CROSS REFERENCE TO PRIOR APPLICATIONS

[1] This application claims priority to U.S. provisional patent application no. 63/109,977 filed November 5, 2020 and entitled “TEMPERATURE-CONTROLLED SYSTEM FOR THE COLLECTION AND/OR TRANSPORTATION OF LIVING AND/OR TEMPERATURE SENSITIVE MATERIAL”, the content of which is incorporated herein by reference in its entirety.

FIELD OF THE DISCLOSURE

[2] The specification relates to the design of a temperature-controlled system for the collection, storage and/or transportation of live cells, tissues, organs, vaccines, therapeutics, or other temperature sensitive materials. In particular, the specification relates to a layered container system design for the collection and/or transportation of temperature sensitive materials.

BACKGROUND OF THE DISCLOSURE

[3] Many designs currently exist for the thermally controlled transportation of cells, tissues, and organs. For example, transportation of live cells, tissues, and organs has been carried out using phase change material (PCM) in containers designed to maintain hypothermic temperatures of 2-8°C over a certain period of time. Examples of such designs include EvoTM™, Thermosafe™, and Credo Cube™. While these and other designs may have been effectively used as a thermally controlled transportation solution for various different cell, tissue, and organ types, these designs are not optimized for use in scenarios where the depositor cells, tissues, organs, and/or other temperature sensitive materials are being deposited in non-industrial settings (for example, if there is a lack of access to laboratory infrastructure and/or samples are collected non-invasively on the spot). Transportation challenges may include, among other things: exposure to extreme temperature ranges, delays in mail, postal, and courier delivery, difficulty enabling non-industrial depositors to properly cold-charge, and low success rates for non-invasive collection and depositing of samples. Cells, tissues, and organs retrieved from non-invasive sources, such as plucked hair follicles, cells derived from hair follicles, sperm, placental cells, umbilical cord cells and tissues, and urine derived cells, are affected by such transportation challenges. These transportation challenges often result in sub-optimal cell viability and/or health, particularly when depositors are collecting, depositing, and shipping cell, tissue, and/or organ samples from a non-laboratory, non-industrial environment. Often, unsuccessful cold-charging, poor collection of samples, poor depositing of samples, and the risks of user error (eg. spills) will compromise or undermine the suitability of the cells, tissues, and organs for future use in applications such as cryopreservation, transplantation, therapeutics, diagnostics, vaccines, etc. In particular, the designs that currently exist are not intended to be used with small amounts of cells and tissues not already contained in a receptacle of their own, especially in the case of plucked hair follicles. The designs that currently exist were designed and optimized for use as a lab-to-lab industrial cold-shipment solution only.

[4] For example, United States patent no. 10549900B2 describes a thermal storage system designed to enclose a retrievable payload using two layers of phase change material. The first layer of phase change material has a phase change temperature within the target temperature range of the payload itself, and the second layer of phase change material has a range outside the target temperature, where the first layer prevents the second layer temperature from affecting the payload temperature. The components of the thermal storage system are arranged in a vertical stack, such that the layers of phase change material do not completely surround the central payload on all sides evenly.

[5] The temperature-controlled system of the present invention has many advantages over existing designs, including the design disclosed in US patent no. 10549900B2. First, the arrangement of components is not a vertical stack, but instead a set of outwardly inscribed cylindrical containers custom-shaped to surround the central payload on all sides evenly. This is a more efficient arrangement because it limits the surface area through which cold-energy can dissipate outward and it ensures the payload has consistent temperature exposure protection from all directions. The design of the present invention also has temperature-maintaining elements designed to be cold-charged using a standard non-laboratory fridge and freezer.

[6] Additionally, the temperature-controlled system of the present invention is designed to improve the rate of success for the depositing of temperature sensitive samples into the payload container, including the depositing of samples of living tissue sometimes collected non- invasively in non-laboratory settings. By widening the mouth of the payload container, reducing the height of the liquid so that it will only reach half way up the walls of the payload container, and integrating a ‘lock’ between the payload container base and the inner core base, the experience of a non-practiced non-expert in depositing sensitive materials successfully without spilling liquid from the payload container may be significantly reduced. With the design of the payload container also incorporating a depression in the lid that limits the volume of air pockets within the payload container when it is sealed shut, these sets of features together create a substantially improved user-success design. These types of features are completely missing from existing designs, including the design disclosed in US patent no. 10549900B2, which only allows for user-success in lab or industrial settings by trained personnel. Furthermore, the inscribed cylindrical containers of the present disclosure that contain PCM and refrigerant surround the payload sample on all sides, which helps enable the entire temperature-controlled system to maintain a smaller footprint for the same cooling performance. This not only means the temperature-controlled system of the present invention may be less expensive to ship through the mail, it also may improve the probability that the cylinder containers will fit in refrigerators and freezers that may already be filled with other materials and therefore may improve user success.

SUMMARY OF THE DISCLOSURE

[7] The present disclosure describes designs for temperature-controlled systems that may be used for the collection, storage and/or transportation of living or temperature-sensitive material.

[8] In various aspects, embodiments of the present invention relate to a temperature- controlled system comprising: (i) an insulation layer comprising a lid and a base; (ii) an outer core plastic cylinder housed in the insulation layer, wherein the outer core plastic cylinder comprises either a phase-change material (PCM) or a standard refrigerant; (iii) an inner core plastic cylinder housed within the outer core plastic cylinder, wherein the inner core plastic cylinder comprises either a PCM or a standard refrigerant; and (iv) a payload container that is housed within the inner core plastic cylinder.

[9] In various aspects, the payload container may be of varying sizes and shapes, including, for example, common off-the-shelf vials or a customized disk-shaped payload vial payload container, sometimes a first layer of phase change material (PCM) as a refrigerating agent and sometimes a standard refrigerant contained in a container which sometimes interlocks with the payload container, a second layer of PCM or standard refrigerant cooled colder than the first refrigerant layer, an insulating layer, and a cardboard layer wherein the design is used for the thermally-controlled storage or transportation of cells, tissues, organs, vaccines, therapeutics, and/or other temperature controlled materials. In some embodiments, the cells, tissues, or organs are plucked hair follicles, cells derived from hair follicles, sperm, placental cells, umbilical cord cells and tissues, and urine derived cells.

[10] According to some embodiments, the payload container has a volume capacity to hold about 0.1 mL to about 100mL of liquid. In some embodiments the payload container is used to transport living cells and is filled with an appropriate viability-maintaining transportation media. In some embodiments the payload container is designed to have interlocking slots that align with slots on the inner core base to prevent the payload container base from twisting when the payload container lid is being twisted off. In some embodiments the payload container lid is designed with a depression that takes some space in the cavity of the payload container base and which can be filled with a wide range of temperature monitors.

[11] According to some embodiments, the amount of PCM or refrigerant in the inner core is between about 0.1L to about 10L.

[12] According to some embodiments, the amount of PCM or refrigerant in the outer core is between about 0.15L to about 15L.

[13] According to some embodiments, the insulating layer has a thickness of between about 5cm to about 50cm. According to some embodiments, the insulating layer has cavities designed to house materials necessary for the successful depositing of non-invasively collected cells, tissues, or organs by a non-expert in a sometimes non-laboratory, non-industrial location.

BRIEF DESCRIPTION OF THE DRAWINGS

[14] The foregoing and other aspects of the invention will become more apparent from the following description of specific embodiments thereof and the accompanying drawings that illustrate, by way of example only, the principles of the invention.

[15] Fig. 1 shows a top-angled exploded view of a particular embodiment of the temperature-controlled system.

[16] Fig. 2 shows a side-angled bisected view of a particular embodiment of the plastic cylinder 12 and the payload container lid 7 and payload container base 9 threaded shut together. [17] Fig. 3 shows a top-down view of a particular embodiment of the plastic cylinder 12 and a bottom-up view of the payload container base 9.

[18] Fig. 4 shows a diagonal-angled view of a particular embodiment of the plastic cylinder 12 and the plastic cylinder 4 in a four-vial configuration.

[19] Fig. 5 shows a step-by-step overview of a particular embodiment of the method by which an embodiment of the temperature-controlled system may be transported, used for sample collection, and transported again while maintaining appropriate temperature control.

[20] Fig. 6 shows the temperature results over time for an embodiment of the temperature-controlled system.

[21] Fig. 7 shows bisected views of a particular embodiment of the Payload Container filled with liquid in three different orientations.

[22] Other features and advantages of the present disclosure will become more apparent from the following detailed description and from the exemplary embodiments.

DETAILED DESCRIPTION OF THE DISCLOSURE

[23] It will be appreciated that numerous specific details have been provided for a thorough understanding of the exemplary embodiments described herein. However, it will be understood by those of ordinary skill in the art that the embodiments described herein may be practiced without these specific details. In other instances, well-known methods, procedures and components have not been described in detail so as not to obscure the embodiments described herein. Furthermore, this description is not to be considered so that it may limit the scope of the embodiments described herein in any way, but rather as merely describing the implementation of the various embodiments described herein.

[24] The description that follows, and the embodiments described therein, are provided by way of illustration of an example, or examples, of particular embodiments of the principles of the present invention. These examples are provided for the purposes of explanation, and not limitation, of those principles and of the invention.

[25] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments of the invention. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[26] As used herein, the singular forms “a”, “an”, and “the”, are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[27] The phrase “and/or” should be understood to mean “either or both” of the elements so conjoined, i.e., elements that are conjunctively present in some cases and disjunctively present in other cases. Thus, as a non-limiting example, a reference to “A and/or B”, when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.

[28] When a range of values is listed herein, it is intended to encompass each value and sub-range within that range. For example, “0.1-1.5 %” is intended to encompass 0.1, 0.2, 0.3, 0.4, 0.5, etc. % and up to 1.5, 1.4, 1.3, 1.2, 1.1 , 1.0, etc. %.

[29] It will be further understood that the terms “comprises”, “comprising”, “includes”, and/or “including”, when used herein, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.

[30] A non-limiting embodiment of a temperature-controlled system is illustrated in Fig. 1. In this embodiment, the temperature-controlled system has an insulation layer 1 comprising a lid and base. The lid and base of insulation layer 1 may be identical. The insulation layer 1 may be made of Styrofoam (polystyrene) or Styrofoam substitutes including vacuum insulated packaging (VIP packaging), poly-coated paper (paperboard), moulded fibres, plant fibres (eg. bamboo), and biodegradable foams. According to some embodiments, the insulation layer 1 has a thickness of between about 5cm to about 50cm. According to some embodiments, the insulation layer 1 has cavities designed to house materials necessary for the successful depositing of non-invasively collected cells, tissues, or organs by a non-expert, which may occur in a non-laboratory, non-industrial location. The lid and base of insulation layer 1 may have simple interlocking grooves 2 to secure the lid to the base. In other embodiments, the lid may be secured to the base of insulation layer 1 by a clasp or by a threading of the lid and the base. The base of insulation layer 1 may have pockets 16 of varied sizes for storage of ancillary materials.

[31] The temperature controlled-system also comprises an outer core plastic cylinder 14, which may be housed inside insulation layer 1. The outer core plastic cylinder 14 is a hollow container. In some embodiments, the walls of the outer core plastic cylinder 14 may be filled with a standard refrigerant (including water, water and thickening agents, silica gels, and water and propylene glycol) or appropriate refrigerants as understood by a person skilled in the art, or PCM (including organic paraffin, organic nonparaffin, inorganic salt hydrates, inorganic metal alloys, and eutectic mixtures). According to some embodiments, the amount of PCM or refrigerant in the outer core plastic cylinder 14 is between about 0.15 L to about 15L. In some embodiments, the outer core plastic cylinder 14 has an instructional label 15, which could include a phrase such as ‘FREEZE 24hrs or longer’.

[32] The temperature controlled-system also comprises an inner core plastic cylinder, which is housed within the outer core plastic cylinder 14. The inner core plastic cylinder may be comprised of an inner core lid 4 and an inner core base 12 that screw into one another using threads. In other embodiments, the inner core lid 4 may be secured to the inner core base 12 by a clasp or by interlocking grooves. The inner core lid 4 and the inner core base 12 are both hollow, and in some embodiments are permanently filled with either a standard refrigerant or phase change material (PCM) with a freezing point above 0°C and below 8°C. According to some embodiments, the amount of PCM or refrigerant in the inner core lid 4 and the inner core base 12 is between about 0.1L to about 10L. In some embodiments, the inner core lid 4 has a logo or other messaging on its top 3 and instructions on its front 5, such as ‘REFRIGERATE 24hrs or longer’. In some embodiments, the inner core base 12 has a ring-shaped cavity into which a rubber seal can be affixed to create a water-tight seal between the inner core lid 4 and the inner core base 12 when they are threaded together, clasped together or otherwise engaged. In some embodiments, the inner core base 12 has a cavity 11 at its center where a payload container may be housed. Inner core lid 4 has, on its open end, a corresponding cavity to cavity 11 that fits the top of the payload container when inner core lid 4 and inner core base 12 are threaded together.

[33] According to some embodiments, the plastic inner core and plastic outer core may be a shape other than a cylinder. [34] The payload container may be comprised of payload container lid 7 and payload container base 9, which screw shut together with threads to form an enclosed cavity. In other embodiments, the payload container lid 7 may be secured to the payload container base 9 by a clasp or by interlocking grooves. The payload container may be of varying sizes and shapes, including, for example, common off-the-shelf vials or a customized disk-shaped vial payload container. According to some embodiments, the payload container has a volume capacity to hold about 0.1 mL to about 100mL of liquid. In some embodiments the payload container is used to transport living cells, tissues or organs and is filled with an appropriate viability-maintaining transportation media.

[35] The payload container lid 7 may have a depression 6 which protrudes into the cavity formed when payload container lid 7 and payload container base 9 are screwed shut together or otherwise engaged. The depression 6 may form a cavity large enough to fit small temperature monitors of various sizes enabling a more accurate measurement of the temperature maintained in the payload container where sensitive samples are being transported. The payload container fits in the major central cavity formed when the inner core lid 4 and the inner core base 12 are screwed shut together or otherwise engaged. In some embodiments, the payload container base 9 may have three cavities 8 arranged around its bottom edges that match protrusions 10 on the inner core base 12. When the payload container is placed in the central cavity of the inner core base 12, the three cavities 8 align with protrusions 10, allowing the payload container to be secured such that it is no longer free to rotate around its z-axis. This ‘lock’ enables the payload container lid 7 to be removed while the payload container base 9 remains held in the central cavity of the inner core base 12. In some embodiments, the payload container base has at least one cavity 8.

[36] Fig. 2 shows a bisected side-view of a non-limiting embodiment of the inner core base 12 and the payload container lid 7 and the payload container base 9 of the temperature- controlled system. In this particular embodiment, the payload container lid 7 and the payload container base 9 are shown threaded shut creating cavity 17. The shape of the payload container lid 7 is designed to protrude into payload container base 9 to reduce the height of the cavity 17. Cavity 6 is necessary to ensure the payload container lid 7 has a uniform thickness to conform to manufacturing processes. Cavity 6 may also house a temperature monitor in very close proximity to the sample being transported which enables more accurate monitoring. In this bisected view, the shape of cavity 8 can be seen along the bottom edge of the payload container base 9. The quarter-circle shape of cavity 8 matches the quarter-circle protrusion 10 of the inner core base 12. When the payload container is placed in the central cavity of inner core base 12, the three cavities 8 arranged in a triangular arrangement along the bottom of the payload container base 9 match the three protrusions 10 along the circumference of the central cavity of the inner core base 12. Once engaged, the payload container base 9 can no longer rotate along its z-axis, but the payload container lid 7 is still free to rotate. This configuration enables a user to easily remove the payload container lid 7 by twisting it while the entire payload container is in place within the major cavity of the inner core base 12. In this particular embodiment, cavity 11 is included in the inner core base 12 to house the payload container. Cavity 11 can be made to be different dimensions to fit different sizes and shapes of vials or containers. The top-side of the inner core base 12 may have a cavity 13 which forms a ring around the perimeter enabling the installation of a rubber seal. The substantial thickness 18 of the plastic that forms the inner core base 12 is shown in this particular embodiment. The cavity 19 of the inner core base 12 is filled with refrigerant, PCM, or other cold-keeping materials. In this particular embodiment, a base-plate 20 is used to seal the material into cavity 19.

[37] Fig. 3 shows a non-limiting embodiment of the temperature-controlled system from both a top-angled view of the outer core plastic cylinder 12 and a bottom-up view of the payload container base 9. From this view, the cavities 8 around the bottom perimeter of the payload container base 9 can be seen in an equidistant triangular arrangement. The same triangular arrangement of corresponding protrusions 10 on the inner core base 12 within its major cavity can also be seen. In other embodiments, the cavities may be arranged in a non-equidistant manner.

[38] Fig. 4 shows a diagonal-angled view of a non-limiting embodiment where the inner core lid 4 and the inner core base 12 are in a four-vial configuration. The central cavity of the inner core base 12 may be a malleable, reconfigurable space that can be configured to house at least one container or vial for temperature-controlled transportation. The particular embodiment of the inner core lid 4 and the inner core base 12 represented in Fig. 4 is designed to house four individual vials in cavities 11. However, the central cavity of the inner core base 12 can be remodeled to any configuration for any vial type with any dimensions small enough to fit in the central cavity of the inner core base 12.

[39] Fig. 5 shows a non-limiting embodiment of a method of using an embodiment of the temperature-controlled system, including how the temperature-controlled system may be prepared, packaged, shipped, cooled, used for sample collection, repackaged, shipped again and received. The steps are as follows:

1. A sterilized payload container is filled with a suitable transportation medium and placed into the temperature-controlled system.

2. The temperature-controlled system is assembled, packaged in a cardboard box and shipped to a sample collection location.

3. The temperature-controlled system is unpackaged at the sample collection location. The inner core plastic cylinder, which houses the payload container, is placed in a standard refrigerator and the outer core plastic cylinder is placed in a standard freezer. Both are left to cool for at least 24 hours.

4. After at least 24 hours, the inner core base and the payload container are both removed from refrigeration. The payload container lid is removed from the payload container base. In some embodiments, the payload container base may be removed from the inner core base, and in other embodiments, the payload container base may remain ‘locked’ with the inner core base for the duration of sample collection.

5. After sample collection is complete, the sample is placed in the payload container base, and the payload container base is sealed shut with the payload container lid. If the payload container had been removed from the inner core plastic cylinder, the payload container is place back into the inner core base. The inner core base is sealed shut with the inner core lid and the inner core plastic cylinder is placed together with the outer core plastic cylinder into an insulation layer.

6. The temperature-controlled system is then packaged into a cardboard box and shipped to the sample processing location.

7. The temperature-controlled system is unpackaged and the sample contents are removed from the payload container for processing, which could include but is not limited to, analysis, data extraction, copying, cryopreserving and/or otherwise preserving of samples.

[40] Fig. 6 shows the temperature performance of a non-limiting embodiment of the temperature-controlled system as measured by a temperature monitor placed inside the depression 6 of the payload container lid over the course of three days. The method described in Fig. 5 was followed to obtain this data. Specifically, the inner core plastic cylinder (housing the payload container) was placed in a standard home refrigerator for 24 hrs. At the same time, the outer core plastic cylinder was placed in a standard home freezer for 24hrs. Live human tissue samples were then collected non-invasively and deposited into the payload container, which was pre-filled with an appropriate transport medium liquid. A temperature monitor was placed in the payload container lid depression 6, and the components of the temperature- controlled system were assembled into their standard configuration with the payload container being housed in the inner core plastic cylinder, the outer core plastic cylinder 14 surrounding the inner core plastic cylinder, and the insulation layer 1 surrounding the outer core plastic cylinder 14. The temperature-controlled system was placed in a cardboard box and was left at room temperature for 3.5 days. As shown in Fig. 6, the temperature-controlled system was surprisingly able to maintain the temperature of the sample payload between 1°C and 6°C for 63hrs.

[41] Fig. 7 shows side-view bisections of a payload container simulating how liquid contained in the main payload container cavity 17 would behave in three different orientations for a non-limiting embodiment of the temperature-controlled system. The darkened area within the major payload container cavity 17 represents the simulated liquid. The small amount of volume occupied by air 21 within the payload container cavity 17 is minimized in each orientation by the depth of the depression 6 into cavity 17. When payload container lid 7 is removed for sample deposit, the volume taken up by liquid only reaches halfway up the payload container base 9. The cavity formed by depression 6 may be sized to fit small temperature monitors of a variety of shapes and sizes. The exact dimensions and configuration of the payload container lid 7 with depression 6 can be modified to fit a variety of temperature monitor dimensions.