Methods and devices for thermal stabilization of perishable biological specimens - Patents.com

Abstract

A method and device are provided for performing temperature-controlled transport of relatively small temperature-sensitive payloads. The vacuum shipper can include a vacuum vessel and a PCM pack having an outer wall that roughly conforms to the vacuum vessel. The PCM pack includes a payload cavity and can be preconditioned at an effective charge temperature for an effective charge time. The temperature-sensitive payload is placed into the payload cavity. An insulating stopper is forced into the mouth of the vacuum vessel. The vacuum shipper can then be transported by commercial express cargo to its destination within the effective endurance time.

Description

[Technical Field]

[0001] FIELD OF THE INVENTION FIELD OF THE INVENTION This application relates to transfer systems and methods for perishable, temperature-sensitive materials, including biological specimens such as, but not limited to, whole blood. [Background technology]

[0002] background Biological samples, such as, but not limited to, blood, often need to be maintained within a specific temperature range to ensure the quality of the biological sample and any analytical or diagnostic tests performed on such samples. Failure to maintain the temperature range can alter the composition of the sample, thereby reducing the accuracy of test results. For example, temperatures that are too low can damage enclosed materials (such as cells) through the formation of intracellular ice or can cause the aggregation of proteins and other solutes to form particulate matter. Conversely, higher temperatures can accelerate the degradation of proteins and enclosed materials due to faster chemical reactions at higher temperatures.

[0003] The temperature of a biological sample can be controlled in a laboratory or other similar setting. However, home diagnostic testing or other remote diagnostic testing may involve a person collecting the biological sample at a location (e.g., at home) away from where the analysis will be performed, and the sample must be transported to a testing facility. During the transportation process, the packaging containing the biological sample may be exposed to various and / or changing temperatures, which may similarly change the temperature of the package and any biological sample within such package, thereby adversely affecting the quality of the biological sample. As an example, the cargo area of ​​a truck may rise to 60°C or fall to -20°C, which may similarly change the temperature of the packages contained therein.

[0004] Applications where relatively small, low-value payloads containing perishable materials must be shipped are not adequately served by typical temperature-controlled packaging systems. Compact packaging systems using expanded polystyrene and ice packs do not have adequate performance to protect payloads from hot or cold excursions for multi-day shipments, do not adequately protect specimens, and are not cost-effective for low-value payloads such as blood samples for routine diagnostic testing. Thicker insulation increases the performance of temperature-controlled packaging systems but increases their weight and size, which in turn increases shipping costs based on the combination of shipping speed and package weight and size. Summary of the Invention [Means for solving the problem]

[0005] Abstract A method and device are disclosed for performing temperature-controlled transport of relatively small temperature-sensitive payloads using mass-produced vacuum bottles. Briefly, the vacuum shipper includes a vacuum bottle and one or more PCM packs having an outer wall that roughly conforms to the vacuum bottle. The PCM pack further includes a payload cavity, such that the PCM pack functions as both a sink for thermal energy and a secondary internal insulating layer. The PCM pack can be preconditioned at an effective charging temperature for an effective charging time. In some cases, the PCM pack can be cylindrical. The PCM pack can optionally include two or more subpacks, each containing a different type of PCM. The preconditioned PCM pack is placed in the vacuum bottle, and the temperature-sensitive payload is placed in the payload cavity. An insulating stopper is pressed into the neck of the vacuum bottle. The insulating stopper can include a handle, a first plug having a diameter approximately equal to the inner diameter of the vacuum bottle, and a second plug having a diameter approximately equal to the diameter of the payload cavity. The vacuum shipper can then be transported by commercial express freight to its destination within the available endurance time.

[0006] The various implementations described herein may include additional systems, methods, features, and advantages that may not necessarily be explicitly disclosed herein, but will become apparent to one of ordinary skill in the art upon review of the following detailed description and the accompanying drawings. It is intended that all such systems, methods, features, and advantages be included within this disclosure and protected by the accompanying claims.

[0007] This specification refers to the following accompanying drawings, in which the use of the same reference numerals in different drawings is intended to indicate the same or similar components. [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 is a cross-sectional view of a temperature controlled packaging system according to an embodiment.

[0009] [Figure 2] FIG. 2 is a cross-sectional view of another temperature controlled packaging system according to an embodiment.

[0010] [Figure 3] FIG. 3 is a cross-sectional view of another temperature controlled packaging system according to an embodiment.

[0011] [Figure 4] FIG. 4 includes a cross-sectional view of another temperature controlled packaging system according to an embodiment.

[0012] [Figure 5] FIG. 5 illustrates an exploded temperature controlled packaging system according to an embodiment.

[0013] [Figure 6] FIG. 6 illustrates an exploded temperature controlled packaging system according to an embodiment.

[0014] [Figure 7]FIG. 7 shows an assembled and disassembled temperature controlled packing system according to an embodiment.

[0015] [Figure 8] FIG. 8 illustrates summer and winter performance of two sub-pack embodiments of a temperature controlled packaging system according to embodiments.

[0016] [Figure 9] FIG. 9 illustrates summer and winter performance of two sub-pack embodiments of a temperature controlled packaging system according to embodiments.

[0017] [Figure 10] FIG. 10 shows the long-term summer performance of an optimized embodiment of a temperature controlled packaging system according to an embodiment.

[0018] [Figure 11] FIG. 11 illustrates a kit configuration including a temperature controlled packaging system according to an embodiment.

[0019] [Figure 12] FIG. 12 illustrates a collection and transport workflow according to an embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0020] Short description The invention described herein relates to the transport of perishable, temperature-sensitive materials, including biological specimens. One such biological specimen is whole blood. The transport can be performed to enable laboratory analysis, such as diagnostic testing. For example, a biological specimen can be collected from a human or animal at a collection site and then transported to a central laboratory for diagnostic testing. The invention may also be applied to the transport of perishable, temperature-sensitive materials, such as food, chemicals, or vaccines.

[0021] Diagnostic tests can be performed on biological samples such as blood. To maintain the quality of biological samples for diagnostic tests and / or other analyses, biological samples such as blood and serum can be stored or otherwise maintained at a certain temperature range for a certain period of time. Different samples can be maintained at different temperature ranges when used for different types of analyses. For example, for valid analysis of a particular analyte, serum can be stored at a temperature range of 8-32°C for up to 48 hours. Alternatively, serum can be stored at a temperature range of approximately 2-8°C for up to 7 days. Alternatively, serum can be frozen at approximately -20°C or lower for up to one month. Whole blood can be stored at a temperature range of approximately 2-8°C, but only for 24 hours and cannot be frozen. If the temperature range is not maintained, the composition of the sample, particularly the liquid portion, can change, thereby resulting in inaccurate test results.

[0022] Temperature-regulated packaging systems designed to address this challenge can include one or more phase-change materials (PCMs) within an insulated container. PCMs, such as water / ice, water / steam, dry ice, hydrated salts, paraffin wax, and biological oils, among other examples, can provide cooling and / or heating energy by releasing or absorbing heat of fusion (or vaporizing), as appropriate, near the PCM's melting or vaporization point. PCMs can provide thermal storage against temperature changes far greater than passive materials that rely solely on heat capacity. PCMs may require active cooling or heating to achieve a desired material phase state initially. For example, PCMs may need to be frozen by conventional refrigeration before being used to thermally regulate the packaged material. Because PCMs can transition between liquid, solid, or gas phases, they can be enclosed within a pouch or other secondary container.

[0023] In a temperature-controlled packaging system, an insulated container encloses one or more PCMs along with a payload (e.g., biological samples, perishable materials, etc.). The insulated container can include an insulating material such as expanded polystyrene, polyurethane foam, a film containing air pockets, or vacuum insulation. A key parameter in the design of a temperature-controlled packaging system is the thermal resistance of the insulating material per unit thickness. Higher thermal resistance or thicker insulating material allows for a smaller amount of PCM and / or longer protection and longer payload delivery time.

[0024] The optimal design of a temperature controlled packaging system requires a balance between cargo cost and payload safety. In certain embodiments, the packaging system is configured to maintain the payload within a target temperature range when subjected to a target maximum thermal load for a specified period of time.

[0025] The thermal load can be expressed as the temperature difference maintained between the exterior of the packaging system and the payload. As a non-limiting example, the thermal load can be expressed as the difference between an external temperature of 30°C and an internal target temperature of 8°C or less (a difference of 22°C).

[0026] The overall performance measure of a packaging system can be expressed as the product of heat load and a specified time period. As a non-limiting example, a packaging system can be designed to maintain a 22°C differential for 48 hours. The packaging systems described herein provide a balance between smaller, lower performance packaging systems that must be shipped via costly express or overnight air rates and larger, higher performance packaging systems that can be shipped at slower, less expensive rates. To make shipping high-value payloads cost-effective, smaller packaging systems with adequate performance at slower shipping rates can be provided.

[0027] Detailed Description Described herein are systems, methods, and devices that provide temperature-controlled transport of relatively small, temperature-sensitive payloads using vacuum-insulated containers (e.g., vacuum bottles, etc.). The present invention may be particularly useful when applied to the transport of relatively low-value payloads requiring simplified operational workflows. As a non-limiting example, the disclosed embodiments can be used to protect the transport of self-collected blood samples for diagnostic testing. In some embodiments, a temperature-controlled packaging system includes a container and one or more PCM packs that (i) conform to the container and (ii) define a payload cavity for a payload, such as, but not limited to, a biological sample. The PCM packs can function as both a sink for thermal energy and a secondary, internal insulating layer. In certain embodiments, the PCM packs are preconditioned at an effective charging temperature for an effective charging time. In various embodiments, the PCM pack includes a first portion and a second portion, the first portion including a first type of PCM and the second portion including a second type of PCM that is different from the first type of PCM. Optionally, the system includes an insulating stopper having at least a first plug and, optionally, a second plug.

[0028] The basic method involves conditioning the structured PCM pack within a specified temperature range, placing the structured PCM pack and payload into a compatible commercially available vacuum bottle of the type commonly used to insulate beverages, pressing a compatible insulating stopper into the mouth of the vacuum bottle to secure the structured PCM pack in place, and transporting the assembly to its destination within its shelf life.

[0029] FIG. 1 illustrates a temperature controlled packaging system 100 according to an embodiment. In the illustrated embodiment, the temperature controlled packaging system 100 is a vacuum shipper 101 that includes a container 102 and one or more PCM packs. In FIG. 1, the temperature controlled packaging system 100 includes a lower (or first) PCM pack 109 and an upper (or second) PCM pack 110. While two PCM packs are shown, in other embodiments, the temperature controlled packaging system 100 can include a single PCM pack or more than two PCM packs, as desired. Optionally, the vacuum shipper 101 includes an insulating stopper 103.

[0030] In one particular embodiment, the container 102 is a vacuum insulated container, and in one non-limiting embodiment, the container 102 is a vacuum container 102. The container 102 includes an outer wall 108 that extends generally vertically and forms the exterior surface of the container 102. The outer wall 108 can have a variety of shapes or profiles, as desired. In one non-limiting example, the outer wall 108 forms a generally cylindrical exterior surface.

[0031] In addition to the outer wall 108, the container 102 includes an inner wall 107, which defines a receiving area 121 of the container 102. In certain embodiments, an upper end 123 of the container 102 defines an opening or mouth that provides access to the receiving area 121. As described in more detail below, the opening can be selectively closed or otherwise sealed or blocked when the vacuum shipper 101 is being transported. Optionally, as shown in FIG. 1 , the inner wall 107 can be tapered such that the lateral dimension of the receiving area 121 proximate the upper end 123 is different from the lateral dimension of the receiving area 121 proximate the lower end 126 of the container 102. In certain embodiments, as shown in FIG. 1 , the lateral dimension of the receiving area 121 proximate the upper end 123 is greater than the lateral dimension of the receiving area 121 proximate the lower end 126 of the container 102. In other embodiments, the inner wall 107 can have various tapers as desired. In some embodiments, the taper of the inner wall 107 may be from about 0.5° to about 3° relative to the vertical axis of the container 102, although in other embodiments the taper may be at other angles as desired. In certain embodiments, the container 102 is a vacuum insulated container, where the diameter of the mouth of the receiving area 121 is no smaller than the diameter of the bottom of the receiving area 121 of the container 102, if desired.

[0032] The first PCM pack 109 and the second PCM pack 110 are positionable within a receiving area 121 of the container 102. In certain embodiments, a taper in the inner wall 107 may facilitate positioning of the PCM packs 109, 110 within the receiving area 121. In various embodiments, the PCM packs 109, 110 are integrally formed, coupled, and / or otherwise attached to form a unitary structure, although in other embodiments this need not be the case.

[0033] 1 , the first PCM pack 109 includes a first PCM 112 within a lower housing 118. In one particular embodiment, the lower housing 118 defines a lower portion 125 of the payload cavity 115. Optionally, a bottom standoff 116 extends from the lower housing 118, and when included, the bottom standoff 116 may enable the formation of a gap 128 between a bottom of the lower housing 118 and a bottom of the inner wall 107. When such a gap 128 is included, the gap 128 may provide additional insulation within the receiving area 121. Optionally, a lower edge 114 may protrude outward from the lower housing 118 and contact the vacuum bottle inner wall 107. The contact between the lower edge 114 and the inner wall 107 may position the first PCM pack 109 within the container 102, forming a gap 130 between the side of the lower housing 118 and the side of the inner wall 107. Such a gap 130 may provide additional insulation within the receiving area.

[0034] The second PCM pack 110 includes a second PCM 111 within the upper housing 117. In certain embodiments, the second PCM 110 is different from the first PCM 112. As a non-limiting example, the first PCM 112 can have a higher melting point than the second PCM 111, such that heat entering the receiving area 121 through an aperture or opening (e.g., through the insulating stopper 103) is first absorbed by the second PCM; therefore, the second PCM preferentially melts under high temperature conditions or freezes under low temperature conditions. This configuration can be advantageous for maximizing payload protection under low temperature external conditions. Conversely, in another non-limiting example, the first PCM 112 can have a lower melting point than the second PCM 111 to provide a different temperature control profile. This configuration tends to reduce temperature gradients under high temperature external conditions, which can be advantageous for maximizing payload production under high temperature external conditions. For example, a second PCM having a peak melting temperature of approximately 18°C ​​and a wide melting temperature range of 10°C to 25°C can be combined with a first PCM having a peak melting temperature of approximately 14°C and a wide melting temperature range of 8°C to 20°C to prevent the payload from exceeding approximately 20°C for 72 hours under hot summer conditions.

[0035] Similar to the first PCM pack 109, the second PCM pack 110 optionally includes an upper edge 113 extending outward from an upper housing 117. As shown in FIG. 1 , the upper housing 117 may define a second portion 127 of the payload cavity 115. Optionally, the second PCM pack 110 may have an annular shape, with a central cavity forming the second portion 127 of the payload cavity 115.

[0036] The insulating stopper 103 is configured to close or otherwise obstruct the mouth of the receiving area 121 when the insulating stopper 103 is assembled to the container 102. Optionally, the insulating stopper 103 seals the receiving area 121 when assembled to the container 102. As shown in FIG. 1 , the insulating stopper 103 includes a plug 105 having a sidewall 106, which may conform to the diameter and / or taper of the vacuum bottle interior wall 107. The plug 105 and the mouth of the container 102 may form a friction fit, such that the insulating stopper 103 is retained within the mouth of the container 102. In certain embodiments, the insulating stopper 103 optionally includes a handle 104 to facilitate handling of the vacuum shipper 101. The handle 104 optionally has an outer diameter that may be approximately equal to the outer diameter of the container 102. In such an embodiment, the handle 104 may function as a stop to indicate when the insulating stopper 103 is properly positioned in the container 102. In other embodiments, the handle 104 can include other diameters and / or shapes, as desired.

[0037] As shown in FIG. 1 , the second PCM pack 110, the first PCM pack 109, and optionally a portion of the stopper 103 together form the walls of a payload cavity 115 that can contain a perishable payload 119. The temperature of the payload cavity can be affected by the phase changes of both the first PCM 112 and the second PCM 111. In certain embodiments, the temperature of the payload cavity 115 can tend to be intermediate between the melting temperatures of the first and second PCMs. Alternatively, one or more PCMs in the vacuum shipper can have a phase transition over a wide temperature range. For example, one PCM can gradually transition from liquid to solid at a temperature between about 8°C and about 18°C. When using a vacuum shipper to protect the payload from both high and low external temperatures, a PCM with a phase transition over a wide temperature range can be advantageous. In other embodiments utilizing a single PCM pack, the PCM pack can achieve bidirectional thermal control using a PCM with a wide phase transition temperature range. In certain embodiments, the transition temperature range may be within a desired effective average kinetic temperature range, and the incubation temperature may be within a phase transition temperature range. As a non-limiting example, a single PCM may have a melting temperature of about 37° C. and an incubation temperature range of about 37° C. to about 60° C. As noted, other embodiments may utilize other configurations and / or types of PCM packs containing one or more types of PCM materials, as desired.

[0038] The second PCM pack 110, the first PCM pack 109, and the payload 119 may be restrained in place and prevented from moving during transport by the stopper 103. In some embodiments, the stopper plug 105 may contact the top of the second PCM pack 110 to prevent and / or minimize relative movement between the second PCM pack and other elements within the vacuum shipper 101.

[0039] 2 illustrates another example of a temperature controlled packaging system 200, according to an embodiment. Similar to temperature controlled packaging system 100, temperature controlled packaging system 200 is a vacuum shipper 201. Vacuum shipper 201 is substantially similar to vacuum shipper 101, except as described below.

[0040] In one aspect, compared to vacuum shipper 101, vacuum shipper 201 includes an insulating stopper 203 that is substantially similar to insulating stopper 103, except that vacuum shipper 201 further includes a second plug 232 extending from stopper plug 105. In this embodiment, as shown in FIG. 2 , second plug 232 can extend partially into payload cavity 115. In these embodiments, second plug 232 extending into payload cavity 115 allows a portion of second PCM pack 110 to act as additional insulation for the payload cavity, if desired. Second plug 232 can further contain any sample positioned within payload cavity 115.

[0041] 2, the second PCM pack 110 and the first PCM pack 109 can include an upper air pocket 234, a lower air pocket 236, and a bottom air pocket 238. When air pockets are included, these air pockets can function to provide additional thermal resistance to the payload cavity 115. The air pockets 236 can have various shapes or sizes as desired. In one non-limiting example, the air pockets 236 can have a thickness of about 0.2 mm to about 5 mm.

[0042] Compared to the vacuum shipper 101, the second PCM pack 110 and the first PCM pack 109 each include at least two PCMs and / or form at least two PCM phases within each of the housings 117, 118. In some embodiments, during the melting process, the first PCM contained within the second PCM pack 110 can form a first low-density phase 240 and a first high-density phase 242. The first high-density phase 242 can be at a lower or higher temperature than the first low-density phase 240. As a non-limiting example, partially frozen water can form a lower-density (ice) phase at 0°C and a higher-density (liquid) phase at 4°C.

[0043] In other embodiments, the first, lower density phase 240 can represent a separate PCM that is less dense than and insoluble in the higher density phase 242. As a non-limiting example, a hydrophobic oil-based PCM can have a lower density than an aqueous, water-based PCM and therefore can float on top of the water-based PCM. As shown, the upper portion 127 of the payload cavity 115 can have a temperature closer to that of the first, higher density phase, which can be advantageous.

[0044] Similarly, the second PCM contained within the first PCM pack 109 can form a second lower density phase 244 and a second higher density phase 246, and / or the second lower density phase 244 can be a separate PCM that is less dense than the second higher density phase 246. As a non-limiting example, a hydrophobic oil-based PCM can have a solid fraction that is denser than a (warmer) liquid fraction. As shown, the lower portion 125 of the payload cavity 115 can have a temperature that is closer to the second lower density phase. Thus, fractionation of the PCM during freezing or thawing can be utilized to moderate the temperature of the payload cavity, particularly if the vacuum shipper device is preferentially transported upright.

[0045] 2, the second PCM pack 110 and the first PCM pack 109 are separate components coupled together. In one particular embodiment, alignment of the second PCM pack 110 and the first PCM pack 109 may be facilitated by alignment grooves 248 and alignment ribs 250. The mating of the alignment grooves 248 and alignment ribs 250 may function to reduce air intrusion into the payload cavity 115, further improving thermal insulation properties.

[0046] 3 illustrates another example of a temperature controlled packaging system 300, according to an embodiment. Similar to temperature controlled packaging system 100, temperature controlled packaging system 300 is a vacuum shipper 301. Vacuum shipper 301 is substantially similar to vacuum shipper 101, except as described below.

[0047] Compared to vacuum shipper 101, vacuum shipper 301 includes three PCM packs: first PCM pack 309, second PCM pack 110, and third PCM pack 352. First PCM pack 309 is substantially similar to first PCM pack 109, except that first PCM pack 309 does not have bottom standoff 116. Second PCM pack 110 may have an annular shape, although in other embodiments, second PCM pack 110 may have other shapes or configurations as desired. Third PCM pack 352 may be shaped to form an upper barrier between payload cavity 115 and stopper plug 105.

[0048] 3 , the third PCM pack 352 can include a third PCM 354. Optionally, the third PCM 354 is different from at least one of the first PCM 112 and / or the second PCM 111. In some embodiments, the second PCM 111 can have a melting point intermediate between the first PCM 112 and the third PCM 354. By way of non-limiting example, the first PCM 112 can have a melting point of approximately 0° C., the second PCM 111 can have a melting point of approximately 10° C., and the third PCM 354 can have a melting point of approximately 18° C. In certain embodiments, the payload cavity 115 can be maintained at a temperature similar to the melting point of the second PCM 111 under both warm and cold external conditions.

[0049] 4 illustrates another example of a temperature controlled packaging system 400 according to an embodiment. In the embodiment of FIG. 4, the temperature controlled packaging system 400 includes a vacuum shipper 401 having a narrow-mouth vacuum vessel 402, an insulating stopper 403, a central PCM pack 456, and a peripheral PCM pack 458.

[0050] The walls of the central PCM pack 456, the walls of the peripheral PCM packs 458, and the plug 405 of the insulating stopper 403 form the payload cavity 415. The vacuum vessel 402 includes a mouth 460 and a body portion 462. In this embodiment, the mouth 460 has an inner diameter that is smaller than the inner diameter of the body portion 462. As shown in FIG. 4, the plug 405 of the stopper 403 can be inserted into the mouth 460 with minimal residual clearance.

[0051] The central PCM pack 456 can include a central PCM 464, and the peripheral PCM pack 458 can include a peripheral PCM 466. The orientation of the peripheral PCM pack 458 and the central PCM pack 456 is shown in the schematic cross-section of FIG. 4. In some embodiments, the central PCM pack 456 is shaped to allow it to be removed from the vacuum shipper 401 through the port 460. By way of non-limiting example, the diameter of the central PCM pack 456 can be equal to or smaller than the diameter of the port 460. The peripheral PCM pack 458 can also have a diameter smaller than the diameter of the port so that it can be inserted into the vacuum shipper 401. The peripheral PCM pack 458 can be permanently attached to the interior of the vacuum vessel 402, if desired. In various embodiments, the vacuum shipper 401 can be ready for use by removing the stopper 403 and then removing and ejecting the central PCM pack 456 by inverting the vacuum vessel 402. The central PCM pack 456 can then be charged by cooling for an effective period and then returned to the vacuum vessel 402. The stopper 403 can then be reinserted into the vacuum vessel 402 to facilitate temperature control.

[0052] FIG. 5 illustrates an exploded view of a temperature-controlled packaging system 100 according to an embodiment in which the insulating stopper 103 and the second PCM pack 110 form an upper assembly 501. In this embodiment, the stopper 103 can be bonded (permanently or temporarily) to the second PCM pack 110. Bonding the stopper 103 and the second PCM pack 110 can facilitate leaving the upper assembly 501 at ambient temperature while the first PCM pack 109 completes cooling. As a non-limiting example, the first PCM pack 109 can be placed in a freezer at a temperature of approximately −20° C. for a period of 10 hours, while the upper assembly 501 is left at room temperature for the same period of 10 hours. A payload 119 can then be placed in the lower portion 125 of the payload cavity 115 within the lower PCM pack 109, as shown. The first PCM pack 109 can be placed in the container 102 before or after receiving the payload 119. Finally, the assembly 501 is placed on the payload 119 and within the receiving area 121, thereby sealing the vacuum shipper 101 and allowing temperature control to begin. The payload 119 can then be held at a temperature intermediate between room temperature and the temperature of the lower PCM pack 109. For materials that are sensitive to freezing, such as blood, this configuration can prevent excessive cooling of the payload 119 by providing a warmer thermal reservoir to balance the initial <0°C temperature of the first PCM pack 109.

[0053] FIG. 6 illustrates an exploded view of a temperature-controlled packaging system 100 according to an embodiment, in which a first PCM pack 109 and a second PCM pack 110 form a lower assembly 601. In this embodiment, the lower assembly 601 includes a second PCM pack 110 permanently or temporarily joined to the first PCM pack 109. The lower assembly 601 includes a payload cavity 115 formed from the walls of the first PCM pack 109 and the second PCM pack 110. In the embodiment of FIG. 6, the lower assembly 601 may facilitate keeping both the second PCM pack and the first PCM pack at the same temperature. As a non-limiting example, the lower assembly 601 may be kept in a commercial refrigerator at approximately 3° C. for a period of 10 hours. This period may be sufficient to solidify the PCM in the first PCM pack 109, but not the PCM in the second PCM pack 110. The payload can then be placed into the payload cavity 115, and then the lower assembly 601 can be placed into the container 102. The stopper 103 can then be placed into the container 102 to seal the container 102. Thus, the lower assembly 601 can be conditioned to withstand both hot and cold external conditions.

[0054] Various other subassemblies can be formed using the components of the temperature controlled packaging systems described herein, and the above examples should not be considered limiting. Additionally, as previously mentioned, the particular arrangement of PCM packs having different PCMs and / or different PCM phases within a container should not be considered limiting, and in various embodiments, the PCM packs can be provided in various arrangements as desired to control temperature as desired and / or provide a desired insulation profile.

[0055] FIG. 7 shows another example of an assembled temperature-controlled packaging system 700A, a first disassembled temperature-controlled packaging system 700B, and a second disassembled temperature-controlled packaging system 700C.

[0056] Temperature controlled packaging system 700A is substantially similar to temperature controlled packaging system 100 and includes a container 702 and a stopper 703.

[0057] Temperature controlled packaging system 700B includes a container 702, a stopper 703, and a PCM assembly 701 including a first PCM pack 709 and a second PCM pack 710. In this embodiment, a payload cavity is defined by first PCM pack 709 and second PCM pack 710, similar to temperature controlled packaging system 100. In one non-limiting example, temperature controlled packaging system 700B can be configured for use with small blood tubing (or any other payload as desired).

[0058] Temperature controlled packaging system 700C includes a container 702 and a stopper 703 (not shown). In comparison to temperature controlled packaging system 700B, temperature controlled packaging system 700C includes a single PCM pack 768 that, when inserted into container 102, forms a payload cavity 715 therearound in receiving area 121. In certain embodiments, PCM pack 768 may have a semicircular cross-section as shown, and in various aspects, PCM pack 768 may fill more than half of receiving area 121 in plan view. In such embodiments, PCM pack 768 filling more than half of the receiving area may facilitate positioning of PCM pack 768 within receiving area 121.

[0059] FIG. 8 shows the internal temperature over time for an embodiment of a temperature-controlled packaging system when exposed to warm (constant 30° C.) conditions (line 801) or cold (equivalent to the ISTA-7D winter standard) conditions (line 803). A 30-ounce capacity vacuum bottle with a 2-inch thick expanded polystyrene insulated stopper was used as the container for the temperature-controlled packaging system. The PCM pack was exposed to commercial refrigeration overnight prior to insertion into the vacuum bottle with the stopper. In both cases, performance criteria were met, with temperatures maintained below approximately 25° C. and above 0° C., as represented by line 805. The average operating temperature was also maintained below 20° C. for 72 hours. In this example, water was used as the second PCM and Puretemp 18 blended with mineral oil was used as the first PCM.

[0060] FIG. 9 shows the internal temperature over time for two embodiments of a temperature-controlled packaging system when exposed to warm (constant 30° C.) conditions 801 or cold (equivalent to the ISTA-7D winter standard) conditions 803. In this example, a 20-ounce capacity vacuum bottle was used as the container for the temperature-controlled packaging system, and a 1-inch thick expanded polystyrene stopper was used as the insulating stopper. The PCM packs were exposed to commercial refrigeration overnight prior to insertion into the vacuum bottle with the stopper. Performance criteria were met for both PCM combinations in both external conditions, with temperatures maintained below approximately 25° C. and above 0° C. The average kinetic temperature was also maintained below 20° C. for 72 hours. In this example, water or Templok 5 was used as the second PCM (represented by line 907), and Puretemp 18 blended with mineral oil or unblended Puretemp 18 was used as the first PCM (represented by line 909). The combination of vacuum insulation and the additional thermal resistance of the PCM element itself produced two-way performance results that were unexpectedly strong given the size of the protective package (approximately 9 inches in diameter x 3 inches). A conventional expanded polystyrene packaging system of similar size would be expected to last less than 24 hours.

[0061] FIG. 10 shows the internal temperature over time for an embodiment of a temperature controlled packaging system when exposed to warm (constant 30° C.) conditions 803. A 30 ounce capacity vacuum bottle was used as the container for the temperature controlled packaging system, and a 2 inch thick expanded polystyrene stopper was used as the insulating stopper. The PCM pack was exposed to commercial refrigeration at approximately -20° C. overnight prior to insertion into the vacuum bottle with the stopper. Performance is shown by line 1011. Performance criteria were met, with the temperature maintained below approximately 25° C. for 120 hours. The average operating temperature was also maintained below 20° C. for 120 hours. In this example, Puretemp 18 was used as both the first and second PCMs.

[0062] FIG. 11 shows a prototype home collection kit layout 1170 including a portable centrifuge 1172, a temperature-controlled packaging system 700B (eg, a vacuum sipper), and a blood self-collection kit 1174 provided with a shipping container 1176.

[0063] FIG. 12 illustrates a workflow for self-collection, centrifugation, and transport of a blood sample according to an embodiment of the present disclosure.

[0064] The invention described herein is particularly applicable to the transport of whole blood specimens or blood-derived specimens, such as serum or plasma, for laboratory testing. For many diagnostic tests, whole blood must be maintained above the freezing point of water (0°C) and below approximately 37°C during transport to avoid invalid results. For many applications, the lower average temperature ranges are, for example, 0-8°C, e.g., 2-8°C, e.g., 0-15°C, e.g., 2-15°C, e.g., 0-20°C, e.g., 2-20°C, e.g., 0-25°C, and / or e.g., 0-25°C. To maintain these temperature ranges under both summer and winter climatic conditions, combinations of different PCMs with different melting temperature (or other phase change temperature) ranges can be used. For example, a PCM with a melting temperature range between -2°C and 20°C, or preferably between 0°C and 15°C, can be used in the second PCM pack. A PCM with a melting temperature range between 0°C and 25°C, or preferably between 5°C and 20°C, can be used in the first PCM pack. To increase the allowable transport time, in some non-limiting examples, it may be advantageous to use a PCM with a relatively low melting temperature in the upper position (where heat first penetrates through the vacuum shipper stopper) and a PCM with a relatively low melting temperature in the lower position. This orientation of the PCMs provides stronger protection against winter, a lower initial payload temperature during summer conditions, and a longer duration during summer conditions before absolute thermal limits are exceeded. In temperate climates, the typical greater difference between average summer temperatures and optimal biostorage conditions compared to average winter conditions allows for the use of a larger amount of the first PCM compared to the upper "freeze-protection" PCM. As a non-limiting example, a ratio of between 2:1 and 10:1 of the first PCM to the second PCM can be used.

[0065] An alternative approach to achieving both summer and winter protection, if desired, may be to use a single PCM with a wide phase-change temperature range and adjusted within this range prior to use. As a non-limiting example, a PCM with a gradual phase transition between 0°C and 20°C can be pre-chilled at temperatures between 2°C and 8°C to produce a partially phase-changed mixture that can withstand both extreme temperatures. A gradual phase transition can be achieved by blending materials with different melting temperatures, such as blends of olefins or waxes or blends of salt hydrates. Alternatively, blends of certain salt hydrates, such as sodium chloride and sodium sulfate decahydrate, can inherently have a wide phase-change temperature range.

[0066] Payload temperatures can be maintained within a tolerance temperature limit and / or an effective mean kinetic temperature range. The effective temperature limit is a high or low temperature threshold above which even momentary exposure will alter the payload. As a non-limiting example, even momentary exposure of a blood sample to temperatures below -2°C or above 40°C can invalidate laboratory analysis results. The effective mean kinetic temperature range for a given sample is typically narrower than the tolerance temperature limit and reflects the mean kinetic temperature range within which the sample must be maintained to avoid alteration within the effective transport time. Liquid blood, serum, or plasma samples are typically maintained within a temperature range between approximately 2°C and 8°C, which corresponds to commercial refrigeration, or between 20°C and 25°C, which is typically considered controlled ambient room temperature. However, blood samples at 2°C and 8°C tend to exhibit increased hemolysis (i.e., red blood cell rupture) over time compared to blood samples maintained at 20°C and 25°C. Conversely, blood samples held at 20°C to 25°C exhibit a higher rate of chemical degradation of laboratory specimens than blood samples held at 2°C to 8°C. For transport times between approximately 8 hours and 1 week, a variable temperature range of 9°C to 19°C can be advantageous to preserve blood quality for general analytical testing. A properly configured vacuum shipper can maintain a temperature range of 9°C to 19°C for up to 1 week under typical environmental conditions.

[0067] Provided below is a collection of exemplary embodiments, at least some of which are expressly listed as "examples," that provide further explanation of various exemplary embodiments in accordance with the concepts described herein. These examples are not intended to be mutually exclusive, exhaustive, or limiting, and the present disclosure is not limited to these exemplary examples, but rather encompasses all possible modifications and variations within the scope of the issued claims and their equivalents.

[0068] Example 1. A temperature-controlled packaging system for a biological sample, the system comprising: a container; and a PCM pack that (i) conforms to the container and (ii) defines a payload cavity for the biological sample.

[0069] Example 2. A temperature-controlled packaging system for a biological sample, comprising a container and a PCM pack, the PCM pack pre-conditioned at an effective charge temperature for an effective charge time, and the PCM pack further defining a payload cavity for the biological sample.

[0070] Example 3. A temperature-controlled packaging system for a biological sample, comprising a container and a PCM pack, the PCM pack comprising a first portion and a second portion, the first portion comprising a first type of PCM and the second portion comprising a second type of PCM different from the first type of PCM, the PCM pack defining a payload cavity for the biological sample.

[0071] Example 4. A temperature-controlled packaging system for a biological sample, the system including a container, a PCM pack defining a payload cavity, and an insulating stopper including a first plug and a second plug.

[0072] Example 5. A temperature-controlled packaging system for biological samples, comprising a vacuum bottle and a cylindrical PCM pack (i) form-fitting to the vacuum bottle and (ii) including a payload cavity, such that the PCM pack acts as both a sink for thermal energy and a secondary internal insulating layer.

[0073] Example 6. A method of transporting a biological sample comprising providing a vacuum shipper, positioning a preconditioned cylindrical PCM pack within the vacuum shipper, and placing a temperature-sensitive payload into the payload cavity defined by the PCM pack.

[0074] Example 7. The method of any of the previous or next examples or combinations of examples, further comprising transporting the vacuum shipper by commercial express cargo to its destination within the effective endurance time.

[0075] Example 8. A temperature control device comprising a vacuum bottle, an insulated stopper, and a primary PCM pack, wherein the vacuum bottle comprises vacuum insulation, a mouth, an outer wall substantially perpendicular to the mouth, and an inner wall tapering inwardly at 0-5 degrees relative to the vertical, the insulated stopper comprises a handle and a plug having a friction fit with the mouth, the insulated stopper comprises a thickness of at least 20 mm, the primary PCM pack has an outer pack wall that conforms to the inner wall of the vacuum bottle, and a payload cavity of at least 3 cc volume configured to hold a perishable payload is formed from the wall of the primary PCM pack, and the payload cavity is at least partially surrounded by the primary PCM pack.

[0076] Example 9. The apparatus of any of the previous or next examples or combinations of examples, wherein the primary PCM pack further includes a rim, and the pack outer wall and rim enclose an air pocket between the pack outer wall and the rim and the inner wall of the vacuum bottle, the air pocket having a thickness of between 0.2 mm and 5 mm.

[0077] Example 10. The apparatus of any of the previous or next examples or combinations of examples, wherein the payload cavity is centered on the vertical axis of the vacuum bottle.

[0078] Example 11. The device of any of the previous or next examples or combinations of examples, wherein the payload cavity is shaped as a vertical cylinder.

[0079] Example 12. The apparatus of any of the previous or next examples or combinations of examples, wherein the stopper further includes a sub-plug having a diameter approximately equal to the payload cavity, centered on the vertical axis of the vacuum bottle.

[0080] Example 13. The device of any of the previous or next examples or combinations of examples, further comprising a secondary PCM pack, the secondary PCM pack comprising a second phase change material.

[0081] Example 14. The apparatus of any of the previous or next examples or combinations of examples, wherein a secondary PCM pack is positioned vertically above the primary PCM pack, and the payload cavity is further at least partially enclosed by the secondary PCM pack.

[0082] Example 15. The device of any of the previous or next examples or combinations of examples, wherein the phase change temperature of the first phase change material is lower than the phase change temperature of the second phase change material.

[0083] Example 16. The device of any of the previous or next examples or combinations of examples, wherein the phase change temperature of the second phase change material is in the range of -2°C to 15°C and the phase change temperature of the first phase change material is in the range of 5°C to 25°C.

[0084] Example 17. The device of any of the previous or next examples or combinations of examples, wherein the phase change temperature of the second phase change material is in the range of 10°C to 25°C and the phase change temperature of the first phase change material is in the range of 8°C to 20°C.

[0085] Example 18. A device of any of the previous or next examples or a combination of examples, wherein the phase transition of the first phase change material occurs over a wide temperature range rather than at a precise temperature, and the target temperature range of the payload overlaps with the wide temperature range.

[0086] Example 19. The device of any of the previous or next examples or combinations of examples, wherein the first phase change material comprises an inorganic hydrated salt.

[0087] Example 20. The device of any of the preceding or following examples or combinations of examples, wherein the second phase change material comprises sodium sulfate decahydrate.

[0088] Example 21. The apparatus of any of the previous or next examples or combinations of examples, wherein the primary and secondary PCM packs are permanently coupled to one another.

[0089] Example 22. The apparatus of any of the previous or next examples or combinations of examples, wherein the secondary PCM pack is permanently bonded to the insulating stopper.

[0090] Example 23. The apparatus of any of the previous or next examples or combinations of examples, wherein the payload cavity is completely surrounded by the primary PCM pack and the secondary PCM pack.

[0091] Example 24. The device of any of the previous or next examples or combinations of examples, further comprising a tertiary PCM pack, the tertiary PCM pack comprising a third phase change material.

[0092] Example 25. A device according to any of the preceding or following examples or a combination of examples, having an overall length of less than 305 mm and a diameter of less than 100 mm.

[0093] Example 26. The device of any of the previous or next examples or combinations of examples, wherein the outer wall of the vacuum bottle further includes printed instructions for use of the device.

[0094] Example 27. The apparatus of any of the previous or next examples or combinations of examples, wherein the insulating stopper comprises a single, integral element of expanded polystyrene, extruded polystyrene, closed-cell polyurethane foam, open-cell polyurethane foam, or polyisocyanurate foam.

[0095] Example 28. The device of any of the previous or next examples or combinations of examples, wherein the insulating stopper includes a hollow plastic portion.

[0096] Example 29. The device of any of the previous or next examples or combinations of examples, wherein the insulating stopper further includes insulating material within the hollow plastic portion.

[0097] Example 30. The apparatus of any of the previous or next examples or combinations of examples, further including a shipping box, wherein the stopper is contained within the vacuum bottle by the structure of the shipping box.

[0098] Example 31. A method for transporting material using the apparatus of any of the previous or next examples or combinations of examples, comprising the steps of: incubating a primary PCM pack at an effective incubation temperature for an effective incubation time; placing the primary PCM pack in a vacuum bottle; placing a perishable material in a payload cavity; forcing an insulating stopper into the mouth of the vacuum bottle; and transporting the apparatus to a destination within an effective transportation time while maintaining a set of allowable internal temperature limits and an effective average operating temperature range.

[0099] Example 32. The method of any of the previous or next examples or combinations of examples, wherein step (a) is accomplished by use of a commercial refrigerator and the effective warming temperature ranges between 0°C and 10°C.

[0100] Example 33. Any of the methods of the previous example or the next example, or a combination of examples, in which the effective transportation time is in the range of 48 hours to 120 hours.

[0101] Example 34. The method of any of the previous or next examples or combinations of examples, wherein the effective internal temperature limit is set between 0°C and 25°C.

[0102] Example 35. The method of any of the previous or next examples or combinations of examples, wherein the effective average operating temperature range is between 2°C and 20°C.

[0103] Example 36. A method for transporting materials, comprising: incubating a PCM pack at an effective incubation temperature for an effective incubation time, the PCM pack including a first phase change material and a payload cavity, the payload cavity being at least partially surrounded by the PCM pack; placing the PCM pack into a vacuum bottle, the PCM pack further including an outer pack wall that conforms to an inner wall of the vacuum bottle; placing a perishable payload into the payload cavity; and forcing an insulating stopper into a mouth of the vacuum bottle, the insulating stopper forming a friction fit with the mouth; and transporting the assembled vacuum bottle, PCM pack, perishable payload, and insulating stopper to a destination while maintaining a set of allowable internal temperature limits and an effective average operating temperature range.

[0104] Example 37. The method of any of the previous or next examples or combinations of examples, further comprising placing the assembled vacuum bottle, PCM pack, and insulated stopper into a shipper box having an interior length equal to the length of the assembled vacuum bottle, PCM pack, and insulated stopper.

[0105] Example 38. The method of any of the previous or next examples or combinations of examples, further comprising placing the perishable payload in a secondary bag.

[0106] Example 39. The method of any of the previous or next examples or combinations of examples, further comprising cleaning and sanitizing the vacuum bottle and PCM pack for reuse.

[0107] Example 40. The method of any of the previous or next examples or combinations of examples, wherein step (a) is accomplished by use of a commercial refrigerator and the effective warming temperature ranges between 0°C and 10°C.

[0108] Example 41. Any of the methods described in the previous or next example, or a combination of examples, in which the effective transportation time ranges from 8 hours to 1 week.

[0109] Example 42. Any of the methods of the previous example or the next example, or a combination of examples, in which the effective transportation time is in the range of 48 hours to 120 hours.

[0110] Example 43. The method of any of the previous or next examples or combinations of examples, wherein the effective internal temperature limit is set between 0°C and 25°C.

[0111] Example 44. The method of any of the previous or next examples or combinations of examples, wherein the effective average operating temperature range is between 2°C and 20°C.

[0112] Example 45. The method of any of the previous or next examples or combinations of examples, wherein the effective average operating temperature range is between 9°C and 19°C.

[0113] Example 46. The method of any of the previous or next examples or combinations of examples, wherein the effective average operating temperature range is between 2°C and 8°C.

[0114] Example 47. The method of any of the previous or next examples or combinations of examples, wherein the vacuum bottle has an outer wall that is substantially perpendicular to the mouth.

[0115] Example 48. The method of any of the previous or next examples or a combination of examples, wherein the vacuum bottle has an inner wall tapered at an angle of about 0° to about 5° relative to a perpendicular to the mouth.

[0116] Example 49. The method of any of the previous or next examples or combinations of examples, wherein the insulating stopper has a thickness of at least 30 mm.

[0117] Example 50. The method of any of the previous or next examples or combinations of examples, wherein the PCM pack further comprises a second phase change material.

[0118] Example 51. The method of any of the previous or next examples or combinations of examples, wherein the first phase change material is disposed below the second phase change material.

[0119] Example 52. The method of any of the previous or next examples or combinations of examples, wherein the phase change temperature of the second phase change material is in the range of 10°C to 25°C and the phase change temperature of the first phase change material is in the range of 8°C to 20°C.

[0120] Example 53. The method of any of the previous or next examples or combinations of examples, wherein the insulating stopper further comprises a stopper PCM, and wherein the insulating stopper is kept warm at a second effective warming temperature during step (a).

[0121] Example 54. The method of any of the previous or next examples or combinations of examples, wherein the insulating stopper comprises a single, integral element of expanded polystyrene, extruded polystyrene, closed-cell polyurethane foam, open-cell polyurethane foam, or polyisocyanurate foam.

[0122] Example 55. The method of any of the previous or next examples or combinations of examples, wherein the assembled vacuum bottle, PCM pack, perishable payload, and insulating stopper have an overall length of less than 305 mm and a diameter of less than 100 mm.

[0123] Example 56. The method of any of the previous or next examples or combinations of examples, wherein the assembled vacuum bottle, PCM pack, perishable payload, and insulating stopper have a total weight of less than 2.5 pounds.

[0124] Example 57. The method of any of the previous or next examples or combinations of examples, wherein the PCM pack further includes a rim, and wherein the outer wall and rim of the PCM pack, when installed, enclose an air pocket between the inner wall of the vacuum bottle and the rim, the air pocket having a thickness of between 0.2 mm and 5 mm.

[0125] Example 58. The method of any of the previous or next examples or combinations of examples, wherein the perishable payload is blood, serum, or plasma.

[0126] Example 59. The method of any of the previous or next examples or combinations of examples, wherein the perishable payload is a biological cell.

[0127] While the subject matter of the embodiments has been described herein with specificity to meet statutory requirements, this description is not necessarily intended to limit the scope of the claims. The claimed subject matter may be embodied in other ways, may include different elements or steps, or may be used in conjunction with other existing or future technologies. This description should not be construed as indicating any particular order or arrangement among various steps or elements, unless the order of individual steps or arrangement of elements is explicitly described. Directional references such as "up," "down," "top," "bottom," "left," "right," "front," and "rear" are intended to refer to the orientation shown and described in the figure(s) to which the components and directions refer. In the figures and description, like numerals are intended to represent like elements. Throughout this disclosure, reference numerals with letters refer to specific instances of elements, while reference numerals without letters refer to elements collectively or collectively. Thus, by way of example (not shown), device "12A" refers to one instance of a class of devices, which may be collectively referred to as device "12," any one of which may be generically referred to as device "12." As used herein, the meanings of "a," "an," and "the" include singular and plural references unless the context clearly dictates otherwise.

[0128] All ranges disclosed herein should be understood to encompass any and all subranges subsumed therein. For example, the stated range "1 to 10" should be considered to include any and all subranges between (and including) the minimum value of 1 and the maximum value of 10, i.e., all subranges beginning with a minimum value of 1 or greater (e.g., 1 to 6.1) and ending with a maximum value of 10 or less (e.g., 5.5 to 10).

[0129] The above-described aspects are merely possible examples of implementations, presented merely for a clear understanding of the principles of the present disclosure. Many variations and modifications can be made to the above-described embodiments without substantially departing from the spirit and principles of the present disclosure. All such variations and modifications are intended to be included herein within the scope of the present disclosure, and all possible claims directed to individual aspects or combinations of elements or steps are intended to be supported by the present disclosure. Moreover, although specific terms are employed in this specification and the claims that follow, these terms are used in a generic and descriptive sense only and not for the purpose of limiting either the described embodiments or the claims that follow.

Claims

1. A temperature-controlled packaging system for a biological sample, the system comprising: a container; and a PCM pack (i) form-fitting to the container and (ii) defining a payload cavity for the biological sample.

2. 10. The temperature controlled packaging system of claim 1, wherein the PCM pack is preconditioned at an effective charge temperature for an effective charge time.

3. 2. The temperature controlled packaging system of claim 1, wherein the PCM pack includes a first portion and a second portion, the first portion including a first type of PCM and the second portion including a second type of PCM different from the first type of PCM, and the PCM pack defines a payload cavity for a biological sample.

4. 10. The temperature controlled packaging system of claim 1, further comprising an insulating stopper comprising a first plug and a second plug.

5. 10. The temperature controlled packaging system of claim 1, wherein the PCM pack functions as both a sink for thermal energy and a secondary internal insulating layer.

6. further comprising an insulating stopper; the container comprises a vacuum bottle including vacuum insulation, a mouth, an outer wall substantially perpendicular to the mouth, and an inner wall tapering inwardly at 0 to 5 degrees relative to the vertical; the insulating stopper includes a handle and a plug having a friction fit with the mouth, the insulating stopper including a thickness of at least 20 mm; the PCM pack having an outer pack wall that fits the inner wall of the vacuum bottle; 2. The temperature controlled packaging system of claim 1, wherein the payload cavity comprises a volume of at least 3 cc and is formed from walls of the PCM pack, the payload cavity being at least partially surrounded by the PCM pack.

7. 10. The temperature controlled packaging system of claim 1, wherein the PCM pack further comprises a rim and an outer pack wall, the outer pack wall and the rim enclosing an air pocket between itself and the inner wall of the container having a thickness of between 0.2 mm and 5 mm.

8. The temperature controlled packaging system of claim 1 , wherein the payload cavity is centered on the vertical axis of the container.

9. 10. The temperature controlled packaging system of claim 8, further comprising an insulating stopper, said insulating stopper further comprising a sub-plug having a diameter approximately equal to said payload cavity, said sub-plug being centered on said vertical axis of said container.

10. 2. The temperature controlled packaging system of claim 1, wherein the PCM pack is a primary PCM pack including a first phase change material, and the temperature controlled packaging system further includes a secondary PCM pack, the secondary PCM pack including a second phase change material.

11. 11. The temperature controlled packaging system of claim 10, wherein the secondary PCM pack is positioned vertically above the primary PCM pack, and the payload cavity is further at least partially enclosed by the secondary PCM pack.

12. 11. The temperature controlled packaging system of claim 10, wherein the first phase change material has a phase change temperature that is lower than the phase change temperature of the second phase change material.

13. 11. The temperature controlled packaging system of claim 10, wherein the second phase change material has a phase change temperature in the range of -2°C to 15°C, and the first phase change material has a phase change temperature in the range of 5°C to 25°C.

14. the primary PCM pack and the secondary PCM pack are permanently coupled to each other; or the secondary PCM pack being permanently bonded to an insulating stopper; 11. The temperature controlled packaging system of claim 10, wherein at least one of:

15. the container comprises a vacuum bottle, the vacuum bottle comprising vacuum insulation, a mouth, an outer wall substantially perpendicular to the mouth, and an inner wall tapering inwardly at 0 to 5 degrees relative to the vertical; the temperature controlled packaging system further comprises an insulating stopper, the insulating stopper comprising a handle and a plug having a friction fit with the mouth, the insulating stopper comprising a thickness of at least 20 mm; the PCM pack includes an outer pack wall that fits over the inner wall of the vacuum bottle; the payload cavity comprises a volume of at least 3 cc and is formed from a wall of the primary PCM pack; The temperature controlled packaging system of claim 1 , wherein the payload cavity is at least partially enclosed by the primary PCM pack.

16. providing a vacuum shipper; positioning a pre-conditioned cylindrical PCM pack within said vacuum shipper; placing a temperature sensitive payload into a payload cavity defined by said PCM pack; A method for transporting a biological sample, comprising:

17. the PCM pack comprises a primary PCM pack; The method comprises: Incubating the primary PCM pack at an effective incubation temperature for an effective incubation time; placing the primary PCM pack in the vacuum shipper; forcing the insulating stopper into the mouth of the vacuum shipper; 17. The method of claim 16, further comprising:

18. 18. The method of claim 17, wherein the effective incubation temperature ranges between 0°C and 10°C.

19. 17. The method of claim 16, further comprising transporting the device to a destination within an effective transport time while maintaining a set of acceptable internal temperature limits and an effective average operating temperature range.

20. 20. The method of claim 19, wherein the effective average operating temperature range is between 2°C and 20°C and the effective transport time ranges from 48 hours to 120 hours.

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