Stopper and cooling method for insulating a container

Abstract

The present specification discloses a device in the form of a stopper for insulating the interior of a container from the surrounding environment, wherein the stopper comprises: a plurality of insulating segments; and one or more barriers for reflecting infrared radiation. A method for preparing a delivery system for maintaining a cryogenically preserved sample is disclosed, wherein the method comprises: loading the cryogenically preserved sample into a container such as a vacuum flask; and fitting the stopper into the container to insulate the interior of the container from the surrounding environment. A method for cooling a container such as a vacuum flask for maintaining the cryogenically preserved sample at a desired temperature is disclosed, wherein the method comprises: injecting a cryogenic fluid such as liquid nitrogen into the container to cool the interior of the container; and, when cooling has occurred at least partially, emptying the cryogenic fluid from the container.

Description

Technology Field

[0001] The present disclosure relates to a stopper device for insulating the interior of a container device from the surrounding environment, and a method for cooling the container. Background Technology

[0002] New cell and gene therapies are successfully treating various cancers. There is a global demand for these treatments. Patients are often located in countries different from where the cells are produced, which means that biological materials, such as tissues and cells, are frequently frozen at cryogenic temperatures (e.g., below -120°C) to ensure storage and transport. Cryogenic freezing is used because cells do not survive long enough to be suitable for treatment when cooled. Biological materials must be maintained at cryogenic temperatures during transport.

[0003] Therefore, cell samples must be transported at cryogenic temperatures. The conventional method for transporting cell samples at cryogenic temperatures utilizes a "dry shipper." A dry shipper is a vacuum-insulated storage container (or "Dewar") containing zeolite material. The zeolite material absorbs liquid nitrogen (at -196°C), providing a low-temperature source for the cell samples being transported within the dry shipper. The absorption of liquid nitrogen by the zeolite prevents the liquid nitrogen from spilling or splashing out of the container. Because nitrogen continuously evaporates from the zeolite, the dry shipper maintains a constant temperature of -196°C for several days. Dry shippers typically provide a cryogenic standby period of 4 to 10 days before being preheated to ambient temperature.

[0004] Conventional dry shippers pose health and safety issues to transporters, airlines, and hospitals handling them. For example, the continuous evaporation of liquid nitrogen from zeolite poses a risk of suffocation to users because the evaporated nitrogen displaces oxygen from the surrounding environment. This risk of suffocation implies that dry shippers must be stored and transported with care.

[0005] Biological samples must be kept free from the risk of contamination during transport. However, there is a risk that biological samples may be contaminated by bacteria, viruses, fungi, and other microorganisms, as well as by DNA, RNA, and cell fragments from biological samples previously transported within the same shipping device. Biological samples may also be contaminated by the cooling medium (e.g., dry ice or liquid nitrogen) or by contamination from the surrounding environment. To minimize the risk of contamination, conventional dry shippers are often preheated to ambient temperature and cleaned between uses. Cleaning may involve covering the surface of the dry shipper with liquid cleaning products such as water, ethanol, methanol, or detergents, or gaseous cleaning reagents such as hydrogen peroxide, or a combination of these methods.

[0006] A delivery vessel for cryopreserved biological samples is described in WO 2018 / 115833, the entirety of which is incorporated herein by reference. One embodiment of the delivery vessel described in WO 2018 / 115833 comprises a thermal mass formed to at least partially contain, hold, or surround one or more cryopreserved samples. The thermal mass is used to slow down the rate of temperature change (increase) within the cavity of the delivery vessel. A heat exchanger is located within the cavity of the delivery vessel. The heat exchanger is attached to a Stirling cryogenic refrigerator located on the lid of the delivery vessel. The Stirling cryogenic refrigerator is used to remove heat from the cavity. The delivery vessel comprises a gravity thermal diode operable to provide cooling to the cavity in a first state and to impede heat transfer to the cavity in a second state. The use of the gravity thermal diode implies that the diode (and the delivery vessel accordingly) must be maintained in an upright position to maintain a temperature gradient between the top and bottom. For this reason, the lid of the shipping container may be equipped with a tilt sensor to ensure that the shipping container is maintained in an upright position.

[0007] However, during transport, it is not uncommon for delivery containers to fall sideways or be transported in an inverted position. This reduces the efficiency of the thermal diodes used in the delivery containers described in WO 2018 / 115833, which means there is a risk of biological sample loss due to the failure to maintain cryogenic temperatures during transport. For example, when a delivery container is placed sideways, the cryogenic source (previously positioned close to the base of the container) moves to be positioned along the side wall of the delivery container (i.e., closer to the periphery area at the top of the container). This reduces the cooling effect provided by the cryogenic source. Furthermore, given that the Stirling cryogenic freezer is part of the delivery container described in WO 2018 / 115833, the Stirling cryogenic freezer is also transported together with the biological samples when they are shipped. Shipping the Stirling cryogenic freezer increases costs. Additionally, some hospitals may not be aware of the requirement to switch on the Stirling cryogenic freezer to maintain cryogenic temperatures within the delivery container. If the Stirling cryogenic freezer is not switched on, the container may heat up to ambient temperature before biological samples are used, potentially leading to sample loss.

[0008] As previously mentioned, the thermal mass of the shipping vessel described in WO 2018 / 115833 is used to slow down the rate of temperature increase within the cavity of the shipping vessel. Due to its high specific heat capacity, the thermal mass takes a long time to cool from ambient temperature to cryogenic temperature. Therefore, after the shipping vessel is preheated to ambient temperature for cleaning, there is a long duration of the idle time (during which the shipping vessel cools). During this idle time, the shipping vessel is not used to transport biological samples.

[0009] Therefore, there is a need to provide an improved approach and related methods for maintaining, particularly transporting, cryopreserved samples that address the shortcomings of the existing systems listed above. means of solving the problem

[0010] This summary introduces concepts that are explained in more detail in the detailed description. It should not be used to identify essential features of the claimed subject or to limit the scope of the claimed subject.

[0011] The container described herein may be intended to hold 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 intended to hold one or more cryopreserved samples whether the container is moving or stationary.

[0012] Such a container must have access for inserting and removing articles to be stored or transported at cryogenic temperatures. In the present invention, access is provided by a stopper for closing the opening of the container, as claimed, to form a cryogenic storage device.

[0013] The present invention extends to the claimed cooling method. All aspects of the claims or features described herein, regardless of whether they are mentioned together herein, form part of the present invention and may be claimed separately without extending the scope of the present invention. Brief explanation of the drawing

[0014] Certain embodiments are described below merely as examples and with reference to the accompanying drawings, in which: FIG. 1 is a schematic cross-sectional view of a container for maintaining, in particular, transporting a frozen sample without a stopper. Figure 2 is a schematic cross-sectional view of a stopper for insulating a container from the surrounding environment. FIG. 3 is a schematic cross-sectional view of a container for maintaining, in particular, transporting a frozen preserved sample fitted with the stopper of FIG. 1. Figure 4 is a schematic cross-sectional view of an alternative plug to the plug shown in Figure 2. Figure 5 is a schematic cross-sectional view of an alternative plug to the plug shown in Figure 2. FIG. 6 is an enlarged view of a part of the stopper shown in FIG. 5 attached to the container. Fig. 7 is a perspective view of the plug shown in Fig. 5. FIG. 8a is a perspective view of the upper part of the plug shown in FIG. 5. Fig. 8b is an exploded view of a part of the plug shown in Fig. 5. Figure 9 is a flowchart of a method for cooling a container for maintaining, specifically for transporting, a frozen sample. Figure 10 is a flowchart of a method for preparing a delivery system to maintain, in particular, frozen samples for transport. FIG. 11 is a schematic diagram of a device for sterilizing containers for maintaining, in particular for transporting, frozen samples. FIG. 12 is a schematic diagram of an alternative device for sterilizing containers for maintaining, in particular for transporting, frozen samples. Figure 13 is a flowchart of a method for sterilizing containers for maintaining, especially for transporting, frozen samples. Figure 14 is a flowchart of an additional method for preparing a delivery system to maintain, in particular, frozen samples for transport. FIG. 15 is a graph showing the temperature change over time of a delivery system including the plug shown in FIG. 2. FIG. 16 is a schematic diagram of an alternative device for sterilizing containers for maintaining, in particular for transporting, cryopreserved samples. Specific details for implementing the invention

[0015] Implementation of the present disclosure is described below in particular with respect to maintaining cryogenically preserved samples 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).

[0016] FIG. 1 illustrates a container for maintaining, in particular, transporting a frozen sample. As illustrated in FIG. 1, the container (10) comprises walls (12) and a base (14). The walls (12) and the base (14) are vacuum insulated to provide insulation to the contents of the container (10). The walls (12) and the base (14) define a cavity (16) within the container (10) (i.e., inside the container (10)).

[0017] Optionally, to facilitate sterilization using ultraviolet light (as described below in relation to 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 of a material that reflects the wavelength of ultraviolet light used to sterilize the container (10) (e.g., a material that reflects ultraviolet light having a wavelength of 100 nm to 300 nm, preferably 275 nm). The wall (12) and / or base (14) may comprise a material suitable for meeting desired thermal requirements, such as glass fiber 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 aid in UV sterilization.

[0018] Returning to the container (10) illustrated 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 cryogenically preserved sample. The cryogenically preserved sample is a sample of biological material that has been frozen to a cryogenic temperature (e.g., at a temperature below -120°C). The container (10) is cooled (e.g., to a temperature below -120°C) to maintain a cryogenic temperature inside the container (10) so that the sample remains in its cryogenically frozen state.

[0019] The thermal mass (18) is formed from a material with a high specific heat capacity (e.g., aluminum), which means that the thermal mass (18) resists temperature changes. The thermal mass (18) may be formed from a material having a high thermal mass to weight and / or volume ratio, such as aluminum, a polymer such as nylon, or water / ice.

[0020] This means that the thermal mass (18) remains cold for a long time after the container (10) itself has cooled. Thus, the thermal mass (18) acts to slow down the rate of temperature increase inside the cavity (16) and provides passive cooling to the cryogenically preserved sample contained within the opening.

[0021] FIG. 2 illustrates a stopper (20) for insulating the interior of the container (10) illustrated in FIG. 1 from the surrounding environment. The stopper (20) illustrated in FIG. 2 is dimensioned such that a portion of the stopper (20) is fitted into the cavity (16) of the container (10). The stopper (20) comprises a lower portion (22) and an upper portion (24). The lower portion (22) is arranged to be fitted into the cavity (16) defined by the wall (12) of the container, as illustrated in FIG. 3. Returning to FIG. 2, the upper portion (24) has a width greater than the width of the cavity (16), and accordingly, when the stopper (20) is fitted into the container (10) (as illustrated in FIG. 3), the upper portion comes into contact with 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 surrounding environment.

[0022] Referring to FIGS. 2 and 3, the plug (20) comprises a plurality of insulating segments (26) and at least one reflective barrier (28) for reflecting infrared radiation. For example, the lower portion (22) of the plug (20) shown in FIG. 2 comprises 14 insulating segments (26) having 13 reflective barriers (28). In one example, the plug (20) may comprise at least 20 insulating segments (26) and reflective barriers (28). The insulating provided by the plug (20) may increase as the number of insulating segments (26) and / or reflective barriers (28) increases.

[0023] Each reflective barrier (28) is arranged between two insulating segments (26) such that the insulating segment (26) and the reflective barrier (28) are provided in alternating layers. That is, the insulating segment (26) and the reflective barrier (28) are provided in alternating layers along the longitudinal axis of the stopper (20), where the longitudinal axis is aligned with the direction in which the stopper (20) is fitted into and / or removed from the container (10). The upper insulating segment (26) of the stopper (20) shown in FIG. 2 is attached to the upper part (24) of the stopper (20).

[0024] The insulating segment (26) may be formed of an insulating material such as foam (i.e., a material having low thermal conductivity and low thermal mass). One or more of the insulating segments (26) may include closed-cell foam, aerogel, and / or one or more vacuum or partial vacuum pockets. The insulating segment (26) provides insulation between the cavity (16) of the container (10) and the surrounding environment, thereby slowing down heat transfer from the surrounding environment to the cavity (16).

[0025] The reflective barrier (28) is formed of a material that reflects infrared radiation, such as a metal foil (i.e., a material with high reflectivity). The reflective barrier (28) reflects infrared radiation from the surrounding environment, thereby preventing infrared radiation from the surrounding environment from heating the cavity (16).

[0026] The stopper (20) further includes a clamp (30) for attaching the upper portion (24) of the stopper (20) to the wall (12) of the container (10) (as shown in FIG. 3). The clamp (30) is mounted on the upper portion (24) of the stopper (20). After the stopper (20) is fitted into the container (10) (i.e., after the lower portion (22) is fitted into the cavity (16), the clamp (30) is tightened. The clamp (30) tightens the seal at the interface between the upper portion (24) of the stopper (20) and the wall (12) of the container (10). Tightening the clamp (30) prevents air flow between the surrounding environment and the interior of the cavity (16), which means that convective heating provided by the surrounding air is reduced.

[0027] The plug (20) further includes an upper seal (32) (as best illustrated in FIG. 2). The upper seal (32) is positioned on the underside of the upper portion (24) of the plug (20) as illustrated in FIG. 2. Thus, 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 fitted into the cavity (16) as illustrated in FIG. 3. The upper seal (32) also reduces convective heating provided by the ambient air by preventing air flow between the surrounding environment and the interior of the cavity (16).

[0028] The plug (20) also includes a flexible seal (34) positioned around the periphery of the lower portion (22) of the plug (20). For easy attachment, the flexible seal (34) may be mounted on the reflective barrier (28). Alternatively or additionally, the flexible seal (34) may be integrated with the insulating segment (26), for example, around the periphery of the insulating segment (26), or mounted on the insulating segment.

[0029] The flexible seal (34) is formed of an elastic material capable of withstanding cryogenic temperatures without deterioration. A suitable material for the flexible seal (34) is rubber. The flexible seal (34) may include a surface formed of a wear-resistant material configured to abut against the wall (12), and a more flexible or elastic portion on the opposite side of the surface from the wall (12) configured to provide compliance / compression of the flexible seal (34).

[0030] When the stopper (20) is not fitted into the container (10) (i.e., as shown in FIG. 2), the total width of the lower part (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 means that when the stopper (20) is fitted into the container (10) (i.e., as shown in FIG. 3), the flexible seal (34) is compressed between the lower part (22) of the stopper (20) and the walls (12) of the container (10), thereby sealing the gap between the lower part (22) of the stopper (20) and the walls (12) of the container (10).

[0031] When the stopper (20) is removed from the container (10), the flexible seal (34) returns to its original shape.

[0032] When the stopper (20) is fitted into the container (10) (i.e., as shown in FIG. 3), the compressed flexible seal (34) prevents air from flowing between the inside of the cavity (16) of the container (10) and the surrounding environment through the gap between the lower part (22) of the stopper (20) and the wall (12) of the container (10). This means that the flexible seal (34) reduces convective heating provided by the surrounding air.

[0033] As described above, the clamp (30), the top seal (32), and the flexible seal (34) each prevent heating from the convective air flow between the stopper (20) and the wall (12) of the container. Each of these components prevents heating of the sample in the cavity (16) when the container (10) is on its side or upside down. Each of these components also serves to maintain cold air in the cavity (16) when the container (10) is on its side or upside down by preventing heat transfer through the top of the container (10) (i.e., the end of the container facing the base (14)). Thus, the thermal mass (18) is effective not only when the container (10) is standing upright but also when the container (10) is on its side or upside down.

[0034] The stopper (20) further includes a vent channel (36). The vent channel (36) passes through the lower part (22) of the stopper (20) and opens into the interior of the cavity (16) when the stopper (20) is fitted into the container (10) (as shown in FIG. 3). The vent channel (36) also passes through the upper part (24) of the stopper (20) and opens into the surrounding environment (as shown in FIG. 2 and FIG. 3). This means that a small amount of air passes between the interior of the cavity (16) and the surrounding environment due to the vent channel (36).

[0035] As shown in FIG. 2, the vent channel (36) extends vertically through the entire lower portion (22) of the plug (20) and through a portion of the upper portion (24) of the plug (20). Subsequently, the vent channel (36) extends horizontally between the vertical range of the upper portion (24) of the plug (20) and the side of the upper portion (24) of the plug (20) exposed to the surrounding environment.

[0036] The vent channel (36) allows air to escape from the cavity (16) to avoid overpressure in the container (10) caused by the expansion of the thermal mass (18) in the cavity (16). To explain, as the thermal mass (18) in the cavity (16) heats up (which occurs over time during transport 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 if the air is not allowed to escape through the vent channel (36), the air pressure in the cavity (16) will increase.

[0037] The vent channel (36) also prevents overpressure in the container (10) by allowing air to escape from the cavity (16) when the stopper (20) is fitted into the container (10). To explain, if air is not allowed to escape through the stopper (20), the action of fitting the stopper (20) into the container (10) increases the air pressure within the cavity (16). Therefore, allowing air to escape through the vent channel (36) prevents such pressure accumulation. This means that the stopper (20) can be fitted into the container (10) more easily, because there is no need to apply additional force to counteract the force applied to the stopper (20) by the compressed air within the cavity (16) when the user inserts the stopper (20) into the container (10).

[0038] Likewise, the vent channel (36) allows air to flow into the cavity (16) when the stopper (20) is removed from the container (10), thereby preventing the creation of a vacuum within the cavity (16). To explain, if air flow through the stopper (20) is not allowed, the action of removing the stopper (20) from the container (10) reduces the air pressure within the cavity (16) (thereby creating a vacuum). Therefore, allowing air flow through the vent channel (36) prevents the creation of such a vacuum. This means that the stopper (20) can be removed more easily from the container (10), because there is no need to apply additional force to counteract the force applied to the stopper (20) by the vacuum within the cavity (16) when the user removes the stopper (20) from the container (10).

[0039] The cross-section of the vent channel (36) is selected to be large enough to allow air flow through the vent channel (36) without being blocked (e.g., by frost / ice as described in more detail with reference to FIG. 4), but narrow enough so that convective heating by air inflow into the cavity (16) through the vent channel (36) is not significant. For example, the vent channel (36) may have a circular cross-section with a diameter of 6 mm or less. Limiting the diameter of the vent channel (36) limits convective heating by air inflow into the cavity (16). Alternatively, or additionally, the vent channel (36) may be formed in a zigzag, serpentine, or coiled shape. This limits convective heating by increasing the path length of the vent channel (36).

[0040] Optionally, the vent channel (36) includes one or more valves (not shown in FIG. 2 or FIG. 3) that reduce convection within the vent channel (36) while allowing air to flow in and out when the plug (20) is removed / inserted. The valves may also help control moisture within the vent channel (36) to prevent the accumulation of frost / ice.

[0041] FIG. 5 illustrates a stopper (50) for insulating the interior of the container (10) illustrated in FIG. 1 from the surrounding environment. The stopper (50) illustrated in FIG. 5 is dimensioned such that a portion of the stopper (50) is fitted into the cavity (16) of the container (10). The stopper (50) includes a lower portion and an upper portion. The lower portion is arranged to be fitted into the cavity (16) defined by the wall (12) of the container. The upper portion has a width greater than the width of the cavity (16), and accordingly, when the stopper (50) is fitted into the container (10) as partially illustrated in FIG. 7 (similar to the example in FIG. 3), the upper portion contacts 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 surrounding environment.

[0042] Referring to FIGS. 5 through 8b, the plug (50) comprises a plurality of chambers (52). Each chamber, as best illustrated in FIGS. 5 and 8b, has a bottom, side walls, and an open top, forming a cavity (e.g., in the form of a bucket), and the cavity accommodates a plurality of insulating segments (54) separated by spacers (55). According to the example illustrated in FIGS. 5 and 8b, each chamber (52) comprises three insulating segments (54) and two spacers (55), with the spacers (55) positioned between adjacent insulating segments (54). However, more or fewer insulating segments (54) and spacers (55) are considered (e.g., the use of two insulating segments (54) with one spacer (55), the use of four insulating segments with three spacers (55), etc.). In other words, each chamber (52) includes alternating layers of insulating segments (54) and spacers (55). The chambers (52) are stacked vertically on top of each other. As illustrated by FIGS. 5 and 7, the plug (50) includes four chambers in a stacked configuration. However, more or fewer chambers may be used (e.g., two, three, or more than four).

[0043] That is, each chamber (52) comprises alternating layers of insulating segments (54) and spacers (55) along the longitudinal axis of the plug (50), wherein the longitudinal axis is aligned with the direction in which the plug (50) is fitted into and / or removed from the container (10). Additionally, a reflective barrier (56) (not illustrated) may be placed on the top and bottom surfaces of each insulating segment (54). In this way, the plug (50) effectively doubles the number of infrared radiation barriers (e.g., a plug having two insulating segments (54) and one spacer (55) comprises four reflective barriers (56). The top insulating segment (54') of the plug (50) illustrated in FIGS. 5, FIGS. 6, and FIGS. 8a is attached to the top surface of the top chamber (52) and is located within the lid (58) of the plug (50).

[0044] As illustrated in FIGS. 5, 6, and 8b, the insulating segment (54) is thicker than the spacer (55) (i.e., has a greater height). According to an embodiment, the insulating segment (54) has a thickness of 75-10 mm, and the spacer has a thickness of 75-1 mm. In one exemplary example, the insulating segment (54) is about 25 mm thick, and the spacer (55) is about 1 mm thick. It should be noted that in an alternative embodiment, 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). Additionally, the thickness of the spacer (55) and / or the insulating element (54) may 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), so that the thickness of the insulating element (54) becomes the minimum value for the insulating element (54) furthest from the lid (58).

[0045] As further illustrated in FIG. 5, at least one rod (57) is positioned within and through a plurality of chambers (52) (and thus through the corresponding insulation segment (54), spacer (55), and reflective barrier (56). The rod (57) provides structural support for each chamber (52) and ensures that the plurality of chambers (52) (and thus the corresponding insulation segment (54), spacer (55), and reflective barrier (56)) are secured together. The rod may be manufactured from any suitable material that provides sufficient strength to maintain the chambers (52) in a stacked configuration (e.g., made of a polymer, etc.). Preferably, the rod is manufactured from a thin 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).

[0046] The chamber may be formed from an insulating material such as foam (i.e., a material having low thermal conductivity and low thermal mass). One or more of the insulating segments (54) may include closed-cell foam, aerogel and / or one or more vacuum or partial vacuum pockets. In a preferred embodiment, the container is formed from an insulating material that is easily machined, such as low-density styrofoam.

[0047] The insulating segment (54) may be formed from an insulating material such as foam (i.e., a material having low thermal conductivity and low thermal mass). One or more of the insulating segments (54) may include a closed-cell foam, aerogel, and / or one or more vacuum or partial vacuum pockets. The insulating segment (54) provides insulation between the cavity (16) of the container (10) and the surrounding environment, thereby slowing down heat transfer from the surrounding environment to the cavity (16). Similarly, the spacer (55) may also be manufactured from an insulating material such as foam (i.e., a material having low thermal conductivity and low thermal mass). One or more of the spacer (55) may include a closed-cell foam, aerogel, and / or one or more vacuum or partial vacuum pockets.

[0048] The reflective barrier (56) is formed of a material that reflects infrared radiation, such as a metal foil (i.e., a material with high reflectivity). The reflective barrier (56) reflects infrared radiation from the surrounding environment, thereby preventing infrared radiation from the surrounding environment from heating the cavity (16).

[0049] The stopper (50) further includes a clamp (53) for attaching the lid (58) of the stopper (50) to the wall (12) of the container (10) (as shown in FIG. 7). The clamp (53) is mounted on the lid (58) or a part of the lid. After the stopper (50) is fitted into the container (10), the clamp (53) is tightened. The clamp (53) tightens the seal at the interface between the upper part of the stopper (50) and the wall (12) of the container (10). Tightening the clamp (53) prevents air flow between the surrounding environment and the interior of the cavity (16), which means that convective heating provided by the surrounding air is reduced.

[0050] The stopper (50) further includes an upper seal (32) (as best illustrated in FIGS. 5 through 7). The upper seal (32) is positioned on the underside of the lid (58) of the stopper (50) as illustrated in FIGS. 6 and 7. Thus, the upper seal (32) is compressed between the upper portion of the stopper (50) and the top of the wall (12) when the stopper (50) is fitted into the cavity (16). The upper seal (32) also reduces convective heating provided by the ambient air by preventing air flow between the surrounding environment and the interior of the cavity (16).

[0051] As described in more detail below with reference to FIG. 11, the plug (20, 40, 50) may optionally include an ultraviolet light source (not shown in FIG. 2, FIG. 4 or FIG. 5).

[0052] As described above, the stopper (20, 40, 50) is fitted into the container (10) illustrated in FIG. 1. Together, the container (10) and the stopper (20, 40, 50) form a delivery system (38). Thus, the delivery system (38) includes a vacuum-insulated container (10) containing a thermal mass (18), and a stopper (20, 40, 50) for insulating the interior of the container (10) from the surrounding environment.

[0053] As described above, the thermal mass (18) acts to slow down the rate of temperature increase inside the cavity (16) and provides passive cooling to the cryogenically preserved sample contained within the opening. Consequently, the container (10) allows the cryogenically preserved sample to be maintained, particularly transported, without the need for liquid nitrogen due to the passive cooling provided by the thermal mass (18). Given that liquid nitrogen is not used in the container (10), the delivery system (38) does not need to provide a discharge of evaporated liquid nitrogen. This means that a stopper (e.g., stopper (20, 40, 50) shown in FIG. 2, FIG. 4 and FIG. 5) can be used to insulate the interior of the container (10) from the surrounding environment.

[0054] The stopper (20, 40, 50) insulates the interior of the container (10) to prevent heat transfer from the surrounding environment to the cavity (16) of the container (10). The insulation provided by the stopper (20, 40, 50) means that the delivery system (38) can maintain samples frozen at cryogenic temperatures even when the delivery system (38) is positioned sideways or upside down. That is, the stopper (20, 40, 50) serves to maintain cold air within the cavity (16) of the container (10) when the delivery system (38) is sideways or upside down by preventing heat transfer through the top of the container (10) (i.e., the end of the container facing the base (14)).

[0055] FIG. 4 illustrates an alternative stopper (40) to the stopper (20) illustrated in FIG. 2. The stopper (40) includes all the components of the stopper (20) illustrated in FIG. 2, identified using the same reference number used in FIG. 2. The stopper (40) can be fitted into the container (10) illustrated in FIG. 1 in the same manner as the stopper (20) illustrated in FIG. 2. In addition to the components of the stopper (20) of FIG. 2, the stopper (40) illustrated in FIG. 4 includes a chamber (42) in the path of the vent channel (36).

[0056] The chamber (42) is positioned toward the top of the vent channel (36) portion extending through the lower portion (22) of the plug (40). The chamber (42) is formed by creating a hole in a portion of the insulation segment (26) and the reflective barrier (28).

[0057] For convenience of reference, a vent channel (36) having two sections, namely a lower part (44) and an upper part (46), is illustrated in FIG. 4. The lower part (44) of the vent channel (36) extends between the chamber (42) and the cavity (16) (when the stopper (20) is fitted into the container (10). The upper part (46) of the vent channel (36) extends between the chamber (42) and the surrounding environment.

[0058] Air flows through the lower part (44) of the vent channel (36) in the lower part (22) of the plug and into the chamber (42) formed by the holes of the insulating segment (26) and the reflective barrier (28). Then, air flows from the chamber (42) into the surrounding environment through the upper part (46) of the vent channel.

[0059] A chamber (42) is formed at a location within the path of a vent channel (36) that is susceptible to frost / ice accumulation. Frost / ice accumulates in the vent channel (36) at a point where the air within the vent channel (36) is approximately 0°C. The formation of frost / ice occurs in a specific area of ​​the vent channel (36). The chamber (42) is formed in the area where frost / ice accumulates (i.e., the part of the vent channel (36) where the air temperature within the vent channel (36) is 0°C). Thus, the chamber (42) has an upper range communicating with the upper part (46) of the vent channel (36) where the air temperature within the vent channel (36) is greater than 0°C, and a lower range communicating with the lower part (44) of the vent channel (36) where the air temperature within the vent channel (36) is less than 0°C. The portion of the vent channel (36) where the air temperature is about 0°C is located at the lower portion (22) of the stopper (40) when the inside of the container is cooled to a cryogenic temperature. When in use, the ambient temperature may typically be in the range of 5°C to 30°C. When in use, the end of the stopper (20) in the cavity (16) may typically be at a temperature in the range of -196°C to -120°C. Within this temperature range, the area of ​​the vent channel (36) where the temperature is about 0°C when in use is relatively narrow, and the chamber (42) may be positioned to coincide with this area.

[0060] That is, a chamber (42) is formed in the lower part (22) of the stopper (40). Specifically, the chamber (42) is located in the lower part (22) of the stopper and is in contact with the upper part (24) of the stopper (40). As shown in FIG. 4, the upper part (24) of the stopper (40) forms one wall of the chamber (42).

[0061] The chamber (42) has a larger cross-sectional area than the vent channel (36), which means that any frost / ice formed in the chamber (42) is less likely to cause blockage in the vent channel (36).

[0062] FIG. 9 is a flowchart of a method (500) for cooling a container for maintaining, in particular transporting, a frozen sample such as the container (10) shown in FIG. 1.

[0063] In step 502, a cryogenic fluid (in this example, liquid nitrogen) is injected into the cavity of the vessel. Heat is transferred from a thermal mass located within the cavity to the liquid nitrogen within the cavity. Thus, the liquid nitrogen cools the thermal mass within the cavity. Optionally, before the liquid nitrogen is injected into the cavity, a stopper (e.g., the stopper (20, 40 50) shown in FIGS. 2, 4 and 5) is removed from the vessel.

[0064] After the thermal mass is cooled by nitrogen (e.g., after a period of about 0.5 to 1 hour), the liquid nitrogen is emptied from the cavity in step 504.

[0065] Injecting liquid nitrogen into the cavity pre-cools it. Pre-cooling the cavity reduces the time required to use an alternative cooling source (e.g., a heat engine) to cool the interior of the vessel to cryogenic temperatures.

[0066] Optionally, in step 506, steps 502 and 504 may be repeated to further lower the temperature within the cavity. For example, these steps may be repeated if the thermal mass is not cooled to a desired temperature. That is, in step 506, additional liquid nitrogen is injected into the cavity to cool the thermal mass, and then drained from the cavity after a certain period. Additional cycles of injecting liquid nitrogen into the cavity and draining liquid nitrogen from the cavity (16) may be performed until the cavity is cooled to a 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 time required to use an alternative cooling source. In some examples, an appropriate amount of cryogenic fluid may be used in step 502 so that the temperature of the cavity (16) reaches a desired temperature without repeating steps 502 and 504 (i.e., without step 506).

[0067] In some examples, cooling of the cavity (16) can be achieved using a heat engine such as a cryogenic refrigerator (e.g., a Stirling cryogenic refrigerator), that is, without the addition or removal of cryogenic fluid. In other words, step 502 can be replaced with the step of inserting a heat engine into the vessel (10) to remove heat from the cavity (16). Similarly, step 504 can be replaced with the step of removing the heat engine from the vessel (10).

[0068] Optionally, at step 508, a stopper (e.g., stopper (20, 40, 50) illustrated in FIG. 2, FIG. 4, and FIG. 5) is fitted into the container to prevent heat transfer from the surrounding environment to the cooled thermal mass. When the stopper is fitted into the container, the rate of temperature increase inside the container is slowed down. Thus, the stopper can be fitted into the container until the frozen sample is ready to be loaded into the container.

[0069] FIG. 10 is a flowchart of a method (600) for preparing a delivery system for maintaining, in particular transporting, frozen samples, such as the delivery system (38) shown in FIG. 3 or the delivery system implementing the plugs of FIG. 4, FIG. 5 and FIG. 11.

[0070] In step 602, the cavity of a container (e.g., container (10) shown in FIG. 1) for maintaining, particularly transporting, a cryogenically preserved sample is cooled to a cryogenic temperature. For example, the interior of the container may be cooled using a heat engine (e.g., a Stirling cryogenic refrigerator). Alternatively, the interior of the container may be cooled by performing the steps of the method (500) described with reference to FIG. 9.

[0071] In step 604, the cryogenically preserved sample is loaded into the container. For example, the cryogenically preserved sample may be placed within the opening of the thermal mass (18) of the container (10) of FIG. 1.

[0072] Optionally, at step 606, a heat engine (in this example, a Stirling cryogenic refrigerator) is fitted into the container (10) to remove heat from the cavity, thereby maintaining the cryogenically preserved sample at an appropriate cryogenic temperature. The Stirling cryogenic refrigerator may be mounted on the container (10) until the cryogenically preserved sample is transported to a different location or stored in a different location. The Stirling cryogenic refrigerator may also be mounted on the container (10) to reverse any temperature increase within the container (10) that occurs while loading the cryogenically preserved sample into the container.

[0073] When a heat engine, such as a Stirling cryogenic refrigerator, is mounted in the container (10) to maintain the cryogenically preserved sample at a cryogenic temperature, the heat engine is removed in step 608 before transporting or storing the cryogenically preserved sample.

[0074] In step 610, a stopper (e.g., the stopper (20) shown in FIG. 2, FIG. 4, FIG. 5 and FIG. 11) is fitted into the container (10) to insulate the inside of the container from the surrounding environment and prevent heat transfer from the surrounding environment to the frozen sample. When the stopper is fitted into the container, a delivery system (38) is formed.

[0075] In step 612, the delivery system (38) containing the frozen preserved sample is delivered for transport or storage.

[0076] FIG. 11 illustrates a device (70) for sterilizing a container for maintaining, in particular transporting, a cryopreserved sample such as the container (10) illustrated in FIG. 1. The container (10) illustrated in FIG. 11 includes all components of the container (10) illustrated in FIG. 1 (i.e., walls (12), base (14), cavity (16), and thermal mass (18)). The device (70) also includes a cartridge (72). The cartridge (72) is dimensioned such that a portion of the cartridge (72) is fitted into the open end of the container (10), and a separate portion of the cartridge (72) is aligned at the open end of the container (10) to abut the end of the container wall (12).

[0077] The cartridge (72) contains an ultraviolet light source (74), such as a 60W fluorescent bulb. Alternatively, the ultraviolet light source (74) may be a single LED (e.g., a 5W LED) or an LED array (e.g., three 2W LEDs). The ultraviolet light source (74) emits ultraviolet light in the lower UVC range or UVB range.

[0078] For example, the ultraviolet light source (74) can emit ultraviolet light having a wavelength of 100 nm to 300 nm. In a specific example, the ultraviolet light source (74) can emit ultraviolet light having a wavelength of 295 nm.

[0079] In the device illustrated 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) accessible when the cartridge (72) is inserted into the open end of the container (10). Alternatively, or additionally, a power supply unit may be mounted on the container (10). The power supply unit may be connected to the main power supply. When the cartridge (72) is mounted on the container (10), it may form an electrical connection with the power supply unit. This electrical connection may be made via a pogo pin, via a connection typically found in a kettle, or via any other suitable connector, preferably allowing the formation and disconnection of the electrical connection to be easily implemented. Alternatively, or additionally, the cartridge (72) may be connected directly to the main power supply.

[0080] When the cartridge (72) is inserted into the container (10), the inside of the cavity (16) of the container (10) can be irradiated with ultraviolet light. By irradiating the cavity (16) of the container (10) with ultraviolet light, the cavity (16) is sterilized. Sterilizing the container (10) prevents contamination of the biological sample from a number of contaminants. For example, the biological sample is prevented from being contaminated by bacteria, viruses, fungi and other microorganisms, as well as DNA, RNA and cell fragments from biological samples previously kept in the container (10).

[0081] The cartridge (72) may include one or more insulating segments (not shown in FIG. 11) to prevent or slow down heat transfer between the surrounding environment and the interior of the cavity (16) while the cavity (16) is being sterilized. Additionally, the cartridge (72) includes a seal (80) located on the underside of the portion of the cartridge (72) that abuts the end of the wall (12) of the container (10). Optionally, the cartridge (72) may include some of the components of the stopper (20) shown in FIG. 2 (or the stopper (40, 50) shown in FIG. 4 and 5) to insulate the interior of the container from the surrounding environment while the interior of the container is being sterilized. For example, the cartridge (72) may include one or more of the insulating segment (26), reflective barrier (28), clamp (30), flexible seal (34), vent channel (36), and chamber (42) shown in FIG. 2 and 4, or the chamber (52), insulating segment (54), spacer (55), reflective barrier (56), lid (58), and flexible seal (34) shown in FIG. 5. As another example, the cartridge (72) may have the same configuration as the plug (20) shown in FIG. 2 (or plugs (40, 50)) shown in FIG. 4 and 5 and further include an ultraviolet light source (74) (and optionally a battery (76) and a switch (78)). Alternatively, the cartridge (72) may be combined with or integrally formed with a heat engine.

[0082] FIG. 12 illustrates the bottom surface of a cartridge (82) which is a variation of the cartridge (72) just described. The cartridge (82) includes at least one clamp (88), a seal (80), and at least one ultraviolet light source (86) and performs the same function as previously described in relation to the cartridge (72). However, in this variation, a plurality of ultraviolet light sources (86) are located within the central region of the cartridge (82) as illustrated. In a specific embodiment illustrated, eight ultraviolet light sources (86) are integrated into the cartridge (82). Specifically, two ultraviolet light sources (86) are located approximately near the center, and the other six ultraviolet light sources (86) are located in a circumferential or radial pattern toward the periphery of the cartridge (82). The ultraviolet light sources (86) located circumferentially or radially may be angled to direct light toward the center of the container (10) when in use. In one specific example, six ultraviolet light sources (86) can be formed inwardly at an angle of inclination of about 30 degrees to provide an optimal light focus for the container (10).

[0083] Similar to the embodiment of FIG. 11, the cartridge (82) is arranged so that a portion of the cartridge (82) is fitted into the open end of the container (10), and a separate portion of the cartridge (82) is arranged to be in contact with the end of the container wall (12) at the open end of the container (10).

[0084] The cartridge (82) includes an ultraviolet light source (86), such as an LED (e.g., a 5W LED or a 2W LED). The ultraviolet light source (86) emits ultraviolet light in the lower UVC range or UVB range.

[0085] For example, the ultraviolet light source (86) can emit ultraviolet light having a wavelength of 100 nm to 300 nm. In a specific example, the ultraviolet light source (86) can emit ultraviolet light having a wavelength of 295 nm.

[0086] In the device illustrated 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 mounted in the container (10). The power supply unit may be connected to a main power source. When the cartridge (82) is mounted in the container (10), it may form an electrical connection with the container (10) through a connector (84). This electrical connection may be made via a pogo pin, a connection typically found in a kettle, or any other suitable connector, preferably allowing the formation and disconnection of the electrical connection to be easily implemented. In one particular example, the connector (84) includes a ground and voltage connection and a serial communication interface (e.g., RS232) to enable bidirectional communication between the electrical components of the cartridge (82) and the electrical components within the container (10), which will be further described below.

[0087] When the cartridge (82) is inserted into the container (10), the inside of the cavity (16) of the container (10) can be irradiated with ultraviolet light. By irradiating the cavity (16) of the container (10) with ultraviolet light, the cavity (16) is sterilized. Sterilizing the container (10) prevents contamination of the biological sample from a number of contaminants. For example, the biological sample is prevented from being contaminated by bacteria, viruses, fungi and other microorganisms, as well as DNA, RNA and cell fragments from biological samples previously kept in the container (10).

[0088] The cartridge (82) may include one or more insulating segments (not shown in FIG. 12) to prevent or slow down heat transfer between the surrounding environment and the interior of the cavity (16) while the cavity (16) is being sterilized. Additionally, the cartridge (82) includes a seal (88) located on the underside of the portion of the cartridge (82) that abuts the end of the wall (12) of the container (10). Optionally, the cartridge (82) may include some of the components of the stopper (20) shown in FIG. 2 (or the stopper (40, 50) shown in FIG. 4 and 5) to insulate the interior of the container from the surrounding environment while the interior of the container is being sterilized. For example, the cartridge (82) may include one or more of the insulating segment (26), reflective barrier (28), clamp (30), flexible seal (34), vent channel (36), and chamber (42) shown in FIG. 2 and 4, or the chamber (52), insulating segment (54), spacer (55), reflective barrier (56), lid (58), and flexible seal (34) shown in FIG. 5. As another example, the cartridge (82) may have the same configuration as the plug (20) shown in FIG. 2 (or plugs (40, 50)) shown in FIG. 4 and 5 and further include an ultraviolet light source (86) (and optionally a battery (76)). Alternatively, the cartridge (82) may be combined with or integrally formed with a heat engine.

[0089] Once connected to the container (10), the cartridges (72, 82) electrically communicate with the container (10) (e.g., via a connector (84)). In an embodiment, the container (10) and the cartridges (72, 82) each include at least one sensing element and at least one controller. As a non-limiting example, the container may include a sensing element that measures temperature (e.g., a thermistor) and light (e.g., a UV sensor for measuring how much light the cartridge emits), and the cartridges (72, 82) may include a sensing element that measures voltage, current, etc. The controller of each container (10) and cartridge (72, 82) may include at least one memory for recording signals from the sensing element and for recording calculations performed by the processor(s) (e.g., deriving a power output based on the detected voltage and current outputs). Each memory unit may also store a unique identification code, so that each cartridge and each container can be identified individually. Additionally, each of the container (10) and cartridges (72, 82) may include a GPS system so that their respective locations can be monitored.

[0090] Each of the container (10) and cartridges (72, 82) may also include a transceiver for wirelessly transmitting information stored in the memory of each controller. The transceiver can transmit information to a remote location to remotely record and monitor the information. For example, a central monitoring station may receive GPS information and / or detected and / or calculated information stored in the container (10) and cartridges (72, 82) to have real-time information regarding the container (10), the thermal mass (18), and the UV sterilization procedure received by the container (10).

[0091] By insulating the cavity (16) from the surrounding environment, the container (10) can be sterilized while the cryogenic temperature is maintained in the cavity (16). This means that the requirement to cool the container (10) after sterilization using an ultraviolet light source (74, 86) can be reduced or even eliminated.

[0092] The reduced amount of time required to cool the container (10) after sterilization reduces the amount of time required to prepare the container (10) for use in maintaining subsequent cryopreserved samples, particularly for transport, which means that the time of suspension of the container (10) between transport or storage is reduced.

[0093] Additionally, if the ultraviolet light source includes a feature that serves to insulate the interior of the container (10) from the surrounding environment (e.g., the feature of the stopper shown in FIG. 2, FIG. 4 and FIG. 5), the interior of the cavity (16) can be sterilized while the cryopreserved sample is transported or stored. In particular, including an ultraviolet light source in the stopper used to insulate the interior of the container (10) from the surrounding environment eliminates the need to remove the stopper to insert a separate device for sterilizing the container (10). Integrating an ultraviolet light source into the stopper used to insulate the interior of the container (10) from the surrounding environment also seals the container (10), thereby maintaining the sterilization of the container (10) even after the interior of the container (10) is irradiated with ultraviolet light.

[0094] If the interior of the cavity (16) is sterilized while the cryopreserved sample is transported or stored, the cryopreserved sample may be kept in a vial or receptacle that is opaque to ultraviolet light, or otherwise the cryopreserved sample may be shielded from ultraviolet light from an ultraviolet light source. Shielding the cryopreserved sample from ultraviolet light ensures that the cryopreserved sample is not damaged by ultraviolet radiation.

[0095] Alternatively, if the cryopreserved sample is a sample requiring sterilization (e.g., blood product), the cryopreserved sample may be sterilized along with the cavity (16) when the sample is exposed to ultraviolet light within the cavity (16).

[0096] FIG. 13 is a flowchart of a method (800) for sterilizing a container for maintaining, in particular transporting, a cryopreserved sample such as the container (10) shown in FIG. 1. The container (10) may be part of a delivery system such as the delivery system (38) shown in FIG. 3 (or the delivery system (38) including the stopper of FIG. 4 or FIG. 5). The interior of the container (10) of the delivery system may be insulated from the surrounding environment using a stopper (e.g., the stopper (20) shown in FIG. 2, the stopper (40) shown in FIG. 4, or the stopper (50) shown in FIG. 5), or may be coupled to a Stirling cryogenic refrigerator. The method (800) may be performed using the device (70) shown in FIG. 11.

[0097] Optionally, in step 802, if a stopper or cryogenic freezer is fitted into the container to form a delivery system, the delivery system is opened to expose the interior of the container. Thus, opening the container may involve removing the stopper or Stirling cryogenic freezer or any other device fitted into the open end of the container.

[0098] In step 804, a cartridge containing an ultraviolet light source is fitted into a container such that the open end of the container is closed using the cartridge. By fitting the cartridge containing the ultraviolet light source into the container, the ultraviolet light source is arranged to irradiate the inside of the container.

[0099] In step 806, the ultraviolet light source of the cartridge is activated, and the inside of the container is irradiated with ultraviolet light.

[0100] In step 808, the inside of the container is irradiated with ultraviolet light for a sufficient amount of time to ensure that the inside of the container is sterilized. For example, the inside of the container may be irradiated with ultraviolet light for 30 to 60 minutes.

[0101] In step 810, the ultraviolet light source is deactivated and the cartridge is removed from the container.

[0102] Optionally, at step 812, a container is prepared to maintain, in particular, a cryogenically preserved sample. For example, the container may be prepared by performing the steps of method (600) described with reference to FIG. 10. Since the container can be sterilized while the cryogenic temperature is maintained within the cavity of the container, the requirement to cool the container at step 602 of method (600) may be reduced or eliminated.

[0103] FIG. 14 is a flowchart of an additional method (900) for preparing a delivery system for maintaining, in particular transporting, a frozen preserved sample such as the delivery system (38) shown in FIG. 3 (or the delivery system (38) including the stopper of FIG. 4 or FIG. 5). The delivery system may include a container (e.g., the container (10) shown in FIG. 1) and a stopper (e.g., the stopper (20) shown in FIG. 2, the stopper (40) shown in FIG. 4, or the stopper shown in FIG. 5).

[0104] In step 902, the cryopreserved sample is loaded into a container. For example, the cryopreserved sample may be placed within the opening of the container (10). Loading the cryopreserved sample into the container may involve positioning the cryopreserved sample within a receptacle that is opaque to ultraviolet light.

[0105] In step 904, the stopper is fitted into the container to insulate the interior of the container from the surrounding environment and prevent heat transfer from the surrounding environment to the cryopreserved sample. Components of the stopper and / or the container may include an ultraviolet light source. When the stopper is fitted into the container, a delivery system is formed.

[0106] In step 906, the delivery system containing the cryopreserved sample is delivered for transport or storage.

[0107] In step 908, the interior of the container is irradiated using ultraviolet light to sterilize the container. The ultraviolet light may have a wavelength of 100 nm to 300 nm (e.g., about 265 to 275 nm). The interior of the container may be sterilized using an ultraviolet light source located in a stopper used to insulate the interior of the container from the surrounding environment. Alternatively or additionally, the walls and / or base of the container (or other components of the container, such as the thermal mass (18) of the container (10) shown in FIG. 1) may include an ultraviolet light source used to irradiate the interior of the container. Thus, sterilizing the container using ultraviolet light may involve activating an ultraviolet light source located in the stopper and / or components of the container.

[0108] The inside of the container may be irradiated with ultraviolet light for 30 to 60 minutes (e.g., if the container is sterilized only once during transport or storage) or for a period of about 10 minutes (e.g., if the container must be sterilized daily during transport or storage of a cryopreserved sample). Sterilizing the container for a short period daily during transport or storage of a cryopreserved sample can ensure that the sample is not contaminated during transport or storage.

[0109] In step 910, the sterilization cycle is completed. Completing the sterilization cycle may include deactivating an ultraviolet light source located on the stopper and / or components of the container.

[0110] FIG. 15 is a graph showing the temperature change over time of a delivery system (lower line) including the plug shown in FIG. 2, compared to the temperature change over time of a delivery system (upper line) without the plug in place.

[0111] From FIG. 16, it can be seen that inserting the stopper shown in FIG. 2 into the container provides a longer period during which the inside of the container remains at a cryogenic temperature. The cryogenic range is -200°C to -120°C. When the stopper shown in FIG. 2 is inserted into the container, the inside of the container is maintained at a cryogenic temperature for 8 days, whereas a container without a stopper is maintained at a cryogenic temperature for only 3 days.

[0112] Therefore, by fitting the stopper shown in FIG. 2 into the container, the cryopreserved sample can be transported and / or stored for a longer period without being damaged by exposure to temperatures outside the cryogenic zone. Allowing the cryopreserved sample to be maintained for a longer period, particularly for transport, increases the distance over which the cryopreserved sample can be transported, thereby increasing the population of patients who can be treated using the cryopreserved sample from a specific source.

[0113] Variations or modifications to the system and method described in this specification are described in the following paragraph.

[0114] The apparatus (70, 82) illustrated in FIGS. 11 and 12 has been described in relation to the sterilization of a container (10) containing a thermal mass (18). As previously described, the thermal mass (18) provides passive cooling to a sample maintained within the container (10) by slowing down the rate of temperature increase within the cavity (16) of the container (10). However, the method and apparatus described herein are not limited to the sterilization of a container containing a thermal mass.

[0115] That is, the method and apparatus described herein may be used to sterilize a container in which a sample maintained within the container is cooled using other means. In particular, an ultraviolet light source may be used to sterilize a delivery system that provides cooling to a sample maintained within the container using a heat engine such as a Stirling cryogenic refrigerator.

[0116] In a delivery system in which a heat engine (e.g., a Stirling cryogenic refrigerator) is used to maintain a sample at a cryogenic temperature, the Stirling cryogenic refrigerator may be positioned on a lid that can be fitted into a container, and a heat exchanger may be attached to the Stirling cryogenic refrigerator such that the heat exchanger is positioned within the cavity of the container when the lid is fitted into the container.

[0117] The vessel may contain liquid nitrogen (or other working fluid) to provide cooling to the cryogenically preserved sample. A Stirling cryogenic refrigerator removes heat from the vessel, which means that the liquid nitrogen is kept in a liquid state to maintain the cryogenic temperature inside the vessel. One or more ultraviolet light sources may be located on the underside of the lid, so that the cavity of the vessel can be irradiated with ultraviolet light while the cavity is cooled by the Stirling cryogenic refrigerator. Alternatively (as further described below), the ultraviolet light source(s) may be located inside the vessel.

[0118] By positioning one or more ultraviolet light sources on the underside of the lid or inside the container, the container can be sterilized while the Stirling cryogenic refrigerator 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 any air or other gases within the container cavity. This ensures that the container is sterilized during transport or storage in a delivery system containing a heat engine.

[0119] As with the apparatus described in relation to FIGS. 11 and 12, the cryopreserved sample may be maintained in a vial or receptacle that is opaque to ultraviolet light or otherwise shielded from ultraviolet light from an ultraviolet light source. A method for preparing a delivery system including a Stirling cryogenic refrigerator may be substantially the same as the method (900) described with reference to FIG. 14. However, instead of fitting a stopper into the container (as described in step 904 of FIG. 14), a lid including a Stirling cryogenic refrigerator (and optionally ultraviolet light source(s)) is fitted into the container.

[0120] The device (70) illustrated in FIG. 11 has been described in relation to the sterilization of a container at cryogenic temperatures. However, it will be understood that the device (70) illustrated in FIG. 11 allows for the sterilization of a container regardless of the container's temperature. In particular, the device (70) illustrated in FIG. 11 can allow the container to be sterilized at room temperature.

[0121] The cartridge (72) has been described as having a portion arranged to be fitted into the open end of the container (10). However, other arrangements for irradiating the inside of the container using an ultraviolet light source may also be used. For example, the ultraviolet light source may be located in a lid seated on the top of the container. As another example, an optical fiber or a light guide may be used to transmit ultraviolet light into the inside of the container, which means that it may not be necessary to cover the container with a lid to irradiate the inside 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 stopper such as the stopper (20) shown in FIG. 2, the stopper (40) shown in FIG. 4, or the stopper shown in FIG. 5. As another alternative, the ultraviolet light source may be located in a lid containing a heat engine (as previously described), thereby allowing the container to be sterilized using ultraviolet light while the inside of the container is cooled to a cryogenic temperature.

[0123] Additionally or alternatively, an ultraviolet light source may be provided on or inside the body of the container (e.g., on or inside the wall of the container and / or on or inside the base of the container), or on a component of the container such as the thermal mass (18) of the container (10) shown in FIG. 1. Such an arrangement is illustrated in FIG. 16, which illustrates an alternative device (100) for sterilizing a container for maintaining, in particular, a cryopreserved sample (i.e., an alternative to the device (70) shown in FIG. 11). However, it should be noted that a device for sterilizing a container for maintaining, in particular, a cryopreserved sample according to the method described herein may include an ultraviolet light source (74) of the device (70) shown in FIG. 11 in addition to the ultraviolet light source (104) of the device (100) shown in FIG. 16.

[0124] The device (100) illustrated in FIG. 16 includes a stopper (102) (or other closure) for closing the open end of the container (10). An ultraviolet light source (104) is located inside the wall (12) of the container (10), and accordingly, the ultraviolet light source (104) is located within the cavity (16) of the container (10). This means that the ultraviolet light source (104) is arranged to irradiate the interior of the container (10). The ultraviolet light source (104) is powered by a battery (106) located inside the wall (12) of the container (10). The ultraviolet light source (104) is controlled using a switch (108) located outside the wall (12) of the container (10).

[0125] By positioning an ultraviolet light source on or inside the body of the container or on a component of the container, the interior of the container is sterilized while the interior of the container is preheated. Sterilization of the container during the preheating process can also be facilitated by positioning the ultraviolet light source on a lid or cartridge that does not contain insulation, thereby allowing heat transfer from the surrounding environment into the interior of the container through the lid.

[0126] If an ultraviolet light source is positioned on or inside the body of the container or on a component of the container, the sterilization method (800) described in relation to FIG. 13 may be adjusted accordingly. Specifically, the method does not require the removal of a stopper or other device from the container to allow a separate cartridge to be fitted. This means that the interior of the container may be irradiated while the insulating stopper (e.g., the stopper shown in FIG. 2, FIG. 4 and FIG. 5, generally shown as stopper (102) in FIG. 16) is fitted into the container, or while the heat device is attached to the container. Consequently, the method may include the step of activating an ultraviolet light source on the body of the container or on a component of the container to irradiate the interior of the container with ultraviolet light. Subsequently, the method may further include the step of irradiating the interior of the container with ultraviolet light for a sufficient amount of time to ensure that the interior of the container is sterilized. Once the interior of the container is sterilized, the ultraviolet light source may be deactivated. Sterilizing the inside of the container in this way means that the inside of the container can be sterilized while the container is cooling (e.g., from ambient temperature to cryogenic temperature), while the container is preheating (e.g., from cryogenic temperature to ambient temperature), or while the container is between uses (e.g., while the inside of the container is at ambient temperature), or during transport (e.g., while the inside of the container is at cryogenic temperature).

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

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

[0129] When multiple ultraviolet light sources are used in the device, specific parts of the ultraviolet light sources may be activated, and accordingly, ultraviolet light of different intensities may be provided to different parts 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 arranged to provide increased sterilization of the base portion facing the cavity compared to other surfaces of the container facing the cavity.

[0130] Optionally, the ultraviolet light source(s) may include an optical fiber or a light guide that transmits ultraviolet light into the interior of the container. When ultraviolet light is transmitted into the interior of the container using an optical fiber or a light guide, the heating provided into the interior of the container is minimized.

[0131] As described above, the interior of the container may be arranged to reflect ultraviolet light, and accordingly, the interior of the container is irradiated by the reflection of ultraviolet light from the walls and / or base of the container. Additionally or alternatively, ultraviolet light source(s) may be arranged within the device such that the entire interior of the container is in a direct line of sight to one or more of the ultraviolet light source(s).

[0132] Ultraviolet light source(s) can be powered by an electrical connection to a grid or by battery operation (as in the devices (70, 82) shown in FIG. 11 and 12 and the device (100) shown in FIG. 16).

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

[0134] Optionally, the total irradiation dose from the ultraviolet light source(s) can be controlled by adjusting the power supplied to the ultraviolet light source(s) according to requirements. For example, supplying additional power to the ultraviolet light source(s) can increase the intensity of the ultraviolet light provided by each individual ultraviolet light source. Additionally, or alternatively, supplying additional power to the ultraviolet light source(s) can cause additional ultraviolet light source(s) to be activated in cases where only some of the ultraviolet light source(s) are activated when less power is supplied.

[0135] The total irradiation dose may be controlled manually (for example, the device may include a control unit that allows the user to control the provided total irradiation dose). Alternatively, the total irradiation dose may be controlled automatically (for example, the device may include a timer that controls the total irradiation dose provided by the ultraviolet light source(s) over time).

[0136] Alternatively, the total irradiation dose from the ultraviolet light source(s) can be controlled by adjusting the irradiation time of the ultraviolet light source(s) (i.e., the amount of time each ultraviolet light source is turned on). The adjustment of the irradiation time of the ultraviolet light source(s) can be manual (e.g., the device may include a control unit that allows the user to adjust the irradiation time) or automatic (e.g., using a timer). As another alternative, the total irradiation dose provided by the ultraviolet light source(s) 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(s) may also be adjusted. If the ultraviolet light source is automatically controlled, the function of the ultraviolet light source can be remotely recoded.

[0138] Optionally, irradiation provided by ultraviolet light source(s) may be recorded. Recording the irradiation provided by the ultraviolet light source provides a record of sterilization provided by the ultraviolet light source(s), allowing an operator to verify whether the container has been sterilized. The irradiation provided by the ultraviolet light source(s) may be recorded by one or more ultraviolet light detectors arranged within the container.

[0139] Optionally, the device may include an alarm that provides a warning sound when the ultraviolet light source(s) are turned on. Alternatively or additionally, the device may include a warning light that is illuminated when the ultraviolet light source(s) are turned on.

[0140] Optionally, the ultraviolet light source(s) may be turned off when the delivery system is opened during the irradiation cycle. To turn off the ultraviolet light source(s) when the delivery system is opened, the connection between the container and the stopper or lid may be arranged so that a switch connected in series with the ultraviolet light source(s) closes when the lid, stopper, or cartridge is fitted into the container, in which case the circuit is shorted when the lid, stopper, or cartridge is removed from the container. Alternatively, the user may be unable to open the delivery system while the ultraviolet light source(s) are turned on. For example, the stopper, lid, or cartridge fitted into the container may be locked to the container while the ultraviolet light source(s) are activated (e.g., automatically locked). That is, the switch controlling the ultraviolet light source(s) may also control a locking mechanism that locks the lid, stopper, or cartridge to the container while the ultraviolet light source(s) are turned on.

[0141] Optionally, ultraviolet light source(s) are positioned within the delivery system, and accordingly, when the delivery system is open during the irradiation cycle, ultraviolet light is not irradiated to the user. For example, a power supply unit may be mounted on the container. The power supply unit can be connected to the mains power. When the cartridge is mounted on the container, it may form an electrical connection with the power supply unit. This electrical connection may be made via pogo pins, via connections typically found on kettles, or via any other suitable connector, preferably allowing the formation and disconnection of the electrical connection to be easily implemented. When the cartridge is removed from the container (i.e., lifted), the electrical connection may be short-circuited so that the ultraviolet light is automatically turned off. Alternatively, or additionally, a light sensor (using light of a different frequency than the ultraviolet light used for sterilization) may be able to control the ultraviolet light to operate only in a dark environment.

[0142] Optionally, the device includes a detector arranged to detect whether a lid, stopper, or cartridge has been removed from the container during an irradiation cycle. If the detector detects that the container has been opened, the detector may transmit a signal to the controller of the ultraviolet light source(s) so that the ultraviolet light source(s) can be deactivated.

[0143] In some examples, the thermal mass may not be contained in the container. The stopper described herein is suitable for use with such examples.

[0144] In some examples, a stopper designed to insulate the interior of a container from the surrounding environment may include an insulating segment and one or more barriers to reflect infrared radiation. In these examples, the insulating segment may be relatively thick. For example, the insulating segment may extend along most of the longitudinal length of the stopper.

[0145] One or more barriers for reflecting infrared insulation may be placed adjacent to the insulation segment(s) when in use, for example, above the insulation segment(s) (i.e., further from the cavity of the container than the insulation segment(s)). Since infrared radiation increases with temperature (proportional to powers of 4), determining the placement of one or more barriers further from the cavity—that is, at a location where the temperature is typically higher—may be most important for the reflection of infrared radiation.

[0146] The singular terms "a" and "an" should not be considered to mean "only one." Rather, unless otherwise specified, they should be considered to mean "at least one" or "more than one." The word "including" and its derivatives including "to include" and "includes" each include the specified feature, but do not exclude the inclusion of one or more other features.

[0147] The above implementation is described merely as an example, and the described implementation is not limiting in all respects and should be considered merely exemplary. It will be understood that variations of the described implementation may be made without departing from the scope of the invention. Furthermore, it will be apparent that there are many variations that are not described but fall within the scope of the appended claims.

Claims

Claim 1 A stopper for insulating the interior of a container from the surrounding environment, wherein the stopper comprises a plurality of insulating segments; and a plurality of barriers for reflecting infrared radiation, wherein one or more of the plurality of barriers are arranged between the insulating segments, and the stopper further comprises a vent channel passing through the plurality of insulating segments and one or more barriers. Claim 2 A plug according to claim 1, characterized in that it comprises at least three insulating segments, and each barrier for reflecting infrared radiation is provided between each adjacent insulating segment. Claim 3 A stopper according to claim 1 or 2, wherein the stopper further comprises a first part and a second part, and the first part is arranged to be inserted into the container when the stopper is fitted into the container. Claim 4 A stopper according to paragraph 3, further comprising one or more seals arranged to be compressed between the second part and the end or interior of the container wall when the stopper is fitted into the container. Claim 5 In paragraph 3, the stopper further comprises a clamp arranged to attach a second portion to the wall of the container. Claim 6 In paragraph 1 or 2, the vent channel comprises one or more valves and cavities in the path of the vent channel, and the cavity is located in an area of ​​the vent channel configured such that the air temperature of the vent channel is 0 degrees Celsius when in use, a plug. Claim 7 A plug according to claim 1 or 2, wherein the plug further comprises one or more chambers, each chamber accommodating at least one of a plurality of insulating segments and at least one of one or more barriers for reflecting infrared radiation. Claim 8 In claim 7, each of one or more chambers comprises a bottom and a side wall that create a cavity, and at least two of a plurality of insulating segments and at least one of one or more barriers for reflecting infrared radiation are located within the cavity, a plug. Claim 9 In claim 8, the plug further comprises at least one spacer, each spacer is positioned between adjacent insulating segments in each cavity, and one or more barriers for reflecting infrared radiation are positioned on the top and / or bottom surface of at least one of the plurality of insulating segments. Claim 10 A stopper according to claim 1 or 2, wherein the stopper further comprises an ultraviolet light source with an output sufficient to provide sterilization inside the container when used. Claim 11 A delivery system for maintaining a frozen sample, wherein the system comprises: a container containing a thermal mass; and a stopper according to claim 1 or 2. Claim 12 In claim 11, a delivery system satisfying one or more of i) to iv): i) the container comprises at least one sensor and at least one controller; ii) the stopper comprises at least one sensor and at least one controller; iii) the stopper comprises a connector, and the container communicates electrically with the stopper through a connection to the connector; and iv) at least one of the stopper and the container comprises a transceiver configured to wirelessly transmit information coming from at least one of the sensors. Claim 13 A method for preparing a delivery system for maintaining a frozen sample, wherein the method comprises the steps of: loading the frozen sample into a container; and fitting a stopper according to claim 1 or 2 into the container to insulate the inside of the container from the surrounding environment. Claim 14 In claim 13, a method comprising one or more of i) to iii): i) cooling the inside of a container to a desired temperature; ii) cooling the inside of a container to a desired temperature by a) inserting a heat engine into the container to remove heat from the inside of the container or b) injecting a cryogenic fluid into the container and then emptying the cryogenic fluid from the container; and iii) cooling a thermal mass inside the container to a desired temperature. Claim 15 delete Claim 16 delete Claim 17 delete Claim 18 delete Claim 19 delete Claim 20 delete

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