Devices for the storage and transport of biological materials

Abstract

The present technology relates to devices and methods for preserving biological materials, such as refrigerated biological materials, such as cells, tissues and organs, for storage and / or transportation. The devices and methods of the present technology preserve biological materials at a target temperature of 8°C to ‑40°C for an extended period of time, such as at least 4 hours. The target temperature and extended period of time can be achieved by using a cold source such as a phase change material (PCM), in combination with an insulating material such as a vacuum insulation panel (VIP) and / or aerogel.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Application No. 63 / 003,073, filed on March 31, 2020, the disclosure of which is hereby incorporated by reference in its entirety for all purposes. Technical Field

[0003] The present technology relates to devices and methods for storing and transporting biological materials, such as DNA, RNA, proteins, lipids, biologics, cellular components, natural and engineered cells, natural or engineered tissues, and organs. Background Art

[0004] The transportation of biological materials can be challenging when they must be maintained within a narrow temperature range in a passive manner due to the inaccessibility or unreliability of refrigeration power during transportation. Currently, biological materials are stored at cryogenic conditions using liquid nitrogen (-140°C to -196°C) or dry ice (-78°C) and transported in Dewar flasks. However, cryoprotectants have been developed that can be stored at high sub-zero temperatures, such as 0°C-20°C, which have the same protective effect as the same biological materials at much lower temperatures associated with liquid nitrogen and dry ice. In order to ensure the safe storage and / or transportation of biological materials and maximize the viability after storage and / or transportation, it is necessary to store the samples in a suitable device or container at a temperature higher than that which can be maintained by liquid nitrogen and dry ice. Therefore, there is a need for devices and methods for transporting biological materials at high sub-zero temperatures of 0°C to -40°C without the use of dry ice or liquid nitrogen. SUMMARY OF THE INVENTION

[0006] The present technology relates to devices and methods for preserving biological materials of any source, and in particular refrigerated biological materials, including DNA, RNA, proteins, lipids, biologics, cellular components, natural and modified cells, natural or modified tissues, and organs, for storage and / or transportation. The devices and methods of the present technology preserve biological materials at a target temperature of 8°C to -40°C (e.g., 2°C to 8°C or 0°C to -40°C) for an extended period of time, such as at least 4 hours. The target temperature and extended period of time can be achieved by using a cold source, such as a phase change material (PCM), in combination with an insulating material, such as a vacuum insulation panel (VIP) and / or aerogel. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The present disclosure will be readily understood by the following detailed description taken in conjunction with the accompanying drawings, in which like reference numerals represent like structural elements, and in which:

[0008] Figure 1A A biomaterial transport device according to an embodiment of the disclosed technology is shown.

[0009] Figure 1B Shown is a cross-section of a biomaterial transport device according to an embodiment of the disclosed technology.

[0010] Figure 1C Shown is a cross-section of internal components of a biomaterial transport device according to an embodiment of the disclosed technology.

[0011] Figure 1D An exploded view of a biomaterial transport device according to an embodiment of the disclosed technology is shown.

[0012] Figure 2 An insulating assembly according to an embodiment of the disclosed technology is shown.

[0013] FIG. 3A to FIG. 3D Views of a cold source assembly and portions thereof are shown according to embodiments of the disclosed technology.

[0014] FIG. 4A to FIG. 4N Views of biomaterial containers for cell and tissue samples and portions thereof are shown in accordance with embodiments of the disclosed technology.

[0015] FIG. 5A to FIG. 5E A view showing a biomaterial container according to an embodiment of the disclosed technology is shown.

[0016] 6A to 6F A view showing a biomaterial container for an organ according to an embodiment of the disclosed technology is shown.

[0017] FIG. 7A to FIG. 7C Shown are views of embodiments of an organ tray in accordance with embodiments of the disclosed technology.

[0018] Figure 8 Shown is a cross section of an assembly including a magnetic coupling according to an embodiment of the disclosed technology.

[0019] 9A to 9C Data related to storage of biological materials according to embodiments of the disclosed technology are shown. DETAILED DESCRIPTION OF THE INVENTION

[0021] The present technology includes devices and methods for transporting biological materials. In an embodiment, for example, as shown in Figure 1, a biological transport device 100 includes a housing 102, an insulation assembly 200, a cold source assembly 300, and one or more containers 400 500 600 for contacting biological materials. The biological transport device can be used to transport biological materials, such as cells, tissues and organs. The biological material can be refrigerated during transportation and passively maintained at a target temperature over an extended period of time. The target temperature can be 8°C to -40°C, and more specifically can be a sub-zero range of 0°C to -15°C (i.e., 0°C> target temperature>-15°C). The extended time period can be at least 4 hours, and up to 10 days or more days, or any duration therebetween. By using a cold source such as a phase change material (PCM) and combining thermal insulation materials such as vacuum insulation panels (VIP) or aerogels, the target temperature can be maintained over a long period of time. Without changing the cold source and without using power refrigeration, the temperature of the biological material can be maintained within a predetermined tolerance range of the target temperature over the entire extended period of time. The predefined tolerance may be based on the type of cryoprotectant used and / or the type of biological material being transported or stored. The predefined tolerance may be between ±0.5°C and ±5°C.

[0022] shell

[0023] The device for transporting biological materials may include an outer housing, which may also be referred to as an outer shell. The outer shell may serve as a protective cover for the internal components of the device. Figure 1A and 1B An embodiment of a device 100 including a housing 102 is shown. The device 100 is shown with the housing 102 in a closed configuration. The housing may include a lower housing portion 104 and a cover 106. The lower housing portion 104 of the body 102 defines a cavity, which may be referred to as a first cavity. Figure 1B As shown in the cross-section of , the cavity of the lower housing portion 104 accommodates the insulation assembly 200, the cold source assembly 300, and one of the plurality of containers 400, 500, 600, 700 containing biological materials, as discussed in more detail below. In an embodiment, the insulation layer can be integrally formed in the lower housing portion 104 and the lid 106.

[0024] The housing may be of any shape. Figure 1A and Figure 1BAs shown, the housing is generally cylindrical. As shown, the lower housing portion defines a generally cylindrical first cavity for accommodating other components of the device, including but not limited to: an insulation layer, a cold source, and a biomaterial container. In an embodiment, the lid can form a watertight and / or airtight seal with the lower housing portion. The lid can be coupled with a hinge so that the lid can pivot between an open / load configuration and a closed / sealed configuration. In an embodiment, the lid and / or the lower housing portion can include a latch for maintaining a seal and preventing the housing from accidentally opening.

[0025] To protect the physical integrity of the device and ensure safe transport of the biomaterial at the target temperature, the housing is made of a material that is rigid and does not become brittle at low temperatures, such as the temperature target of the biomaterial. In addition, the housing includes a material with low thermal conductivity or high thermal resistivity. Non-limiting examples of suitable materials that can be used to construct the housing include expanded polystyrene (EPS) and expandable polypropylene (EPP).

[0026] In an embodiment, the housing may include elements that facilitate movement or carrying, such as wheels, straps, and handles. For example, the lower housing portion may include wheels on casters on the underside, and the lid may include handles around the perimeter to allow the device to be pushed in any direction along a surface. The housing may be considered a "hard shell" to resist deformation from an external pressure of about 90 to about 110 kPa at a temperature of about -40°C to about 50°C.

[0027] Thermal insulation assembly

[0028] like Figure 1B As shown, the insulation assembly 200 can be located in the first cavity of the housing. The insulation assembly 200 includes one or more materials with low thermal conductivity. The insulation assembly forms a second cavity. In an embodiment, the second cavity can be cylindrical. In an embodiment, for example, Figure 2 As shown, the insulation assembly 200 includes a bottom insulation board 202, a cylindrical insulation sidewall panel 204 and an insulation cover 206, which define a closed cylindrical second cavity. Each of the bottom insulation board 202, the cylindrical insulation sidewall panel 204 and the insulation cover 206 can include an outer layer that is impermeable to gas or liquid that defines the internal volume of the panel. The internal volume of the panel assembly of the insulation assembly can be vacuum. In addition, the internal volume can include a getter material that absorbs trace gases in the internal volume to maintain a vacuum. Non-limiting examples of getter materials include substances (e.g., metals, oxides, etc.), including one or more of titanium, sodium, potassium, magnesium, calcium, strontium, barium, cesium-rubidium alloys, tantalum, zirconium and rare earth elements (e.g., hafnium).

[0029] In an embodiment, the components of the insulation assembly can each be a vacuum insulation panel (VIP). For example, a cylindrical insulating sidewall panel can be a cylindrical VIP panel. The VIP can include a fiberglass core and an adsorbent material sealed within an outer layer of a laminate film. The adsorbent and outer film together maintain the integrity of the vacuum. At least a portion of the insulating properties of the VIP is due to the internal vacuum. In a vacuum, heat transfer by conduction and convection is suppressed. In an embodiment, the insulation layer includes two or more layers of VIP panels.

[0030] In an embodiment, each component of the insulation assembly may include a vacuum port in fluid communication with the interior space of each component. The vacuum port may be connected to a vacuum pump for evacuating air from the interior volume of each panel to define a vacuum.

[0031] In an embodiment, the components of the insulation assembly include aerogels in the internal volume. Aerogels are synthetic porous materials with low thermal conductivity and very low density, which are derived from gels in which the liquid components of the gel are replaced by gases. Aerogels can be produced by using supercritical drying to extract the liquid components of the gel, slowly drying the liquid without causing the solid matrix in the gel to collapse. The advantage of aerogels is that they achieve low heat transfer rates and do not lose strength when subjected to vacuum. In an embodiment, the aerogels are selected from, but are not limited to, silica aerogels, alumina aerogels, zirconia aerogels, carbon aerogels, boron aerogels, tungsten aerogels, titanium dioxide aerogels, aerogels made from sol-gel polymerization of resorcinol and formaldehyde, and aerogels made from sol-gel polymerization of melamine and formaldehyde. In an embodiment, the aerogels are arranged in a metallized polyethylene layer.

[0032] Cold source assembly

[0033] like Figure 1CAs shown in the cross section, the heat sink assembly 300 is located between the heat insulation assembly 200 and one or more containers 400 that keep the biomaterial. The heat sink assembly absorbs heat energy from the environment and the biomaterial so that the biomaterial is maintained at the target temperature. In an embodiment, the heat sink assembly 300 comprises a plurality of panels. The panels are assembled to limit the hollow cavity to receive one or more containers that contain the biomaterial. In an embodiment, the assembly shape of the heat sink assembly panels can be, for example, a cylinder, a multi-prism (for example, a cube, a rectangular prism, a pentagonal prism, a hexagonal prism, an octagonal prism) or a sphere. In an embodiment, the panels of the heat sink assembly can limit the sub-portion of the inner cavity of the heat sink assembly separately. For example, a cylindrical heat sink assembly can be composed of two panels, each panel is a cylindrical side half, and each panel limits the semi-cylindrical sub-portion (i.e., curved sidewall, semicircular top and semicircular bottom) of the cylindrical inner cavity. In addition, for example, the cylindrical heat sink assembly can include two or more panels, each panel is a longitudinal portion of the cylindrical assembly, and each panel defines a cylindrical sub-portion of a longer cylindrical inner cavity defined by the longitudinally stacked cylindrical panels. The longitudinal portion can be any relative longitudinal length relative to each other, for example, two cylindrical panels can each be half of the longitudinal length of the heat sink assembly. In an embodiment comprising a polygonal prism heat sink assembly, the panel of the heat sink assembly can include a bottom panel and a top panel of a polygonal shape, and a plurality of rectangular side panels corresponding to the number of sides of the polygon.

[0034] In one embodiment, for example, Figure 3A and Figure 3B As shown, the plurality of panels of the cold source assembly 300 include a bottom panel 302, a plurality of curved side wall panels 304, and a top cover panel 306. In an embodiment, for example, Figure 3A and Figure 3B As shown, the panels of the heat sink assembly can be assembled to define an overall hollow cylindrical heat sink container, wherein a subset of the panels, and as shown, the curved sidewall panels 304 define the radial sides of the hollow cylinder. Figure 1C As shown in the cross-section of FIG. 1 , the hollow center of the cold source assembly accommodates a container for holding biological material, such as container 400 , 500 , 600 , and 700 .

[0035] In an embodiment, the panels of the heat sink assembly may include features for retaining adjacent panels in an assembled configuration, such as interlocking tabs and corresponding grooves along adjacent edges / faces of adjacent panels. Figure 3A and Figure 3BAs shown, the panel of the cold source assembly includes a periphery with a tongue and groove feature 308, and when in an assembled configuration, the tongue and groove feature 308 forms a tongue and groove joint with the adjacent panel of the cold source assembly. Interlocking lugs and corresponding grooves, such as tongue and groove joints, have multiple advantages, including self-alignment of the panel, improved structural integrity and reducing the space between the panels, which would undesirably allow air to flow into the hollow center cavity of the cold source assembly for accommodating the biomaterial container. In an embodiment, the interlocking lugs and corresponding grooves define the portion of the internal volume of the panel containing the PCM, which will be discussed in more detail below.

[0036] To assemble the heat sink assembly, the panel can be assembled outside the second cavity of the heat insulation assembly and / or inside the second cavity of the heat insulation assembly. Figure 3A and Figure 3B The cold source assembly of the heat insulation assembly is related to the bottom panel that can be placed on the bottom of the second cavity of the heat insulation assembly. Then, the first side wall panel is vertically placed in the second cavity of the heat insulation assembly, and cooperates with the corresponding tongue and groove features of the bottom panel. Then the second side wall panel is vertically placed in the space of the heat insulation assembly, and cooperates with the corresponding tongue and groove features of the bottom panel and the installed side wall panel. Repeat this step for each side wall panel, thereby forming a cold source sub-assembly with an open top, wherein the hollow center is open from above. Then the container containing the biomaterial can be placed in the sub-assembly, and the top panel of the cold source assembly can be placed on the top of the sub-assembly, and cooperate with the tongue and groove features of each side wall panel. In this configuration, all sides of the container are surrounded by cold source panels. In an embodiment, the cold source assembly can be assembled around the container before the cold source assembly is placed in the heat insulation assembly. For example, a heat sink assembly comprising two panels, each panel defining a side half of a cylinder, can be placed around one or more containers containing biomaterial, and a cylindrical assembly of two heat sink panels and containers containing biomaterial can be placed together with an insulating assembly.

[0037] The size and shape of the container containing the biological material can be substantially the same as the third cavity of the cold source assembly, for example Figure 1CAs shown in the cross-sectional view. In addition, the size and shape of the heat sink assembly can be substantially identical with the second cavity of the heat insulation assembly. The close nesting of the heat insulation assembly, the heat sink assembly and the container provides the advantage of preventing the biomaterial from moving during transportation and preventing ambient air from occupying the gap and increasing the biomaterial temperature. In addition, the heat insulation assembly provides the structural support to the heat sink assembly by the outer surface of the paneling of the direct contact heat sink assembly. In an embodiment, after the cover paneling of the heat sink assembly is located on the subassembly of other heat sink panels, the cover paneling of the heat insulation assembly can be closed by the cylindrical sidewall of the heat insulation assembly, and the cover of the lower shell part closed shell can be used, so as to fully seal the biomaterial in the device.

[0038] Each panel of the cold source assembly can include a shell defining one or more connected and / or separated internal spaces. For example, the panel defining the side wall of the cold source assembly can have separate upper and lower internal spaces. The internal space of each panel of the cold source assembly can contain a material that can absorb heat, such as a phase change material or a low-temperature material. Phase change material (PCM) is a substance with high melting heat, and when it melts at a specific temperature, it absorbs a large amount of heat energy during the melting process due to the high melting heat. On the contrary, after solidification at a specific temperature, PCM releases a large amount of heat energy. The specific temperature at which PCM changes from solid to liquid or from liquid to solid is a characteristic of a specific PCM. In an embodiment, PCM is selected to make the target temperature of biomaterial transportation consistent with the specific temperature at which PCM changes from solid to liquid. For example, if the biomaterial is to be stored and / or transported at a temperature of about -5°C, a PCM that melts or solidifies at a temperature of about -5°C is selected. For further example, if the biomaterial is to be stored and / or transported at a temperature of about -20°C, a PCM that melts or solidifies at a temperature of about -20°C is selected. In an embodiment, any target temperature can be achieved by selecting a PCM material or a combination of PCM materials that results in melting or solidification at the desired temperature. In addition, the volume / mass of PCM used in the panels of the heat sink assembly is based on considerations such as the desired length of time to maintain the biomaterial at the target temperature, the amount, mass or size of the biomaterial, the thermal conductivity of the insulation layer, and the expected operating environment conditions.

[0039] As used herein, some PCMs may be classified as "sub-zero PCMs," which are PCMs having a melting and / or solidification temperature below, but not including, 0° C. In addition, as used herein, some PCMs may be classified as "non-sub-zero PCMs," which are PCMs having a melting and / or solidification temperature above and including 0° C. (e.g., water / ice and glycerol). Non-limiting examples of PCMs include paraffin wax, lithium chloride, n-tetradecane, 1-decanol, n-pentadecane, chloroacetic acid-o-cresol eutectic, tetradecylbenzene, sodium chromate decahydrate, n-octanoic acid, chloroacetic acid-phenol eutectic, acetic acid, 37% NaSO4 , 17% NaCl and 46% H 2 O salt mixture, 1-octadecene, glycerol, n-hexadecane, polyethylene glycol 600, water double inclusion complex with tetrahydrofuran and hydrogen sulfide, lithium chloride ethanolate, n-heptadecane, copper nitrate hexahydrate, lactic acid, manganese nitrate hexahydrate, n-octadecane, methyl palmitate, 3-methylpentane, orthophosphoric acid hemihydrate, lithium nitrate trihydrate, calcium chloride hexahydrate, gallium, sodium sulfate decahydrate, levulinic acid and n-eicosane.

[0040] In an embodiment, the PCM in the heat sink panel is charged prior to use by cooling the panel to a temperature below the solidification temperature of the selected PCM. For example, charging is accomplished by placing the heat sink panel containing the PCM in a cold room (e.g., a freezer). In an embodiment, for example, Figure 3A and Figure 3B As shown, the bottom panel and the top panel of the cold source assembly can be flat and space-efficient in the freezer space. The sidewall panel can be shaped as the radial portion of the hollow tube. The advantage of this shape is that it can be stacked in various configurations so as to occupy less freezer space than a single hollow tube. For example, the sidewall panels can be stacked so that the curved surface of the outside of one sidewall panel faces the inner curved surface of the second sidewall panel. In an embodiment, the curved surface of the outside of one sidewall panel contacts the inner curved surface of the second sidewall panel. For example, the sidewall panels can be stacked like the roof tiles in the freezer space.

[0041] In an embodiment, the PCM of the cold source panel can be charged by filling a cooling coil arranged in the PCM with a refrigerant (e.g., cold gas). In addition, in an embodiment, the PCM can be charged using a cryogenic material. Non-limiting examples of suitable cryogenic materials include solid carbon dioxide, compressed gas, and liquid nitrogen. When a cryogenic material is used, the cryogenic material can be placed, for example, in one or more cutouts placed in the cold source panel containing the PCM for the purpose of receiving the cryogenic material.

[0042] In an embodiment, the PCM may be activated by mixing two components, each stored in a separate compartment within each panel of the heat sink assembly, which react using an endothermic reaction.

[0043] In an embodiment, the PCM is charged while placed in the device. In an embodiment, the PCM is placed into other components of the device (e.g., housing and insulation assembly) after the PCM is charged. In an embodiment, a cryogenic material is used to charge the PCM within the device.

[0044] The particular PCM, volume / mass of the PCM, and thermal conductivity of the insulating assembly are selected to enable the device to maintain the biological material at the target temperature for the desired length of time.

[0045] In embodiments, the PCM may be permanently sealed in each panel of the heat sink assembly, or the PCM may be reversibly insertable into each panel of the heat sink assembly, for example using valves or ports on the outer surface of the panel wall.

[0046] Figure 3C Another embodiment of the cold source assembly is shown. As shown in the figure, the main panel is Figure 3A and Figure 3B The thickness of the body panel may determine the internal volume, and the thickness may be selected based on the volume of PCM required to reach the target temperature for the target duration.

[0047] Figure 3D Shown is an embodiment of a bottom panel 302 of a cold source assembly 300. The bottom panel comprises an upper portion 310 and a lower portion 312, wherein the upper portion 310 has an upper groove 311 for accommodating a first magnetic wiring coupler 314, and the lower portion 312 has a lower groove 313 for accommodating a second magnetic wiring coupler 316. The couplers are connected by wires extending from each coupler to the periphery of the bottom panel so as to reduce the thermal bridge between the two couplers. The magnetic coupling on the upper side engages with a complementary coupler on a container placed in the cold source assembly, as will be described in more detail below. The magnetic coupling on the lower side engages with a complementary coupler on the insulation assembly.

[0048] container

[0049] In an embodiment, one or more containers holding biological materials are placed in the empty space of the sink assembly, e.g. Figure 1C As shown, one or more containers can be specific for the type of biological material being transported. For example, one or more containers can be specific for transporting cells, tissues, and / or organs. For example, FIG. 4A to FIG. 4N Different views of containers used to transport cell and tissue samples are shown. Figure 4A As shown in the exploded view of FIG. 4 , the container 400 includes a body portion 402, a cover 404, a vial 406 for a biological material sample, and a component 408 of a vial unloading assembly 410. The body portion 402 defines a cylindrical opening for placing the vial 406 in the body portion 402, such as Figure 4B The main body portion may be aluminum or another highly thermally conductive material, such as another metal, so that heat is transferred from the biological material to be absorbed by the heat sink assembly to maintain the target temperature. The cover 404 may be sealed to the main body portion 402, such as Figure 4C and Figure 4DAs shown. The vial unloading assembly 410 can be used to pull the vial 406 out of the main body 402, such as Figure 4E and Figure 4F shown. FIG. 4G to FIG. 4I A view of the main body portion 402 is shown. Figure 4J Another embodiment of a vial unloading assembly 410 is shown, and Figures 4K to 4N Shows Figure 4J Unload the assembly into the unloading vial.

[0050] For processing purposes, in embodiments, the container holding the biological material may be an inner container and may be placed within the outer container 500, e.g. FIG. 5A to FIG. 5C The outer container may include features, such as ribs, that allow a user to easily handle and open the outer container.

[0051] FIG. 5D to FIG. 5F Shows something like FIG. 5A to FIG. 5C The embodiment of the embodiment of the outer container 500-1 of the outer container 500 shown. The outer container 500-1 includes a body portion 502, a lid 504 and a compression clip 508 for sealing the lid. The outer container 500-1 includes a foldable handle 512, which is rotatably connected to the lid 504 for manipulating the outer container 500-1. In an embodiment, the outer container, such as 500 and 500-1, includes a groove to receive an alignment magnet for engagement with a cold source assembly.

[0052] In embodiments, for example, FIG. 6A to FIG. 6D As shown, the container for transporting the organ can be placed in one or more external containers placed in the cold source assembly. Examples of organs to be transported include, but are not limited to, the heart, kidney, pancreas, liver, intestines, and lungs. Fig.6D As shown in the exploded view of , the container 600 includes a body portion 602, a lid 604, a sealing ring 606, and a compression clip 608 for sealing the lid. The volume of the container can be between about 200 mL and about 2,000 mL. Body portions 602 of different sizes can be coupled to the sealing ring 606 to achieve containers of different volumes with the same closure mechanism. In an embodiment, the sealing ring 606 can be coupled to the body portion 602 using an adhesive, threads, a press fit, or a clip. FIG. 6A to FIG. 6C As shown, the cover 604 includes a first cover 610 and a second cover 612, which can be used to fill the container with a fluid, such as a cryoprotectant, and to remove air bubbles, respectively.

[0053] Fig. 6E and 6F An embodiment of a container 600-1 for transporting an organ is shown, which is similar to FIG. 6A to FIG. 6DContainer 600 is shown. Container 600-1 also includes a body portion 602, a lid 604, a sealing ring 606, and a compression clip 608 for sealing the lid. The lid of container 600-1 includes a single cap 611 for filling the container with a fluid, such as a cryoprotectant, and for venting air bubbles. Container 600-1 also includes a foldable handle 612 that is rotatably coupled to the lid 604 for manipulating container 600-1. The body portion 602 of container 600-1 defines a recess 614 that is sized to accommodate wiring for a sensor, such as a thermocouple coupled to the exterior of the body portion for determining the temperature inside the container.

[0054] The volume of the container holding the biological material is waterproof when sealed. During use, the volume of the container holding the biological material may contain a cryoprotectant composition, such as, but not limited to, a cryoprotectant composition disclosed in U.S. Pat. No. 9,986,733 assigned to X-Therma Inc, the contents of which are incorporated herein by reference for all purposes. The cryoprotectant composition can be used to reduce or prevent freezing damage caused by ice crystal formation. In an embodiment, the cryoprotectant composition preserves the biological material for a longer period of time than when the biological material is not exposed to a reduced temperature. In an embodiment, using, for example, a cryoprotectant composition disclosed in U.S. Pat. No. 9,986,733, it is advantageous to store the biological sample between 0°C and -15°C to avoid ice formation and thus ice phase transitions. In addition, in an embodiment, it is advantageous to store the biological sample, particularly partially frozen, at a temperature range including even lower temperatures, such as 0°C to -40°C, so as to provide further metabolic protection due to lower temperatures.

[0055] Organ Tray

[0056] In embodiments, an organ tray for supporting and limiting the movement of an organ in a container for transporting an organ can be used. The organ tray can include one or more panels, which are for example connected together by hinges, buckles and / or integrally formed clips to limit the inner cavity in which the organ is placed. The one or more panels of the organ tray can include holes for allowing cryoprotectants to flow around the organ positioned in the organ tray. The organ tray can also include a handle extending from one or more panels to allow the organ tray to be inserted and removed from the container. FIG. 7A to FIG. 7C An embodiment of an organ tray 700 is shown. The organ tray 700 can be positioned within the container 600. As shown, the organ tray 700 includes a bottom 702 and two side portions 704. The side portions 704 are pivotally coupled to the bottom 702, which has hinges, so that the organ tray can be moved in a variety of ways, such as Fig. 7A The open configuration shown is the same as Figure 7BThe organ tray 700 can be switched between closed configurations in the open configuration. The organ can be placed into the organ tray in the open configuration, transported in the closed configuration, and removed from the organ tray in the open configuration. The bottom 702 and the side 704 can each define a plurality of slots 706 that allow cryoprotectant to flow around the organ positioned in the organ tray. The organ tray 700 also includes a handle 708 coupled to each side 704. The handle can be used to place the organ tray in / out of the container 600.

[0057] Additional Features

[0058] In an embodiment, the device includes computer hardware and software, including a processor, storage, memory, user input device, and sensor, which is configured to sense, detect, record, transmit (e.g., to a remote server (e.g., but not limited to a cloud server), a mobile device, a desktop computer, or a combination thereof), and / or report the value of a parameter, such as temperature, humidity, position, motion, time, lid opening. In an embodiment, the device includes one or more of the following: a temperature sensor, an external temperature sensor, a humidity sensor, a motion sensor, a global positioning system (GPS) antenna, a cellular network and / or a Wi-Fi antenna, a lid opening sensor, a digital display, a keyboard, an audible alarm device, a memory storage unit, and a power source (e.g., a battery and / or a socket that can be connected to an external power source). Any component of the system can be connected by wire or wireless means, such as RFID, UFID, Bluetooth, or a combination of the two.

[0059] In embodiments, the device includes a digital display, which may include, but is not limited to, a light emitting diode (LED) or a liquid crystal display (LCD). In embodiments, the digital display reports one or more parameters selected from the temperature of the container, the external temperature, the humidity in the container, the time elapsed since the biomaterial was placed in the container, a visual temperature and / or humidity alarm, the amount of motion detected in the container, the number of uncapping events since the biomaterial was initially placed and / or sealed in the container, the time and / or position of the uncapping event, the elapsed time of the uncapping event, and the power supply (e.g., battery) level. In addition, one or more of these parameters can be transmitted from the device (e.g., via a cellular or Wi-Fi antenna) to a remote server, a mobile device, and / or a desktop computer, for example, so that a user can use real-time information about the device and / or the biomaterial state (e.g., the temperature of the internal container or the biomaterial). In embodiments, the event log is stored in the device (e.g., in a memory storage unit) and / or on a remote server, and is subsequently available to the user (e.g., information is reported by a digital display on the device and / or mobile device or desktop computer). As non-limiting examples, the event log can report the location of the device (e.g., GPS coordinates), the time the location was recorded (e.g., local time), the time since the biological material was placed or sealed within the device, the location and / or time the device lid was opened, the time the device lid was opened (e.g., local time), the elapsed time of the opening event, and the amount of motion detected in the container (e.g., the amount of motion experienced by the biological material).

[0060] Figure 8 A portion of the assembly is shown, showing a series of magnetic couplings 801 between the cold source base plate 302, the outer container 500, and the container 600. The magnets of each coupling 801 hold together the electrical contacts of the wiring 802 to electrically connect a sensor 803, such as a thermocouple, to a processor. As shown, the sensor is positioned at an intermediate height on the container 600 to be close to the organ within the container. The magnetic coupling is advantageous because the user of the assembly does not have to engage directly with the wiring to connect the temperature sensor, but rather the assembly of the nested components will automatically connect the sensor to the electronics.

[0061] data

[0062] 9A to 9C Data corresponding to the use of the components of the biological transport device 100 discussed above are shown. As background, organs are currently transported in plastic bags in coolers filled with ice, i.e., frozen water. Organs passing through the plastic bags may come into substantial direct contact with the ice, resulting in freezing and subsequent ice damage, which is harmful.

[0063] The first example results involve the successful preservation of murine hearts at -5°C using the components of the biotransport device 100 discussed above. Male C57BL / 6 mice were used for heterotopic heart transplantation in syngeneic donor / recipient combinations. Three groups were studied: Group 1 (baseline control group); no ischemia as a baseline control; Group 2 (experimental group); hearts stored at -5°C for 24 hours using a cryoprotectant (e.g., as described in U.S. Pat. No. 9,986,773) using the biotransport device discussed above, and Group 3 (control group); hearts stored in HTK solution at 4°C for 24 hours. Static storage was performed without machine perfusion or oxygenation. Post-transplant functional graft assessment was assessed by daily palpation. Graft viability and tissue integrity were assessed by histology, immunohistochemistry, and gene expression on post-operative days 3 and 30. The results showed that all experimental group heart grafts regained normal heartbeat and sinus rhythm on post-operative day 30 and survived at the study endpoint. The control group grafts did not regain any heartbeat. Thus, the components of the biotransport device 100 discussed above, including the use of cryoprotectants, were demonstrated to prevent ice damage at high subzero temperatures, maintain biomaterials in a stable environment, and enable successful preservation and transplantation of murine heart grafts, well beyond the critical ischemic time of conventional static cold storage.

[0064] Fig.9A 1 shows the internal temperature of the biotransport device 100 discussed above over the course of 8 days. Fig.9A As shown, TF-1 cells were stored at a consistent -16°C for an extended period of more than 7 days. TF-1 is a cell line derived from human erythroleukemia cells that is dependent on GM-CSF and interleukin 3 IL-3. Fig. 9B Post-thaw viability was assessed using the alamarBlue assay on day 0 (2 h after thawing) and day 1 (24 h after thawing) as shown. Cell viability, defined as total viable cell number after thawing / total cell number before freezing, was more than 95% after 2 h and 24 h after thawing, and the cells exhibited regular morphology, as shown in Figure 2. Fig. 9C As shown, the expression of TF-1 cells was comparable to that of fresh TF-1 cells.

[0065] The biological transport device and method of use as described above can be used for a variety of purposes. Non-limiting examples of biological samples suitable for preservation, storage and transportation of the present technology include nucleic acids (e.g., DNA, RNA), amino acids, proteins, stem cell growth factors, peptides, antibodies, lipids and complex structures (e.g., liposomes), cells, cell components (e.g., exosomes), cell clusters, tissues, tissue transplants, and some or all organs from any biological kingdom (e.g., animal kingdom (including but not limited to humans and livestock), plant kingdom, fungi kingdom (including but not limited to mushrooms), protists, archaea / archaea and bacteria / true bacteria). In embodiments, the present technology can be further used for organoids, iPSCs, MSCs, HSCs, whole bone marrow and platelets. In addition, in embodiments, the present technology can be applied to food. In embodiments, frozen foods are selected from ice cream, yogurt, seafood, freshwater products, fruits and meat products.

[0066] The various aspects, embodiments, implementations or features of the described embodiments may be used alone or in any combination. In particular, it should be understood that the various aspects, embodiments, implementations or features of the described embodiments may be combined without departing from the spirit or scope of the invention. Figures 1A to 9C elements of the concept of.

[0067] The use of the terms "a" and "an" and "the" and similar references in the context of describing the present invention (especially in the context of the appended claims) should be interpreted as covering the singular and the plural, unless otherwise stated herein or clearly contradicted by the context. Unless otherwise stated, the terms "comprising", "having", "including" and "containing" are to be interpreted as open-ended terms (i.e., meaning "including but not limited to"). Unless otherwise stated herein, the enumeration of numerical ranges herein is intended only to be used as a shorthand method of individually referring to each individual value or gradient thereof falling within the range, and each individual value is incorporated into the specification as if it were individually listed herein. Unless otherwise stated herein or clearly contradicted by the context, all methods described herein can be performed in any suitable order. The use of any and all examples or exemplary language (e.g., "such as") provided herein is intended only to better illustrate the embodiments of the present invention and does not limit the scope of the present invention unless otherwise stated. No language in the specification should be interpreted as indicating that any unclaimed element is essential to the practice of the present invention.

[0068] As used herein, the term "substantially" refers to the extent or degree of completeness or near completeness of an action, characteristic, property, state, structure, item, or result. For example, a "substantially" closed object means that the object is either completely closed or nearly completely closed. In some cases, the exact degree of deviation from absolute completeness that is permitted may depend on the circumstances. In general, however, a degree of nearness to completeness will have the same overall result as obtaining absolute completeness and completeness.

[0069] Preferred embodiments of the present invention are described herein, including the best mode known to the inventor for implementing the present invention. The present invention is susceptible to various modifications and alternative configurations, and some of its illustrated exemplary embodiments are shown in the accompanying drawings and have been described in detail above. Within the spirit of the present invention, after reading the above description, the changes of those preferred embodiments will become apparent to those of ordinary skill in the art. The inventor expects that skilled technicians will appropriately adopt such changes, and the inventor intends to practice the present invention in other ways than those specifically described herein. Therefore, it should be understood that it is not intended to limit the present invention to one or more specific forms disclosed, but on the contrary, the present invention includes all modifications and equivalents of the subject matter recorded in the appended claims where permitted by applicable law. In addition, unless otherwise specified herein or clearly contradicted by the context, the present invention includes any combination of all possible variations of the above elements. For the purpose of explanation, the foregoing description uses specific nomenclature to provide a thorough understanding of the described embodiments. However, it is obvious to those skilled in the art that specific details are not required in order to practice the described embodiments. Therefore, for the purpose of illustration and description, the foregoing description of specific embodiments is presented. They are not intended to be exhaustive or limit the described embodiments to the precise form disclosed. It will be obvious to those of ordinary skill in the art that, in view of the above teachings, many modifications and changes are possible.

Claims

1. An apparatus comprising: a housing defining a first cavity, the housing comprising a cover and a lower housing portion, the lower housing portion defining the first cavity, and the cover being hingedly coupled to the lower housing portion such that the cover is pivotable between an open configuration and a closed configuration; an insulating assembly located in the first cavity, wherein the insulating assembly includes a bottom insulating board, a cylindrical insulating sidewall panel, and an insulating cover defining a closed cylindrical second cavity; a heat sink assembly located in the second cavity, wherein the heat sink assembly comprises a plurality of panels, wherein the plurality of panels comprises a plurality of curved sidewall panels connectable to each other to form a closed boundary, wherein the closed boundary of the heat sink assembly defines a third cavity, wherein the plurality of curved sidewall panels define radial sides of a hollow cylinder of the third cavity, and wherein each of the plurality of panels comprises a phase change material; and a container located in the third cavity; The container is configured to contain a biological material, and wherein the phase change material in the panel of the heat sink assembly is configured to maintain the biological material at a target temperature of 0°C to -40°C for a target duration of at least 4 hours.

2. The device of claim 1, wherein the biological material is maintained at a temperature of 0°C to -15°C for at least 4 hours.

3. The apparatus of claim 1, wherein the container comprises a cryoprotectant composition configured to prevent cryodamage to the biological material at the target temperature for the target duration.

4. The apparatus of claim 1, wherein the insulation assembly comprises a plurality of vacuum insulation panels, and wherein the plurality of vacuum insulation panels comprise cylindrical vacuum insulation panels.

5. The apparatus of claim 1, wherein the plurality of curved sidewall panels consists of four identical curved sidewall panels, each curved sidewall panel defining one quarter of the circumference of the hollow cylinder.

6. An apparatus as claimed in claim 5, wherein the four identical curved side wall panels are configured to be stacked so that the outer curved surface of one side wall panel contacts the inner curved surface of a second side wall, so that the stacked side wall panels are placed in a refrigerator to charge the phase change material in the stacked side wall panels.

7. The apparatus of claim 5, wherein the cold source assembly comprises a circular bottom panel and a circular cover panel, and wherein each of the four identical curved side wall panels joins the circular bottom panel, the circular cover and two adjacent curved side wall panels with a tongue and groove joint.

8. The apparatus of claim 1 , wherein the insulation assembly comprises a plurality of vacuum insulation panels, wherein the plurality of vacuum insulation panels comprise cylindrical vacuum insulation panels, wherein the plurality of curved side wall panels consist of four identical curved side wall panels, each curved side wall panel defining a quarter of the circumference of the hollow cylinder, and wherein each of the curved side wall panels contacts an inner surface of the cylindrical vacuum insulation panel.

9. The apparatus of claim 1 , wherein the biological material is a cell sample, wherein the cell sample is contained in a vial containing a cryoprotectant composition configured to prevent freezing damage to the cell sample at the target temperature for the target duration, and wherein the container defines a cavity to hold the vial.

10. The apparatus of claim 1, wherein the biological material is an organ, wherein the organ is contained in a container having a cryoprotectant composition configured to prevent cryoinjury to the organ at the target temperature for the target duration.

11. The apparatus of claim 1, wherein the biological material is tissue, wherein the biological material is contained in a container having a cryoprotectant composition configured to prevent cryodamage to the biological material at the target temperature for the target duration.

12. The device of claim 11, wherein the tissue is a transplantable tissue or a modified tissue.

13. A method for transporting biological material, comprising: placing the biological material in a container; placing the container in a heat sink assembly, wherein the heat sink assembly comprises a plurality of panels, wherein the plurality of panels comprises a plurality of curved sidewall panels connectable to each other to form a closed boundary, wherein the closed boundary of the heat sink assembly defines a third cavity, wherein the plurality of curved sidewall panels define radial sides of a hollow cylinder of the third cavity, and wherein each of the plurality of panels comprises a phase change material; placing the heat sink assembly into an insulation assembly, wherein the insulation assembly comprises a base insulation board, a cylindrical insulation side wall panel and an insulation cover defining a closed cylindrical second cavity to receive the heat sink assembly; placing the insulating assembly into a housing defining a first cavity to receive the insulating assembly, the housing comprising a cover and a lower housing portion, the lower housing portion defining the first cavity, and the cover being hingedly coupled to the lower housing portion such that the cover is pivotable between an open configuration and a closed configuration; as well as The temperature of the biological material is maintained at a target temperature of 0°C to -40°C for a target duration of at least 4 hours using phase change materials in the panels of the heat sink assembly.

14. The method of claim 13, wherein the biological material is maintained at a temperature of 0°C to -15°C for at least 4 hours.

15. The method of claim 13, further comprising placing a cryoprotectant composition in the container with the biological material, the cryoprotectant composition being configured to prevent cryoinjury to the biological material at the target temperature for the target duration.

16. The method of claim 13, wherein the insulation assembly comprises a plurality of vacuum insulation panels, and wherein the plurality of vacuum insulation panels comprise cylindrical vacuum insulation panels.

17. A method as claimed in claim 13, wherein the plurality of curved side wall panels are composed of 4 identical curved side wall panels, each curved side wall panel defines a quarter of the circumference of the hollow cylinder, and wherein the method further includes placing the 4 identical curved side wall panels in a circle so as to form at least a portion of the cold source assembly.

18. The method of claim 17 further includes stacking the four identical curved side wall panels such that the outer curved surface of one side wall panel faces the inner curved surface of a second side wall, and placing the stacked side wall panels in a refrigerator to charge the phase change material in the side wall panels.

19. A method as claimed in claim 17, wherein the cold source assembly includes a circular bottom panel and a circular cover panel, and wherein the method also includes placing the circular bottom in the insulation assembly, joining the circular bottom in the insulation assembly with the four identical curved side wall panels using tongue and groove joints to form a cold source sub-assembly, placing a container with the biological material in the cold source sub-assembly, and joining the circular cover panel with the four identical curved side wall panels of the sub-assembly so as to contain the container in the cold source assembly using tongue and groove joints.

20. The method of claim 13, wherein the insulation assembly comprises a plurality of vacuum insulation panels, wherein the plurality of vacuum insulation panels comprise cylindrical vacuum insulation panels, wherein the plurality of curved side wall panels consist of four identical curved side wall panels, each curved side wall panel defining a quarter of the circumference of the hollow cylinder, and wherein placing the cold source assembly in the insulation assembly comprises placing each of the curved side wall panels in contact with an inner surface of the cylindrical vacuum insulation panel.

21. The method of claim 13, wherein the biological material is a cell sample, wherein the method comprises placing the cell sample in a vial containing a cryoprotectant composition configured to prevent freezing damage to the cell sample at the target temperature for the target duration, and wherein the container defines a cavity to hold the vial.

22. The method of claim 13, wherein the biological material is an organ, wherein the method comprises placing the organ in a container having a cryoprotectant composition configured to prevent cryoinjury to the organ at the target temperature for the target duration.

23. The method of claim 13, wherein the biological material is tissue, and wherein the method comprises placing the biological material in the container having a cryoprotectant composition configured to prevent cryoinjury to the biological material at the target temperature for the target duration.

24. The method of claim 23, wherein the tissue is a transplantable tissue or a modified tissue.

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