to slow the rate of temperature change (rise) within a cavity of the transport container. A heat exchanger is positioned within the cavity of the transport container. The heat exchanger is attached to a Stirling cryocooler positioned in a lid of the transport container. The Stirling cryocooler is used to remove heat from the cavity. The transport container comprises a gravitational heat diode operable in a first state to provide cooling to the cavity and a second state to reduce heat transfer to the cavity. The use of a gravity heat diode means that the diode (and therefore the transport container) needs to be maintained in an upright position to maintain the temperature gradient between the upper and lower limits. For this reason, the lid of the transport container may be equipped with a tilt sensor to ensure that the transport container is maintained in an upright position.

[0006] However, during transport, it is not uncommon for the transport container to tip over or be transported upside down. This reduces the effectiveness of the thermal diodes used in the transport container described in WO 2018 / 115833, meaning that the cryogenic temperature is not maintained during transport, risking the loss of the biological sample. For example, when the transport container is on its side, the cooling source (previously positioned near the base of the container) shifts to be positioned along the sidewall of the transport container (i.e., near the surrounding area at the top of the transport container). This reduces the cooling effect provided by the cooling source. Also, if a Stirling cryocooler is part of the transport container described in WO 2018 / 115833, the Stirling cryocooler is also transported when the biological sample is transported. Transporting the Stirling cryocooler increases costs. Also, some clinics cannot afford the requirement to turn on the Stirling cryocooler to maintain the cryogenic temperature within the transport container. If the Stirling cryocooler is not switched on, the container may warm to ambient temperature before the biological sample is used, resulting in loss of the sample.

[0007] As explained above, the thermal mass of the transport container described in WO 2018 / 115833 is used to slow the rate of temperature rise within the cavity of the transport container. Given its large specific heat capacity, the thermal mass takes a long time to cool from ambient temperature to cryogenic temperatures. Therefore, after the transport container is warmed to ambient temperature for cleaning, there is a long period of inoperability (during which the transport container cools down). During this inoperability, the transport container is not used to transport biological samples. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] International Publication No. 2018 / 115833 Summary of the Invention [Problem to be solved by the invention]

[0009] Thus, there is a need to provide improved techniques for holding, and particularly transporting, cryopreserved samples that address the shortcomings of the existing systems and related methods listed above. [Means for solving the problem]

[0010] This Summary introduces concepts that are more fully described in the Detailed Description. It is not intended to identify essential features of the claimed subject matter, nor should it be used to limit the scope of the claimed subject matter.

[0011] The containers described herein may be for holding one or more cryopreserved samples. As used herein, holding one or more cryopreserved samples may include transporting one or more cryopreserved samples and / or storing one or more cryopreserved samples. In other words, the container may be for holding one or more cryopreserved samples, regardless of whether the container is moving or stationary.

[0012] Such a container must have an access port for inserting and removing items to be cryogenically stored or transported, and in the present invention, that access port is made available by a plug for closing the opening of the container as claimed to form a cryogenic storage device.

[0013] The invention also extends to a cooling method as claimed. All aspects or features of the claims described herein, whether or not referred to together in this specification, form part of the present invention and may be claimed separately without broadening the scope of the invention.

[0014] Specific embodiments are now described, by way of example only, and with reference to the accompanying drawings. [Brief explanation of the drawings]

[0015] [Figure 1] 1 is a schematic cross-sectional view of a container for holding, and in particular transporting, cryopreserved samples, with the stopper not attached. FIG. [Figure 2] 1 is a schematic cross-sectional view of a plug for insulating a container from the ambient environment. [Figure 3] 2 is a schematic cross-sectional view of a container for holding, and particularly for transporting, cryopreserved samples, with the stopper of FIG. 1 installed; FIG. [Figure 4] 3 is a schematic cross-sectional view of an alternative plug to that shown in FIG. 2. FIG. [Figure 5] 3 is a schematic cross-sectional view of an alternative plug to that shown in FIG. 2. FIG. [Figure 6] 6 is an enlarged view of a portion of the stopper shown in FIG. 5 attached to a container. [Figure 7] FIG. 6 is a perspective view of the stopper shown in FIG. 5. [Figure 8A] FIG. 6 is a perspective view of the upper portion of the stopper shown in FIG. 5. [Figure 8B] FIG. 6 is an enlarged view of a portion of the stopper shown in FIG. 5. [Figure 9] 1 is a flow diagram of a method for cooling a container for holding, and particularly for transporting, cryopreserved samples. [Figure 10] 1 is a flow diagram of a method for preparing a transport system for holding, and specifically transporting, cryopreserved samples. [Figure 11] 1 is a schematic diagram of an apparatus for sterilizing containers for holding, and particularly for transporting, cryopreserved samples. [Figure 12] FIG. 1 is a schematic diagram of an alternative apparatus for sterilizing containers for holding, and particularly for transporting, cryopreserved samples. [Figure 13]1 is a flow diagram of a method for sterilizing a container for holding, and particularly for transporting, cryopreserved samples. [Figure 14] 10 is a flow diagram of an additional method for preparing a transport system for holding, and specifically transporting, cryopreserved samples. [Figure 15] 3 is a graph showing the temperature change over time of the delivery system with the plug shown in FIG. 2. [Figure 16] FIG. 1 is a schematic diagram of an alternative apparatus for sterilizing containers for holding, and particularly for transporting, cryopreserved samples. DETAILED DESCRIPTION OF THE INVENTION

[0016] Implementations of the present disclosure are described below with particular reference to maintaining cryopreserved samples that are maintained at cryogenic temperatures during transport or storage, however, it will be understood that the devices and methods disclosed herein are also applicable to maintaining materials at other temperatures (i.e., non-cryogenic temperatures).

[0017] Figure 1 illustrates a container for holding, and particularly for transporting, cryopreserved samples. As shown in Figure 1, container 10 includes walls 12 and a base 14. Walls 12 and base 14 are vacuum insulated to provide thermal insulation for the contents of container 10. Walls 12 and base 14 define a cavity 16 within container 10 (i.e., the interior of container 10).

[0018] Optionally, to facilitate sterilization using ultraviolet light (as described below in connection with FIGS. 11 and 13 ), the interior of the cavity (i.e., the portion of the wall 12 and / or base 14 in contact with the cavity 16) may be formed from a material that is reflective to the wavelength of ultraviolet light used to sterilize the container 10 (e.g., a material that is reflective to ultraviolet light having a wavelength between 100 nm and 300 nm, preferably 275 nm). The walls 12 and / or base 14 may include a material suitable for meeting the desired thermal requirements, such as, for example, fiberglass or stainless steel. The interior of the cavity 16 (i.e., the portion of the wall 12 and / or base 14 in contact with the cavity 16) may be coated with a thin reflective layer to assist in UV sterilization.

[0019] Returning to the container 10 shown in FIG. 1 , a thermal mass 18 is positioned within the cavity 16 of the container 10. The thermal mass 18 includes an opening (not shown) for receiving a cryopreserved sample. A cryopreserved sample is a sample of biological material that is cryogenically frozen (e.g., at a temperature below −120° C.). The container 10 is cooled (e.g., to a temperature below −120° C.) to maintain the cryogenic temperature within the container 10 such that the sample remains in its cryogenically frozen state.

[0020] Thermal mass 18 is formed from a material (such as aluminum) with a large specific heat capacity, meaning that thermal mass 18 is resistant to changes in temperature. Thermal mass 18 can be formed from materials with a large thermal mass to weight and / or volume ratio, for example, aluminum, polymers such as nylon, or water / ice.

[0021] This means that thermal mass 18 remains cool for an extended period of time after container 10 itself has cooled, thereby acting to slow the rate of temperature increase within cavity 16 and providing passive cooling to a cryopreserved sample received within the opening.

[0022] Figure 2 shows a plug 20 for insulating the interior of the container 10 shown in Figure 1 from the ambient environment. The plug 20 shown in Figure 2 is sized so that a portion of the plug 20 fits within the cavity 16 of the container 10. The plug 20 comprises a lower portion 22 and an upper portion 24. The lower portion 22 is positioned to fit within the cavity 16 defined by the container wall 12, as shown in Figure 3. Returning to Figure 2, the upper portion 24 has a width greater than the width of the cavity 16 so that when the plug 20 is attached to the container 10 (as shown in Figure 3), the upper portion abuts the top of the wall 12 and covers the opening at the top of the cavity 16, thereby insulating the interior of the container 10 from the ambient environment.

[0023] 2 and 3, plug 20 includes a plurality of insulating segments 26 and at least one reflective shield 28 for reflecting infrared radiation. For example, lower portion 22 of plug 20 shown in FIG. 2 includes 14 insulating segments 26 with 13 reflective shields 28. In one example, plug 20 may include at least 20 insulating segments 26 and reflective shields 28. The thermal insulation provided by plug 20 can increase with an increase in the number of insulating segments 26 and / or reflective shields 28.

[0024] Each reflective shield 28 is disposed between two insulating sections 26 such that the insulating sections 26 and the reflective shields 28 are provided in alternating layers. That is, the insulating sections 26 and the reflective shields 28 are provided in alternating layers along the longitudinal axis of the plug 20, where the longitudinal axis is aligned with the direction in which the plug 20 is installed in and / or removed from the container 10. The top insulating section 26 of the plug 20 shown in FIG. 2 is mounted on the upper portion 24 of the plug 20.

[0025] The insulating sections 26 may be formed from an insulating material (i.e., a material with a low thermal conductivity and a low thermal mass), such as foam. One or more of the insulating sections 26 may comprise closed-cell foam, aerogel, and / or one or more cavities with a vacuum or partial vacuum. The insulating sections 26 provide insulation between the cavity 16 of the container 10 and the ambient environment to slow heat transfer from the ambient environment to the cavity 16.

[0026] The reflective shield 28 is formed from a material that reflects infrared radiation (i.e., a material with high reflectivity), such as metal foil. The reflective shield 28 reflects infrared radiation from the surrounding environment to prevent the infrared radiation from the surrounding environment from heating the cavity 16.

[0027] The plug 20 further comprises a fastener 30 for attaching the upper portion 24 of the plug 20 to the wall 12 of the container 10 (as shown in FIG. 3 ). The fastener 30 is mounted to the upper portion 24 of the plug 20. After the plug 20 is attached to the container 10 (i.e., after the lower portion 22 is installed within the cavity 16), the fastener 30 is tightened. The fastener 30 tightens a seal at the interface between the upper portion 24 of the plug 20 and the wall 12 of the container 10. Tightening the fastener 30 prevents air flow between the ambient environment and the interior of the cavity 16, which means that convective heating provided by the ambient air is reduced.

[0028] The plug 20 further includes an upper seal 32 (best seen in FIG. 2), which is positioned below the upper portion 24 of the plug 20, as shown in FIG. 2. As such, the upper seal 32 is compressed between the upper portion 24 of the plug 20 and the top of the wall 12 when the plug 20 is installed in the cavity 16, as shown in FIG. 3. The upper seal 32 also prevents air from flowing between the ambient environment and the interior of the cavity 16, thereby reducing convective heating provided by ambient air.

[0029] The plug 20 also includes a flexible seal 34 positioned around the periphery of the lower portion 22 of the plug 20. For ease of installation, the flexible seal 34 may be mounted to the reflective shield 28. Alternatively or additionally, the flexible seal 34 may be integral with or mounted to the insulating section 26, for example around the periphery of the insulating section 26.

[0030] The flexible seal 34 is formed from a resilient material that can withstand extremely low temperatures without degradation. A suitable material for the flexible seal 34 is rubber. The flexible seal 34 may include a surface configured to abut the wall 12 and formed from a wear-resistant material, and a softer or spring-like component on the surface opposite the wall 12 that is configured to provide compliance / compressibility for the flexible seal 34.

[0031] When the stopper 20 is not attached to the container 10 (i.e., as shown in FIG. 2), the overall width of the lower portion 22 of the stopper 20 and the flexible seal 34 exceeds the width of the cavity 16 (i.e., the gap between the walls 12 of the container 10). This is because when the stopper 20 is attached to the container 10 (i.e., as shown in FIG. 3), the flexible seal 34 is compressed between the lower portion 22 of the stopper 20 and the walls 12 of the container 10, thereby sealing the gap between the lower portion 22 of the stopper 20 and the walls 12 of the container 10.

[0032] When the closure 20 is removed from the container 10, the flexible seal 34 returns to its original shape.

[0033] When the plug 20 is attached to the container 10 (i.e., as shown in FIG. 3), the compressed flexible seal 34 prevents air from flowing between the interior of the cavity 16 of the container 10 and the ambient environment through the gap between the lower portion 22 of the plug 20 and the wall 12 of the container 10. This means that the flexible seal 34 reduces convective heating provided by ambient air.

[0034] As discussed above, catch 30, top seal 32, and flexible seal 34 each prevent overheating from convective airflow between closure 20 and container wall 12. Each of these components prevents heating of the sample in cavity 16 when container 10 is on its side or upside down. Each of these components also acts to retain cool air within cavity 16 when container 10 is on its side or upside down by preventing heat transfer through the top of container 10 (i.e., the end of the container opposite base 14). Thus, thermal mass 18 is effective not only when container 10 is upright, but also when container 10 is on its side or upside down.

[0035] The plug 20 further comprises a vent passage 36. The vent passage 36 passes through the lower portion 22 of the plug 20 and opens to the interior of the cavity 16 when the plug 20 is attached to the container 10 (as shown in FIG. 3). The vent passage 36 also passes through the upper portion 24 of the plug 20 and opens to the ambient environment (as shown in FIGS. 2 and 3). This means that the vent passage 36 allows a small amount of air to pass between the interior of the cavity 16 and the ambient environment.

[0036] 2, the vent passage 36 extends vertically through the entire lower portion 22 of the plug 20 and also extends vertically through a portion of the upper portion 24 of the plug 20. The vent passage 36 then extends horizontally between its vertical extension in the upper portion 24 of the plug 20 and the side of the upper portion 24 of the plug 20 that is exposed to the ambient environment.

[0037] The vent passages 36 allow air to escape from the cavity 16 to avoid over-pressurization of the container 10 resulting from the expansion of the thermal mass 18 in the cavity 16. To explain, when the thermal mass 18 in the cavity 16 heats up (which may occur over time during transportation or storage of the container 10), the thermal mass 18 expands. The expansion of the thermal mass 18 displaces the air in the cavity 16, which means that the pressure of the air in the cavity 16 will increase if the air is not allowed to escape via the vent passages 36.

[0038] The vent passage 36 also allows air to escape from the cavity 16 when the stopper 20 is attached to the container 10 to avoid over-pressurizing the container 10. To explain, if air were not allowed to escape through the stopper 20, the act of attaching the stopper 20 to the container 10 would increase the air pressure in the cavity 16. Therefore, allowing air to escape through the vent passage 36 prevents this increase in pressure. This means that the stopper 20 can be attached to the container 10 more easily, as the user does not need to apply additional force when inserting the stopper 20 into the container 10 to overcome the force exerted on the stopper 20 by the pressurized air in the cavity 16.

[0039] Similarly, the vent passage 36 allows air to enter the cavity 16 when the stopper 20 is removed from the container 10 to avoid creating a vacuum in the cavity 16. To explain, if air were not allowed to enter through the stopper 20, the act of removing the stopper 20 from the container 10 would reduce the air pressure in the cavity 16 (thereby creating a vacuum). Therefore, allowing air to enter through the vent passage 36 prevents such a vacuum from forming. This means that the stopper 20 can be more easily removed from the container 10 because the user does not need to apply additional force when removing the stopper 20 from the container 10 to overcome the force applied to the stopper 20 by the vacuum in the cavity 16.

[0040] The cross-section of the ventilation passages 36 is selected to be large enough to allow airflow through the ventilation passages 36 without obstruction (e.g., by frost / ice, as described in more detail in connection with FIG. 4 ), but narrow enough so that convective heating due to air ingress into the cavity 16 via the ventilation passages 36 is negligible. For example, the ventilation passages 36 may have a circular cross-section with a diameter of 6 mm or less. Limiting the diameter of the ventilation passages 36 limits convective heating due to air ingress into the cavity 16. Alternatively or additionally, the ventilation passages 36 may be formed in a zigzag, serpentine, or serpentine shape. This limits convective heating by increasing the path length of the ventilation passages 36.

[0041] Optionally, the vent passage 36 includes one or more valves (not shown in FIGS. 2 or 3) that reduce convection in the vent passage 36 while allowing air to enter and exit when the plug 20 is removed / inserted. The valves may also help control moisture in the vent passage 36 to prevent frost / ice buildup.

[0042] Figure 5 shows a plug 50 for insulating the interior of the container 10 shown in Figure 1 from the ambient environment. The plug 50 shown in Figure 5 is sized so that a portion of the plug 50 fits within the cavity 16 of the container 10. The plug 50 comprises a lower portion and an upper portion. The lower portion is positioned to fit within the cavity 16 defined by the container wall 12. The upper portion has a width greater than the width of the cavity 16 such that when the plug 50 is attached to the container 10 (as shown in Figure 3), the upper portion abuts the top of the wall 12 and covers the opening at the top of the cavity 16, thereby insulating the interior of the container 10 from the ambient environment.

[0043] 5-8B, the plug 50 includes multiple chambers 52. Each chamber, as best shown in FIGS. 5 and 8B, has a bottom, sidewalls, and an open top, creating a cavity (e.g., bucket-shaped) that houses multiple insulating sections 54 separated by spacers 55. According to the example shown in FIGS. 5 and 8B, each chamber 52 includes three insulating sections 54 and two spacers 55, with the spacers 55 positioned between adjacent insulating sections 54. However, more or fewer insulating sections 54 and spacers 55 are contemplated (e.g., using two insulating sections 54 with one spacer 55, using four insulating sections with three spacers 55, etc.). Stated differently, each chamber 52 includes alternate layers of insulating sections 54 and spacers 55. The chambers 52 are stacked on top of each other. As shown in FIGS. 5 and 7, the plug 50 includes four chambers in a stacked configuration. However, more or fewer chambers may be used (eg, two, three, five or more).

[0044] That is, each chamber 52 comprises alternating layers of insulating sections 54 and spacers 55 along the longitudinal axis of the plug 50, where the longitudinal axis is aligned with the direction in which the plug 50 is installed and / or removed from the container 10. Reflective shields 56 (not shown) may also be disposed on the top and bottom surfaces of each of the insulating sections 54. In this manner, the plug 50 effectively doubles the number of infrared radiation shields (e.g., a plug with two insulating sections 54 and one spacer 55 comprises four reflective shields 56). The upper insulating section 54' in the plug 50 shown in FIGS. 5, 6, and 8A is mounted on the top surface of the uppermost chamber 52 and positioned within the lid 58 of the plug 50.

[0045] As shown in FIGS. 5, 6, and 8B, the insulating section 54 is thicker (i.e., has a greater height) than the spacer 55. According to embodiments, the insulating section 54 has a thickness between 75 and 10 mm, while the spacer has a thickness between 75 and 1 mm. In one illustrated example, the insulating section 54 is approximately 25 mm thick, while the spacer 55 is approximately 1 mm thick. Note that in alternative embodiments, the spacer 55 and the insulating element 54 may have the same thickness, or the spacer 55 may be thicker than the insulating element 54. The thickness of the spacer 55 and / or the insulating element 54 may also vary along the length of the plug 50. In one example, the thickness of the insulating element 54 decreases along the length of the plug 50, reaching a minimum value for the insulating element 54 furthest from the lid 58.

[0046] As further shown in FIG. 5 , at least one rod 57 is positioned through the plurality of chambers 52 (and thus through the corresponding insulating sections 54, spacers 55, and reflective shields 56). The rod 57 provides structural support to each of the plurality of chambers 52 to ensure that the plurality of chambers 52 (and thus the corresponding insulating sections 54, spacers 55, and reflective shields 56) are secured together. The rod may be made of any suitable material (e.g., a polymer) that provides sufficient strength to hold the chambers 52 in a stacked configuration. Preferably, the rod is thin and made of a material with low thermal conductivity. Alternatively, the rod 57 may be omitted, and the stacked chambers may be secured to each other through other means (e.g., adhesive).

[0047] The chamber may be formed from an insulating material (i.e., a material with low thermal conductivity and low thermal mass) such as foam. One or more of the insulating sections 54 may comprise closed-cell foam, aerogel, and / or one or more vacuum or partial vacuum cavities. In a preferred embodiment, the container is formed from an insulating material that is easily machinable, such as low-density Styrofoam.

[0048] The insulating sections 54 may be formed from an insulating material (i.e., a material with low thermal conductivity and low thermal mass), such as foam. One or more of the insulating sections 54 may comprise closed-cell foam, aerogel, and / or one or more cavities with a vacuum or partial vacuum. The insulating sections 54 provide insulation between the cavity 16 of the container 10 and the ambient environment to slow heat transfer from the ambient environment to the cavity 16. Similarly, the spacers 55 may be made from an insulating material (i.e., a material with low thermal conductivity and low thermal mass), such as foam. One or more of the spacers 55 may comprise closed-cell foam, aerogel, and / or one or more cavities with a vacuum or partial vacuum.

[0049] The reflective shield 56 is formed from a material that reflects infrared radiation (i.e., a material with high reflectivity), such as metal foil. The reflective shield 56 reflects infrared radiation from the surrounding environment to prevent the infrared radiation from the surrounding environment from heating the cavity 16.

[0050] The plug 50 further comprises a fastener 53 for attaching a lid 58 of the plug 50 to the wall 12 of the container 10 (as shown in FIG. 7 ). The fastener 53 is attached to the lid 58, or to a portion of the lid 58. After the plug 50 is attached to the container 10, the fastener 53 is tightened. The fastener 53 tightens a seal at the interface between the upper portion of the plug 50 and the wall 12 of the container 10. Tightening the fastener 53 prevents air flow between the ambient environment and the interior of the cavity 16, which means that convective heating provided by ambient air is reduced.

[0051] The plug 50 further includes an upper seal 32 (best seen in FIGS. 5-7). The upper seal 32 is positioned under the lid 58 of the plug 50, as shown in FIGS. 6 and 7. As such, the upper seal 32 is compressed between the upper portion 24 of the plug 50 and the top of the wall 12 when the plug 50 is installed in the cavity 16. The upper seal 32 also prevents air from flowing between the ambient environment and the interior of the cavity 16, thereby reducing convective heating provided by ambient air.

[0052] As described in more detail below with reference to FIG. 11, the plugs 20, 40, 50 may optionally include an ultraviolet light source (not shown in FIGS. 2, 4, or 5).

[0053] As mentioned above, the plugs 20, 40, 50 are attached to the container 10 shown in Figure 1. Together, the container 10 and the plugs 20, 40, 50 form a transport system 38. As such, the transport system 38 includes the vacuum-insulated container 10 with the thermal mass 18 and the plugs 20, 40, 50 for insulating the interior of the container 10 from the ambient environment.

[0054] As discussed above, thermal mass 18 acts to slow the rate of temperature increase within cavity 16, providing passive cooling to a cryopreserved sample received within the opening. As a result, container 10 can hold, and particularly transport, cryopreserved samples without requiring the use of liquid nitrogen, thanks to the passive cooling provided by thermal mass 18. If liquid nitrogen is not used in container 10, transport system 38 does not need to provide a vent for evaporated liquid nitrogen. This means that a plug (such as plugs 20, 40, 50 shown in FIGS. 2, 4, and 5) can be used to insulate the interior of container 10 from the ambient environment.

[0055] The plugs 20, 40, 50 insulate the interior of the container 10 to prevent heat transfer from the ambient environment to the cavity 16 of the container 10. The insulation provided by the plugs 20, 40, 50 means that the cryopreserved samples can be maintained at cryogenic temperatures even when the transport system 38 is positioned on its side or upside down. That is, the plugs 20, 40, 50 act to retain cool air within the cavity 16 of the container 10 when the transport system 38 is positioned on its side or upside down by preventing heat transfer through the top of the container 10 (i.e., the end of the container opposite the base 14).

[0056] Figure 4 shows a plug 40 that is an alternative to the plug 20 shown in Figure 2. The plug 40 includes all of the components of the plug 20 shown in Figure 2, which are identified using the same reference numerals as used in Figure 2. The plug 40 can be attached to the container 10 shown in Figure 1 in the same manner as the plug 20 shown in Figure 2. In addition to the components of the plug 20 in Figure 2, the plug 40 shown in Figure 4 includes a chamber 42 in the path of the vent passageway 36.

[0057] The chamber 42 is located toward the top of the portion of the vent passage 36 that extends through the lower portion 22 of the plug 40. The chamber 42 is formed by drilling holes in the insulating section 26 and a portion of the reflective shield 28.

[0058] For ease of reference, the vent passageway 36 is shown in Figure 4 in two sections: a lower section 44 and an upper section 46. The lower section 44 of the vent passageway 36 extends between the chamber 42 and the cavity 16 (when the plug 20 is installed in the container 10). The upper section 46 of the vent passageway 36 extends between the chamber 42 and the ambient environment.

[0059] Air flows through the lower portion 44 of the vent passage 36 in the lower portion 22 of the plug and into the chamber 42 formed by the holes in the insulating section 26 and the reflective shield 28. The air then flows from the chamber 42 through the upper portion 46 of the vent passage to the ambient environment.

[0060] The chamber 42 forms in a location in the path of the vent passage 36 that is susceptible to frost / ice accumulation. Frost / ice accumulates within the vent passage 36 at locations where the air in the vent passage 36 is approximately 0°C. Frost / ice formation occurs in a specific zone of the vent passage 36. The chamber 42 forms in the zone where frost / ice accumulates (i.e., in the portion of the vent passage 36 where the air temperature in the vent passage 36 is 0°C). As such, the chamber 42 has an upper extent that communicates with an upper portion 46 of the vent passage 36 where the air temperature in the vent passage 36 is above 0°C, and a lower extent that communicates with a lower portion 44 of the vent passage 36 where the air temperature in the vent passage 36 is below 0°C. The portion of the vent passage 36 where the air temperature is approximately 0°C is located in the lower portion 22 of the stopper 40 when the interior of the container is cooled to cryogenic temperatures. During use, ambient temperatures may typically range from 5°C to 30°C. During use, the end of plug 20 within cavity 16 may typically be at a temperature ranging from −196° C. to −120° C. Within this temperature range, the region in vent passage 36 where the temperature is approximately 0° C. during use is relatively narrow, and chamber 42 may be positioned to coincide with this region.

[0061] That is, the chamber 42 is formed in the lower portion 22 of the plug 40. Specifically, the chamber 42 is located in the lower portion 22 of the plug and is in contact with the upper portion 24 of the plug 40. As shown in FIG. 4, the upper portion 24 of the plug 40 forms one wall of the chamber 42.

[0062] The chamber 42 has a larger cross-sectional area than the ventilation passage 36, which means that frost / ice that forms in the chamber 42 is less likely to cause a blockage in the ventilation passage 36.

[0063] FIG. 9 is a flow diagram of a method 500 for cooling a container for holding, and particularly for transporting, cryopreserved samples, such as the container 10 shown in FIG.

[0064] In step 502, a cryogenic fluid (in this example, liquid nitrogen) is poured into the cavity of the container. Heat is transferred from a thermal mass located within the cavity to the liquid nitrogen in the cavity. The liquid nitrogen thus cools the thermal mass in the cavity. Optionally, a plug (such as plugs 20, 40, 50 shown in FIGS. 2, 4, and 5) is removed from the container before the liquid nitrogen is poured into the cavity.

[0065] After the thermal mass has been cooled by the nitrogen (eg, after a period of approximately 0.5 to 1 hour), the liquid nitrogen is emptied from the void in step 504 .

[0066] The cavity can be pre-cooled by pouring liquid nitrogen into it. Pre-cooling the cavity reduces the amount of time that an alternative cooling source (such as a heat engine) is required to cool the interior of the vessel to cryogenic temperatures.

[0067] Optionally, in step 506, steps 502 and 504 are repeated to further reduce the temperature within the cavity. For example, these steps may be repeated if the thermal mass has not cooled to the desired temperature. That is, in step 506, additional liquid nitrogen is poured into the cavity to cool the thermal mass, followed by pouring from the cavity after a period of time. Additional cycles of pouring liquid nitrogen into the cavity and emptying it from cavity 16 may be performed until the cavity is cooled to the desired temperature. For example, additional cycles may be repeated until the thermal mass is cooled to a cryogenic temperature. Repeating these cycles further shortens (or even eliminates) the length of time an alternative cooling source is required to be used. In some examples, an appropriate amount of cryogenic fluid may be used in step 502 so that the temperature of cavity 16 reaches the desired temperature without repeating steps 502 and 504 (i.e., without step 506).

[0068] In some examples, cooling of cavity 16 may be achieved using a heat engine, such as a cryocooler (e.g., a Stirling cryocooler), i.e., without the addition or removal of cryogenic fluid. Alternatively, step 502 may be replaced by attaching a heat engine to vessel 10 to remove heat from cavity 16. Similarly, step 504 may be replaced by removing the heat engine from vessel 10.

[0069] Optionally, in step 508, a stopper (such as stopper 20, 40, 50 shown in FIGS. 2, 4, 5) is attached to the container to prevent heat transfer from the ambient environment to the cooled thermal mass. Attaching the stopper to the container slows the rate of temperature rise within the container. Therefore, the stopper may be attached to the container until the cryopreserved sample is ready to be loaded into the container.

[0070] FIG. 10 is a flow diagram of a method 600 of preparing a transport system for holding, and specifically transporting, cryopreserved samples, such as the transport system 38 shown in FIG. 3 or the transport systems implementing the plugs of FIGS. 4, 5, and 11.

[0071] In step 602, a cavity of a container (such as container 10 shown in FIG. 1) for holding, and particularly transporting, a cryopreserved sample is cooled to cryogenic temperatures. For example, the container interior may be cooled using a heat engine (e.g., a Stirling cryocooler). Alternatively, the container interior may be cooled by performing the steps of method 500 described with reference to FIG. 9.

[0072] A cryopreserved sample is loaded into the container in step 604. For example, the cryopreserved sample can be placed into an opening in the thermal mass 18 of the container 10 of FIG.

[0073] Optionally, in step 606, a heat engine (in this example, a Stirling cryocooler) is attached to the container 10 to remove heat from the cavity so that the cryopreserved samples are maintained at an appropriate cryogenic temperature. The Stirling cryocooler may remain attached to the container 10 until the cryopreserved samples are transported to or stored at a different location. The Stirling cryocooler may be attached to the container 10 to withstand temperature increases within the container 10 that occur during loading of the cryopreserved samples into the container.

[0074] If a heat engine, such as a Stirling cryocooler, is installed in the container 10 to maintain the cryopreserved samples at extremely low temperatures, the heat engine is removed in step 608 prior to transporting or storing the cryopreserved samples.

[0075] In step 610, a stopper (such as stopper 20 shown in Figures 2, 4, 5, and 11) is attached to container 10 to insulate the interior of the container from the ambient environment and to prevent heat transfer from the ambient environment to the cryopreserved sample. Attaching the stopper to the container forms transport system 38.

[0076] In step 612, the transport system 38 containing the cryopreserved sample is sent for transportation or storage.

[0077] Figure 11 illustrates an apparatus 70 for sterilizing a container for holding, and particularly for transporting, cryopreserved samples, such as the container 10 illustrated in Figure 1. The container 10 illustrated in Figure 11 includes all of the components of the container 10 illustrated in Figure 1 (i.e., the wall 12, the base 14, the cavity 16, and the thermal mass 18). The apparatus 70 also includes a cartridge 72. The cartridge 72 is sized so that a portion of the cartridge 72 fits within the open end of the container 10, while another portion of the cartridge 72 is positioned to abut the edge of the container wall 12 at the open end of the container 10.

[0078] Cartridge 72 includes an ultraviolet light source 74, such as a 60 W fluorescent tube bulb. Alternatively, ultraviolet light source 74 can be a single LED (e.g., a 5 W LED) or an array of LEDs (e.g., three 2 W LEDs). Ultraviolet light source 74 emits ultraviolet light in the UVC range or at the lower end of the UVB range.

[0079] For example, the ultraviolet light source 74 may emit ultraviolet light at a wavelength between 100 nm and 300 nm. In a particular example, the ultraviolet light source 74 may emit ultraviolet light having a wavelength of 295 nm.

[0080] In the device shown in FIG. 11 , the ultraviolet light source 74 is powered by a battery 76 located in the cartridge 72. The ultraviolet light source 74 is controlled using a switch 78 that is accessible when the cartridge 72 is inserted into the open end of the container 10. Alternatively or additionally, a power supply unit may be installed in the container 10. The power supply unit is connectable to an electrical outlet. The cartridge 72, when installed in the container 10, can form an electrical connection with the power supply unit. This electrical connection can preferably be via a pogo pin, via a connection typically found in a kettle, or via any other suitable connector, which allows for easy making and breaking of the electrical connection. Alternatively or additionally, the cartridge 72 can be directly connected to an electrical outlet.

[0081] Attaching cartridge 72 to container 10 allows ultraviolet light to illuminate the interior of cavity 16 of container 10. Irradiating cavity 16 of container 10 with ultraviolet light sterilizes cavity 16. Sterilizing container 10 prevents contamination of the biological sample from several contaminants. For example, the biological sample is prevented from being contaminated with bacteria, viruses, fungi, and other microorganisms, as well as DNA, RNA, and cellular debris from biological samples previously held within container 10.

[0082] Cartridge 72 may include one or more insulating sections (not shown in FIG. 11 ) to prevent or slow heat transfer between the ambient environment and the interior of cavity 16 while cavity 16 is being sterilized. Cartridge 72 also includes a seal 80 positioned under a portion of cartridge 72 that abuts the edge of wall 12 of container 10. Optionally, cartridge 72 may include some of the components of stopper 20 shown in FIG. 2 (or stoppers 40, 50 shown in FIGS. 4 and 5 ) to insulate the interior of the container from the ambient environment while it is being sterilized. For example, cartridge 72 may include one or more of insulating section 26, reflective shield 28, fastener 30, flexible seal 34, vent passage 36, and chamber 42 shown in FIGS. 2 and 4 , or chamber 52, insulating section 54, spacer 55, reflective shield 56, lid 58, flexible seal 34 shown in FIG. 5 . As a further example, cartridge 72 may have the same structure as stopcock 20 shown in Figure 2 (or stopcocks 40, 50 shown in Figures 4 and 5) and may further include ultraviolet light source 74 (and, optionally, battery 76 and switch 78). Alternatively, cartridge 72 may be integrally coupled to or formed with the heat engine.

[0083] FIG. 12 shows the underside of cartridge 82, a variation of cartridge 72 just described. Cartridge 82 includes at least one fastener 88, a seal 80, and at least one ultraviolet light source 86 to perform the same functions as previously described with respect to cartridge 72. However, in this variation, multiple ultraviolet light sources 86 are positioned within a central region of cartridge 82, as shown. In the particular embodiment depicted, eight ultraviolet light sources 86 are incorporated into cartridge 82. Specifically, two ultraviolet light sources 86 are positioned approximately near the center, while the other six ultraviolet light sources 86 are positioned in a circumferential pattern or a radial pattern further toward the periphery of cartridge 82. The circumferentially or radially positioned ultraviolet light sources 86 may be angled to direct light toward the center of container 10 during use. In one particular example, the six ultraviolet light sources 86 may be angled inward at a tilt angle of approximately 30 degrees, which provides an optimal focus of light on container 10.

[0084] As with the embodiment of FIG. 11, cartridge 82 is sized so that a portion of cartridge 82 fits within the open end of container 10, while another portion of cartridge 82 is positioned to abut the edge of container wall 12 at the open end of container 10.

[0085] The cartridge 82 includes an ultraviolet light source 86, such as an LED (e.g., a 5W LED or a 2W LED), that emits ultraviolet light in the UVC range or at the lower end of the UVB range.

[0086] For example, the ultraviolet light source 86 may emit ultraviolet light at a wavelength between 100 nm and 300 nm. In a particular example, the ultraviolet light source 86 may emit ultraviolet light having a wavelength of 295 nm.

[0087] In the device shown in FIG. 12 , the ultraviolet light source 86 is powered by a battery located in the cartridge 82. Alternatively or additionally, a power supply unit may be installed in the container 10. The power supply unit is connectable to an electrical outlet. When installed in the container 10, the cartridge 82 can form an electrical connection with the container 10 via a connector 84. This electrical connection can preferably be via a pogo pin, a connection typically found in a kettle, or any other suitable connector, which allows for easy making and breaking of the electrical connection. In one particular example, the connector 84 includes ground and voltage connections and a serial communication interface (e.g., RS232) that allows bidirectional communication between the electrical components in the cartridge 82 and the electrical components within the container 10, as will be discussed further below.

[0088] Attaching cartridge 82 to container 10 allows ultraviolet light to be irradiated into the interior of cavity 16 of container 10. Irradiating the interior of cavity 16 of container 10 with ultraviolet light sterilizes cavity 16. Sterilizing container 10 prevents contamination of the biological sample from several contaminants. For example, the biological sample is prevented from being contaminated with bacteria, viruses, fungi, and other microorganisms, as well as DNA, RNA, and cellular debris from biological samples previously held within container 10.

[0089] Cartridge 82 may include one or more insulating sections (not shown in FIG. 12 ) to prevent or slow heat transfer between the ambient environment and the interior of cavity 16 while cavity 16 is being sterilized. Cartridge 82 also includes a seal 80 positioned under a portion of cartridge 82 that abuts the edge of wall 12 of container 10. Optionally, cartridge 82 may include some of the components of stopper 20 shown in FIG. 2 (or stoppers 40, 50 shown in FIGS. 4 and 5 ) to insulate the interior of the container from the ambient environment while it is being sterilized. For example, cartridge 82 may include one or more of insulating section 26, reflective shield 28, fastener 30, flexible seal 34, vent passage 36, and chamber 42 shown in FIGS. 2 and 4 , or chamber 52, insulating section 54, spacer 55, reflective shield 56, lid 58, flexible seal 34 shown in FIG. 5 . As a further example, cartridge 82 may have the same structure as plug 20 shown in Figure 2 (or plugs 40, 50 shown in Figures 4 and 5) and may further include ultraviolet light source 86 (and, optionally, battery 76). Alternatively, cartridge 82 may be integrally coupled to or formed with the heat engine.

[0090] When coupled to the container 10, the cartridges 72, 82 are in electrical communication with the container 10 (e.g., through connector 84). In embodiments, the container 10 and cartridges 72, 82 each include at least one sensing element and at least one controller. By way of non-limiting example, the container may include a sensing element that measures temperature (e.g., a thermistor) and a sensing element that measures light (e.g., a UV sensor to measure how much light the cartridge emits), while the cartridges 72, 82 may include sensing elements to measure voltage, current, etc. The controller in each of the container 10 and cartridges 72, 82 may include at least one memory for recording signals from the sensing elements and for recording calculations made by the processor (e.g., deriving a power output based on the sensed voltage and current outputs). The memory units may each store a unique identification code so that each cartridge and each container can be individually identified. Furthermore, the container 10 and cartridges 72, 82 may each include a GPS system so that their locations can be monitored.

[0091] Each of the container 10 and cartridges 72, 82 may include a transceiver for wirelessly transmitting information stored in the memory of the respective controller. The transceiver can transmit the information to a remote location so that the information can be remotely recorded and monitored. By way of example, a central monitoring station can receive GPS and / or sensed and / or calculated information stored on the container 10 and cartridges 72, 82 to have real-time information regarding the container 10, the thermal mass 18, and the UV sterilization treatment the container 10 has undergone.

[0092] By insulating cavity 16 from the surrounding environment, container 10 can be sterilized while a cryogenic temperature is maintained in cavity 16. This means that the requirement to cool container 10 after sterilization with ultraviolet light sources 74, 86 can be reduced or even eliminated.

[0093] The reduced amount of time required to cool the container 10 after sterilization further reduces the amount of time required to prepare the container 10 for subsequent use in holding, and specifically transporting, cryopreserved samples, which means that the amount of time the container 10 is out of operation during transport or storage is reduced.

[0094] The ultraviolet light source also includes features (e.g., features of the stopper shown in Figures 2, 4, and 5) that act to insulate the interior of container 10 from the ambient environment, so that the interior of cavity 16 can be sterilized while the cryopreserved sample is being transported or stored. Specifically, including an ultraviolet light source in a stopper used to insulate the interior of container 10 from the ambient environment eliminates the requirement to remove the stopper to attach a separate device for sterilizing container 10. Incorporating an ultraviolet light source into a stopper used to insulate the interior of container 10 from the ambient environment also seals container 10 such that the sterility of container 10 is maintained after the interior of container 10 is irradiated with ultraviolet light.

[0095] If the interior of cavity 16 is to be sterilized while the cryopreserved sample is being transported or stored, the cryopreserved sample may be kept in a vial or container that is opaque to ultraviolet light, or the cryopreserved sample may otherwise be shielded from ultraviolet light from the ultraviolet light source. Shielding the cryopreserved sample from ultraviolet light ensures that the cryopreserved sample is not damaged by ultraviolet radiation.

[0096] Alternatively, if the cryopreserved sample is a sample requiring sterilization (such as a blood product), the cryopreserved sample can be sterilized simultaneously with cavity 16 when the sample is exposed to ultraviolet light within cavity 16.

[0097] Figure 13 is a flow diagram of a method 800 for sterilizing a container for holding, and particularly for transporting, a cryopreserved sample, such as the container 10 shown in Figure 1. The container 10 may be part of a transport system, such as the transport system 38 shown in Figure 3 (or the transport system 38 with a bung of Figures 4 or 5). The interior of the transport system container 10 may be insulated from the ambient environment using a bung (such as the bung 20 shown in Figure 2, the bung 40 shown in Figure 4, or the bung 50 shown in Figure 5) or may be coupled to a Stirling cryocooler. Method 800 may be performed using the apparatus 70 shown in Figure 11.

[0098] Optionally, in step 802, if a bung or cryocooler is attached to the vessel to form a transport system, the transport system is opened to expose the interior of the vessel. Thus, opening the vessel may include removing a bung, Stirling cryocooler, or any other device attached to the open end of the vessel.

[0099] In step 804, a cartridge with an ultraviolet light source is attached to the container such that the open end of the container is closed with the cartridge. By attaching the cartridge with the ultraviolet light source to the container, the ultraviolet light source is positioned to irradiate the interior of the container.

[0100] In step 806, the ultraviolet light source in the cartridge is activated such that the interior of the container is illuminated with ultraviolet light.

[0101] In step 808, the interior of the container is irradiated with ultraviolet light for a sufficient length of time to ensure that the interior of the container is sterilized. For example, the interior of the container may be irradiated with ultraviolet light for 30 to 60 minutes.

[0102] In step 810, the ultraviolet light source is deactivated and the cartridge is removed from the container.

[0103] Optionally, in step 812, a container is prepared to hold, and specifically transport, the cryopreserved sample. For example, the container may be prepared by performing the steps of method 600 described with reference to Figure 10. The requirement to cool the container in step 602 of method 600 may be reduced or eliminated because the container may be sterilized while the cryogenic temperature is maintained in the container cavity.

[0104] Figure 14 is a flow diagram of an additional method 900 of preparing a transport system for holding, and specifically transporting, a cryopreserved sample, such as transport system 38 shown in Figure 3 (or transport system 38 including a bung of Figures 4 or 5). The transport system may include a container (such as container 10 shown in Figure 1) and a bung (such as bung 20 shown in Figure 2, bung 40 shown in Figure 4, or bung shown in Figure 5).

[0105] In step 902, a cryopreserved sample is loaded into the container. For example, the cryopreserved sample may be placed into an opening in the container 10. Loading the cryopreserved sample into the container may include positioning the cryopreserved sample in a receptacle that is opaque to ultraviolet light.

[0106] In step 904, a stopper is attached to the container to insulate the interior of the container from the ambient environment and to prevent heat transfer from the ambient environment to the cryopreserved sample. The stopper and / or components of the container may include an ultraviolet light source. Attaching the stopper to the container forms a transport system.

[0107] In step 906, the transport system containing the cryopreserved sample is sent for transportation or storage.

[0108] In step 908, the interior of the container is irradiated with ultraviolet light to sterilize the container. The ultraviolet light may have a wavelength between 100 nm and 300 nm (e.g., approximately 265-275 nm). The interior of the container may be sterilized using an ultraviolet light source positioned on a closure used to insulate the interior of the container from the surrounding environment. Alternatively or additionally, the walls and / or base of the container (or some other component of the container, such as thermal mass 18 of container 10 shown in FIG. 1) may include an ultraviolet light source used to irradiate the interior of the container. Thus, sterilizing the container with ultraviolet light may include activating an ultraviolet light source positioned on the closure and / or a component of the container.

[0109] The interior of the container can be irradiated with ultraviolet light for 30 to 60 minutes (e.g., if the container is only sterilized once during transport or storage), or for approximately 10 minutes (e.g., if the container is sterilized daily during transport or storage of cryopreserved samples). Sterilizing the container for a short period of time each day during transport or storage of cryopreserved samples can ensure that the samples are not contaminated during transport or storage.

[0110] The sterilization cycle is completed in step 910. Completing the sterilization cycle may include deactivating ultraviolet light sources positioned on the stopper and / or container components.

[0111] FIG. 15 is a graph showing the temperature change over time for a delivery system with the plug shown in FIG. 2 (lower line) compared to the temperature change over time for a delivery system without the plug in place (upper line).

[0112] It can be seen from Figure 16 that fitting the plug shown in Figure 2 to the container provides a longer period of time during which the interior of the container is at a cryogenic temperature. The cryogenic zone is between -200°C and -120°C. Fitting the plug shown in Figure 2 to the container can maintain a cryogenic temperature inside the container for up to 8 days, while a container without the plug only provides cryogenic temperatures for 3 days.

[0113] 2 to the container allows the cryopreserved sample to be transported and / or stored for a longer period of time without being damaged by exposure to temperatures outside the cryogenic zone. Allowing the cryopreserved sample to be stored, and in particular transported, for a longer period of time increases the distance the cryopreserved sample can be transported, thereby increasing the number of patients that can be treated with cryopreserved samples from a particular source.

[0114] Variations or improvements to the systems and methods described herein are set forth in the following paragraphs.

[0115] The apparatuses 70, 82 shown in Figures 11 and 12 are described with respect to sterilizing a container 10 that includes a thermal mass 18. As previously explained, the thermal mass 18 provides passive cooling to a sample held within the container 10 by slowing the rate of temperature rise within the cavity 16 of the container 10. However, the methods and apparatus described herein are not limited to sterilizing containers that include a thermal mass. That is, the methods and apparatus described herein may be used to sterilize containers in which samples held within the container are cooled using other means. In particular, an ultraviolet light source may be used to sterilize a transport system in which a heat engine, such as a Stirling cryocooler, is used to provide cooling to a sample held within the container.

[0116] In transport systems where a heat engine (such as a Stirling cryocooler) is used to maintain the sample at cryogenic temperatures, the Stirling cryocooler can be positioned in a lid that can be attached to the vessel, and a heat exchanger can be attached to the Stirling cryocooler so that it is positioned within the vessel cavity when the lid is attached to the vessel.

[0117] The container may contain liquid nitrogen (or other working fluid) to provide cooling to the cryopreserved samples. A Stirling cryocooler removes heat from the container, meaning that the liquid nitrogen is maintained in its liquid state to maintain the extremely low temperature within the container. One or more ultraviolet light sources may be positioned under the lid so that the cavity of the container can be illuminated with ultraviolet light while the cavity is being cooled by the Stirling cryocooler. Alternatively (as described further below), the ultraviolet light source may be positioned inside the container.

[0118] By positioning one or more ultraviolet light sources under the lid or inside the container, the container can be sterilized while the Stirling cryocooler is operating. Sterilizing the container with UV light decontaminates all components within the container. That is, sterilizing the container sterilizes the solid components of the container itself, the liquid nitrogen used as the working fluid, and the air or other gases within the container's voids. This allows the container to be sterilized during transport or storage in a transportation system that includes a heat engine.

[0119] 11 and 12, the cryopreserved samples may be kept in a vial or container that is opaque to ultraviolet light or may otherwise be shielded from the ultraviolet light from the ultraviolet light source. A method of preparing a transport system with a Stirling cryocooler may be substantially the same as method 900 described in connection with Figure 14. However, instead of attaching a stopper to the container (as described in step 904 in Figure 14), a lid that includes a Stirling cryocooler (and optionally a ultraviolet light source) is attached to the container.

[0120] The apparatus 70 shown in Figure 11 is described with respect to sterilizing containers at cryogenic temperatures. However, it is understood that the apparatus 70 shown in Figure 11 allows for sterilization of containers regardless of the temperature of the container. Specifically, the apparatus 70 shown in Figure 11 is capable of sterilizing containers that are at room temperature.

[0121] Cartridge 72 is described above as having a portion that is positioned to fit within the open end of container 10. However, other arrangements for illuminating the interior of the container using the ultraviolet light source may be used. For example, the ultraviolet light source may be positioned in a lid that sits on top of the container. As a further example, an optical fiber or light guide may be used to transmit the ultraviolet light to the interior of the container, meaning that it may not be necessary to cover the container with a lid to illuminate the interior of the container.

[0122] As an additional example, the ultraviolet light source may be located in a separate cartridge that can be placed inside the container. Alternatively, as previously described, the ultraviolet light source may be located in a closure, such as closure 20 shown in FIG. 2, closure 40 shown in FIG. 4, or closure 5. As a further alternative, the ultraviolet light source may be located in a lid that includes a heat engine (as described above), whereby ultraviolet light can be used to sterilize the container while the interior of the container is cooled to cryogenic temperatures.

[0123] Additionally or alternatively, the ultraviolet light source may be provided on or in the main body of the container (e.g., on or in a wall and / or on or in the base of the container), or may be provided within a component of the container, such as thermal mass 18 of container 10 shown in FIG. 1. Such an arrangement is shown in FIG. 16, which shows an alternative apparatus 100 for sterilizing containers for holding, and particularly for transporting, cryopreserved samples (i.e., an alternative to apparatus 70 shown in FIG. 11). However, it should be noted that an apparatus for sterilizing containers for holding, and particularly for transporting, cryopreserved samples according to the methods described herein may include ultraviolet light source 74 of apparatus 70 shown in FIG. 11 in addition to ultraviolet light source 104 of apparatus 100 shown in FIG. 16.

[0124] The device 100 shown in Figure 16 includes a plug 102 (or other closure) for closing the open end of the container 10. An ultraviolet light source 104 is positioned inside the wall 12 of the container 10 so as to be positioned within the cavity 16 of the container 10. This means that the ultraviolet light source 104 is positioned to irradiate the interior of the container 10. The ultraviolet light source 104 is powered by a battery 106 located within the wall 12 of the container 10. The ultraviolet light source 104 is controlled using a switch 108 positioned on the outside of the wall 12 of the container 10.

[0125] The interior of the container can be sterilized while it is being warmed by placing an ultraviolet light source on or in the main body of the container or a component of the container. Sterilization of the container during the warming process may be facilitated by positioning the ultraviolet light source in a lid or cartridge that does not provide insulation so that heat transfer from the ambient environment to the interior of the cavity is permitted through the lid.

[0126] If the ultraviolet light source is located on or in the main body of the container or in a component of the container, the sterilization method 800 described in connection with FIG. 13 may be adapted accordingly. Specifically, the method does not require removing a stopper or other device from the container to allow a separate cartridge to be attached. This means that the interior of the container can be irradiated while an insulating stopper (such as the stopper shown in FIGS. 2, 4, and 5, generally shown as stopper 102 in FIG. 16) is attached to the container or while a heat engine is installed on the container. Consequently, the method includes activating an ultraviolet light source in the main body of the container or a component of the container to irradiate the interior of the container with ultraviolet light. The method further includes irradiating the interior of the container with ultraviolet light for a sufficient length of time to ensure that the interior of the container is sterilized. Once the interior of the container is sterilized, the ultraviolet light source can be deactivated. Sterilizing the interior of the container in this manner means that the container can be sterilized while it is being cooled (e.g., from ambient temperature to cryogenic temperature), while it is being warmed (e.g., from cryogenic temperature to ambient temperature), or while it is between uses (e.g., while the interior of the container is at ambient temperature), or while the interior of the container is in transit (e.g., while the interior of the container is at cryogenic temperature).

[0127] Optionally, device 70 shown in Figure 11 and / or device 100 shown in Figure 16 may include multiple ultraviolet light sources. The ultraviolet light sources may be located in the same component of the device (e.g., multiple ultraviolet light sources positioned in the cartridge) or in different components of the device (e.g., one or more ultraviolet light sources positioned in the cartridge and one or more ultraviolet light sources positioned in the wall of the container).

[0128] When multiple ultraviolet light sources are used in the device, each ultraviolet light source may emit ultraviolet light of a different wavelength, such that a range of ultraviolet wavelengths is used during sterilization of the container.

[0129] When multiple ultraviolet light sources are used in the device, certain portions of the ultraviolet light sources may be activated to provide different intensities of ultraviolet light to different portions of the container. For example, the ultraviolet light sources may be controlled so that only a portion of the interior of the container is irradiated. By irradiating a portion of the interior of the container, the interior of the container can be sterilized without irradiating the cryopreserved sample. In some examples, multiple ultraviolet light sources may be positioned to increase sterilization of a portion of the base facing the cavity relative to other surfaces of the container facing the cavity.

[0130] Optionally, the plurality of ultraviolet light sources may comprise optical fibers or light guides that transmit the ultraviolet light to the interior of the container. Using optical fibers or light guides to transmit the ultraviolet light to the interior of the container minimizes heat provided to the interior of the container.

[0131] As previously described, the interior of the container may be positioned to reflect ultraviolet light such that it is illuminated by reflection of the ultraviolet light from the walls and / or base of the container. Additionally or alternatively, the ultraviolet light sources may be positioned within the device such that the entire interior of the container has a direct line of sight to one or more of the ultraviolet light sources.

[0132] The ultraviolet light source may be powered by an electrical connection to the power grid or by battery operation (as in devices 70, 82 shown in Figures 11 and 12, and device 100 shown in Figure 16).

[0133] Optionally, the ultraviolet light source used in the device can be controlled using an automatic timer. For example, the ultraviolet light source can be controlled so that the interior of the container is irradiated for 10 minutes per day during transport or storage of the cryopreserved sample. Alternatively, the ultraviolet light source can be manually controlled (e.g., the device can include a control that allows the user to turn individual ultraviolet light sources on or off). Manual control can be facilitated using a switch (as in device 70 shown in FIG. 11 and device 100 shown in FIG. 16). As a further alternative, the ultraviolet light source can be remotely controllable, meaning that the container can be sterilized remotely. To enable remote control of the ultraviolet light source, the device can include a wireless transceiver arranged to receive irradiation control commands from a remote device.

[0134] Optionally, the overall illumination from the ultraviolet light sources can be adjusted by adjusting the power supplied to the ultraviolet light sources according to requirements. For example, supplying additional power to the ultraviolet light sources can increase the intensity of the ultraviolet light provided by each individual ultraviolet light source. Additionally or alternatively, if only a portion of the ultraviolet light sources are activated when a smaller amount of power is supplied, the additional ultraviolet light sources can be activated by supplying additional power to the ultraviolet light sources.

[0135] The adjustment of the total irradiance may be manual (e.g., the device may include a control that allows a user to adjust the total irradiance provided), or alternatively, the adjustment of the total irradiance may be automatic (e.g., the device may include a timer that controls the total irradiance provided by the ultraviolet light source over time).

[0136] The total irradiance from the ultraviolet light sources may alternatively be adjusted by adjusting the irradiation time of the ultraviolet light sources (i.e., the length of time each ultraviolet light source is on). Adjustments to the irradiation time of the ultraviolet light sources may be manual (e.g., the device may include a control that allows a user to adjust the irradiation time) or automatic (e.g., using a timer). As a further alternative, the total irradiance provided by the ultraviolet light sources may be remotely controllable.

[0137] In addition to or as an alternative to adjusting the irradiation time and / or power, the wavelength of the ultraviolet light provided by the ultraviolet light source may also be adjustable. If the ultraviolet light source is automatically controlled, the function of the ultraviolet light source may be recorded remotely.

[0138] Optionally, the irradiation provided by the ultraviolet light source may be recorded. Recording the irradiation provided by the ultraviolet light source provides a record of the sterilization provided by the ultraviolet light source so that an operator can verify whether the container has been sterilized. The irradiation provided by the ultraviolet light source may be recorded by one or more ultraviolet detection devices located within the container.

[0139] Optionally, the device may include an alarm that provides an audible warning when the ultraviolet light source is on. Alternatively or additionally, the device may include a warning light that is illuminated when the ultraviolet light source is on.

[0140] Optionally, the ultraviolet light source may be turned off if the transport system is opened during an irradiation cycle. To turn off the ultraviolet light source when the transport system is opened, the connection between the container and the bung or lid is arranged so that a switch in series with the ultraviolet light source is closed when the lid, bung, or cartridge is attached to the container, thereby interrupting the circuit when the lid, bung, or cartridge is removed from the container. Alternatively, a user may be prevented from opening the transport system while the ultraviolet light source is on. For example, a bung, lid, or cartridge attached to the container may be locked (e.g., automatically locked) to the container while the ultraviolet light source is activated. That is, a switch controlling the ultraviolet light source may control a locking mechanism that locks the bung, lid, or cartridge to the container while the ultraviolet light source is on.

[0141] Optionally, the ultraviolet light source is positioned within the transport system so that the user is not exposed to ultraviolet light if the transport system is opened during an irradiation cycle. For example, a power supply unit may be installed in the container. The power supply unit is connectable to an electrical outlet. When the cartridge is installed in the container, an electrical connection can be made with the power supply unit. This electrical connection can preferably be made via a pogo pin, a connection typically found in a kettle, or any other suitable connector, which allows for easy making and breaking of the electrical connection. When the cartridge is removed from the container (i.e., lifted), the electrical connection can be broken so that the ultraviolet light is automatically turned off. Alternatively or additionally, a light sensor (using a different frequency of light than the ultraviolet light used for sterilization) may allow for control of the ultraviolet light so that it operates only in dark environments.

[0142] Optionally, the device comprises a detection device arranged to detect whether a lid, bung or cartridge is removed from the container during an irradiation cycle, and if the detection device detects that the container has been opened, the detection device may send a signal to a controller of the ultraviolet light source so that the ultraviolet light source may be deactivated.

[0143] In some instances, the thermal mass may not be included in the container, and the plugs described herein are suitable for use with such instances.

[0144] In some examples, a plug for insulating the interior of a container from the surrounding environment may include an insulating section and one or more shields for reflecting infrared radiation. In these examples, the insulating section may be relatively thick. For example, the insulating section may extend along a majority of the longitudinal extent of the plug.

[0145] The one or more shields for reflecting infrared insulation may be positioned adjacent to the insulating section, for example, above the insulating section during use (i.e., further from the container cavity than the insulating section). Because infrared radiation increases with temperature (proportional to temperature as a power of four), locating the one or more shields far from the cavity, i.e., where the temperature is typically higher, may be most important for reflecting infrared radiation.

[0146] The singular terms "a" and "an" should not be understood to mean "only one." Rather, they should be understood to mean "at least one" or "one or more," unless otherwise stated. The word "comprises" and derivatives containing "comprises" include each of the stated features but do not exclude the inclusion of one or more additional features.

[0147] The above implementations have been described by way of example only, and the described implementations are to be considered in all respects as illustrative only and not restrictive. It will be understood that modifications of the described implementations may be made without departing from the scope of the invention. Many variations not described will become apparent which are within the scope of the appended claims. [Explanation of symbols]

[0148] 10 containers 12 Wall 14 Base 16 blank spaces 18 Thermal Mass 20 stoppers 22 Lower part 24 Upper part 26 Insulation Classification 28 Reflective shield 30 Fasteners 32 Upper seal 34 Flexible Seal 36 Ventilation passage 40 stopper 42 rooms 44 Lower part 46 Upper part 50 stoppers 53 Fasteners 54 Insulation classification, insulation element 54' Upper insulation section 55 spacer 56 Reflective shield 57 Bar material 58 Lid 70 equipment 72 cartridges 74 Ultraviolet light source 76 Batteries 78 Switch 80 stickers 82 Cartridges, devices 84 connectors 86 Ultraviolet light source 88 Fasteners 100 devices 102 Stopper 104 Ultraviolet light source 106 Batteries 108 Switch

Claims

1. 1. A plug for insulating the interior of a container from the ambient environment, comprising: A plurality of insulation sections; one or more shields for reflecting infrared radiation; Equipped with wherein the one or more shields for reflecting infrared radiation are disposed between adjacent ones of the plurality of insulating sections such that the insulating sections and the one or more shields are provided in alternating layers.

2. 10. The stopper of claim 1, further comprising a first portion and a second portion, the first portion being positioned to be inserted into the container when the stopper is attached to the container.

3. 3. The stopper of claim 2, further comprising one or more seals arranged to be compressed between the second portion and an edge or interior wall of the container when the stopper is attached to the container.

4. 4. The plug of claim 2 or 3, further comprising a fastener arranged to attach the second portion to a wall of the container.

5. A plug for insulating the interior of a container from the surrounding environment, comprising: A plurality of insulation sections; one or more shields for reflecting infrared radiation; Equipped with the one or more shields for reflecting infrared radiation are disposed between adjacent ones of the plurality of insulating sections; The plug further comprises a ventilation passageway passing through the plurality of insulating sections and the one or more shields, the ventilation passageway comprising one or more valves and a void space in the path of the ventilation passageway, the void space being located in a region of the ventilation passageway configured such that the temperature of the air in the ventilation passageway is 0 degrees Celsius during use.

6. 6. The plug of claim 1, further comprising one or more chambers, each of the chambers housing at least one of the plurality of insulating sections and at least one of the one or more shields for reflecting infrared radiation.

7. 7. The plug of claim 6, wherein each of the one or more chambers has a bottom and a sidewall to create a cavity, and at least two of the plurality of insulating sections and at least one of the one or more shields for reflecting infrared radiation are positioned within the cavity.

8. 8. The plug of claim 7, further comprising at least one spacer, each spacer being positioned between adjacent insulating sections in each of the cavities, and wherein the one or more shields for reflecting infrared radiation are positioned on a top and / or bottom surface of at least one of the plurality of insulating sections.

9. 9. The stopper of any one of claims 1 to 8, further comprising an ultraviolet light source of sufficient power to provide sterilization to the inside of the container during use.

10. 1. A transport system for holding cryopreserved samples, comprising: a vessel having a thermal mass; A plug for insulating an interior of a container from an ambient environment, the plug comprising a plurality of insulating sections and one or more shields for reflecting infrared radiation, the one or more shields for reflecting infrared radiation being disposed between adjacent ones of the plurality of insulating sections; A transportation system comprising:

11. 11. The transport system of claim 10, wherein the container comprises at least one sensor and at least one controller.

12. 12. The delivery system of claim 11, wherein the bung comprises at least one sensor and at least one controller.

13. 13. The delivery system of claim 12, wherein the stopcock comprises a connector, and the container is in electrical communication with the stopcock via a connection to the connector.

14. 14. The transport system of claim 12 or 13, wherein at least one of the bung and the container comprises a transceiver configured to wirelessly transmit information coming from at least one of the sensors.

15. 1. A method of preparing a transport system for holding a cryopreserved sample, comprising: loading a cryopreserved sample into a container; attaching a plug to the container to insulate the interior of the container from the ambient environment, the plug comprising: A plurality of insulation sections; one or more shields for reflecting infrared radiation; Equipped with the one or more shields for reflecting infrared radiation are disposed between adjacent ones of the plurality of insulating sections; A method comprising:

16. 16. The method of claim 15, further comprising the step of cooling the interior of the vessel to a desired temperature.

17. 17. The method of claim 16, wherein cooling the interior of the vessel to the desired temperature comprises attaching a heat engine to the vessel to remove heat from the interior of the vessel.

18. 17. The method of claim 16, wherein cooling the vessel comprises pouring a cryogenic fluid into the vessel and subsequently emptying the cryogenic fluid from the vessel.

19. 19. The method of claim 16, 17 or 18, wherein cooling the interior of the vessel comprises cooling a thermal mass within the vessel to the desired temperature.

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