WO2026036117A1 - Devices and methods for thawing biological substances - Google Patents

Abstract

Devices, systems, and methods herein relate to controlling a temperature (e.g., thawing) of a low volume biological substance. Devices may include a container configured to receive a biological substance and to be used with a temperature control device to control a temperature of the biological substance. In some variations, the container includes a top portion, a body portion, and a bottom portion. The body portion may include a fluid reservoir to receive the biological substance. The bottom portion may include a temperature sensor configured to measure the temperature of the biological substance received in the fluid reservoir. In some variations, the top portion and the bottom portion may couple to the body portion via connectors. Systems may include the container and the temperature control device configured to receive the container and control the temperature of the biological substance.

Description

Attorney Docket No. 132631-0008W001

PATENT COOPERATION TREATY PATENT APPLICATION

DEVICES AND METHODS FOR THAWING BIOLOGICAL SUBSTANCES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application Serial No. 63/681,753, filed August 9, 2024, and entitled “DEVICES AND METHODS FOR THAWING BIOLOGICAL SUBSTANCES”, the disclosure of which is incorporated herein by reference in its entirety.

BACKGROUND

[0002] Bags and vials containing biological substances such as, for example, plasma, blood, blood products, medications, and prophylactics may be supplied to medical facilities for transfer to patients on a regular basis. These biological substances may be frozen for storage and later thawed to a designated temperature just prior to use. Other times, these biological substances may need to be cooled or the temperature may need to be maintained at a designated temperature. The quality of the thawed biological substances may depend upon the process by which they are heated or cooled. Underheating or overheating a biological substance may reduce its effectiveness, thereby endangering patients, especially for low volume biological substances. Accordingly, improved devices and methods are needed for controlling the temperature of biological substances.

SUMMARY

[0003] In an aspect of the present disclosure, a polymer synthesis and assembly chip is disclosed. The chip includes a semiconductor integrated circuit device that contains a plurality of pixels, wherein each pixel of the plurality of pixels contains an electrode; and wherein a set of pixels of the plurality of pixels is capable of synthesizing a polymer; and wherein a set of pixels of the plurality of pixels is capable of assembling a synthesized polymer, either independently or in concert with one or more pixels of the plurality of pixels; and control circuity capable of applying voltages to the electrode. In certain embodiments, every pixel functions as a synthesis, assembly, motion, and confinement pixel. In other embodiments each pixel has a distinct function. In other preferred embodiments each pixel has a set of functions.

[0004] In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: a cavity configured to receive a container including the biological substance; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing; and an identifier for the biological substance.

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[0005] In some variations, the biological substance includes one or more of an mRNA vaccine, DNA vaccine, exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, and cell therapy product.

[0006] In some variations, the identifier receives the temperature measurement from the temperature sensor.

[0007] In some variations, the cavity includes a shape configured to funnel the container to a predetermined position and location within the enclosure.

[0008] In some variations, the container enclosure is configured to receive a container with a temperature of down to about -90°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -140°C or lower.

[0009] In some variations, the container enclosure is configured to receive a container with a temperature of down to about -190°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -100°C or lower and up to about 25 °C or higher. In some variations, the temperature sensor is configured to measure a temperature of down to about -150°C or lower and up to about 35 °C or higher.

[0010] In some variations, the temperature sensor includes a plurality of temperature sensors respectively configured to measure different temperature ranges. In some variations, the temperature sensor includes a thermocouple sensor, thermistor sensor, IR sensor, RFID-integrated sensor, and a combination thereof. In some variations, the temperature sensor includes a thermistor and a thermocouple. In some variations, the temperature measured by the temperature sensor is processed to provide complementary temperature monitoring and safety cutoff.

[0011] In some aspects, the techniques described herein relate to a system including the container enclosure, further including a temperature control device including a chamber and a thermal source, wherein the temperature control device is configured to receive the container enclosure in the chamber and the thermal source is configured to control the temperature of the biological substance.

[0012] In some aspects, the techniques described herein relate to a system, wherein the thermal source includes a Peltier element.

BRIEF DESCRIPTION OF THE DRAWING FIGURES

[0013] It is to be expressly understood that the drawings set forth herein are illustrative of exemplary embodiments provided herein and are not meant to limit the scope of the invention as encompassed by the claims.

[0014] FIG. 1 is a block diagram of an illustrative variation of a temperature control system configured to control a temperature of a biological substance.

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[0015] FIG. 2A is a side view of an illustrative variation of a temperature device for use in a temperature control system configured to control a temperature of a biological substance in a closed configuration. FIG. 2B is a side view of the device shown in FIG. 2A in an open configuration. FIG. 2C is a schematic cross-sectional side view of an illustrative variation of a temperature control device configured to control a temperature of a biological substance. FIG. 2D is a schematic cross- sectional side view of an illustrative variation of a temperature control device configured to control a temperature of a biological substance.

[0016] FIG. 3 is a schematic cross-sectional view of an illustrative variation of a container enclosure.

[0017] FIG. 4 is a schematic cross-sectional view of another illustrative variation of a container enclosure.

[0018] FIG. 5A is a schematic side view of an illustrative variation of a container. FIG. 5B is a schematic cross-sectional side view of an illustrative variation of an adapter. FIG. 5C is a schematic cross-sectional side view of the container shown in FIG. 5 A received within the adapter shown in FIG. 5B. FIG. 5D is a schematic plan view of the container and adapter shown in FIG. 5C.

[0019] FIG. 6A is a schematic cross-sectional side view of an illustrative variation of a conductive housing of one variation of a container enclosure. FIG. 6B is a schematic plan view of the conductive housing shown in FIG. 6A. FIG. 6C is a schematic cross-sectional side view of an illustrative variation of the container enclosure and a container disposed therein. FIG. 6D is a schematic plan view of the container enclosure and the container shown in FIG. 6C.

[0020] FIG. 7A is a schematic cross-sectional side view of an illustrative variation of a temperature control system configured to control a temperature of a biological substance. FIG. 7B is a schematic plan view of the system shown in FIG. 7A.

[0021] FIG. 8A is a schematic side view of another illustrative variation of a container. FIG. 8B is a schematic cross-sectional side view of an illustrative variation of the container shown in FIG. 8A partially received within another variation of a container enclosure. FIG. 8C is a schematic cross- sectional side view of the container shown in FIG. 8A fully received within the container enclosure shown in FIG. 8B.

[0022] FIG. 9A is a schematic cross-sectional side view of an illustrative variation of a temperature control system configured to control a temperature of a biological substance. FIG. 9B is a schematic plan view of the system shown in FIG. 9A.

[0023] FIG. 10A is a schematic cross-sectional view of an illustrative variation of a sensor and an identifier. FIG. 10B is a schematic cross-sectional view of another illustrative variation of a sensor

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 and an identifier. FIG. IOC is a schematic bottom view of an illustrative variation of the sensor and the identifier. FIG. 10D is a schematic bottom view of the sensor and the identifier shown in FIG. 10B.

[0024] FIG. 11 A is a schematic plan view of an illustrative variation of an adapter of a container enclosure. FIG. 1 IB is a schematic plan view of another illustrative variation of an adapter of a container enclosure.

[0025] FIG. 12 is a schematic block diagram of an illustrative variation of a temperature control system configured to control a temperature of a biological substance.

[0026] FIG. 13 is a flowchart of an illustrative variation of a method of controlling a temperature of a biological substance.

[0027] FIGS. 14A and 14B depict a schematic cross-sectional view of an illustrative variation of a container enclosure.

[0028] FIG. 15 is a plot of cycle threshold for a negative control set of patient samples.

[0029] FIG. 16 is a plot of cycle threshold for a set of diluted patient blood samples.

[0030] FIG. 17A is a plot of cycle threshold for RNA extracted from a set of fresh plasma samples. FIG. 17B is a plot of cycle threshold for RNA extracted from a set of plasma thawed from

[0031] -80°C plasma at room temperature. FIG. 17C is a plot of cycle threshold for RNA extracted from a set of plasma thawed from -80°C plasma in a container enclosure.

[0032] FIG. 18 is a flowchart illustrative of an exemplary method of thawing a low volume biological substance.

[0033] FIG. 19A is a schematic cross-sectional view of an illustrative variation of a container for holding a biological substance.

[0034] FIG. 19B is another schematic cross-sectional view of an illustrative variation of a container for holding a biological substance.

[0035] FIG. 19C is another schematic cross-sectional view of an illustrative variation of a container for holding a biological substance.

[0036] FIG. 20 illustrates an example container as a bag (e.g., ZipSleeve™ Technology) showing bag construction, leak containment, RF antenna integration, and wireless sensor placement in some variations.

[0037] FIG. 21 shows schematic illustrating a multi-sensor (e.g., sensor II, e.g., ZipLabel™-II) as a wireless label, dome-shaped thermal insulators, RFID circuitry, and temperature range extension to -196°C in some variations.

[0038] FIG. 22A illustrates an embodiment of a container (e.g., ZipSleeve™-B) configuration comprising a sensor II (ZipLabel™-II) integrated into the lower portion of the sleeve in some

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 variations. FIG. 22B illustrates an embodiment of a container (e.g., a ZipSleeve™-V) configuration adapted for vials in some variations. FIG. 22C shows an embodiment of a container (e.g., a ZipSleeve™-S) configuration, similar in purpose to the V variant in some variations, with a different funnel geometry and an integrated retention structure or insert (shown in red) that maintains vial alignment against the sensor II.

[0039] FIG. 23A illustrates an embodiment of a chamber concept comprising two vertically oriented heating cushions, each filled with approximately mL of sealed, water-based gel in some variations. FIG. 23B shows an embodiment of the Gen II chamber system incorporating advanced cushions formed from thermally conductive silicone doped with carbon or ceramic particles in some variations. FIG. 23 C provides a detailed sectional view of a Gen II cushion assembly compatible with the chamber shown in FIG. 23B in some variations.

[0040] FIG. 24A illustrates a simplified cryo-freeze to thawing workflow for cell and gene therapy substances prepared in standard commercial vials, in some variations. FIG. 24B illustrates a variant of the process supporting multiple vial formats and container geometries, in some variations. FIG. 24C demonstrates an integrated dual-format thawing procedure that supports both vials and cryogenic bags, in some variations.

[0041] FIG. 25 illustrates a modular thawing chamber architecture designed to accommodate a standardized outer-diameter well with internal adapters for variable vial formats, in some variations.

[0042] FIG. 26 illustrates a thermal chamber configuration utilizing a fixed-diameter cylindrical well with thermoelectric elements and multiple temperature sensors, in some variations.

[0043] FIG. 27A illustrates a sectional view of a thermal well containing a vertically aligned set of temperature sensors and an integrated lift mechanism, in some variations. FIG. 27B depicts the load position of the system, in some variations. FIG. 27C shows the home position, in some variations.

[0044] FIG. 28 illustrates multiple structural variations of a cryogenic-compatible vial device with outer diameter, configured for sterile use in cell and gene therapy workflows, in some variations. [0045] FIG. 29 illustrates a modular gapping system used to adapt commercial vial diameters to a fixed-diameter thermal well, in some variations.

[0046] FIG. 30 illustrates a disposable chamber structure configured for thawing biological vials to temperatures up to 37 °C, using water gel or silicone-based thermal transfer materials, in some variations.

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[0047] FIG. 31 illustrates a thawing chamber module (TCM) configured for thermal processing of cryogenically stored vials using a disposable adapter system and Peltier-based thermoelectric control, in some variations.

[0048] FIG. 32A illustrates a cryo-compatible vial structure incorporating a bottom-mounted thermocouple for precise temperature sensing, in some variations. FIG. 32B shows a variant with similar material construction and thermal profile but with a modified tapering vial body and bottom housing for enhanced heat transfer and sensor contact.

DETAILED DESCRIPTION

[0049] Conventional systems for thawing a frozen biological substance operate by placing a bag containing the biological substance in contact with heated water (e.g., water baths or water bladders). Heat is transferred from the water to the biological substance over a selected time duration to thaw the biological substance to a desired temperature range. However, these systems do not individually monitor the temperature of each bag for quality control during the thawing process. Typically, the ambient temperature of the water bath or water bladder is monitored during the thawing process. It may also be difficult to ensure that small volume biological substances do not overheat while thawing in heated water. Thus, it may be difficult to achieve reproducible and consistent thawing of the biological substances, creating opportunities for errors that may be harmful to patients.

[0050] Some biological substances such as mRNA are fragile and degrade easily at room temperature. For example, ribonucleases are commonly found even within controlled environments such as a clinical lab, and contact with ribonucleases may degrade mRNA. Accordingly, uncontrolled thawing may accelerate a degradation process. The devices, systems, and methods described herein may reduce degradation of low volumes of fragile biological substances such as mRNA.

[0051] Described here are devices and methods for thawing biological substances. These devices and methods may, for example, rapidly thaw a small volume of a biological substance such as a vaccine to a suitable temperature for use. In some variations, a container enclosure for use in thawing a biological substance may comprise a cavity configured to receive a container comprising the biological substance. The container may have a volume of up to about 50 mL. A temperature sensor may be configured to measure a temperature of the biological substance. The temperature sensor may overlie a portion of the cavity configured to hold the container during thawing. The container may comprise an identifier for the biological substance.

[0052] In some variations, a ratio of a diameter of the container to a width of the cavity may be between about 1 : 1 and about 5:32. In some variations, the biological substance may comprise one

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 or more of an mRNA vaccine, DNA vaccine, exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, and cell therapy product. In some variations, the cell therapy product may comprise one or more of stem cells and T-cells. In some variations, the identifier may receive the temperature measurement from the temperature sensor. In some variations, the cavity may comprise a shape configured to funnel the container to a predetermined position and location within the enclosure.

[0053] In some variations, the container enclosure may be configured to receive a container with a temperature of down to about -80°C. In some variations, the container may comprise one or more of a vial and cuvette. In some variations, the enclosure may comprise a thermally conductive material configured to transfer thermal energy to regulate a temperature of the biological substance. In some variations, the enclosure may be configured for single use.

[0054] Also described herein is a container enclosure for use in thawing a biological substance comprising an adapter configured to receive a container comprising the biological substance, and a housing comprising a thermal conductor defining a cavity configured to receive the adapter, a temperature sensor configured to measure the temperature of the biological substance, and an identifier for the biological substance.

[0055] In some variations, a system comprising the container enclosure may further comprise a temperature control device comprising a chamber and a thermal source. The temperature control device may be configured to receive the container enclosure in the chamber and the thermal source is configured to control the temperature of the biological substance. In some variations, a controller may include a processor and memory. The controller may be configured to control the thermal source. In some variations, the thermal source may comprise a Peltier element. In some variations, the temperature control device may further comprise an agitator configured to agitate the container enclosure. In some variations, the temperature control device may further comprise a reader configured to receive one or more of biological substance data and the measured temperature from one or more of the identifier and the temperature sensor.

[0056] Also described herein is a container enclosure for use in thawing a biological substance comprising an adapter configured to receive a container comprising the biological substance. The adapter may comprise an adapter temperature sensor configured to measure the temperature of the biological substance, and an identifier for the biological substance.

[0057] In some variations, the adapter may comprise a protrusion configured to releasably contact the container. In some variations, the adapter may comprise a connector coupled to the temperature sensor and disposed on an outer surface of the adapter. In some variations, the adapter may comprise a sleeve.

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[0058] In some variations, a system may comprise the container enclosure and further comprise a temperature control device comprising a thermal source, a thermal conductor, and a chamber configured to receive the container enclosure.

[0059] In some variations, the thermal source may be configured to control a temperature of the biological substance.

[0060] In some variations, the thermal conductor may comprise a thermal conductor temperature sensor configured to measure the temperature of the thermal conductor. In some variations, the thermal source may comprise a Peltier element. In some variations, the temperature control device may further comprise an agitator configured to agitate the container enclosure. In some variations, a controller may include a processor and memory. The controller may be configured to control the thermal source.

[0061] In some variations, the temperature control device may further comprise a reader configured to receive one or more of biological substance data and the measured temperature from one or more of the identifier and the temperature sensor. In some variations, the housing may comprise a handle. In some variations, the housing may be configured to transition between an open configuration and a closed configuration. The closed configuration may be configured to hold the container enclosure within the chamber. In some variations, the adapter may comprise a thermally conductive material. In some variations, the adapter may comprise a sleeve. In some variations, the thermal conductor may comprise one or more of a fluid, gel, metal, ceramic, polymer, and silicone.

[0062] In some variations, the adapter may comprise one or more of a metal, ceramic, polymer, and silicone. In some variations, the adapter may comprise a rigid material. In some variations, the temperature sensor may comprise a thermocouple. In some variations, one or more of the thermal conductor and the adapter may be configured for single use.

[0063] Also described herein is a system comprising a plurality of temperature control devices configured to control a temperature of a biological substance. Each device may comprise a container enclosure configured to receive a container comprising a biological substance, a temperature sensor configured to measure a temperature of the biological substance, an identifier for the biological substance, and a controller coupled to the plurality of temperature control devices. The controller may comprise a processor and memory. The controller may be configured to receive the temperature corresponding to one or more of the biological substances from one or more of the temperature control devices, and control the temperature of one or more of the biological substances using one or more of the temperature control devices based on its respective temperature sensor.

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[0064] In some variations, each temperature control device may comprise an agitator. The controller may be configured to control agitation of one or more of the temperature control devices based on its respective temperature sensor. In some variations, controlling the temperature of one or more of the biological substances may comprise controlling the temperature of the biological substance between down to about -80°C and up to about 37°C.

[0065] Also described herein is a system for controlling a temperature of a biological substance comprising an adapter configured to receive a container comprising the biological substance, a thermal conductor in thermal communication with the adapter, a thermal source in thermal communication with the thermal conductor, a temperature sensor configured to measure the temperature of the biological substance, and an identifier for the biological substance.

[0066] Also described herein is a method for thawing a biological substance comprising positioning a container comprising a biological substance in an adapter, where the biological substance is in a frozen state, positioning the adapter with the biological substance in a chamber such that the enclosed biological substance is in thermal communication with a first heating assembly located within the housing, and activating the heating assembly to heat and thereby thaw the enclosed biological substance. The enclosed biological substance may comprise mRNA, and the mRNA may have a post-thaw cycle threshold (Ct) value below about 30. In some variations, the post-thaw Ct value may be between about 27.0 and about 29.0.

[0067] In some variations, positioning the container in the adapter may further include positioning the container such that a side portion of the adapter overlaps a sidewall portion of the container and a bottom portion of the adapter overlaps and a bottom portion of the container. In some variations, a top portion of the container may remain uncovered. In some variations, at least one of a neck and a lip of the container may remain uncovered.

[0068] In some variations, positioning the container in the adapter may further include positioning the container in the adapter with an interference fit. In some variations, positioning the adapter in the chamber may further include positioning the adapter such that a longitudinal axis of the container is about parallel to a longitudinal axis of the chamber. In some variations, positioning the adapter may further include positioning the adapter in a cavity of a container enclosure and positioning the container enclosure in the chamber. After positioning the adapter in the cavity of the container enclosure, a portion of the container may overlap with a temperature sensor of the container enclosure. In some variations, positioning the container in the adapter may include positioning the container such that the adapter holds the container in an upright position.

[0069] Also described herein is a method of heating a biological substance comprising positioning a container comprising a biological substance in an adapter, positioning the adapter with the

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 container in a container enclosure, placing the container enclosure into a chamber of a thawing device, heating the enclosed biological substance to an endpoint temperature using the thawing device, and removing the container enclosure from the chamber of the thawing device after the biological substance has reached the endpoint temperature. The biological substance may be in a frozen state. The container enclosure may comprise a temperature sensor configured to measure a temperature of the biological substance. Positioning the adapter may result in at least a portion of the container overlapping the temperature sensor.

[0070] In some variations, heating the biological substance may further comprise heating a thermal conductor positioned in the chamber. In some variations, the biological substance may comprise mRNA and the endpoint temperature may be 4°C. In some variations, the biological substance may comprise blood plasma and the endpoint temperature may be 15°C.

[0071] In some variations, positioning the adapter in the container enclosure may include positioning the adapter such that the adapter holds the container in alignment with the temperature sensor. In some variations, the adapter may hold the container in an upright position in the container enclosure. In some variations, the adapter may maintain the container in a position in which a longitudinal axis of the container is parallel to a longitudinal axis of the chamber when the container enclosure is positioned within the chamber.

[0072] Also described herein is a system forthawing a biological substance comprising an adapter configured to receive a container comprising the biological substance, a container enclosure comprising a cavity configured to receive the adapter and a temperature sensor configured to measure a temperature of the biological substance, and an identifier for the biological substance. [0073] The temperature sensor may overlie a portion of the cavity.

[0074] In some variations, the adapter may be configured to maintain a position of the container relative to the temperature sensor during thawing. In some variations, the adapter may be configured to maintain the container in an upright position during thawing. In some variations, the adapter may comprise a thermally conductive material.

[0075] Also described herein is a container which may be configured to be received in a temperature control device to control a temperature of a biological substance contained therein. The container may comprise a body portion, a top portion, and a bottom portion. The body portion may comprise a first proximal connector, a first distal connector, and a fluid reservoir configured to receive the biological substance. The top portion may comprise an opening for transferring the biological substance into the fluid reservoir and a second proximal connector configured to couple with the first proximal connector of the body portion. The bottom portion may comprise a

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 temperature sensor configured to measure the temperature of the biological substance and a second distal connector configured to couple with the first distal connector of the body portion.

[0076] In some variations, the fluid reservoir may be configured to hold a volume of about 1 mL to about 26 mL of the biological substance. In some variations, the fluid reservoir may be configured to hold a maximum volume of about 26 mL to about 30 mL of the biological substance. [0077] In some variations, the body portion may comprise a diameter or width between about 5 mm and about 30 mm.

[0078] In some variations, the fluid reservoir may comprise a length between about 15 mm and 100 mm.

[0079] In some variations, the fluid reservoir may comprise a proximal diameter or width and a distal diameter or width. The proximal diameter or width may be between about 5 mm and about 10 mm, and the distal diameter or width may be between about 10 mm and about 15 mm.

[0080] In some variations, the fluid reservoir may comprise a diameter or width which may vary along a longitudinal axis of the container.

[0081] In some variations, a cross-sectional shape of the fluid reservoir along a longitudinal axis of the container may be different than a cross-sectional shape of the container along the longitudinal axis.

[0082] In some variations, the fluid reservoir may have a trapezoidal cross-sectional shape.

[0083] In some variations, the body portion of the container may comprise a proximal end with a first diameter or width and distal end with a second diameter or width, and the fluid reservoir may have a third diameter or width which may be greater than both the first and second diameters or widths.

[0084] In some variations, the temperature sensor may be configured to measure temperatures between about -200°C and about 40°C.

[0085] In some variations, a system for use in controlling the temperature of the biological substance may comprise the container and the temperature control device. The temperature control device may comprise a thermal source and a chamber which may be configured to receive the container. The top and bottom portions of the container may be configured to hold the container upright within the chamber of the temperature control device.

[0086] In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: a cavity configured to receive a container including the biological substance; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing.

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[0087] In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: a cavity configured to receive a container including the biological substance; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing; and an identifier for the biological substance.

[0088] In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: a cavity configured to receive a container including the biological substance, wherein the container has a volume of up to about 50 mL; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing; and an identifier for the biological substance.

[0089] In some aspects, the techniques described herein relate to an enclosure, further including a ratio of a diameter of the container to a width of the cavity between about 1 : 1 and about 5:32. In some variations, the biological substance includes one or more of an mRNA vaccine, DNA vaccine, exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, and cell therapy product. In some variations, the cell therapy product includes one or more of stem cells and T-cells. In some variations, the identifier receives the temperature measurement from the temperature sensor. In some variations, the cavity includes a shape configured to funnel the container to a predetermined position and location within the enclosure. In some variations, the container enclosure is configured to receive a container with a temperature of down to about - 80°C. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -80°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -100°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -120°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -140°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -150°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -190°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -100°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -120°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -140°C or lower. In some variations, the temperature sensor is configured to measure a

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 temperature of down to about -150°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -190°C or lower.

[0090] In some variations, the temperature sensor is configured to measure a temperature of down to about -100°C or lower and up to about 25 °C or higher. In some variations, the temperature sensor is configured to measure a temperature of down to about -120°C or lower and up to about 30 °C or higher. In some variations, the temperature sensor is configured to measure a temperature of down to about -140°C or lower and up to about 35 °C or higher r. In some variations, the temperature sensor is configured to measure a temperature of down to about -150°C or lower and up to about 35 °C or higher. In some variations, the temperature sensor is configured to measure a temperature of down to about -190°C or lower and up to about 45 °C or higher. In some variations, the temperature sensor includes a plurality of temperature sensors. In some variations, the temperature sensor includes a plurality of temperature sub-sensors. In some variations, the temperature sensor includes a plurality of temperature sensors respectively configured to measure different temperature ranges. In some variations, the temperature sensor includes a thermocouple sensor, thermistor sensor, IR sensor, RFID-integrated sensor, and a combination thereof. In some variations, the temperature sensor includes a thermistor and a thermocouple. In some variations, the temperature measured by the temperature sensor is processed to provide complementary temperature monitoring and safety cutoff. In some aspects, the techniques described herein relate to an enclosure, further including an antenna configured for both energy harvesting and RF communication. In some variations, the container is selected from a group consisting of: a commercial cryogenic vial, a disposable cryo-vial with fixed outer dimensions, and a custom vial having variable inner volume. In some variations, the container includes one or more of a vial and cuvette. In some aspects, the techniques described herein relate to an enclosure, further including a gap adapter configured to receive the container and maintain a fixed outer diameter. In some variations, the gap adapter includes a rigid body with high thermal conductivity, fabricated from aluminum, PTFE, or doped silicone.

[0091] In some variations, the temperature sensor is affixed to the base of the gap adapter, and aligned with an RFID reader embedded in a chamber base. In some variations, the enclosure includes a thermally conductive material configured to transfer thermal energy to regulate a temperature of the biological substance. In some variations, the enclosure is configured for single use.

[0092] In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: an adapter configured to receive a container including the biological substance; and a housing including: a thermal conductor defining a cavity

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 configured to receive the adapter; and a temperature sensor configured to measure the temperature of the biological substance. In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: an adapter configured to receive a container including the biological substance; and a housing including: a thermal conductor defining a cavity configured to receive the adapter; a temperature sensor configured to measure the temperature of the biological substance; and an identifier for the biological substance.

[0093] In some aspects, the techniques described herein relate to a system including the container enclosure, further including a temperature control device including a chamber and a thermal source, wherein the temperature control device is configured to receive the container enclosure in the chamber and the thermal source is configured to control the temperature of the biological substance. In some aspects, the techniques described herein relate to a system, further including a controller including a processor and memory, the controller configured to control the thermal source. In some aspects, the techniques described herein relate to a system, wherein the thermal source includes a Peltier element. In some aspects, the techniques described herein relate to a system, wherein the temperature control device further includes an agitator configured to agitate the container enclosure. In some aspects, the techniques described herein relate to a system, wherein the temperature control device further includes a reader configured to receive one or more of biological substance data and the measured temperature from one or more of the identifier and the temperature sensor.

[0094] In some aspects, the techniques described herein relate to a system, wherein the system is configured to perform temperature-controlled thawing based on approximately real-time wireless monitoring during thawing. In some aspects, the techniques described herein relate to a system wherein the system is configured to perform temperature-controlled thawing from cryogenic to physiologic range based on approximately real-time wireless monitoring during thawing.

[0095] In some aspects, the techniques described herein relate to a system, further including a thermal chamber including a thermal conductor, wherein the thermal chamber includes a pair of opposed thermoelectric modules for simultaneous heating and cooling. In some aspects, the techniques described herein relate to a system, wherein the thermal chamber further includes at least one embedded thermistor and at least one thermocouple.

[0096] In some aspects, the techniques described herein relate to a system, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling. In some aspects, the techniques described herein relate to a system, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling at frequencies up to 50 Hz.

14

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

[0097] In some aspects, the techniques described herein relate to a system, wherein the temperature control device operates based on a filtering algorithm configured to perform adaptive averaging on temperature readings to reduce noise. In some aspects, the techniques described herein relate to a system, wherein the system includes a thermal protection logic that disconnects power if the sensed temperature exceeds a threshold.

[0098] In some aspects, the techniques described herein relate to a system, wherein the system is configured to execute a thawing protocol including ice-free thawing from about -196 °C or higher, warming a target temperature between 30-37 °C. In some aspects, the techniques described herein relate to a system, further including a hybrid platform configured with a first chamber adapted for cryo-bags and a second chamber adapted for cryo-vials. In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: an adapter configured to receive a container including the biological substance, the adapter including: an adapter temperature sensor configured to measure the temperature of the biological substance. [0099] In some aspects, the techniques described herein relate to a container enclosure for use in thawing a biological substance including: an adapter configured to receive a container including the biological substance, the adapter including: an adapter temperature sensor configured to measure the temperature of the biological substance; and an identifier for the biological substance. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -80°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -100°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about - 120°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -140°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -150°C or lower. In some variations, the container enclosure is configured to receive a container with a temperature of down to about -190°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -100°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -120°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -140°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -150°C or lower. In some variations, the temperature sensor is configured to measure a temperature of down to about -190°C or lower.

[0100] In some variations, the temperature sensor is configured to measure a temperature of down to about -100°C or lower and up to about 25 °C or higher. In some variations, the temperature

15

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 sensor is configured to measure a temperature of down to about -120°C or lower and up to about 30 °C or higher. In some variations, the temperature sensor is configured to measure a temperature of down to about -140°C or lower and up to about 35 °C or higher r. In some variations, the temperature sensor is configured to measure a temperature of down to about -150°C or lower and up to about 35 °C or higher. In some variations, the temperature sensor is configured to measure a temperature of down to about -190°C or lower and up to about 45 °C or higher. In some variations, the temperature sensor includes a plurality of temperature sensors. In some variations, the temperature sensor includes a plurality of temperature sub-sensors. In some variations, the temperature sensor includes a plurality of temperature sensors respectively configured to measure different temperature ranges. In some variations, the temperature sensor includes a thermocouple sensor, thermistor sensor, IR sensor, RFID-integrated sensor, and a combination thereof. In some variations, the temperature sensor includes a thermistor and a thermocouple. In some variations, the temperature measured by the temperature sensor is processed to provide complementary temperature monitoring and safety cutoff.

[0101] In some aspects, the techniques described herein relate to an enclosure, further including an antenna configured for both energy harvesting and RF communication. In some variations, the container is selected from a group consisting of a commercial cryogenic vial, a disposable cryo- vial with fixed outer dimensions, and a custom vial having variable inner volume.

[0102] In some variations, the container includes one or more of a vial and cuvette. In some aspects, the techniques described herein relate to an enclosure, further including a gap adapter configured to receive the container and maintain a fixed outer diameter. In some variations, the gap adapter includes a rigid body with high thermal conductivity, fabricated from aluminum, PTFE, or doped silicone. In some variations, the temperature sensor is affixed to the base of the gap adapter, and aligned with an RFID reader embedded in the chamber base. In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes a protrusion configured to releasably contact the container. In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes a connector coupled to the temperature sensor and disposed on an outer surface of the adapter.

[0103] In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes a sleeve. In some aspects, the techniques described herein relate to a system including the container enclosure, further including a temperature control device including a thermal source, a thermal conductor, and a chamber configured to receive the container enclosure. In some aspects, the techniques described herein relate to a system, wherein the system is configured to perform temperature-controlled thawing based on approximately real-time wireless

16

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 monitoring during thawing. In some aspects, the techniques described herein relate to a system wherein the system is configured to perform temperature-controlled thawing from cryogenic to physiologic range based on approximately real-time wireless monitoring during thawing. In some aspects, the techniques described herein relate to a system, further including a thermal chamber including the thermal conductor, wherein the thermal chamber includes a pair of opposed thermoelectric modules for simultaneous heating and cooling. In some aspects, the techniques described herein relate to a system, wherein the thermal chamber further includes at least one embedded thermistor and at least one thermocouple.

[0104] In some aspects, the techniques described herein relate to a system, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling. In some aspects, the techniques described herein relate to a system, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling at frequencies up to 50 Hz. In some aspects, the techniques described herein relate to a system, wherein the temperature control device operates based on a filtering algorithm configured to perform adaptive averaging on temperature readings to reduce noise. In some aspects, the techniques described herein relate to a system, wherein the system includes a thermal protection logic that disconnects power if the sensed temperature exceeds a threshold. In some aspects, the techniques described herein relate to a system, wherein the system is configured to execute a thawing protocol including ice-free thawing from about -196 °C or higher, warming a target temperature between 30-37 °C. In some aspects, the techniques described herein relate to a system, further including a hybrid platform configured with a first chamber adapted for cryo-bags and a second chamber adapted for cryo-vials.

[0105] In some aspects, the techniques described herein relate to a system, wherein the thermal source is configured to control a temperature of the biological substance. In some aspects, the techniques described herein relate to a system, wherein the thermal conductor includes a thermal conductor temperature sensor configured to measure the temperature of the thermal conductor. In some aspects, the techniques described herein relate to a system, wherein the thermal source includes a Peltier element. In some aspects, the techniques described herein relate to a system wherein the temperature control device further includes an agitator configured to agitate the container enclosure. In some aspects, the techniques described herein relate to a system, further including a controller including a processor and memory, the controller configured to control the thermal source. In some aspects, the techniques described herein relate to a system, wherein the temperature control device further includes a reader configured to receive one or more of

17

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 biological substance data and the measured temperature from one or more of the identifier and the temperature sensor.

[0106] In some aspects, the techniques described herein relate to a system, wherein the housing includes a handle. In some aspects, the techniques described herein relate to a system, wherein the housing is configured to transition between an open configuration and a closed configuration, wherein the closed configuration is configured to hold the container enclosure within the chamber. In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes a thermally conductive material. In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes a sleeve. In some aspects, the techniques described herein relate to a system, wherein the thermal conductor includes one or more of a fluid, gel, metal, ceramic, polymer, and silicone. In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes one or more of a metal, ceramic, polymer, and silicone.

[0107] In some aspects, the techniques described herein relate to a container enclosure, wherein the adapter includes a rigid material. In some aspects, the techniques described herein relate to a container enclosure, wherein the temperature sensor includes a thermocouple. In some aspects, the techniques described herein relate to a system, wherein one or more of the thermal conductor and the adapter are configured for single use. In some aspects, the techniques described herein relate to a system, including: a plurality of temperature control devices configured to control a temperature of a biological substance, wherein each device includes: a container enclosure configured to receive a container including a biological substance; a temperature sensor configured to measure a temperature of the biological substance; an identifier for the biological substance; and a controller coupled to the plurality of temperature control devices, the controller including a processor and memory, and configured to: receive the temperature corresponding to one or more of the biological substances from one or more of the temperature control devices; and control the temperature of one or more of the biological substances using one or more of the temperature control devices based on its respective temperature sensor. In some aspects, the techniques described herein relate to a system, wherein each temperature control device includes an agitator, and the controller is configured to control agitation of one or more of the temperature control devices based on its respective temperature sensor. In some aspects, the techniques described herein relate to a system, wherein controlling the temperature of one or more of the biological substances includes controlling the temperature of the biological substance between down to about -80°C and up to about 37°C.

18

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

[0108] In some aspects, the techniques described herein relate to a system, wherein controlling the temperature of one or more of the biological substances includes controlling the temperature of the biological substance between down to about -100°C and up to about 37°C. In some aspects, the techniques described herein relate to a system, wherein controlling the temperature of one or more of the biological substances includes controlling the temperature of the biological substance between down to about -120°C and up to about 37°C. In some aspects, the techniques described herein relate to a system, wherein controlling the temperature of one or more of the biological substances includes controlling the temperature of the biological substance between down to about -150°C and up to about 37°C. In some aspects, the techniques described herein relate to a system, wherein controlling the temperature of one or more of the biological substances includes controlling the temperature of the biological substance between down to about -190°C and up to about 37°C.

[0109] In some aspects, the techniques described herein relate to a system for controlling a temperature of a biological substance, including: an adapter configured to receive a container including the biological substance; a thermal conductor in thermal communication with the adapter; a thermal source in thermal communication with the thermal conductor; a temperature sensor configured to measure the temperature of the biological substance; and an identifier for the biological substance. In some aspects, the techniques described herein relate to a system, wherein the system is configured to perform temperature-controlled thawing based on approximately realtime wireless monitoring during thawing. In some aspects, the techniques described herein relate to a system wherein the system is configured to perform temperature-controlled thawing from cryogenic to physiologic range based on approximately real-time wireless monitoring during thawing. In some aspects, the techniques described herein relate to a system, further including a thermal chamber including a thermal conductor, wherein the thermal chamber includes a pair of opposed thermoelectric modules for simultaneous heating and cooling. In some aspects, the techniques described herein relate to a system, wherein the thermal chamber further includes at least one embedded thermistor and at least one thermocouple. In some aspects, the techniques described herein relate to a system, wherein the thermoelectric modules are regulated by a PID- based analog controller that performs continuous sampling.

[0110] In some aspects, the techniques described herein relate to a system, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling at frequencies up to 50 Hz. In some aspects, the techniques described herein relate to a system, wherein the temperature control device operates based on a filtering algorithm configured to perform adaptive averaging on temperature readings to reduce noise. In some aspects, the

19

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 techniques described herein relate to a system, wherein the system includes a thermal protection logic that disconnects power if the sensed temperature exceeds a threshold. In some aspects, the techniques described herein relate to a system, wherein the system is configured to execute a thawing protocol including ice-free thawing from about -196 °C or higher, warming a target temperature between 30-37 °C. In some aspects, the techniques described herein relate to a system, further including a hybrid platform configured with a first chamber adapted for cryo-bags and a second chamber adapted for cryo-vials. In some aspects, the techniques described herein relate to a method for thawing a biological substance, the method including: positioning a container including a biological substance in an adapter, wherein the biological substance is in a frozen state; positioning the adapter with the biological substance in a chamber of a thawing device such that the biological substance is in thermal communication with a first heating assembly located within a housing of the thawing device; and activating the heating assembly to heat and thereby thaw the enclosed biological substance, wherein the enclosed biological substance includes mRNA, and the mRNA has a post- thaw cycle threshold (Ct) value below about 30. In some aspects, the techniques described herein relate to a method, wherein the post-thaw Ct value is between about 27.0 and about 29.0.

[OHl] In some aspects, the techniques described herein relate to a method, wherein positioning the container in the adapter further includes positioning the container such that a side portion of the adapter overlaps a sidewall portion of the container and a bottom portion of the adapter overlaps and a bottom portion of the container. In some aspects, the techniques described herein relate to a method, wherein a top portion of the container remains uncovered. In some aspects, the techniques described herein relate to a method, wherein at least one of a neck and a lip of the container remains uncovered. In some aspects, the techniques described herein relate to a method, wherein positioning the container in the adapter further includes positioning the container in the adapter with an interference fit. In some aspects, the techniques described herein relate to a method, wherein positioning the adapter in the chamber further includes positioning the adapter such that a longitudinal axis of the container is about parallel to a longitudinal axis of the chamber. In some aspects, the techniques described herein relate to a method, wherein positioning the adapter further includes positioning the adapter in a cavity of a container enclosure and positioning the container enclosure in the chamber.

[0112] In some aspects, the techniques described herein relate to a method, wherein after positioning the adapter in the cavity of the container enclosure, a portion of the container overlaps with a temperature sensor of the container enclosure. In some aspects, the techniques described

20

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 herein relate to a method, wherein positioning the container in the adapter includes positioning the container such that the adapter holds the container in an upright position.

[0113] In some aspects, the techniques described herein relate to a method of heating a biological substance, including: positioning a container including a biological substance in an adapter, wherein the biological substance is in a frozen state; positioning the adapter with the container in a container enclosure, wherein the container enclosure includes a temperature sensor configured to measure a temperature of the biological substance, and wherein positioning the adapter results in at least a portion of the container overlapping the temperature sensor; placing the container enclosure into a chamber of a thawing device; heating the enclosed biological substance to an endpoint temperature using the thawing device; and removing the container enclosure from the chamber of the thawing device after the biological substance has reached the endpoint temperature. In some aspects, the techniques described herein relate to a method, wherein heating the biological substance further includes heating a thermal conductor positioned in the chamber. In some aspects, the techniques described herein relate to a method, wherein the biological substance includes mRNA and the endpoint temperature is 4°C. In some aspects, the techniques described herein relate to a method, wherein the biological substance includes blood plasma and the endpoint temperature is 15°C. In some aspects, the techniques described herein relate to a method, wherein positioning the adapter in the container enclosure includes positioning the adapter such that the adapter holds the container in alignment with the temperature sensor. In some aspects, the techniques described herein relate to a method, wherein the adapter holds the container in an upright position in the container enclosure.

[0114] In some aspects, the techniques described herein relate to a method, wherein the adapter maintains the container in a position in which a longitudinal axis of the container is parallel to a longitudinal axis of the chamber when the container enclosure is positioned within the chamber. In some aspects, the techniques described herein relate to a system for thawing a biological substance, including: an adapter configured to receive a container including the biological substance; a container enclosure including a cavity configured to receive the adapter and a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity; and an identifier for the biological substance. In some aspects, the techniques described herein relate to a system, wherein the adapter is configured to maintain a position of the container relative to the temperature sensor during thawing. In some aspects, the techniques described herein relate to a system, wherein the adapter is configured to maintain the container in an upright position during thawing. In some aspects, the techniques described herein relate to a system, wherein the adapter includes a thermally

21

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 conductive material. In some aspects, the techniques described herein relate to a container configured to be received in a temperature control device to control a temperature of a biological substance contained therein, the container including: a body portion including a first proximal connector, a first distal connector, and a fluid reservoir configured to receive the biological substance; a top portion including an opening for transferring biological substance into the fluid reservoir and a second proximal connector configured to couple with the first proximal connector of the body portion; and a bottom portion including a temperature sensor configured to measure the temperature of the biological substance and a second distal connector configured to couple with the first distal connector of the body portion.

[0115] In some aspects, the techniques described herein relate to a container, wherein the fluid reservoir is configured to hold a volume of about 1 mL and about 26 mL of the biological substance. In some aspects, the techniques described herein relate to a container, wherein the fluid reservoir is configured to hold a maximum volume of about 26 mL to about 30 mL of the biological substance. In some aspects, the techniques described herein relate to a container, wherein the body portion includes a diameter or width between about 5 mm and about 30 mm. In some aspects, the techniques described herein relate to a container, wherein the fluid reservoir includes a length of between about 15 mm and about 100 mm. In some aspects, the techniques described herein relate to a container, wherein the fluid reservoir includes a proximal diameter or width between about 5 mm and about 10 mm, and a distal diameter or width between about 10 mm and about 15 mm. In some aspects, the techniques described herein relate to a container, wherein a diameter or width of the fluid reservoir varies along a longitudinal axis of the container. [0116] In some aspects, the techniques described herein relate to a container, wherein the cross- sectional shape of the fluid reservoir along a longitudinal axis of the container is different than a cross-sectional shape of the container along the longitudinal axis. In some aspects, the techniques described herein relate to a container, wherein the fluid reservoir has a trapezoidal cross-sectional shape. In some aspects, the techniques described herein relate to a container, wherein the body portion includes a proximal end with a first diameter or width and distal end with a second diameter or width, and wherein the fluid reservoir has a third diameter or width and the third diameter or width is greater than both the first and second diameters or widths. In some aspects, the techniques described herein relate to a container, wherein the temperature sensor is configured to measure temperatures between about -200°C and about 40°C. In some aspects, the techniques described herein relate to a system for use in controlling the temperature 155; and the temperature control device including a thermal source and a chamber configured to receive the container, wherein one or more of the top portion and the bottom portion are configured hold the container

22

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 upright within the chamber. Described herein are devices, systems, and methods for controlling a temperature of a biological substance, such as, for example, a low volume biological substance. A low volume biological substance (e.g., vaccine, medication, prophylactic, plasma, glycerolized blood, red blood corpuscles (RBCs)) that is frozen and stored in a container may need to be thawed to a predetermined temperature before it is suitable for its intended application. At times, a low volume biological substance may need to be cooled or maintained at a designated temperature prior to use. Thus, systems for controlling a temperature (e.g., heating, cooling, maintaining at a designated temperature) of a low volume biological substance may be critical to effective use of such substances.

[0117] Generally, a system for controlling the temperature of the biological substance may comprise a thermal source such as a heating and/or cooling element. The thermal source may be in thermal communication with a container enclosure configured to function as a thermal interface between the thermal source and the biological substance. For example, the container may be placed within the container enclosure and the container enclosure may be placed in thermal communication with the thermal source. The thermal source may generate thermal energy such as heat that will be transmitted through the container enclosure to alter (increase, decrease) or maintain the temperature of the biological substance. A controller coupled to the thermal source may be configured to control a temperature of the biological substance by, for example, instructing the thermal source to generate thermal energy to thaw a frozen biological substance to room temperature and maintain that temperature for a predetermined amount of time using closed-loop temperature control.

[0118] In some variations, a biological substance may include, but is not limited to, mRNA vaccine, DNA vaccine, exosome, liquid biopsy, cryo-preserved tissue, therapeutic, prophylactic, and cell therapy product, whole blood, blood products, plasma derivatives, breast milk, ovaries, eggs, sperm, embryos, tissue, drugs, cells, such as chimeric antigen receptors t-cell (CAR-T) or other T- cells, molecular reagents, antibodies, combinations thereof, and the like.

[0119] Systems

[0120] The systems (e.g., temperature control system) described herein may be configured to control the temperature of a biological substance (e.g., heat or thaw, cool, maintain at a desired set point) disposed within a container. The temperature control systems may comprise a container enclosure and a temperature control device (e.g., thawing device, cooling device) comprising a thermal source. The temperature control device may comprise a controller, or may be coupled to an external controller, configured to control the temperature of the biological substance. The thermal source may be provided in thermal communication with the biological substance in a

23

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 number of configurations. For example, a container enclosure comprising a bag as described in more detail with respect to FIGS. 2-4 may be configured to receive the container and be placed within a chamber of the temperature control device. In other variations, a container enclosure comprising a conductive housing and an adapter as described in more detail with respect to FIGS. 5 A-7B may be placed within a chamber of a temperature control device. In yet other variations, a container enclosure comprising an adapter as described in more detail with respect to FIGS. 8A- 9B may be placed within a chamber of a temperature control device. The container enclosure may function as a thermal interface between the thermal source and the biological substance and may facilitate placement and alignment of the container within the temperature control device.

[0121] As mentioned above, the temperature control systems described herein may regulate the temperature (e.g., thaw from frozen, warm, maintain, cool) of biological substances such as, for example, mRNA vaccines and cryo-preserved tissues, stored in containers such as low volume vials (e.g., having a volume of less than about 100 mL). FIG. l is a block diagram of an illustrative variation of a temperature control system (100) configured to control a temperature of a biological substance. As shown there, the system (100) may comprise a chamber (102) (e.g., dry thawing chamber), a controller (104), a user interface (106), thermal sources (112, 114), thermal conductors (116, 118), a container enclosure (120), a biological substance (122), temperature sensors (124, 126, 130, 132), and an agitator (128).

[0122] In some variations, the chamber (102) may comprise one or more thermal sources (112, 114) (e.g., heating and/or cooling element such as a Peltier element or other heater or cooler) configured to be in thermal communication with a thermal conductor (116, 118) (e.g., enclosed gel, water). The chamber (102) may be configured to receive the container enclosure (120) having the biological substance (122) disposed therein. In some variations, one or more of the thermal conductors (116, 118) may be configured to be positioned in contact with the container enclosure [0123] (120) surrounding or otherwise containing therein an enclosed biological substance (122) (e.g., container having a biological substance). In some variations, one or more of the thermal conductors (116, 118) may be part of the container enclosure (120). In some variations, one or both of the thermal conductors (116, 118) may be heating cushions. The heating cushions may be formed from a material of relatively high thermal conductivity and may be filled with fluid. In some variations, the thermal conductors (116, 118) may be formed from a reversibly deformable material. The container enclosure (120) may function as a thermal interface between the thermal source (112, 114) and the biological substance (122).

[0124] In some variations, the system may comprise one or more temperature sensors for monitoring (e.g., measuring) a temperature of the biological substance (122) as described in more

24

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 detail herein, and one or more temperature sensors (130, 132) for monitoring the temperature of the thermal conductors (116, 118). Additionally or alternatively, the system (100) may comprise an optional agitator (128) in mechanical communication with the container enclosure (120). In some variations, the controller (104) may be configured to control the thermal source (112, 114) and the temperature sensors by wired and/or wireless communication links (134a, 134b, 135a, 135b). The controller (104) may further be configured to control the temperature of the biological substance based at least on the temperature measurements.

[0125] In some variations, the temperature sensors may have different configurations. FIG. 1 illustrates a first configuration of temperature sensors including first contact temperature sensors (124, 126) and second contact temperature sensors (130,132). For example, first contact temperature sensors (124, 126) may be integrated with, or secured to, the container enclosure (120) (e.g., secured to an inner or outer surface of the container enclosure (120), secured to a portion of the container enclosure (120), such as, for example, an adapter or a conductive housing) for measurement of the temperature of the biological substance. The first contact temperature sensors (124, 126) may be positioned on the same side or surface of the container enclosure (120) or on opposite sides or surfaces of the container closure (120). For example, in some variations, each of the first contact temperature sensors (124, 126) may be positioned on an inner surface of the container enclosure (120) (e.g., the same inner surface or opposed inner surfaces) of the container enclosure (120) for contact with the container (e.g., vial) holding the biological substance (122). In another variation, each of the first contact temperature sensors (124, 126) may be positioned on outer surfaces of the container enclosure (120). As another example, one first contact temperature sensor (124, 126) may be positioned on an inner surface of the container enclosure (120) and the other first contact temperature sensor (124, 126) may be positioned on an outer surface of the container enclosure (120). In some variations, one or more of the first contact temperature sensors (124, 126) may be positioned on a surface (e.g., internal surface, bottom) of an adapter and/or a conductive housing of a container enclosure. In some variations, a single first contact temperature sensor (124,126) may be used and it may be disposed in any of the locations described herein.

[0126] As further shown in FIG. 1, second contact temperature sensors (130, 132) may be integrated with, or secured to, thermal conductors (116, 118) (e.g., an inner or outer surface of the thermal conductor) for measurement of the temperature of thereof. As shown, second contact temperature sensors (130, 132) may be positioned on outer surfaces of each thermal conductor (116, 118). Additionally or alternatively, the location and/or number of the second contact temperature sensors (130, 132) may be varied. For example, each of the second temperature

25

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 sensors (130, 132) may be positioned on inner surfaces of its corresponding thermal conductors (116, 118) for contact with the container enclosure (120), and thus the container holding the biological substance (122). As another example, one of the second contact temperature sensors (130, 132) may be positioned on an inner surface of its corresponding thermal conductor (116, 118) and the other second contact temperature sensor (130, 132) may be positioned on an outer surface of its corresponding thermal conductor (116, 118). In another aspect, the second contact temperature sensors may be distributed between the thermal conductors in any combination. In some variations, a single second contact temperature sensor (130,132) may be used, and it may be disposed in any of the locations described herein.

[0127] In some variations, the system (100) may include one or more non-contact temperature sensors. For example, the non-contact temperature sensors may be arranged at a predetermined distance from one or more targets (e.g., the biological substance, the container enclosure or a portion thereof (e.g., an adapter, a conductive housing or any portion thereof) and configured to measure a temperature of the target(s). As an example, non-contact temperature sensors may be configured to measure electromagnetic radiation emitted from the enclosure (e.g., infrared radiation). In some variations, one or more non-contact temperature sensors may be used in combination with one or more contact temperature sensors. In some variations, the contact temperature sensors (e.g., first contact temperature sensors (124, 126) and second contact temperature sensors (130, 132)) and non-contact temperature sensors may communicate with the controller (104) via communication links that are wired and/or wireless. In some variations, the systems, devices, and methods described herein may comprise one or more components, steps, and features of any of the devices and systems described in International Application No. PCT/US2019/031215, filed on May 7, 2019, the entirety of which is hereby incorporated by reference herein.

[0128] In some variations, one or more of the contact temperature sensors may be integrated with a radiofrequency identification (RFID) tag mounted to the container enclosure or any portion thereof (e.g., an adapter, a conductive housing or a portion thereof). Mounting may include being printed on a surface, adhered to a surface by an adhesive, combinations thereof, and the like. In further variations, respective temperature sensors may be a sensor of a smart label, as discussed in International Patent Application No. WO 2016/023034, filed August 10, 2015, entitled “Smart Bag Used In Sensing Physiological And/Or Physical Parameters Of Bags Containing Biological Substance,” the entirety of which is hereby incorporated by reference. The RFID tag may be configured to wirelessly transmit data (e.g., temperature measurements, authentication information) to a receiver in communication with the controller. In some variations, the non-

26

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 contact temperature sensors may also be configured to communicate wirelessly with the controller. Exemplary variations of RFID tags are described in more detail in International Patent Application No. WO 2016/023034, which is hereby incorporated by reference in its entirety.

[0129] In some variations, two or more temperature sensors selected from contact temperature sensors or non-contact temperature sensors may be used to improve the accuracy of temperature measurements and provide redundancy. For example, in some variations, the controller (104) may receive temperature data from a contact temperature sensor and temperature data from a noncontact temperature sensor, and may use both to control a temperature regulation process, which may result in more accurate and precise control of the temperature of the biological substance. As another example, faulty temperature sensors may be identified using a plurality of sensors. For instance, temperature measurements of the biological substance (122) acquired by two different temperature sensors may be compared to one another. If a deviation is observed between these measurements, the controller (104) may output an alarm (e.g., an audio and/or visual signal) for replacement of the faulty temperature sensor. The alarm may also include a signal transmitted to the controller (104) configured to control the controller 104 to cease measurement using the faulty temperature sensor in a thawing process. Redundancy may be provided by having the controller (104) employ a non-faulty temperature sensor in place of the faulty temperature sensor for control of a thawing processes. In this manner, faulty temperature sensors may be identified and replaced while avoiding the use of inaccurate temperature measurements for control of a thawing process. [0130] In some variations, the system may be configured to provide a failsafe functionality in which one or both of the thermal sources (112, 114) inhibit heat generation when the temperature measured at the selected thermal source (112, 114) and/or the thermal conductor (116, 118) exceed predetermined threshold temperatures. For example, the system may comprise one or more failsafe temperature sensors. In some variations, the failsafe temperature sensors may be disposed on the same surfaces as the other temperature sensors described herein (e.g., contact temperature sensor, non-contact temperature sensor) or on other surfaces, such as on the thermal source itself. In some variations, a failsafe signal may be configured to terminate delivery of electrical power independently to thermal source (112, 114) using the power supply (107). For example, if a first failsafe signal is transmitted to the power supply (107) in response to a temperature measurement made by a failsafe temperature sensor, delivery of electrical power may be terminated to one or more of the thermal source (112, 114). In some variations, the failsafe temperature sensors may comprise one or more of a thermocouple and a thermistor.

[0131] In some variations, the predetermined failsafe threshold temperature value may be different for the thermal source (112, 114) and the thermal conductor (116, 118). For example, the

27

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 predetermined failsafe threshold temperature for the thermal source (112, 114) may be about 105°C, and the predetermined failsafe threshold temperature for the thermal conductor (116, 118) may be about 40°C for thermocouple failsafe temperature sensors and about 40°C to about 60°C for thermistor failsafe temperature sensors (e.g., negative temperature coefficient (NTC) thermistors and positive temperature coefficient (PTC) thermistors). Thus, failsafe temperature sensors may help prevent damage to the biological substance (122), container enclosure (120), and/or other components of the temperature control system (100).

[0132] In some variations, the container enclosure (120) containing the biological substance (122) may be positioned in contact with the one or more thermal conductors (116, 118), while in other variations the thermal conductors may be part of the container enclosure (120) and may be thermally coupled to the biological substance directly, or via an adapter. The thermal conductor (116, 118) may be deformable to accommodate the shape and volume of the container enclosure (120), the adapter, and/or the container holding the biological substance (122). In this manner, contact between the container enclosure (120) or an adapter of the container enclosure and the thermal conductor (116, 118) may be ensured, promoting heat transfer from one or more thermal conductor (116, 118) to the biological substance (122). In some variations, a thermal conductor may be fixed to a thermal source, as described in more detail with respect to FIGS. 2 and 9. In other variations, the thermal conductor may be removably coupled to a thermal source, as described in more detail with respect to FIGS 6 and 7.

[0133] In some variations, the controller (104) may transmit first command signals to a first thermal source (112) and a second thermal source (114) to cause the first thermal source (112) and the second thermal source (114), respectively, to generate thermal energy, at least a portion of which is transferred through the first thermal conductor (116) and the second thermal conductor (118), respectively, to the biological substance (122). The temperature of a component may be measured by one or more contact temperature sensors (e.g., first contact temperature sensors (124, 126) and/or second contact temperature sensors (130, 132)) and/or one or more non-contact temperature sensors and transmitted to the controller (104) via a communication link. The component may be at least one of the thermal conductor (116, 118), the container enclosure (120) itself or portion thereof, and the biological substance (122). In some variations, the temperature of a portion of the container enclosure (120) may be approximately equal to the temperature of the biological substance (122). Accordingly, the temperature of the biological substance (122) may be measured via measurement of the temperature of a portion of the container enclosure (120).

28

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

[0134] In some variations, the controller (104) may receive temperature data corresponding to one or more of the thermal source (112, 114) and thermal conductor (116, 118), as feedback for closed- loop control of the thermal source (112, 114) in order to provide a predetermined temperaturetime response. Additionally or alternatively, the controller (104) may receive temperature data corresponding to the biological substance (122) for closed-loop feedback control of the thermal source (112, 114). Thus, regardless of the geometry or volume of the biological substance (122), thermal energy applied for controlling a temperature of the biological substance (122) may be controlled to avoid over-heating or under-heating the biological substance (122). Controlling a temperature of the biological substance may refer to heating the biological substance (122), cooling the biological substance (122), and/or maintaining the temperature of the biological substance (122) at a set-point or within a predetermined range.

[0135] As mentioned above, the temperature control system (100) may optionally comprise an agitator (128). The agitator (128) may be configured to provide substantially uniform heat transfer. For example, in some variations, an agitator (128) may comprise a cam, and motor configured to pivot, a support holding a container to agitate the biological substance within the chamber. In other variations, the agitator (128) may comprise a motor configured to vibrate a support holding a container. The controller (104) may be configured to transmit second command signals to the agitator (128) to agitate the biological substance (122). Substantially uniform heat transfer may include a difference between a maximum and minimum temperature of the biological substance that is less than or equal to a predetermined temperature difference (e.g., between about 0.5°C to about 2°C). In some variations, an agitator (128) may agitate the biological substance based on a predetermined weight threshold and/or volume threshold. For example, agitation during a temperature regulation process for a low volume biological substance (e.g., mRNA vaccine) may be inhibited, but agitation may be applied during a temperature regulation process for a blood bag. In some variations, an operator may manually select agitation as desired, and in some instances, it may be desirable not to utilize agitation for low volume biological substances. In some variations, the controller (104) may be configured to provide commands to a thermal source (112, 114) and an agitator (128) based at least in part on temperature sensor measurements and a method of regulating a temperature of a biological substance, as described in more detail with respect to FIG. 13. In some variations, an operator may select a desired temperature control (e.g., thawing) program from a list of predetermined thawing programs stored in memory in communication with the controller.

[0136] Additionally or alternatively, a temperature control program may be selected by the controller (104) from a plurality of predetermined temperature control programs. As an example,

29

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 the predetermined temperature control program may be selected by the controller based upon one or more of a volume, weight, and type of biological substance.

[0137] In some variations, the controller may receive the volume and/or weight of the biological substance in a variety of ways. For example, the controller may receive the volume and/or weight from manual input by an operator using a user input device (e.g., barcode reader, optical character reader, radiofrequency tag reader). The user input device may be configured to read the volume of the biological substance from markings on a container enclosure itself representing the volume and/or weight (e.g., a barcode, text) or an identifier secured to the enclosure (e.g., an RFID tag) that electronically stores data including the volume and/or weight above. In other variations, the temperature control system itself (e.g., the temperature control device) may be configured to measure the weight of the biological substance.

[0138] In some variations, the controller may be implemented in digital electronic circuitry, in computer hardware, firmware, and/or software. The implementation may be as a computer program product. The implementation may, for example, be in a machine-readable storage device, for execution by, or to control the operation of, data processing apparatus. The implementation may, for example, be a programmable processor, a computer, and/or multiple computers.

[0139] A computer program may be written in any form of programming language, including compiled and/or interpreted languages, and the computer program may be deployed in any form, including as a stand-alone program or as a subroutine, element, and/or other unit suitable for use in a computing environment. A computer program may be deployed to be executed on one computer or on multiple computers at one site.

[0140] Processors suitable for the execution of a computer program may include, by way of example, both general and special purpose microprocessors, and any one or more processors of any kind of digital computer. Generally, a processor receives instructions and data from a readonly memory or a random access memory or both. The essential elements of a computer are a processor for executing instructions and one or more memory devices for storing instructions and data.

[0141] Generally, a computer may include, may be operatively coupled to receive data from and/or transfer data to one or more mass storage devices for storing data (e.g., magnetic, magnetooptical disks, or optical disks). Information carriers suitable for embodying computer program instructions and data include all forms of non-volatile memory, including by way of example semiconductor memory devices. The information carriers may, for example, be EPROM, EEPROM, flash memory devices, magnetic disks, internal hard disks, removable disks, magneto-

30

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 optical disks, CD-ROM, and/or DVD-ROM disks. The processor and the memory may be supplemented by, and/or incorporated in special purpose logic circuitry.

[0142] In some variations, the temperature control system (100) may comprise a vacuum mechanism, such as a vacuum pump in fluid communication with an interior of the container enclosure (e.g., via a one-way valve) or a portion thereof. For example, the vacuum pump may be activated to remove air from the interior of the container enclosure and create a partial vacuum. By reducing the pressure within the container enclosure, as compared to the ambient pressure outside the container enclosure, the container enclosure may be urged into contact with the enclosure by the ambient pressure. In this manner, the accuracy of temperature measurements acquired by temperature sensor(s) mounted to the container enclosure may be improved.

[0143] Temperature Control Device

[0144] In some variations, the temperature control device (e.g., a dry thawing device) for controlling a temperature of a biological substance may be compact and portable. FIG. 2A is a side view of an illustrative variation of a temperature control device (200) configured to control a temperature of a biological substance in a closed configuration. FIG. 2B is a side view of the device

[0145] (200) shown in FIG. 2A in an open configuration. In some variations, the temperature control device (200) in the open configuration may receive a container enclosure (300, 400) such as shown

[0146] and described with respect to FIGS. 3, 4, and 14. In some variations, the system (200) may comprise a housing (210) comprising a main body (220), a first door (230), a second door (232), a handle (240), and a user interface (270). The housing (210) may further enclose a first chamber (250) and a second chamber (252). The first and second doors (230, 232) enable access to an interior of the respective first and second chambers (250, 252), thereby allowing an operator to insert or remove a container enclosure (260, 262) (e.g., container enclosure (300, 400, 1400)) having the biological substance contained therein. Each of the first and second doors (230, 232) may comprise a respective thermal source (114, 116) coupled thereto as described herein. In some variations, the user interface (270) may comprise a display and a user input device (e.g., keyboard, mouse, trackball, optical or resistive touch screen) by which the operator may provide input to the system (200). In some variations, input from the operator may, for example, be received in any form, including acoustic, speech, and/or tactile input.

[0147] FIG. 2C and 2D are schematic cross-sectional side views of additional variations of a temperature control device configured to control a temperature of a biological substance. The temperature control device (202) of FIG. 2C may be used with a container enclosure and a

31

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 container to regulate the temperature of a biological substance inside. For example, the temperature control device (202) comprising a thermal source (282) to control a temperature of a biological substance, a sidewall (272), and an agitator (292). The sidewall (272) and/or thermal source (282) may comprise a temperature sensor (244). In some variations, a container enclosure may be received within a chamber (222) formed between the sidewalls (272). For example, a conductive housing receiving (e.g. holding) an adapter and a container may be configured to be received in the chamber (222) of the temperature control device (202), which is formed between the sidewalls (272). In this manner, the thermal source (282) may be releasably coupled to, and in thermal communication with, the conductive housing. In this way, the temperature control device (202) may control the temperature of the biological substance in the container.

[0148] The temperature control device (204) of FIG. 2D may be used with a container enclosure (e.g., adapter) and container to regulate a temperature of a biological substance inside. For example, a temperature control device (204) comprising a thermal source (282), and an agitator (292), a thermal conductor (212) having a first portion (212a) and a second portion (212b), a support (214), an identifier (236), and a temperature sensor (244). For example, the thermal conductor (212) may be rectangular in shape with a first conductor portion (212a) and a second conductor portion (212b). In other variations, the thermal conductor may be a different shape, such as, for example, cylindrical. A container may be received within an adapter of the container enclosure, and the container enclosure may be received within a cavity (223) formed between the first portion of the thermal conductor (212a) and the second portion of the thermal conductor (212b). For example, the thermal conductor (212) may be configured to receive (e.g. hold) the adapter and the container may be configured to be received in the cavity (223) of the temperature control device (204), which is formed between the first portion of the thermal conductor (212a) and the second portion of the thermal conductor (212b). In this manner, the thermal source (282) may be in thermal communication with the thermal conductor (212). In this way, the temperature control device (204) may control the temperature of the biological substance in the container. In some variations, each of the temperature control devices (202, 204) may be durable components while the components disposed within the devices (202, 204) may be limited use (e.g., single use) components. In other variations, the temperature control devices (202, 204) and the components disposed within the devices (202, 204) may all be limited use (e.g., single use components) or may all be durable components.

[0149] Container Enclosure

[0150] Generally, containers (e.g., vials) having a biological substance therein may be held, disposed, received, or otherwise positioned within a container enclosure, which may in turn, be

32

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 held, disposed, received, or otherwise positioned within a chamber of a temperature control device, such as that shown in FIGS. 2A-2D. For example, the container enclosure may be placed within a chamber (250) of the temperature control system (200) and, may either itself comprise, or may be placed in contact with, a thermal conductor. Accordingly, the container enclosure may function as a thermal interface to facilitate temperature control (e.g., heating or cooling) of the biological substance using a temperature control device (e.g., device (200, 202, 204)). For example, the container enclosure may function as a thermal interface between a thermal source (e.g., heater, cooler, or combination thereof) and the biological substance. In some variations, the container enclosure may comprise a temperature sensor and an identifier to measure temperature and aid in identification and tracking of the biological substance, respectively. Furthermore, the container enclosure may contain the biological substance within the container enclosure, or a portion thereof in the event that the container itself ruptures or breaks, thereby reducing contamination.

[0151] In some variations, the container enclosure may enable temperature monitoring, temperature distribution, and identification. For example, the container enclosure may comprise one or more temperature sensors configured to measure a temperature of the biological substance. The container enclosure may further include a unique identifier (e.g., RFID tag, barcode, label) that may be used to track the biological substance and/or its container and/or may be used to authenticate the container enclosure. The identifier may operate utilizing one or more of passive and active identification techniques. Moreover, one or more elements of the container enclosure may be a durable component configured for multiple heating and/or cooling cycles or a consumable component (e.g., limited use, single use, disposable) configured to be used and replaced at predetermined intervals (e.g., predetermined number of heating and/or cooling cycles, monthly, yearly). For example, the container enclosure (300) may be formed from materials capable of being sterilized and reused in accordance with the requirements of domestic and/or international governing organizations and regulatory bodies. In some variations, the container enclosure may be configured to provide anti-microbial properties, whether intrinsically or through the use of coatings or additives. Examples of materials forming the container enclosure may comprise one or more of metal, ceramic, polymer, silicone, fluid, gel, combinations thereof, and the like.

[0152] In some variations, a container enclosure may be configured to receive, for example, a low volume container of a biological substance for temperature regulation such as thawing. FIG. 3 is a schematic cross-sectional view of an illustrative variation of a container enclosure (300) (e.g., bag) that may enclose or surround a container (320). The container enclosure (300) may be

33

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 configured to receive a container (320) (e.g., vial, tube, or the like) having a biological substance as described herein. The container enclosure (300) may be placed within a chamber of a temperature control device (e.g., device (200)), which may then be used to regulate the temperature of the biological substance contained therein. The container enclosure (300) may be composed of a thermally conductive material configured to transfer heat generated by the system (100) to the biological substance. In some variations, the container enclosure (300) may be configured for limited (e.g., one, between one and 10, between one and 20, etc.) use. In some variations, an opening of the container enclosure (300) may be reversibly sealed. For example, the container enclosure (300) may be opened to receive the container therein, and then may be sealed such that in the event that the container (320) leaks or ruptures during the thawing process, the container enclosure (300) may isolate the biological substance from the temperature control device, thereby minimizing contamination and waste.

[0153] As depicted in FIG. 3, the container enclosure may comprise a coupling mechanism (302), a cavity (310), an identifier (330) of a biological substance (e.g., RFID tag) as described in more detail herein, and a temperature sensor (340) configured to measure a temperature of the biological substance. While depicted in FIG. 3 with a single temperature sensor (340) and identifier (330), it should be appreciated that any of the container enclosures described herein may comprise a plurality of temperature sensors and/or identifiers, such as, for example, two, three, four, five, six, seven, eight, or more. The coupling mechanism (302) may be configured to reversibly close the container enclosure (302) for insertion and removal of a container of biological substance. The coupling mechanism (302) may also be configured to aid in attaching and/or releasably coupling the container enclosure (300) to chamber of a temperature control device such as device (200). For example, the coupling mechanism (302) may comprise one or more of holes, fasteners, hooks, adhesives, reversible adhesives, interlocking grooves and ridges, magnets, combinations thereof, and the like. For example, in one variation, the coupling mechanism (302) may comprise interlocking grooves and ridges to reversibly close the container enclosure (302) and holes through which hooks of a corresponding thawing device (not shown) may be placed to support and properly position the container enclosure, and thus the container (320) and biological substance therein, within a chamber of a temperature control device. In some variations, the coupling mechanism (302) may be configured to form a seal, such as, for example, a hermetic seal.

[0154] The cavity (310) of the container enclosure (300) may be configured to receive a container (320). In some variations, the cavity (310) may comprise a shape configured to direct the container [0155] (320) to a predetermined position and location within the enclosure (300). For example, as shown in FIG. 3, the cavity (310) may comprise a funnel shape that enables an operator to easily

34

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 place the container (320) into the enclosure (300) and facilitates proper placement of the container (320) within the container enclosure (300) for temperature regulation. Thus, in this variation, the angled or tapered edges of the top portion of the cavity (310) may guide the container (320) to a predetermined position and orientation (e.g., upright at a bottom-center portion of the enclosure (300)).

[0156] In some variations, the cavity (310) may comprise a first cavity width wl and a second cavity width w2 (e.g., dl+A) that is smaller than the first cavity width wl. The diameter dl of a container is described in more detail herein. In some variations, the first cavity width wl may be equal to or less than about 155 mm. For example, the first cavity width wl may be equal to or less than about 145 mm, equal to or less than about 135 mm, equal to or less than about 125 mm, equal to or less than about 115 mm, equal to or less than about 105 mm, equal to or less than about 95 mm, equal to or less than about 85 mm, equal to or less than about 75 mm, or equal to or less than about 65 mm. In some variations, the first cavity width wl may be between about 155 mm and about 65 mm, including all values and sub-ranges therein. For example, the first cavity width wl may be between about 145 mm and about 75 mm, between about 135 mm and about 85 mm, between about 125 mm and about 95 mm, or between about 115 mm and about 105 mm. In some variations, the second cavity width w2 may be between about 14 mm and about 57 mm, including all values and sub-ranges therein. For example, the second cavity width w2 may be between about 15 mm and about 50 mm, between about 20 mm and about 45 mm, between about 25 mm and about 40 mm, or between about 30 mm and about 35 mm. The cavity (310) may define an opening of the container enclosure (300) extending along the first cavity width wl. In some variations, the first cavity width wl may be less than a width of the container enclosure (300), while in other variations, the cavity width wl may be equal to the width of the container enclosure (see, e.g., FIG. 4).

[0157] The second width w2 may be configured to have a predetermined tolerance A with respect to a container (320) such that the second width w2 may be equal to a diameter or width the container plus the predetermined tolerance A. For example, the container (320) may have at least an interference fit with the cavity (310). In some variations, the predetermined tolerance A may be between about 5 mm and about 21 mm, including all values or sub-ranges therein. For example, the predetermined tolerance A may be between about 8 mm and about 18 mm, between about 10 mm and about 15 mm, or between about 12 mm and about 13 mm.

[0158] In some variations, the container enclosure (300) may be constructed such that the container (320) may tilt a predetermined amount relative to a longitudinal axis of the enclosure (300) while the container (320) is positioned within the cavity (310). For example, the container

35

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 enclosure (300) may be configured such that the container (320) may tilt up to about 5 degrees, up to about 4 degrees, up to about 3 degrees, up to about 2 degrees, up to about 1 degree, or between about 1 degree and about 5 degrees within the cavity (310) relative to a longitudinal axis of the enclosure (300). In some variations, the container enclosure (300) may be configured such that the container (320) may not tilt relative to a longitudinal axis of the enclosure (300).

[0159] The cavity (310) may have a length L3 equal to or less than a length of the container enclosure (300). In some variations, the cavity (310) may have a cavity width of w2 for a length L2. The cavity (310) may have a generally conical shape between an opening of the container enclosure (300) and the portion of the cavity (310) having the width w2. In some variations, the reduction in width of the cavity (310) from wl to w2 may have a shape that is one or more of sloped, stepped, constant, irregular, concave, convex, and the like. Alternatively, the cavity (310) may not have a funnel shape. For example, the cavity (310) may have a constant width wl along a length of the enclosure that is less than a width of the container enclosure (300).

[0160] The container (320) may comprise a length LI and diameter dl or width w3, depending on cross-sectional shape. In some variations, the container (320) may comprise a diameter or width of between about 1 mm and about 5 mm, between about 5 mm and about 10 mm, between about 10 mm and about 20 mm, between about 20 mm and about 30 mm, between about 30 mm and about 40 mm, between about 40 mm and about 50 mm, between about 50 mm and about 75 mm, between about 75 mm and about 100 mm, including all ranges and sub-values in-between. In some instances, the diameter or width of the container (320) may be between about 9 mm and about 36 mm, including all values and sub-ranges therein. For example, the diameter or width may be between about 10 mm and about 35 mm, between about 15 mm and about 30 mm, or between about 20 mm and about 25 mm.

[0161] In some variations, a ratio of a diameter or width of the container (320) to a width of the cavity (310) wl may be between about 1 : 1 and about 5:32, including all ranges and sub-values in-between. For example, the ratio of the diameter or width of the container (320) to the width of the cavity (310) may be between about 30:32 and about 8:32, between about 25:32 and about 12:32, or between about 20:32 and about 18:32. In some variations, the length LI may be less than, equal to, or more than length L2. The length L2 may correspond to a lower portion of the cavity (310) configured to hold the container (320). In some variations, the length LI may be between about 50 mm and about 25 mm, including all values and sub-ranges therein. For example, the length LI may be between about 45 mm and about 30 mm, about 40 mm and about 35 mm, or between about 38 mm and about 36 mm. In some variations, the length L2 may be between about 60 mm and about 25 mm, including all values and sub-ranges therein. For example, the length L2

36

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 may be between about 55 mm and about 30 mm, between about 50 mm and about 35 mm, between about 45 mm and about 40 mm, or between about 44 mm and about 42 mm.

[0162] In some variations, the cavity (310) of the container enclosure (300) may be formed by heat welding predetermined portions of opposing surfaces (e.g., front, back) of the enclosure container (300) together. For example, tapered and straight lines may be welded to form a cavity (310) having a generally funnel shape. In some variations, the welding may form a cavity (310) having parallel edges without a taper.

[0163] In some variations, the cavity (310) may be configured to receive and orient the container (320) within the container enclosure (300). For example, the cavity (310) may be configured to position the container (320) such that a longitudinal axis of the container (320) is parallel to a longitudinal axis of the container enclosure (300). Put another way, the cavity (310) may be configured to position the container (320) in an upright position within the container enclosure (300). In some variations, the cavity (310) may be configured to position the container (320) such that the longitudinal axis of the container (320) is about parallel to a longitudinal axis of the container enclosure (300). In some variations, the cavity (310) may be configured to position the container (320) such that a longitudinal axis of the container (320) is transverse ) to a longitudinal axis of the container enclosure (300). For example, the cavity (310) may be configured to position the container (32) such that an angle formed between the longitudinal axis of the container (32) and the longitudinal axis of the container enclosure (300) is about 90 degrees, about 75 degrees, about 60 degrees, about 45 degrees, about 30 degrees, about 15 degrees, or about 10 degrees. In some of these variations, the container (320) may be positioned such that a longitudinal axis of the container (320) may be generally parallel to a width of the container enclosure (300). Moreover, the cavity (320) may be configured to laterally position the container (320) within the container enclosure (300). For example, in some variations, the cavity (320) may be positioned to laterally center the container (320) along a width of the container enclosure (300), as is depicted in FIGS. 3 and 4. In other variations, the cavity (320) may be configured to position the container (320) in a different location, such as along either of the edges of the container. It should be appreciated that the configuration of cavity (320) may vary depending on, for example, the size and/or shape of the container (320) and the position of other system components, such as the thermal source or temperature sensor.

[0164] As mentioned above, the container enclosure (300) may comprise an identifier (330), which may assist in identifying and tracking the biological substance and/or its container, and/or a temperature sensor (340), which may measure the temperature of the external surface of the container (320), and thus of the biological substance contained therein. In some variations, the

37

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 identifier (330) may comprise data corresponding to one or more of the container enclosure (300), the container (320), and the biological substance as described in more detail herein. For example, the identifier (330) may comprise one or more of an RFID tag, label, barcode, QR code, and memory. Additionally or alternatively, the identifier (330) may be configured to store, receive, and/or transmit sensor data such as temperature measurements generated by one or more temperature sensors and/or authentication data. For example, the identifier (330) may receive a measured temperature (or set of measured temperatures) from the temperature sensor (340) during a temperature control process.

[0165] In some variations, one or more of the identifier (330) and the temperature sensor (340) may be positioned to overlap at least a portion of the container disposed in the container enclosure (300). For example, the identifier (330) and/or the temperature sensor (340) may be positioned to overlap about the entire width of the container. In some variations, the identifier (330) and/or the temperature sensor (340) may be positioned to overlap more than about 90 percent, more than about 80 percent, more than about 70 percent, more than about 60 percent, more than about 50 percent, more than about 40 percent, more than about 30 percent, more than about 20 percent, or more than about 10 percent of the width of the container (320), including all values and sub-ranges therein. In some variations, the identifier (330) and/or the temperature sensor (340) may be positioned to overlap about the entire length of the container (320). For example, the identifier (330) and/or the temperature sensor (340) may be positioned to overlap more than about 90 percent, more than about 80 percent, more than about 70 percent, more than about 60 percent, more than about 50 percent, more than about 40 percent, more than about 30 percent, more than about 20 percent, or more than about 10 percent of the length of the container (320). In variations comprising two or more temperature sensors and/or identifiers, each of the temperature sensors and/or identifiers may be positioned to overlap the container as described herein.

[0166] As mentioned above, the identifier (330) and/or the temperature sensor (340) may be positioned on the enclosure container (300) to overlie or overlap the portion of the cavity (310) configured to hold the container (320) during a thawing or cooling process, such that when the container (320) is inserted into the cavity (310), the identifier (330) and/or the temperature sensor (340) directly contacts and/or directly overlies the container (320). For example, the identifier (330) and/or temperature sensor (340) may be located at a second portion of the cavity (310) (e.g., bottom portion of the container enclosure) opposed to a first portion of the cavity (310) (e.g., top portion or funnel portion of the container enclosure, adjacent to the opening of the container enclosure (300)). Furthermore, the identifier (330) and/or temperature sensor (340) may be located at a portion configured to overlie or overlap a center of a container (320) disposed within the

38

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 cavity (310). This may improve temperature measurement of the container (320) and biological substance, as well as simplify manufacture of the container enclosure (300). In some variations, two or more identifiers (330) and/or temperature sensors (340) (e.g., two, three, four, five, six, seven, eight or more) may be positioned on the enclosure (300) to overlie or overlap the portion of the cavity (310) configured to hold the container (320) during a temperature control process (e.g., thawing or cooling process).

[0167] In some variations, the temperature sensor (340) may comprise one or more of a contact temperature sensor and a non-contact temperature sensor. In some variations, a contact temperature sensor may be integrated with, or secured to, the container enclosure (300) to measure the temperature of the biological substance through the container (320). For example, a contact temperature sensor may be positioned on an inner surface (e.g., cavity surface) of the container [0168] enclosure (300) to contact the container (320), or on an outer surface of the container enclosure (300). In the latter variation, the temperature of the container (320) may be measured through a wall of the container enclosure (320). In some variations, a non-contact temperature sensor may be configured to measure electromagnetic radiation emitted from the biological substance (e.g., infrared radiation). Additionally, in some variations, the container enclosure (300) may comprise a contact temperature sensor positioned on an outer surface of the container enclosure (300) to contact a thermal interface or thermal source of device (200). In these variations, the contact temperature sensor may measure a temperature of the thermal interface or thermal source, which may be useful in controlling or otherwise informing a temperature control process. In some variations, one or more temperature sensors (contact and non-contact) may be configured to communicate with a controller (104) via communication links that are wired and/or wireless.

[0169] In some variations, the identifier (330) and the temperature sensor (340) may be coupled to or integrated with one another. For example, in a variation in which the identifier (330) comprises a radiofrequency identification (RFID) tag, the temperature sensor (340) may be integrated with the RFID tag, and the integrated device may be mounted to a surface (e.g., inner surface, outer surface, cavity surface) of the container enclosure (300). Mounting may include being printed on a surface, adhered to a surface by an adhesive, and the like. The RFID tag may be configured to wirelessly transmit data (e.g., temperature measurements, authentication data) to a reader in communication with the controller. In some variations, the temperature sensor may be a sensor of a smart label, as discussed in International Patent Application No. WO 2016/023034, filed August 10, 2015, entitled “Smart Bag Used In Sensing Physiological And/Or Physical

39

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Parameters Of Bags Containing Biological Substance,” the entirety of which is hereby incorporated by reference.

[0170] FIG. 3 further illustrates the container (320) comprising a biological substance (not shown) received within the cavity (310) of the container enclosure (300). The container (320) may be any container suitable for transporting small volumes of biological substances, such as, for example, a vial or a cuvette. In some variations, the volume of the container and/or a predetermined volume of the biological substance within the container may be between about 0.5 mL and about 1 mL, between about 1 mL and about 3 mL, between about 3 mL and about 5 mL, between about 5 mL and about 10 mL, between about 10 mL and about 20 mL, between about 20 mL and about 50 mL, between about 50 mL and about 100 mL, between about 100 mL and about 250 mL, between about 250 mL and about 500 mL, including all ranges and sub-values inbetween.

[0171] In some variations, the biological substance may comprise one or more of a vaccine (e.g., an mRNA vaccine, a DNA vaccine), exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, cell therapy product such as stem cells and T-cells, combinations thereof, and the like. In some variations, the container and biological substance may be transported and/or stored at a temperature of as low as about -80°C (between about 0°C and about -80°C). The biological substance may be then be thawed from this temperature to a predetermined temperature such as room temperature.

[0172] In some variations, the container enclosure (300) may comprise a thermally conductive material configured to transfer thermal energy to and from the biological substance. Additionally, the container enclosure (300) may be configured to withstand temperatures within a predetermined temperature range (e.g., between about -196°C to about 40°C). In some variations, the container enclosure (300) may comprise one or more layers of thermally conductive material. For example, the container enclosure (300) may comprise a plurality of layers bonded together. Each of the plurality of layers may be the same material, or a different material, of each of the remaining plurality of layers. Additionally or alternatively, the plurality of layers may comprise one or more separate (e.g., non-bonded) layers. In some variations, the container enclosure (300) may be composed of a compliant material to allow the container enclosure to generally conform to a shape of the container disposed therein. In some variations, the container enclosure may comprise one or more of a rigid portion, semi-rigid portion, and compliant (e.g., soft) portion. For example, the welds may form a rigid portion, an opening of the container enclosure (300) may comprise the semi- rigid portion, and the cavity (310) of the enclosure (300) may correspond to the compliant

40

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 portion. In some variations, the container enclosure (300) may be configured to provide antimicrobial properties, whether intrinsically or through the use of coatings or additives.

[0173] In some variations, one or more portions of the container enclosure (300) may comprise an insulator coupled to one or more of the identifier (330) and the temperature sensor (340). For example, the container enclosure (300) may comprise an encapsulated air pocket (not shown) or an insulating material (e.g., a material having a low thermal conductivity) that may insulate the identifier (330) and/or the temperature sensor (340), thus promoting thermal isolation of the identifier (330) and/or temperature sensor (340) from the environment external to the container enclosure (300). In further variations, the container enclosure (300) may comprise a portion made of an insulating material, and the identifier (330) and/or the temperature sensor (340) may be coupled to this portion of the container enclosure (300).

[0174] The container enclosures described herein may have dimensions configured to receive containers having various shapes and sizes. For example, FIG. 4 is a schematic cross-sectional view of another illustrative variation of a container enclosure (400) similar to container enclosure (300) such that the detailed description of corresponding elements such as a coupling mechanism (402), a cavity (410), an identifier (430), and a temperature sensor (440) is omitted for the sake of brevity.

[0175] The container enclosure (400) may be configured to receive a container (420) having a biological substance where the container (420) is larger than the container (320) shown in FIG. 3. The container enclosure (400) may also be received within a chamber of a temperature control device (e.g., device (200)) to regulate the temperature of the biological substance within the container (420) contained therein.

[0176] Relative to the container enclosure (300) of FIG. 3, the container enclosure (400) of FIG. 4 has a wider cavity in order to accommodate a container (420) having a larger width. For example, the cavity (410) of the container enclosure (400) may be configured to receive a rectangular-prism- shaped container (420). In some variations, the cavity (410) may comprise a shape configured to funnel the container (420) to a predetermined position and location within the enclosure (400). For example, as shown in FIG. 4, the cavity (410) may comprise a funnel shape that enables an operator to easily place the container (420) into the enclosure (400), and for the shape of the cavity (410) to guide the container (420) into a predetermined position and orientation (e.g., at a bottomcenter portion of the enclosure (400)). The funnel shape may, for example, extend across the entire width of the container enclosure (400) at its widest point. In some variations, the container enclosures described herein may be in the form of an overwrap bag as discussed in previously

41

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 mentioned International Patent Application No. WO 2016/023034, which is incorporated by reference herein in its entirety.

[0177] The container enclosures described herein may have dimensions configured to receive containers having various shapes and sizes. For example, FIG. 14A is a schematic cross-sectional view of another illustrative variation of a container enclosure (1400) similar to container enclosures (300, 400) such that the detailed description of corresponding elements such as a coupling mechanism (1402), a cavity (1410), an identifier (1430), and a temperature sensor (1440) is omitted for the sake of brevity. The container enclosure (1400) may be configured to receive a container (1420) having a biological substance where the container (1420) is positioned within a holder or adapter (1450). The container enclosure (1400) may also be received within a chamber of a temperature control device (e.g., device (200)) to regulate the temperature of the biological substance within the container (1420) contained therein.

[0178] As shown in FIG. 14A, the cavity (1410) may comprise a holder or adapter (1450) that enables an operator to easily place the container (1420), which may be a small volume container, into the enclosure (1400), which may be much larger than the container (1420). The adapter (1450) may be configured to hold the container (1420) in a predetermined position and at a predetermined location within the enclosure (1400) (e.g., in an upright position and/or in alignment with the temperature sensor (1440) and/or identifier (1430)) and may be configured to transfer heat generated by the system (100) to the biological substance. In some variations, the adapter (1450) may be configured to hold the container at a bottom-center portion of the container enclosure (1400). In some variations, the adapter (1450) may extend across the entire width of the container enclosure (1400), or across substantial portion of the width of the container enclosure (1400), such as, for example, across about 60%, about 70%, about 75%, about 80%, about 85%, and about 90%, including all values and sub-ranges therein.

[0179] The adapter (1450) may be sized to receive the dimensions of the container (1420). For example, the adapter (1450) may comprise a cavity, lumen, hole, aperture, or other opening that may be configured to receive a container (1420). In some instances, the adapter (1450) may be configured to hold the container (1420) such that a longitudinal axis of the adapter (1450) may be parallel to or about parallel to a longitudinal axis of the container (1420). The adapter may have a length between about 25 mm and about 50 mm, including all values and sub-ranges therein. For example, the adapter may have a length between about 28 mm and about 48 mm, between about 30 mm and about 45 mm, or between about 35 mm and about 40 mm . For instance, the adapter may have a length of about 30 mm, about 35 mm, about 40 mm, about 45 mm, or about 55 mm. In some variations, a length of the adapter may be greater than or equal to a length of the container.

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

In some variations, a ratio of the length of the adapter to the length of the container may be between about 1 : 1 to about 2: 1, including all values and sub-ranges therein. For instance, a ratio of the length of the adapter to the length of the container may be between about 12: 10 and about 18: 10, between about 13: 10 and about 17: 10, or between about 14: 10 and about 16: 10.

[0180] As depicted in FIG. 14A, the cross-sectional view of the adapter (1450) parallel to the Z- X plane may comprise a U-shaped cross-sectional shape where a bottom portion of the container (1420) is held by the bottom of the adapter (1450), and the sidewalls of the container (1420) are in contact with the sides of the adapter (1450) and the sidewalls of the container enclosure (1400). [0181] While the portions (e.g., sidewalls, bottom) of the U-shaped adapter are depicted as having a rectangular cross-sectional shape, it should be appreciated that the portions may have other cross- sectional shapes, such as, for example, trapezoidal or square, and/or may have curved surfaces, such as for example, concave or convex internal (container-facing) or external (enclosure-facing) surfaces (e.g., concave or convex bottom surface, concave or convex sidewall surfaces). In some variations, the adaptor may conform to the shape of the container (1420).

[0182] The adapter (1450) may comprise any shape suitable to hold the container (1420) in a desired, predetermined position (e.g., in an upright position and aligned with a temperature sensor and/or identifier) and may be, for example, cylindrical, rectangularly, frustoconical, pyramidal, a triangular prism, or the like. For example, in variations in which the adapter (1450) may be cylindrical in shape, the cross-sectional view of the adapter parallel to the X-Y plane may be circular. In some variations, the adapter (1450) may have one or more openings and/or slots (e.g., two) that allow contact between the container and a thermal source through the container enclosure.

[0183] In some variations, the adapter (1450) may be composed of a thermally conductive material and may be configured to receive the container with an interference fit. Put differently, in some variations, the container (1420) may be positioned within the adapter (1450) by exerting force on the container (1420) and/or on the adapter (1450) such that the container (1420) tightly fits within the adapter (1450). An amount of interference (e.g., a difference between a width of the container (1420) and the width of the cavity, lumen, hole, aperture, or other opening of the adapter (1450)) may indicate the tightness of the fit between the container (1420) and the adapter (1450). In some variations, the amount of interference (e.g., allowance) may be between about 0.12 mm and about 0.4 mm, including all values and sub-ranges therein. For example, the allowance may be between about 0.15 mm and about 0.35 mm, between about 0.2 mm and about 0.3 mm, between about 0.22 mm and about 0.28 mm, or between about 0.24 mm and about 0.26 mm.

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

[0184] In some variations, the adapter (1450) may be composed of a compliant material to allow the container enclosure to generally conform to a shape of the container disposed therein. In some variations, the adapter (1450) may be composed of one or more of an open cell material, a closed cell material, a porous material, a compressible material, a compliant material, an absorbent material, a semi-rigid material, and a rigid material. For example, an adapter (1450) comprising an absorbent material may be configured to absorb a spilled biological substance (e.g., from a broken or cracked container (1420). In some variations, at least a portion of the adapter may comprise a sponge. In some variations, the adapter (1450) may be formed from a reversibly deformable material. For example, the adapter (1450) may include a covering/body that may be filled with a fluid. Some non-limiting examples of suitable fluids may include water, gel, synthetic oils, non- synthetic oils, other heat-absorbing materials, or any combination thereof. The covering may be composed of a compliant material so that the adapter conforms to a shape of the container disposed therein. In some variations, the adapter (1450) may be configured to have anti-microbial properties, whether intrinsically or through the use of coatings or additives. In some variations, the adapter (1450) may be configured to be sterilized. Additionally or alternatively, the adapter (1450) may be pretreated to ensure no contamination to air surrounding the container (1420).

[0185] The adapter (1450) may be configured to be insertable and removable from the container enclosure or fixedly coupled to the container enclosure. For example, the adapter (1450) may be configured to be insertable and removable from the container enclosure (1400) so as to be disposable (e.g., a limited use component) after a specific number of uses. For example, the adapter (1450) may be removed from the container enclosure (1400) and replaced. In these variations, the adapter (1450) may be coupled to the container enclosure (1400) by virtue of being received within the container enclosure, but may not be otherwise attached to the container enclosure (1400). In other variations, the adapter (1450) may be fixed to the container enclosure (1400), using, for example, adhesive, mechanical connectors, or the like, and may not be configured to be easily removed from the container enclosure (1400). In yet other variations, the adapter (1450) may be freely placed within the container enclosure (1400) and may be releasably fixedly coupled to the container enclosure (1400) for use during thawing using any suitable coupler (e.g., mechanical coupling, friction fit coupling, magnetic coupling, and/or the like). For example, the container enclosure (1400) may have a recessed portion at the inner surface of the bottom portion of the container enclosure (1400). The adapter (1450) may have a protrusion at the bottom surface of the bottom portion of the adapter (1450) that may be configured to fit into the recessed portion of the container enclosure (1400), thereby coupling the adapter (1450) to the container enclosure (1400). After one or more uses, the container enclosure (1400) be may be

44

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 configured to release the adaptor (1450) such that the adapter may then be easily removed from the container enclosure (1400). In some variations, the adapter (1450) may be replaced with a different adapter (1450) after predetermined time and/or after predetermined number of usages. In variations in which the adapter (1450) may be removable from the container enclosure (1400), the adapter (1450) may be coupled to the container enclosure (1400) via a suitable In variations in which the adapter is removable from the container enclosure, the adapter may be configured to be removed from the container enclosure and disposed of after at least one use, after at least two uses, after at least three uses, after at least four uses, after at least five uses, after at least six uses, after at least seven uses, after at least eight uses, after at least nine uses, after at least ten uses, or more.

[0186] In some variations, the adapter (1450) may be configured to overlap at least a portion of the container (1420). For example, the adapter (1450) may be configured to cover or overlap a predetermined area (e.g., sidewall) of the container (1420) (e.g., about 100%, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30% or about 20%.). For example, the adapter (1450) may cover a bottom portion and a sidewall portion of the container (1420) while leaving a top portion of the container (1420) uncovered. For instance, the adapter (1450) may cover the bottom portion, the sidewall portion , and if applicable depending on the configuration of the container (1420), the neck and/or lip portion, of the container (1420) while leaving just the orifice or a lid (e.g., the top portion) of the container (1420) uncovered. Additionally or alternatively, the adapter (1450) may cover the bottom portion and the sidewall of the container (1420) while leaving a neck and/or lip (e.g., including an orifice and lid portion) of the container (1420) uncovered. As another example, the adapter (1450) may cover a sidewall portion of the container (1420) while leaving both a lid of the container (1450) and a bottom portion of the container (1450) uncovered. In such variations, at least a part of the bottom portion of the container (1450) may be in direct contact with the container enclosure. As yet another example, the adapter (1450) may cover the bottom portion of the container (1450) and a sidewall portion and the lid portion of the container (1450) such that a height of the adapter (1450) may be greater than the height of the container (1450). In some variations, the adapter (1450) may have a height corresponding to about a third, two-thirds, equal to, or greater than a height of the container (1420). In some variations, this may enable the adapter (1450) to hold the container (1420) in a predetermined position and location without wholly covering the container (1420).

[0187] Additionally or alternatively, the cavity (1410) of the enclosure (1400) may comprise a funnel shape similar to that of cavity (310, 410) described herein to funnel the adapter (1450) and the container (1420) to a predetermined position and location within the enclosure (1400) (e.g.,

45

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 within a cavity of the holder (1450)), and/or to hold the adapter (1450) and the container (1420) in the predetermined location and position.

[0188] In some variations, the identifier (1430) and/or the temperature sensor (1440) may be coupled to the enclosure and may be positioned to overlap at least a portion of the container (1420) as described above with respect to FIG. 3. Additionally or alternatively, the identifier (1430) and/or the temperature sensor (1440) may be mounted on, carried by, or otherwise coupled to the adapter (1450). For example, FIG. 14B is a schematic cross-sectional view of another illustrative variation of a container enclosure (1400) similar to container enclosure (1400) in FIG. 14A such that the detailed description of corresponding elements such as a coupling mechanism (1402), a cavity (1410), an identifier (1430), and a temperature sensor (1440) is omitted for the sake of brevity.

[0189] However, in FIG. 14B, the identifier (1430) and/or the temperature sensor (1440) may be carried by of the adapter (1450) itself (i.e., the adapter may comprise the identifier and/or the temperature sensor). For example, the identifier (1430) and/or the temperature sensor (1440) may be positioned on the adapter (1450) such that the temperature sensor (1440) contacts or is otherwise in thermal communication with the container (1430). For example, the identifier (1430) and/or the temperature sensor (1440) may be on an internal (e.g., container-facing) surface of the adapter (1450). For instance, as depicted in FIG. 14B, the identifier (1430) and/or the temperature sensor (1440) may be positioned on a sidewall of the adapter (1450) such that the temperature sensor (1440) and/or the identifier (1430) are facing the container (1420). The identifier (1430) and/or the temperature sensor (1440) may be positioned on any container-facing surface, such as, for example, on either sidewall and/or the bottom portion of the adapter (1450) such that the identifier (1430) and/or the temperature sensor (1440) are container-facing. In some variations, the identifier (1430) and/or the temperature sensor (1440) may be positioned to overlap at least a portion of the adapter (1450).

[0190] Although FIGS. 14A and 14B illustrate a single identifier (1430) and a single temperature sensor (1440) positioned to overlap the container (1420) and/or the adapter (1450), it should be readily understood that any suitable number of identifiers and/or temperature sensors (e.g., two, three, four, five, six, seven, eight or more) may be positioned to overlap with a container and/or an adapter. In some variations, a plurality of temperature sensors and/or identifiers may be used in order to provide additional information about biological substances contained within a container during a thawing process. In these variations, one or more temperature sensors and/or identifiers may be positioned to provide information about a first portion of the container and one or more temperature sensors may be positioned to provide information about a second, different portion

46

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 of the container. Use of a plurality of temperature sensors can assist in assuring uniform thawing. For example, a first identifier and a first temperature sensor may be positioned to overlap with a first portion or side of the container (1420) while a second identifier and a second temperature sensor may be positioned to overlap with a second portion or side of the container (1420) (e.g., a side opposite the first side of the container (1420)). In variations in which more than one temperature sensor and/or identifier are configured to overlap with the container (1420) and/or the adapter (1450), the adapter (1450) may be configured to hold the container (1420) in alignment with one or more of the temperature sensors and/or identifiers, including all of the temperature sensors and/or identifiers or a sub-set of the temperature sensors and/or identifiers. For example, if the container enclosure comprises three temperature sensors and/or identifiers, the adapter (1450) may be configured to hold the container (1420) in alignment with each of the three temperature sensors.

[0191] In some variations, a plurality of temperature sensors and/or identifiers may be used to on a single container enclosure to allow for use of that container enclosure with different adapters and/or containers having different sizes and shapes. In these variations, different sets of temperature sensors and/or identifiers may be used depending on which container and/or biological substance is selected for a thawing process. For example, the container enclosure may comprise five temperature sensors and/or identifiers, and a portion of the temperature sensors and/or identifiers may be intended for use with a first container having a first size and a first shape, a different portion of the temperature sensors and/or identifiers may be intended for use with a second container having a different size and/or different shape. In this variation, a first adapter may be configured to hold the first container in alignment with a first set of the temperature sensors and/or identifiers (e.g., sensors and/or identifiers 1, 2, 3, and 4 ) and the same, or a different adapter, may be configured to hold the second container in alignment with a second, different set of the temperature sensors and/or identifiers (e.g., sensors and/or identifiers 1, 2, 3, and 5). While described above in relation a container enclosure, it should be appreciated that any of the temperature sensor(s) and/or identifier(s) may be provided on the adapter instead of, or in addition to, those on the container enclosure.

[0192] In variations in which the temperature sensor (1440) is positioned to overlap with the container (1420) and/or the adapter (1450), the temperature sensor (1440) may be positioned on an inward facing surface of the container enclosure (1400) and/or a container-facing surface of an adapter. Opposing the temperature sensor (1440) may be an insulator. For instance, an insulator may be on an exterior surface of the container enclosure (1400) opposing the temperature sensor.

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

[0193] Similarly, an insulator may be positioned between the adapter and the temperature sensor and/or on a surface of the adapter facing away from the container opposing the temperature sensor (1440). In some variations, the insulator may be an air pocket or any suitable insulative material. The insulator may promote thermal isolation of the temperature sensor (1440) from an environment outside of the container enclosure (1400), outside of the adapter (1450), and/or from the adapter (1450).

[0194] FIGS. 5-11 depict additional variations of a container enclosure for use with a temperature control device and as part of a temperature control system as described herein. In these variations, the container enclosure may comprise the components forming a thermal interface between a container having a biological substance and a thermal source of a temperature control device. The container enclosure may be releasably coupled to the container and the thermal source, and may further provide temperature monitoring, identification, and tracking of the biological substance.

[0195] FIGS. 5-11 depict container enclosure variations as well as associated containers and temperature control devices. The systems and components depicted in FIGS. 5-11 may be compact and particularly useful in controlling a temperature of a low volume biological substance such as a vaccine. FIG. 5A is a schematic side view of an illustrative variation of a container (500) (e.g., a low volume container) comprising a biological substance as described herein. The container (500) may have any shape or size suitable for transporting, storing, heating, and/or cooling of a biological substance, and particularly, small volumes of a biological substance. For example, the container (500) may comprise a circular, square, or rectangular cross-sectional shape and may be configured to receive between about 1 mL and about 100 mL of a biological substance. In some variations, the container (500) may be a vial or a cuvette.

[0196] In some variations, the container enclosure may comprise an adapter configured to receive the container, which may function as a thermal interface between the biological substance and a thermal source to facilitate heat transfer. The adapter may further aid engagement and alignment with other portions of the container enclosure, such as a conductive housing comprising a thermal conductor. In some variations, the adapter may be configured to directly contact a thermal source or indirectly contact the thermal source via the thermal conductor.

[0197] FIG. 5B is a schematic cross-sectional side view of an illustrative variation of an adapter (510) having a cavity configured to receive the container (500). The adapter (510) may be configured to receive the container (500) such that the adapter may cover a sidewall portion of the container (500) and, if present, a neck/lip of the container, leaving the top portion (e.g., orifice, lid) of the container (500) uncovered. The adapter (510) may have a shape and size corresponding to the container (500). For example, in variations in which a cylindrical container (500) is

48

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 employed, the adapter (510) may also have a cylindrical shape, whereas in variations in which a container with a rectangular cross-sectional shape is employed, the adapter (510) may have a rectangular cross- sectional shape. In some variations, the adapter may be in the form of a sleeve with open ends, closed ends, or a combination thereof (i.e., one open end and one closed end). FIG. 5C is a schematic cross-sectional side view of the container (500) received within the cavity of the adapter (510) and FIG. 5D is a schematic plan view of the container (500) and the adapter (510).

[0198] FIGS. 11A and 11B are schematic plan views of an illustrative variations of an adapter (1100, 1150) configured to enable the container to thermally interface with a temperature control device. In some variations, the adapter may be composed of a thermally conductive, rigid material configured to receive the container with an interference fit. Additionally or alternatively, the adapter (1100, 1150), or a portion thereof (e.g., internal surface) may be configured to conform to a shape of the container, which may be, for example, cylindrical and/or rectangular. The adapter may comprise one or more of a metal (e.g., aluminum, copper thread), ceramic, polymer, and silicone. In some variations, the adapter may be transparent to aid visual identification of the container.

[0199] In some variations, the adapter may comprise a plurality of sleeves configured to be nested together. The adapter may have any inner and outer dimensions suitable to receive a container and to releasably couple to a conductive housing and/or a temperature control device. For example, a set of adapters may have different dimensions (e.g., inner diameter, shape) to accommodate containers of different dimensions, but have consistent outer diameters in order to fit properly into the conductive housing and/or the temperature control device. In some variations, the adapter may comprise a thickness between about 0.5 mm and about 2 mm.

[0200] In some variations, the container enclosure may comprise a conductive housing configured to receive the adapter. In these variations, the conductive housing may further serve as a thermal interface between the thermal source and a biological substance. The use of a conductive housing may allow the container received within the container enclosure to be handled more easily as compared to conventional water heating methods. FIG. 6A is a schematic cross-sectional side view of an illustrative variation a conductive housing (600) of a container enclosure. FIG. 6B is a schematic plan view of a container enclosure (601) (e.g., assembly) including the conductive housing (600) shown in FIG. 6 A. As shown there, the conductive housing (600) may comprise a support (614), a thermal conductor (610), a handle (620), an identifier (630), and a temperature sensor (640) (e.g., thermistor) configured to measure the temperature of the biological substance. The conductive housing (600) may further comprise a cavity (612), which may be formed by the

49

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 support (614) and the thermal conductor (610). The cavity (612) may be configured to receive an adapter (660) and a container (650). In some variations, the conductive housing (600) may be releasably coupled to both the adapter and the thermal source. FIG. 6A depicts the conductive housing (600) of the container enclosure (601) separated from the adapter (660), container (650), and temperature control device. The adapter (660) may be configured to receive the container (650) such that the adapter (660) covers at least a portion of the sidewall portion of the container (650) leaving a lip, a neck, an orifice, and/or a lid of the container (650) uncovered. The handle (620) may enable the container enclosure (601) to be manipulated by an operator so as to be inserted/removed into a chamber of a temperature control device. In some variations, the thermal conductor (610) may function as a thermal interface between a thermal source and the biological substance (e.g., via the adapter (660) and container (650)). In some variations, the thermal conductor (610) and the adapter (660) may each comprise a thermally conductive material such as one or more of a metal, ceramic, polymer, and silicone. In some variations, the handle (620) may comprise a set of tabs (e.g., protrusions, grips, ears) for grasping.

[0201] In some variations, the conductive housing (600) may comprise a temperature sensor and/or an identifier. For example, in some variations, the support (614) may comprise a temperature sensor (640) as described in more detail herein. The temperature sensor (640) may be any temperature sensor suitable for measuring the temperature of the biological substance within a temperature control device, such as, for example, a thermocouple. Additionally or alternatively, the support (614) may comprise the identifier (630) as described in more detail herein. In some variations, one or more of the identifier (630) and the temperature sensor (640) may be configured to contact the adapter (660) and/or the container (650) directly. While described above as part of or coupled to the support (614), one or more of the identifier and the temperature sensor may be disposed on any portion of the conductive housing (e.g., sidewall, top side, bottom side). For example, the temperature sensor may be a non-contact temperature sensor disposed within the thermal conductor (610) and/or on an outer surface of the conductive housing (600).

[0202] FIG. 6C is a schematic cross-sectional side view of an illustrative variation of a container enclosure (601) with a container (650) disposed therein. As depicted there, the container enclosure (601) may comprise the conductive housing (600) and the adapter (660), and the adapter (660) may be received within the cavity (612) of the conductive housing (600). FIG. 6D is a schematic plan view of the container enclosure (601) and the container (650). The adapter (660) may have dimensions suitable for an interference fit with the thermal conductor (610). The container (650) may be received within or otherwise releasably coupled to the adapter (660), and the adapter (660) may be received within or otherwise releasably coupled to the conductive housing (600) in a

50

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 similar manner as discussed with respect to the container and adapter in FIGS. 5A-5D. In some variations, the container enclosure (601) may be configured for limited use (e.g., single use). For example, in some variations, one or both of the adapter (660) and the conductive housing (600), or portions thereof (e.g., thermal conductor (610)) may be configured for limited use and may thus be disposable.

[0203] The container enclosure (601) may be used with a temperature control device to regulate the temperature of a biological substance inside. For example, the container enclosure (601) comprising the conductive housing (600) and adapter (660) may be received within or otherwise releasably coupled to a temperature control device comprising a thermal source to control a temperature of a biological substance. FIG. 7A is a schematic cross-sectional side view of an illustrative variation of a temperature control system (700) comprising a temperature control device (702) configured to control a temperature of a biological substance received within the container enclosure (601). FIG. 7B is a schematic plan view of the temperature control device (702). The temperature control system (700) may comprise a temperature control device (702) comprising a thermal source (780), sidewalls (770), and an agitator (790), and a container enclosure comprising an adapter (760) and a conductive housing (704). The conductive housing (704) may comprise a thermal conductor (710), a support (714), a handle (720), an identifier (730), and a temperature sensor (740). The container (750) may be received within the adapter (760) of the container enclosure, and the container enclosure may be received within a chamber (772) formed between the sidewalls (770). For example, the conductive housing (704) receiving (e.g. holding) the adapter (760) and the container (750) may be configured to be received in the chamber (772) of the temperature control device (702), which is formed between the sidewalls (770). In this manner, the thermal source (780) may be releasably coupled to, and in thermal communication with, the conductive housing (704). In this way, the temperature control device (702) may control the temperature of the biological substance in the container (750).

[0204] The thermal source (780) may comprise a heater, a cooler, and a combination of thereof. For example, in some variations, the thermal source (780) may comprise a Peltier element. In these variations, the Peltier element may be configured to regulate the temperature of the biological substance by generating heat and/or by cooling as desired. In some variations, the temperature control device (702) may comprise a plurality of thermal sources (780) such that thermal sources (780) are positioned on several sides of the container enclosure and/or the thermal source (780) may be configured to surround the container enclosure, as shown in FIG. 7B.

[0205] As mentioned above, the temperature control system (700) may comprise one or more (e.g., a plurality, two, three, four, five or more) temperature sensors. One or more temperature

51

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 sensors (740) may be positioned on one or more sidewalls (770) and disposed between the sidewall (770) and a thermal conductor (710) of the conductive housing (704) (e.g., on an internal surface of the sidewall (770), on the support (714), on any portion of the conductive housing (704), and/or on the adapter (714). For example, one or more temperature sensors (740) may be disposed on an upper outer surface of the support (714) and configured to contact a container (750).

[0206] In some variations, one or more components of the container enclosure (e.g., conductive housing (704) and adapter (760)) may be configured for single use, while the temperature control device (702) may be configured to be reusable. For example, in some variations, the conductive housing (704) and/or the adapter (760) of the container enclosure may be configured for single or limited use (e.g., between 1 and 5 uses), while one or more of the sidewalls (770), the thermal source (780), and the agitator (790) of the temperature control device (702) may comprise reusable (e.g., durable) components. This may be useful where the conductive housing (704) is releasably coupled to the agitator (790).

[0207] As mentioned above, the temperature control device (702) may optionally comprise an agitator (790). The agitator (790) may be configured to agitate the container enclosure. More [0208] specifically, the agitator (790) may be configured to agitate the adapter (760) holding the container (750) and thus the biological substance contained therein, and in some variations, the thermal conductor (710) of the conductive housing, during a temperature regulation process (e.g., heating). In some variations, the agitator (790) may comprise a motor and cam (not shown) configured to generate a pivoting motion, a motor configured to generate longitudinal motion, and/or a motor configured to generate vibrational motion. The frequency and magnitude at which an agitator applies force to the container enclosure may be controlled by the controller (e.g., controller 104). For example, the agitator (790) may be configured to operate at about 0.5 Hz. In some variations, the agitator (790) may be configured to raise a height of the container (750) and housing (714) which may aid insertion and removal of the housing (714) from the temperature control device (702). However, in some variations, the system (700) may not comprise an agitator (790), or the agitator (790) may be turned off or otherwise deactivated such that agitation is inhibited.

[0209] In another variation of a container enclosure, as shown in FIGS. 8-10, a compact container enclosure (e.g., assembly) may be used with an associated temperature control system. With respect to the container enclosure depicted in FIGS. 6A-6D, the removable container enclosure includes an adapter but not a thermal conductor. Instead, a temperature control device includes a thermal conductor fixedly coupled to a thermal source. This may reduce the number of disposable components used in controlling a temperature of a biological substance. FIG. 8A is a schematic

52

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 side view of a container (800). FIG. 8B is a schematic cross-sectional side view of an illustrative variation of the container (800) partially received within an adapter (810) (e.g., sleeve) of a container enclosure. FIG. 8C is a schematic cross-sectional side view of the container (800) fully received within the adapter (810). The container (800) may have any shape or size and the corresponding adapter (810) may have a corresponding shape and size suitable to receive the container (800), as well as any of the features described with respect to the adapters described herein. For example, in variations in which a cylindrical container (800) is employed, the adapter (810) may also have a cylindrical shape, whereas in variations in which a container with a rectangular cross-sectional shape is employed, the adapter (810) may have a rectangular cross- sectional shape. In some variations, the adapter may be in the form of a sleeve with open ends, closed ends, or a combination thereof (i.e., one open end and one closed end). In some variations, the adapter (810) may be composed of a thermally conductive rigid material and have dimensions configured to receive the container (800) with an interference fit. In some variations, the adapter (810) may function as a thermal interface between the container (800) and one or more of a thermal conductor and thermal source (not shown). In some variations, the adapter (800) may comprise one or more of a metal, ceramic, polymer, and silicone. In some variations, the adapter (800) may be open at one or more ends to allow one or more of an identifier and contact temperature sensor to contact the container (800). In some variations, at least a portion of the adapter (800) may be transparent to aid visual identification of the container (800). In some variations, the adapter (810) may comprise the temperature sensor (830). For example, one or more temperature sensors may be disposed on an inner surface of the adapter (810) and configured to contact the container (800). In some variations, the adapter (810) may comprise the identifier (820). For example, the identifier (820) may be configured to overlie or overlap a bottom portion of the container (800). The adapter (810) may be configured for limited use (e.g., single use).

[0210] FIG. 9A is a schematic cross-sectional side view of an illustrative variation of a temperature control system (900) comprising a temperature control device (902) configured to control a temperature of a biological substance received within a container enclosure (950). FIG. 9B is a schematic plan view of the system (900). The container (950) and adapter (910) may be releasably coupled to a thermal conductor (970) of the temperature control device (902). The temperature control device (902) may comprise a conductive housing (914) having a thermal conductor (970), an identifier reader (932), temperature sensor (940), thermal source (980), and agitator (990). The container (950) may be received within the adapter (910) of the container enclosure, and the container enclosure may be received within a chamber formed between the conductive housing (914). For example, the conductive housing (914) receiving (e.g. holding) the

53

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 adapter (910) and the container (950) may be configured to be received in the chamber of the temperature control device (902), which is formed between the conductive housing (914). In this manner, the thermal source (980) may be in thermal communication with the thermal conductor (970). In this way, the temperature control device (902) may control the temperature of the biological substance in the container (950).

[0211] In some variations, the temperature sensor (940) may comprise a thermistor. For example, one or more temperature sensors (940) may be coupled to the thermal conductor (970) and/or thermal source (980). The thermal conductor (970) may be configured to surround the container (950), as shown in FIG. 9B. The container enclosure in FIGS. 9A and 9B may include the adapter (910). In some variations, the thermal source (980) may comprise a Peltier element. In some variations, the Peltier element may be configured to regulate temperature by generating heat or cooling as desired. In some variations, one or more of the thermal conductor (970), thermal source (980), and agitator (990) may comprise reusable (e.g., durable) components while the adapter (910) and container (850) may be configured for limited (e.g., single) use. In some variations, the adapter (910) may comprise an inner diameter of up to about 1 mm greater than an outer diameter of the container (950). In some variations, the temperature control device (902) may comprise a plurality of thermal sources (980) such that thermal sources (980) are positioned on several sides of the container enclosure and/or the thermal source (980) may be configured to surround the container enclosure, as shown in FIG. 9B.

[0212] In some variations, the identifier reader (932) (e.g., RFID reader) may be configured to communicate with the identifier (930) to receive data corresponding to the biological substance. For example, the reader (932) may be configured to receive one or more of biological substance data, the measured temperature from one or more of the identifier (930) and the temperature sensor (940), and authentication data. Additionally or alternatively, the reader (932) may comprise an optical sensor configured to generate an image of the identifier (930). In some variations, the identifier (930) and the reader (932) may be placed within a predetermined proximity (e.g., adapter (910) within the chamber of the temperature control device (902)) to facilitate communication and/or data transfer.

[0213] In some variations, the housing (914) of the temperature control device (902) may be configured to transition between an open configuration and a closed configuration to aid in placement and removal of the container (950) within the temperature control device (900). The closed configuration may be configured to hold the container (950) within a chamber of the temperature control device (902). In the open configuration, an operator may more easily place

54

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 and remove the adapter (910) and container (950) within the chamber of the temperature control device (902).

[0214] In some variations, the temperature control device (902) may be configured to transition between open and closed configurations. For example, FIG. 9B illustrates a first portion (972) and second portion (974) of the conductive housing (914) where the first portion (972) and second portion (974) may be configured to pivot relative to each other in order to facilitate access to the temperature control device (902), thereby aiding insertion and removal of the container (950) from the temperature control device (902). In some variations, the first portion (972) and the second portion (974) may be coupled by a hinge (not shown) such that one of the portions remains fixed in place while the other portion may swing like a door. In some variations, the first portion (972) and the second portion (974) may slide relative to each other. The agitator (990) may be configured to raise or lower the container (950) and adapter (910) relative to the conductive housing (914) to facilitate insertion and removal of the container (950) from the temperature control device (902). [0215] For example, the container (950) and adapter (910) may be inserted vertically into the cavity of the temperature control system (900).

[0216] In some variations, the temperature sensor and identifier may be integrated within a container enclosure to improve temperature measurement of a biological substance. FIG. 10A is a schematic cross-sectional view of an illustrative variation of a sensor (1030) and an identifier (1010) disposed within a support (1000) of an adapter or thermal conductor. FIG. 10B is a schematic cross- sectional view of another illustrative variation of a sensor (1032) and an identifier (1012) disposed within a support (1050) of the container enclosure. In some variations, the support (1000, 1050) (e.g., sleeve, thermal conductor) may comprise a protrusion (1002, 1052) (e.g., hemisphere, curved portion) configured to releasably contact a bottom portion of a container (not shown). The protrusion (1002, 1052) may ensure contact with a container and increase the accuracy of temperature measurements.

[0217] In some variations, a wired connection may be formed between a reader and one or more of a temperature sensor and identifier. For example, the housing (1050) may comprise a first connector (1090) coupled to the temperature sensor (1032) and a second connector (1092) coupled [0218] to the identifier (1012). Each connector (1090, 1092) may be disposed on an outer surface of the housing (1050) and comprise a lead wire configured to couple to a reader (not shown) to transfer data such as temperature measurements and data corresponding to the biological substance.

[0219] FIG. 10C is a schematic bottom view of an illustrative variation of the sensor connector (1090) and an identifier (1010). For example, a portion of the identifier (1010) may be exposed

55

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 on an outer surface of a support and a connector (1090) coupled to a sensor (e.g., temperature sensor) may form a ring shape. A reader (not shown) may be configured to contact the identifier (1010) and sensor connector (1090) to receive data from one or more of the identifier (1010) and the sensor connector (1090), for example using the temperature control system (900) shown in FIG. 9A.

[0220] FIG. 10D is a schematic bottom view of the sensor connector (1090) and the identifier (1092) shown in FIG. 10B. An outer surface of the support (1050) may comprise one or more ring connectors (1090, 1092) configured to contact a corresponding reader (not shown) to receive data from one or more of the identifier (1012) and the sensor (1032) as shown in FIG. 10B. In some variations, a temperature regulation process may be inhibited unless contact between the connector(s) (1090, 1092) is made to a reader to ensure that the container is in a predetermined position for heat transfer. In this way, the temperature control system may be configured to detect whether the container is properly placed within the temperature control device, so as to enable a temperature control process to be executed.

[0221] FIG. 19A is a schematic cross-sectional view of an illustrative variation of a container (1900a) for holding a biological substance. The container (1900a) may be received in any suitable temperature control device described herein. For instance, the container (1900a) may be received in a chamber and/or a container enclosure of a temperature control device (e.g., within a cavity of a chamber and/or a cavity of a container enclosure) as described herein. In some variations, the container (1900a) may be received in a temperature control device without an adapter. In such variations, a top portion (described below) of the container (1900a) and/or a bottom portion (described below) of a container (1900a) may hold the container (1900a) in position (e.g., upright position, aligned with respect to one or more electrical contacts of temperature sensor(s), and/or aligned with respect to thermal source(s) and/or thermal conductor(s)) within the temperature control device. For example, the container (1900a) may be received within temperature control device (202) described in FIG. 2C. In particular, the container (1900a) may be received within the chamber (222) of the temperature control device (202). Additionally or alternatively, the container (1900a) may be received within the temperature control device (204) depicted in FIG. 2C. For instance, the container (1900a) may be received within the cavity (223) of the temperature control device (204). In a similar manner, the container (1900a) may be received in a container enclosure (600) described in FIGS. 6A-6D. More specifically, the container (1900a) may be received within a cavity (612) of the container enclosure (600) with thermal conductor (610). Similarly, the container (1900a) may be received within temperature control device (702) described in FIGS. 7A

56

132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 and 7B. In a similar manner, the container (1900a) may be received within temperature control device (902) in FIG. 9A.

[0222] The container (1900a) may include a top portion (1952a), a bottom portion or base (1958a), and a body portion (1956). The top portion (1952a) may be a covering (1955a) (e.g., cap, lid) and/or the bottom portion (1958a) may be a base. In some variations, the covering 1955a may include an opening (1953a) to receive the biological substance. The opening (1953a) may be sealed after the container (1900a) receives the biological substance. In some variations, the opening (1953a) may include a septum through which the biological substance may be received. In some variations, the biological substance may be injected into the container (1900a) through the opening (1953a). Additionally or alternatively, the covering (1955a) itself may act as seal when the biological substance is received in the container (1900a). For example, the covering (1955a) may be a lid that may be opened to receive the biological substance and closed to seal the biological substance within the container (1900a). The top portion may comprise one or more polymers that may be resistant to high temperatures such as, for example, Polytetrafluoroethylene (PTFE), Polychlorotrifluoroethylene (PCTFE), Fluorinated ethylene propylene (FEP), etc.

[0223] In some variations, one or more of the top portion (1952a), bottom portion (1958a), and body portion (1956a) may comprise a connector configured to mate, receive, or otherwise couple the top portion (1952a) and bottom portion (1958a) to the body portion (1956a). In variations in which the top portion (1952a) and/or bottom portion (1958a), and the body portion (1956a) each comprise a connector, the connectors on the top portion (1952a) and/or bottom portion (1958a) may be corresponding connectors with the respective connectors on the body portion (1956a). For example, the top portion (1952a) may include a connector (1954a’) configured to couple the top portion (1952a) with the body portion (1956a). Additionally or alternatively, the body portion (1956a) may include a connector (1954a’) configured to couple the top portion (1952a) with the body portion (1956a). For instance, the connector (1954a’) of the body portion (1956a) may be configured to mate with the connector (1954a’) of the top portion (1952a). The connector (1954a’) of the body portion (1956a) may be configured to couple with the connector (1954a’) of the top portion (1952a). In some variations, the connector (1954a’) of the top portion (1952a) and/or the body portion (1956a) may include thread(s), adhesive(s), one or more snap-fit assembly, a combination thereof, and/or the like. The top portion (1952a) may be coupled with the body portion (1956a) in any suitable manner. For example, the top portion (1952a) and the body portion (1956a) may be coupled to one another via a molding process such as over molding. Additionally or alternatively, the top portion (1952a) and the body portion (1956a) may be attached to one another via an adhesive. Additionally or alternatively, the top portion (1952a) and the body portion

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

(1956a) may be coupled to one another via a snap-fit connection. Additionally or alternatively, the connector (1954a’) of the top portion (1952a) and the body portion (1956a) may include threaded structures configured to couple the top portion (1952a) with the body portion (1956a). In some variations, the top portion (1952a) may be fixedly coupled to the body portion (1956a) via the connector (1954a’). Additionally or alternatively, the top portion (1952a) may be removably coupled to the body portion (1956a) via the connector (1954a’). In some variations, the top portion or the bottom portion may be integrally formed with the body portion, and the container may not include one or more of the above-mentioned connectors.

[0224] In some variations, the top portion (1952a) may include a chamber or hollow portion configured to receive a proximal end of the body portion (1956a). The hollow portion of the top portion (1952a) may have a length between about 3 mm and about 20 mm (including all values and sub-ranges therein) and/or a diameter (e.g., inner diameter of top portion) of between about

15 mm and about 30 mm (including all values and sub-ranges therein). For example, the hollow portion of the top portion (1952a) may have a length of between about 5 mm and about 18 mm, between about 7 mm and about 16 mm, between about 9 mm and about 14 mm, or between 10 mm and about 12 mm. The hollow portion of the top portion (1952a) may have a diameter of between about 18 mm and about 28 mm, between about 20 mm and about 26 mm, or between about 22 mm and about 24 mm. The entire top portion (1952a) may have a length between about

5 mm and about 25 mm (including all values and sub-ranges therein) and/or a diameter (e.g., outer diameter of top portion) of between about 17 mm and about 30 mm (including all values and subranges therein). For example, the entire top portion (1952a) may have a length of between about

6 mm and about 20 mm, between about 8 mm and about 18 mm, between about 10 mm and about

16 mm, or between about 12 mm and about 14 mm. The entire top portion (1952a) may have a diameter of between about 18 mm and about 28 mm, between about 20 mm and about 26 mm, or between about 22 mm and about 24 mm.

[0225] The body portion (1956a) may be configured to hold the biological substance. The body portion (1956a) may comprise a proximal end (1955a’), which may include the connector (1954a’), a central portion (1955a”) comprising a fluid reservoir (1957a) configured to receive and contain the biological substance, and a distal end (1955a’”), which may include a connector (1954a”). The proximal end (1955a’) of the body portion (1956a) may be configured to couple with the top portion (1952a) and the distal end (1955a’”) of the body portion (1956a) may be configured to couple with the bottom portion (1958a). For example, the proximal and distal ends of the body portion may be configured to be received in a chamber in the top portion (1952a) and a chamber in the bottom portion (1958a) respectively. In some variations, an outer dimension

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

(e.g., diameter, width) of the proximal end (1955a’) of the body portion (1956a) may be equal to a dimension (e.g., diameter, width) of the chamber of the top portion (1952a) (e.g., may be equal to an inner dimension (e.g., diameter, width) of the top portion). In some variations, the diameter or width of the proximal end (1955a’) may be equal to a diameter or width of the central portion (1955a’ ’). In a similar manner, the diameter or width of the central portion (1955a’ ’) may be equal to the diameter or width of the distal end (1955a’”).

[0226] In some variations, the length LI and the diameter or width d (e.g., diameter of the proximal, central, and/or distal portion) of the body portion may be such that the body portion (1956a) may hold a volume of biological substance between about 1 mL and about 30 mL, including all values and sub-ranges therein. For example, in some variations, the length LI and the diameter or width d of the body portion may be such that the body portion (1956a) may hold about 2 mL to about 8 mL, about 4 mL to about 7 mL, or about 5 mL to about 6 mL of the biological substance. In further variations, the length LI and the diameter or width d of the body portion may be such that the body portion (1956a) may hold a volume of about 1 mL to about 28 mL, about 1 mL to about 26 mL, about 1 to about 20 mL, about 5 mL to about 30 mL, about 5 mL to about 28 mL, about 5 mL to about 26 mL, about 5 mL to about 20 mL, about 10 mL to about 30 mL, about 10 mL to about 28 mL, about 10 mL to about 26 mL, about 10 mL to about 20 mL, about 12 mL to about 18 mL, or about 14 mL to about 17 mL. In some variations, the body portion may be configured to hold a maximum volume of about 15 mL, about 16 mL, about 17 mL, about 18 mL, about 19 mL, about 20 mL, about 21 mL, about 22 mL, about 23 mL about 24 mL, about 25 mL, about 26 mL, about 27 mL, about 28 mL, about 29 mL, or about 30 mL. It should be appreciated that while described with respect to the container (1900a) depicted in FIG. 19 A, any of the containers (1900b, 1900c) may comprise body portions configured to contain any of the volumes described herein.

[0227] The body portion (1956a) may have any length suitable to contain any of the volumes of biological fluid described herein while still being configured to be received within a temperature control device. For example, the length LI of the body portion may be between about 15 mm and about 100 mm, including all values and sub-ranges there. In some variations, the length LI of the body portion (1956a) may be between about 15 mm and about 20 mm between about 16 mm and about 19 mm, or between about 17 mm and about 18 mm. In further variations, the length LI of the body portion (1956a) may be between about 70 mm and about 90 mm, or between about 75 mm and about 85 mm. It should be appreciated that while described with respect to the container (1900a) depicted in FIG. 19A, any of the containers (1900b, 1900c) may comprise body portions with any of the lengths described herein.

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001

[0228] In some variations, the body portion (1956a) may have a diameter or width d. The diameter or width d of the body portion (1956a) may be between about 1 mm and about 35 mm, including all values and sub-ranges therein. For example, the diameter or width d of the body portion (1956a) may be between about 16 mm and about 28 mm, between about 18 mm and about 26 mm, between about 20 mm and about 24 mm, or between about 22 mm and about 23 mm. As another example, the diameter or width d of the body portion (1956a) may be between about 2 mm and about 12 mm, between about 3 mm and about 11 mm, between about 4 mm and about 10 mm, between about 5 mm and about 9 mm, or between about 6 mm and about 8 mm. It should be appreciated that while described with respect to the container (1900a) depicted in FIG. 19 A, any of the containers (1900b, 1900c) may comprise body portions configured to contain any of the diameters or widths described herein.

[0229] In some variations, the length LI and the diameter or width d (e.g., diameter of the proximal, central, and/or distal portion) of the fluid reservoir (1957a) may be such that the fluid reservoir may hold a volume of biological substance between about 1 mL and about 30 mL, including all values and sub-ranges therein. For example, the length LI and the diameter or width d of the fluid reservoir (1957a) may be such that the fluid reservoir (1957a) may hold about ImL to about 10 mL, about 2 mL to about 8 mL, about 4 mL to about 7 mL, or about 5 mL to about 6 mL of the biological substance. In further variations, the length LI and the diameter or width d of the fluid reservoir (1957a) may be such that the fluid reservoir (1957a) may hold a volume of about 1 mL to about 28 mL, about 1 mL to about 26 mL, about 1 to about 20 mL, about 5 mL to about 30 mL, about 5 mL to about 28 mL, about 5 mL to about 26 mL, about 5 mL to about 20 mL, about 10 mL to about 30 mL, about 10 mL to about 28 mL, about 10 mL to about 26 mL, about 10 mL to about 20 mL, about 12 mL to about 18 mL, or about 14 mL to about 17 mL. In some variations the fluid reservoir may be configured to hold a maximum volume of about 15 mL, about 16 mL, about 17 mL, about 18 mL, about 19 mL, about 20 mL, about 21 mL, about 22 mL, about 23 mL about 24 mL, about 25 mL, about 26 mL, about 27 mL, about 28 mL, about 29 mL, or about 30 mL. It should be appreciated that while described with respect to the container (1900a) depicted in FIG. 19A, any of the containers (1900b, 1900c) may comprise fluid reservoirs configured to contain any of the volumes described herein.

[0230] In some variations, the length LI of fluid reservoir (1957a) may be between about 15 mm and about 100 mm, including all values and sub-ranges therein. For example, the length LI of the fluid reservoir (1957a) may be between about 15 mm and about 20 mm, between about 16 mm and about 19 mm, or between about 17 mm and about 18 mm. In further variations, the length LI of the fluid reservoir (1957a) may be between about 70 mm and about 90 mm, or between about

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75 mm and about 85 mm. It should be appreciated that while described with respect to the container (1900a) depicted in FIG. 19A, any of the containers (1900b, 1900c) may comprise fluid reservoirs configured to contain any of the lengths described herein.

[0231] In some variations, the fluid reservoir (1957a) may have a constant diameter or width d. For example, in these variations, the diameter or width d of the fluid reservoir may be between about 1 mm and about 30 mm, including all values and sub-ranges therein. In some variations, the diameter or width d of the fluid reservoir (1957a) may be between about 1 mm and about 15 mm, between about 4 mm and about 10 mm, between about 5 mm and about 9 mm, between about 6 mm and about 8 mm. In other variations, the diameter or width d of the fluid reservoir (1957a) may be between about 16 mm and about 28 mm, between about 18 mm and about 26 mm, between about 20 mm and about 24 mm, or between about 22 mm and about 23 mm. In other variations, the fluid reservoir may have a variable diameter or width d as described in more detail herein with respect to FIG. 19C. In these variations, the diameter or width d may range between 1 mm and 30 mm, depending on position within the fluid reservoir along the longitudinal axis of the container. In some variations, the diameter or width d of the body portion (1956a) may be greater than the diameter or width of the fluid reservoir (1957a).

[0232] The body portion (1956a) may also include a connector (1954a”) to couple (e.g., fixedly, releasably) the body portion (1956a) with the bottom portion (1958a). Similarly to the top portion (1952a), the bottom portion (1958a) may additionally or alternatively include a connector (1954a”). The connector (1954a”) of the body portion (1956a) may be configured to mate with the connector (1954a”) of the bottom portion (1958a). In some variations, the connector (1954a”) of the body portion (1956a) and/or the bottom portion (1958a) may include thread(s), adhesive(s), one of more snap-fit assembly, a combination thereof, and/or the like. Similarly to the top portion (1952a), the bottom portion (1958a) may be coupled with the body portion (1956a) in any suitable manner. For example, the bottom portion (1958a) and the body portion (1956a) may be coupled to one another via a molding process such as over molding. Additionally or alternatively, the bottom portion (1958a) and the body portion (1956a) may be attached to one other via an adhesive. Additionally or alternatively, the bottom portion (1958a) and the body portion (1956a) may be coupled to one another via a snap-fit connection. Additionally or alternatively, the connector (1954a”) of the bottom portion (1958a) and the body portion (1956a) may include threaded structures configured to couple the bottom portion (1958a) with the body portion (1956a). In some variations, the bottom portion (1958a) may be fixedly coupled with the body portion (1956a). Additionally or alternatively, the bottom portion (1958a) may be removably coupled with the body portion (1956a).

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[0233] In some variations, the bottom portion (1958a) may include a chamber or hollow portion configured to receive the distal end of the body portion (1956a). The hollow portion of the bottom portion (1958a) may have a length between about 3 mm and about 20 mm (including all values and sub-ranges therein) and/or a diameter or width (e.g., inner diameter or width of bottom portion) of between about 15 mm and about 30 mm (including all values and sub-ranges therein). For example, the hollow portion of the bottom portion (1958a) may have a length of between about 5 mm and about 18 mm, between about 7 mm and about 16 mm, between about 9 mm and about 14 mm, or between 10 mm and about 12mm. The hollow portion of the bottom portion (1958a) may have a diameter of between about 18 mm and about 28 mm, between about 20 mm and about 26 mm, or between about 22 mm and about 24 mm. The entire bottom portion (1958a) may have a length between about 5 mm and about 25 mm (including all values and sub-ranges therein) and/or a diameter (e.g., outer diameter of bottom portion) of between about 17 mm and about 30 mm (including all values and sub-ranges therein). For example, the entire bottom portion (1958a) may have a length of between about 6 mm and about 20 mm, between about 8 mm and about 18 mm, between about 10 mm and about 16 mm, or between about 12 mm and about 14 mm. The entire bottom portion (1958a) may have a diameter of between about 18 mm and about 28 mm, between about 20 mm and about 26 mm, or between about 22 mm and about 24 mm.

[0234] In some variations, an outer dimension (e.g., diameter, width) of the distal end (1955a’”) of the body portion (1956a) may be equal to a dimension (e.g., diameter, width) of the chamber of the bottom portion (1958a) (e.g., may be equal to an inner dimension (e.g., diameter, width) of the bottom portion). In some variations, the bottom portion (1958a) may include a guide or alignment feature (1962) configured to assist in positioning the container within and relative to a temperature control device (e.g., a cavity of a temperature control device, a chamber of a temperature control device) and/or a container enclosure. For example, the guide or alignment feature may be configured to interact with (e.g., receive, be received within) a corresponding guide or alignment feature of a temperature control device (e.g., within a cavity or chamber of a temperature control device) and/or a container enclosure. The guide (1962) may include any suitable mechanism (e.g., a slot, a cavity, a hole, a groove, a protrusion) configured to position the container (1900a) relative to the temperature control device and/or container enclosure. In some variations, the guide may be used to center the container (1900a) when the container (1900a) is placed in the temperature control device. For example, the container guide may be configured to interact with a temperature control device guide and/or a container enclosure guide to center the container (1900a) within a cavity or chamber of the temperature control device and/or within a container enclosure, to position and/or maintain the container (1900a) in an upright position,

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 and/or to align the container (1900a) with or relative to one or more electrical contacts or connectors (e.g., for temperature sensor 1960a in FIG. 19A), one or more thermal sources, and/or one or more thermal conductors.

[0235] In some variations, the bottom portion (1958a) may include one or more temperature sensors (1960a) to measure a temperature of the biological substance in the container (1900a). The temperature sensor (1960a) may be positioned on a surface (e.g., an inner surface of the bottom portion (1958a)) near (e.g., adjacent to) the biological substance (e.g., adjacent to the central portion (1955a”) of the body portion (1956a) holding the biological substance). In some variations, the temperature sensor (1960a) may comprise a thermocouple or a thermistor. In some variations, the bottom portion (1958a) may include electrical contacts for the temperature sensor (1960a). For example, electrical contacts (1964a) may be positioned on a surface (e.g., outer surface) of the bottom portion (1958a) such that the electrical contacts (1964a) may interact with the temperature control device. Although FIG. 19A illustrates a container (1900a) with a single temperature sensor (1960a), it should be readily understood that the container (1900a) may comprise any suitable number of temperature sensors (1960a). For example, the container (1900a) may include two, three, four, five, six, seven, eight or more temperature sensors. The temperature sensors may be positioned in any suitable configuration. For instance, one or more temperature sensors may be positioned on the bottom portion (1958a) while one or more temperature sensors may be positioned on the top portion (1952a). Additionally or alternatively, the temperature sensors may be positioned in a circular configuration on the bottom portion (1958a). In some variations, the temperature sensors may be positioned in a line across (e.g., along the diameter; along a central line, in an X shape, in a cross shape) the hollow portion of the bottom portion (1958a).

[0236] In some variations, each temperature sensor (1960a) may be configured to measure the same temperature range, advantageously providing several temperature measurements for a biological substance in the container during a thawing process. In some variations, one or more temperature sensors may be configured to measure a temperature range of about -200°C to 50°C. For example, one or more temperature sensors may be configured to measure the following temperature ranges: about -196°C to about -80°C, about -80°C to about -30°C, about -30°C to about 0°C, or about 0°C to about 40°C. In other variations, the container (1900a) may include a plurality of temperature sensors configured to measure different temperature ranges. For example, a first temperature sensor may be configured to measure temperatures ranging between about - 200°C to about -80°C, a second temperature sensor may be configured to measure temperatures ranging between about -80°C to about -30°C, a third temperature sensor may be configured to

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 measure temperatures ranging between about -30°C to about 0°C, and a fourth temperature sensor may be configured to measure temperatures ranging between about 0°C and about 50°C. Having multiple temperature sensors may improve the resolution of temperature measurement, decrease possibilities for error and/or allow a single container to be capable of use with a variety of different biological substances. In some variations, the bottom portion may comprise one or more polymers that may withstand extreme temperatures (e.g., low temperatures) such as PTFE, PCTFE, FEP, etc.

[0237] A length and/or diameter or width of the top portion (1952a) may be any of the lengths and/or diameters or widths described above with respect to the bottom portion (1958a). In some variations, the length of the top portion (1952a) may be equal to the length of the bottom portion (1958a), while in other variations, the length of the top portion (1952a) may be greater than, or less than, the length of the bottom portion (1958a). In some variations, the diameter or width of the top portion (1952a) may be equal to the diameter or width of the bottom portion (1958a), while in other variations, the diameter or width of the top portion (1952a) may be great than, or less than, the diameter or width of the bottom portion (1958a). Similarly, as described with respect to the distal end (1955a’”) of the body portion (1956a), an outer dimension (e.g., diameter, width) of the proximal end (1955a’) of the body portion (1956a) may be equal to a dimension (e.g., diameter, width) of a chamber of the top portion (1952a) (e.g., may be equal to an inner dimension (e.g., diameter, width) of the top portion). It should be appreciated that while described with respect to the container (1900a) depicted in FIG. 19A, any of the containers (1900b, 1900c) may comprise top portions, bottom portions, and dimensions configured to contain any of the lengths, diameters or widths described herein.

[0238] The container (1900a) (e.g., top portion, bottom portion, body portion) may comprise any shape suitable to hold the biological substance, and may be, for example, cylindrical, rectangular, frustoconical, pyramidal, a triangular prism, or the like. In some variations, the fluid reservoir may have the same cross-sectional shape as the container generally, while in other variations, as will be described in more detail with respect to FIG. 19C, the fluid reservoir may have a different cross- sectional shape than the container generally.

[0239] FIG. 19B is a schematic cross-sectional view of another variation of a container (1900b) for holding a biological substance. Similar to the container (1900a) depicted in FIG. 19A, the container (1900b) depicted in FIG. 19B may include atop portion (1952b), a body portion (1956b) and a bottom portion (1958b). The body portion (1956b) may include a proximal end (1955b’), a central portion (1955b”) including a fluid reservoir (1957b), and a distal end (1955b’”). The top portion (1952b) may include a connector (1954b’) that may be coupled to the connector (1954b’)

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 of the proximal end (1955b’) of the body portion (1956b). The bottom portion (1958b) may include a connector (1954b”) that may be coupled to the connector (1954b”) of the distal end (1955b’”) of the body portion (1956b). The bottom portion (1958b) may include a temperature sensor (1960b) with electrical contacts (1964b). The container (1900b) depicted in FIG. 19B may include any of the features described with respect to the container (1900a) depicted in FIG. 19 A, with like elements similarly numbered. As one example, the top portion (1952b) may include an opening and/or a septum as and/or the bottom portion (1958b) may include a guide element as described with respect to the container (1900a) depicted in FIG. 19 A.

[0240] In contrast to FIG. 19A, in FIG. 19B, the diameter or width of the central portion (1955b”) of the body portion (1956b) may be different from the diameter or width of the proximal end (1955b’) and/or the distal end (1955b’”). More specifically, referring to FIG. 19B in particular, which depicts a cylindrically shaped container, the diameter of the proximal end (1955b’) may be such that the proximal end (1955b’) may be received within the hollow portion of the top portion (1952b). For instance, the diameter of the proximal end (1955b’) may be less than or about equal to a diameter of the hollow portion of the top portion (1952b) (an inner diameter of the top portion (1952b)). In some variations, a connector (1954b’) at the proximal end (1955b’) may mate with a connector (1954b’) of the top portion (1952b). In a similar manner, again referring specifically to FIG 19B, which depicts a cylindrically shaped container, the outer diameter of the distal end (1955b’”) may be such that the distal end (1955b’”) may be received within the hollow portion of the bottom portion (1958b). For instance, the outer diameter of the distal end (1955b”) may be less than or about equal to a diameter of the hollow portion of the bottom portion (1958b) (an inner diameter of the bottom portion (1958b)). It should be appreciated that the outer diameters or outer widths of the top and/or bottom portions (1952b, 1958b) may be any diameters or widths suitable to interface with a temperature control device and may be independent from the inner diameter or inner width of the top and/or bottom portions (1952b, 1958b).

[0241] The central portion (1955b”) of the body portion (1958b), and the fluid reservoir (1957b) therein in particular, may be configured to hold the majority of, or all of, the volume of the biological substance. Thus, in some variations, it may be desirable for the central portion (1955b”) to have a different diameter or width than the proximal (1955b’) and/or distal (1955b’”) ends, which may be configured to be received in the top (1952b) and/or bottom (1958b) portions, respectively. In some variations, the central portion (1955b”), and particularly the fluid reservoir (1957b), may have a different diameter or width than the proximal (1955b’) and/or distal (1955b’”) ends. In some variations, the proximal end (1955b’) may have a first diameter or width, the distal end (1955b’”) may have a second diameter or width, and the fluid reservoir (1957b)

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 may have a third diameter or width. For example, the third diameter or width of the fluid reservoir (1957b) may be greater than both the first and second diameters or widths of the proximal (1955b’) and distal (1955b’”) ends, respectively. While the diameters or widths of the proximal end (1955b’) and/or the distal end (1955b’”) may be constrained by the ability to mate and/or fit within the top portion (1952b) and the bottom portion (1958b) respectively, which may, in some variations, be constrained by the ability to interface with a temperature control device, the diameter or width of the central portion (1955b”), and thus the fluid reservoir contained therein, is not so limited. Thus, the diameter or width of the central portion (1955b”) may be different (e.g., larger, smaller) than the diameter or width of one or more of the proximal end (1955b’) and the distal end (1955b’”) of the body portion, which may allow for containers with different volumes to be used interchangeably with the same top portion and/or bottom portion. Thus, the central portion (1955b”) may have any suitable length and diameter or width to accommodate a biological substance of any suitable volume while the top portion (1952b) and the bottom portion (1958b) may still be configured to interact with a temperature control device. In this manner, body portions (1958b) configured to hold different volumes (e.g., body portions with different sized reservoirs, different central portion lengths and/or diameters or widths) may be used with standard top portions (1952b) and bottom portions (1958b) such that body portions configured to hold different volumes may be interchangeable with the same or similar top and/or bottom portions.

[0242] In some variations, the bottom portion (1958b) may include a stem (1959b) (depicted in FIG. 19B) extending from a distal surface toward and in some variations, to, a proximal end of the bottom portion. In some variations, the stem may be centrally located within the bottom portion (1958b) and additionally or alternatively may be substantially solid. The stem (1959b) may be configured to be received within the distal end (1955b”) of the body portion and may be configured to appropriately position one or more temperature sensors (1960) relative to the biological substance within the container. The stem (1959b) may include one or more temperature sensors (1960b) (e.g., positioned at a proximal end thereof) and electrical connectors for the temperature sensors (1960b), which may traverse the stem to electrically couple the temperature sensors (1960b) with corresponding electrical contacts (1964b). The electrical contacts (1964b) may be positioned on a distal surface of the stem so as to interact with corresponding contacts of a temperature control device. In some variations, one or more temperature sensors (1960b) may be inset in, or otherwise received in, a cavity in the stem. The stem (1959b) may align the temperature sensor (1960b) such that the temperature sensor (1960b) may be near (e.g., adjacent to) the central portion (1955b”) of the body (1956b) and in particular the fluid reservoir contained therein, which holds the biological substance.

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[0243] FIG. 19C is a schematic cross-sectional view of another variation of a container (1900c) for holding a biological substance. Similar to the containers (1900a, 1900b) depicted in FIGS. 19A and 19B, the container (1900c) depicted in FIG. 19C may include top portion (1952c), a body portion (1956c), and a bottom portion (1958c). The body portion (1956c) may include a proximal end (1955c’), a central portion (1955c”) comprising a fluid reservoir (1957c), and a distal end (1955c’”). The top portion (1952c) may include a connector (1954c’) that may be coupled to the connector (1954c’) of the proximal end of the body portion (1956c). The bottom portion (1958c) may include a connector (1954c”) that may be coupled to the connector (1954c”) of the distal end of the body portion (1956c). The bottom portion (1958c) may include a temperature sensor (1960c) with electrical contacts (1964c). The container (1900c) depicted in FIG. 19C may include any of the features described with respect to the containers (1900a, 1900b) depicted in FIGS. 19A and 19B, with like elements similarly numbered. Additionally, the container (1900c) may be received in a temperature control device without an adapter as described with respect to FIGS. 19A and 19B.

[0244] In contrast to the containers (1900a, 1900b) depicted in FIGS. 19A and 19B, the container (1900c) depicted in FIG. 19C may comprise a fluid reservoir (1957c) with a diameter or width that varies along a longitudinal axis of the container (1900c). For example, in some variations, the diameter or width of the fluid reservoir (1957c) may decrease from the distal end (1966c) to the proximal end (1968c) of the fluid reservoir (1957c), while in other variations, the diameter or width of the fluid reservoir (1957c) may increase from the distal end (1966c) to the proximal end (1968c) of the fluid reservoir. In some variations, the diameter or width of the fluid reservoir (1957c) may taper at a fixed angle between the distal end (1966c) of the fluid reservoir (1957c) and the proximal end (1968c) of the fluid reservoir (1957c). The inner diameter or width of the central portion (1955c”) may taper inward (as depicted in FIG. 19C) or outward at a fixed angle from the distal end (1966c) to the proximal end (1968c).

[0245] As noted above, the cross-sectional shape of the fluid reservoir may be different from the general cross-sectional shape of the container. For example, in some variations, the container may have a rectangular cross-sectional shape along a longitudinal axis of the container (i.e., the container may be cylindrical), and the fluid reservoir may have a trapezoidal cross-sectional shape, as depicted in FIG. 19C. In other variations, the fluid reservoir may have a triangular, square or other parallelogram, tear-drop, ovular, or other suitable cross-sectional shape along the longitudinal axis of the container.

[0246] In some variations, the diameter or width of the fluid reservoir (1957c) may vary along a longitudinal axis of the container. For example, in some variations, the fluid reservoir may have a

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 first diameter or width d at a first cross-sectional plane, or along a first portion, of the fluid reservoir (e.g., at the distal end (1966c), along a distal portion) and the fluid reservoir may have a second diameter or width d at a second, different cross-sectional plane, or along a second, second, different portion of the fluid reservoir (e.g., at the proximal end (1968c), along a proximal portion). In some instances, the fluid reservoir may have a third diameter or width d at a third, different cross- sectional plane, or along a third, different portion, of the fluid reservoir, such as, for example, at a midplane of the fluid reservoir along the longitudinal axis of the container, or in a central portion of the fluid reservoir. In some variations, the fluid reservoir may have more than three different diameters or widths.

[0247] In variations in which the fluid reservoir has at least two diameters or width, the fluid reservoir may have a first diameter or width d at the distal end (1966c) of the fluid reservoir (1957c), and a second diameter or width r at a proximal end (1968c) of the fluid reservoir (1957c). In some variations, the first diameter or width d and the second diameter or width r of the fluid reservoir (1957c) may each be between about 1 mm and about 30 mm, including all values and sub- ranges therein. For example, the first diameter or width d and the second diameter or width r of the fluid reservoir (1957c) may each be between about 5 mm and about 15 mm, or between about 7 mm and about 12 mm. In some variations, the first diameter or width d may be greater than the second diameter or width r (as depicted in FIG. 19C), while in other variations the first diameter or width d may be less than the second diameter or width r. For example, the first diameter or width d may be between about 10 mm and about 14 mm, or between about 11 mm and about 13 mm, while the second diameter or width r may be between about 5 mm and about 9 mm, or between about 6 mm and about 8 mm. In one instance, the first diameter or width d may be about 12 mm and the second diameter or width r may be about 7 mm. In some variations, the ratio of the first diameter or width d to the second diameter or width r may be between about 1 : 1 to about 3:1. For example, the ratio of the first diameter or width d to the second diameter or width r may be between about 1.25: 1 and about 2.75: 1, or between about 1.5: 1 and about 2.5: 1.

[0248] It should be appreciated that any of the features of the containers (1900a, 1900b, 1900c) described above with respect to FIGS. 19A, 19B, and 19C may be implemented with any of the other features described with respect to these embodiments, and any combination of the described features may be utilized.

[0249] FIG. 12 is a schematic block diagram of an illustrative variation of a system (1200) configured to control the temperature of a plurality of biological substances. The system (1200) may comprise a plurality of temperature control devices (1210, 1212, 1214), controller (1240), memory (1250), and user interface device (1260). In some variations, the controller (1240) may

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 be coupled to one or more of the temperature control devices (1210, 1212, 1214) over wired and/or wireless communication links (e.g., network, Internet, LAN) as described in more detail herein. Each temperature control device (1210, 1212, 1214) may be coupled to one or more container enclosures (1220, 1222, 1224, 1226, 1228, 1230). The heating algorithm applied to each container may be based on at least the type of biological substance (e.g., blood, vaccine, etc.) and volume of each respective container in the container enclosure (1220, 1222, 1224, 1226, 1228, 1230). For example, a blood bag having a volume of about 500 mL may be thawed at a different rate than a vial of mRNA vaccine having a volume of about 5 mL. In some variations, each temperature control device (1210, 1212, 1214) may comprise a respective user interface (e.g., input device, output device) configured to receive a control signal and provide output to an operator. Similarly, the controller (1240) may be coupled to a user interface device (1260) for remote operation of the temperature control systems (1210, 1212, 1214). In some variations, the controller (1240) may be coupled to a memory (1250) (e.g., database, Electronic Information System).

[0250] In some variations, a system (1200) may comprise a plurality of devices (1210, 1212, 1214) configured to control a temperature of a biological substance. Each device (1210, 1212, 1214) may comprise one or more temperature sensors, such as a temperature sensor configured to measure a temperature of the biological substance and/or a temperature sensor configured to measure a temperature of a thermal conductor, and an identifier of to the biological substance. A controller (1240) may be coupled to the plurality of devices (1210, 1212, 1214). The controller (1240) may comprise a processor and memory (1250), and configured to receive the temperature measurements from one or more of the devices, and control the temperature of one or more of the biological substances using one or more of the devices (1210, 1212, 1214) based on the received temperatures for each respective system. In some variations, one or more of the devices (1210, 1212, 1214) may comprise an agitator (not shown in FIG. 12). The controller (1240) may be configured to control agitation of one or more of the devices (1210, 1212, 1214) based on the received temperature. In some variations, controlling the temperature of the biological substance may comprise thawing the biological substance between down to about -80°C and up to about 37°C using any of the temperature control systems (100, 200, 202, 204, 700, 900) as described herein.

[0251] Methods

[0252] Also described here are methods for controlling a temperature of a biological substance using the systems and devices described herein. The methods of controlling temperature described herein may facilitate rapid thawing and/or cooling of, for example, a vaccine or other low volume biological substance. For example, when thawing, the methods may raise the temperature of a

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 frozen biological substance to a predetermined temperature (e.g., room temperature) using a container enclosure and associated temperature control device comprising a thermal source (e.g., Peltier element). As another example, the methods may monitor the temperature of the biological substance and facilitate identification and tracking of the biological substance (and corresponding container enclosure and container). In some variations, methods may include use of a temperature control device and a consumable container enclosure configured to receive a container having the biological substance to provide a closed-loop temperature feedback system for temperature control. In these variations, the methods may include pre-heating the device and transitioning the biological substance between an ice stage, liquid stage, and standby stage based at least in part on temperature sensor measurements and/or other parameters such as biological substance type, weight, and volume. Additionally or alternatively, methods may include adjusting one or more of the above mentioned parameters based on user input.

[0253] FIG. 13 is a flowchart of an illustrative variation of a method (1300) of controlling a temperature of a biological substance. In some variations, the temperature control device may transition to a pre-heating stage (1302). The pre-heating stage may include a built-in-test (BIT) to initiate a device and determine device characteristics such as temperature. The pre-heating stage may also include setting system parameters. In some variations, pre-heating may comprise maintaining a temperature of one or more elements of the device (e.g., thermal conductor, thermal source) at a predetermined idle temperature when the device is not actively controlling a temperature of a biological substance. The pre-heating stage may, for example, reduce a total time required for thawing a biological substance.

[0254] In some variations, the system (e.g., temperature control device) may transition to an ice stage (1304) upon receiving one or more predetermined command signals to increase the temperature of a biological substance by applying heat using a thermal source. In general, the ice stage corresponds to a condition of the biological substance in which a predetermined fraction of the biological substance is solid (e.g., frozen). In some variations, the system may transition to a liquid stage (1306). The liquid stage corresponds to a condition of the biological substance in which a predetermined fraction of the biological substance is liquid (e.g., thawed).

[0255] In some variations, the transition from ice stage to liquid stage may occur when the temperature of the biological substance (e.g., transition temperature) is between about 0°C and about 15°C, including all values and sub-ranges therein. For instance, the transition temperature of the biological substance may be between about 0°C and about 2°C, between about 0°C and about 4°C, between about 0°C and about 6°C, between about 0°C and about 8°C, between about 0°C and about 10°C, between about 0°C and about 12°C, or between about 0°C and about 14°C.

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For example, the transition temperature of the biological substance may be about 0°C, about 1°C , about 2°C, about 3°C, about 4°C, about 5°C, about 6°C , about 7°C, about 8°C, about 9°C, about 10°C, about 11°C , about 12°C, about 13°C, about 14°C, or about 15°C. In some variations, the transition from ice stage to liquid stage for vaccines such as mRNA vaccines may occur at about 4°C.

[0256] In some variations, the system may heat the biological substance to an endpoint temperature. The container and/or container enclosure holding the biological substance may be removed from the temperature control device after the biological substance has been heated to the endpoint temperature. In some variations, the biological substance may be stored in the system by maintaining the biological substance at the endpoint temperature. In some variations, the endpoint temperature may be the same as the transition temperature. For example, the endpoint temperature may be between about 0°C and about 15°C, including all values and sub-ranges therein. For instance, the endpoint temperature may be between about 0°C and about 2°C, between about 0°C and about 4°C, between about 0°C and about 6°C, between about 0°C and about 8°C, between about 0°C and about 10°C, between about 0°C and about 12°C, or between about 0°C and about 14°C. For example, the endpoint temperature may be about 0°C, about 1°C , about 2°C, about 3°C, about 4°C, about 5°C, about 6°C , about 7°C, about 8°C, about 9°C, about 10°C, about 11°C , about 12°C, about 13°C, about 14°C, or about 15°C.

[0257] In some variations, the biological substance may be maintained (e.g., in the temperature control device) at a temperature between about -80°C and about 37°C, including all values and sub- ranges therein. In some variations, the biological substance may be placed in the temperature control device at a temperature between about -196°C and about 40°C, including all values and sub- ranges therein. For example, the biological substance may be maintained and/or placed in the device at a temperature between about -80°C and about 37°C, between about -60°C and about 30°C , between about -50°C and about 25°C, between about -40°C and about 20°C, between about -30°C and about 15°C, between about -20°C and about 10°C, between about -10°C and about 5°C, between about -5°C and about 4°C, or between about 0°C and about 2°C. In some variations, to transition from the ice stage to the liquid stage, the biological substance may be thawed to a temperature of about 15°C. In some variations, the container with the biological substance may be removed from the temperature control device after the biological substance has been thawed to the end point temperature.

[0258] In some variations, such as, for example, in which the biological substance is a vaccine, (e.g., an mRNA vaccine), one or more of the thermal conductors (e.g., thermal conductors 116, 118 in FIG. 1) and the thermal sources (e.g. thermal sources 112, 114) of a temperature control

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 system (100) may be heated to a temperature of between about 20°C and about 25°C, including all values and sub-ranges therein. For example, the one or more thermal conductors, thermal sources, and/or the biological substance may be heated to a temperature of about 24°C, about 23°C, about 22°C, or about 21°C. As yet another example, 250 mL of plasma may be thawed in less than about 16 minutes and about 1.5 mL to about 5 mL of an mRNA vaccine may be thawed in less than about 3 minutes.

[0259] In some variations, the system may transition to a standby stage (1308). During the standby stage, the temperature of the biological substance may be maintained at the end point temperature. In some variations, the methods described herein may comprise one or more steps described in International Application No. PCT/US2019/031215, filed on May 7, 2019, the entirety of which is hereby incorporated by reference herein.

[0260] Methods may generally comprise placing a container comprising a biological substance within a container enclosure, placing the container enclosure in a chamber of a temperature control device (e.g., thawing device), and activating a heating assembly to thaw or otherwise control the temperature of the biological substance in the container. The heating assembly may be controlled using, for example, temperatures received from one or more temperature sensors aligned with the container holding the biological substance. In some variations, methods may further include positioning the container comprising the biological substance in an adapter.

[0261] FIG. 18 is a flowchart illustrative of an exemplary method (1800) of thawing a biological substance, such as a low volume biological substance. The method may include positioning a container comprising a biological substance in an adapter (1802), positioning the adapter in a chamber of a temperature control device (1804), and activating a heating assembly (1806) of the temperature control device. In some variations, methods may further include positioning the adapter holding the container with the biological substance in a container enclosure, as will be described in more detail below. In some variations, the biological substance may be in a frozen state when the container is positioned within the adapter. The biological substance may comprise one or more of mRNA vaccine, DNA vaccine, exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, and/or cell therapy product. Positioning the container in the adapter may include positioning the container in the adapter with an interference fit. In some variations, positioning the container in the adapter may include positioning the container such that a longitudinal axis of the container may be parallel, about parallel, or transverse (e.g., about perpendicular, or perpendicular) to a longitudinal axis of the adapter. In some variations, positioning the container in the adapter may include positioning the container such that the adapter may overlap at least a portion of the container as described herein. In some variations, positioning

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 the container in the adapter may include positioning an identifier and/or a temperature sensor such that the identifier and/or the temperature sensor may overlie and/or overlap with at least a portion of the container. For example, a temperature sensor integrated into an adapter may be positioned to overlap and/or overlie a center portion of the container. In some variations, positioning the container in the adapter may include positioning the container such that the adapter may hold the container in alignment with one or more temperature sensors and/or identifiers.

[0262] In some variations, methods may also include positioning the container having the biological substance contained there (e.g., in a frozen state) in a container enclosure. In some variations, the container may be positioned within the adapter prior to placement of the container in the container enclosure. In these variations, methods may include placing the adapter holding the container in the container enclosure. In other variations, the container may be placed within the adapter during placement within the container enclosure. In these variations, the adapter may be positioned within the container enclosure before placement of the container within the adapter, such that the container is advanced into the container enclosure and then positioned within the adapter while the adapter is also within the container enclosure.

[0263] In some variations, the container enclosure may comprise a cavity that may be configured to receive the adapter and the container therein and positioning the container within the container enclosure may include positioning the adapter within the cavity of the container enclosure. A length of the adapter may be greater than, equal to, or less than the length of the cavity. Positioning the container within the container enclosure may include positioning the adapter such that a width of the adapter overlaps with at least a portion of a width of the cavity of the container enclosure as described herein.

[0264] Methods may further include positioning the adapter, and in some variations, a container enclosure containing the adapter, into a chamber (e.g., a chamber of a temperature control device). A housing of a temperature control device may enclose the chamber. The container enclosure may be positioned in the chamber such that the enclosed biological substance may be in thermal communication with a heating assembly that may be located within the housing of the temperature control device. For example, the heating assembly may include a thermal source and optionally a thermal conductor, as described in more detail herein. The thermal conductor and/or the adapter may function as a thermal interface between the thermal source and the biological substance.

[0265] The method (1800) further comprises activating the heating assembly to heat and thereby thaw the enclosed biological substance (1804). For example, activating the heating assembly may include activating the thermal source to generate thermal energy. The thermal energy may be transmitted to the biological substance via the adapter and the container. Activating the heating

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 assembly may also include monitoring the temperature of the adapter and/or the temperature of the biological substance via one or more temperature sensors. In variations with two or more temperature sensors, the temperature of the adapter and/or the biological substance may be determined and/or controlled (e.g., by controlling/adjusting the temperature of a thermal source and/or a thermal conductor) based on an average of the temperature measurements from two or more (including all) of the temperature sensors, a change in temperature measurements from one or more (including all) of the temperature sensors, a rate of change in temperature measurement from one or more (including all) of the temperature sensors, a prediction of the rate of change of temperature for one or more (including all) of the temperature sensors, a maximum value of temperature measurement from one or more of (including all) the temperature sensors, a minimum value of temperature measurement from one or more of (including all) the temperature sensors, a combination thereof, and/or the like. In some variations, the method may further include removing the container from the temperature control device after the biological substance reaches an endpoint temperature as described herein. Removing the container may include removing the container from an adapter after the biological substance reaches the endpoint temperature. In some variations, removing the container may include removing the container and/or the adapter from a container enclosure after the biological substance reaches an endpoint temperature. In some variations, removing the container may include removing the container, the adapter, and/or the container enclosure from the chamber after the biological substance reaches an endpoint temperature.

[0266] In some variations, a system and disposable component can be provided, analogous to a razor blade model. In some variations, the disposable component may comprise an overwrap bag configured to house a plasma or blood bag. In some variations, the zip sleeve can include an RFID- enabled label equipped with a temperature sensor for direct temperature measurement of the enclosed plasma or blood. In some variations, the zip sleeve may serve a secondary function to contain leakage in approximately 30% of cases where frozen bags develop cracks, thereby preventing system contamination and obviating the need for complex decontamination processes. [0267] In some variations, the label substrate can include an antenna capable of transmitting and receiving radio-frequency (RF) signals at approximately 13.75 MHz. In some variations, the antenna may also function to absorb electromagnetic energy, converting it into power for the integrated smart chip. In some variations, the integrated smart chip can include both a temperature sensor and memory components. In some variations, the chip may harness RF energy to selfpower, achieving remote communication and power charging simultaneously.

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[0268] In some variations, the temperature sensor embedded within the smart chip may operate effectively in the temperature range of approximately -40°C to +45°C or up to +50°C. In some variations, this temperature range may be extended to accommodate substances used in cell and gene therapy, which may require freezing temperatures as low as -196°C, typically achieved using liquid nitrogen or its vapor at around -150°C. In some variations, extending the sensor capability to span from approximately -196°C to +45°C can enable a single label technology applicable to both blood/plasma and cell/gene therapy substances.

[0269] In some variations, the label technology can transition from a single integrated chip to a small circuit incorporating a thermocouple sensor capable of reliably measuring temperatures at the low end of this extended range. In some variations, the system may incorporate a main computer, touchscreen interface, barcode reader, power supply, battery, and multiple chambers (up to four), although currently only two chambers are implemented.

[0270] In some variations, the chambers may utilize cushions filled with water-based liquid (approximately 350 ml per cushion), with heating elements capable of maintaining temperatures around 37°C. In some variations, heating control may utilize PID (proportional-integral- derivative) control with continuous analog measurement to maintain precise temperature. In some variations, to mitigate the risk of leakage from water-filled cushions, the cushions can be replaced with molded cushions comprising silicone material doped with conductive impurities, such as carbon or ceramic dust, enhancing thermal conductivity by approximately tenfold compared to water.

[0271] In some variations, the chambers may replace simple heating plates with Peltier thermoelectric modules capable of both heating and cooling, depending on the direction of electrical current. In some variations, the system may incorporate load cells for accurately determining the volume and weight of the substance being thawed, allowing for precise adjustment of thawing parameters.

[0272] In some variations, adapters or vial gaps can accommodate vials ranging from approximately 1 ml to 50 ml, maintaining consistent external dimensions while varying internal dimensions to suit the specific volume of the substance. In some variations, vials may incorporate thermocouple-based temperature sensors or be used with adapters containing sensors to avoid sensor damage during freezing. In some variations, hybrid machines can be developed to handle both bagged substances and vial-based substances, ensuring versatility across different medical applications.

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[0273] In some variations, the provisional application may be periodically updated or amended to incorporate new technical advancements, maintaining appropriate priority dates for each disclosure, ensuring comprehensive patent protection.

[0274] In some variations, the system can comprise a platform including a reusable system and a disposable component configured for processing biological samples. In some variations, the disposable component may include a bag such as an overwrap bag configured to receive another container such as a plasma or blood bag, or a vial or other types of containers configured to contain various biomaterials and fluids, such as nucleic acids(e.g., different types of RNAs and DNAs), amino acids, proteins, cells, and other chemicals and biochemicals. In some variations, the disposable bag can measure the temperature of the frozen materials, such as liquids and fluids (e.g., blood, plasma, different solutions, etc.) directly. In some variations, the disposable bag or a container thereof can contain any leaks of the main container that is being overwrapped, e.g., due to cracks in the frozen bag, thus preventing contamination of the biosample, liquid thereon and/or the system. In some variations, the system can eliminate the need for anti-contamination procedures that would otherwise be required, for example, if using a water bath, as contaminated bags can simply be discarded without system contamination.

[0275] In some variations, the disposable bag can incorporate a substrate and an antenna capable of both transmitting and receiving information at a frequency, such as 13.75 MHz. In some variations, the antenna may also absorb electromagnetic energy from RF transmission, allowing remote charging of components embedded within the bag. In some variations, the embedded component can include a smart chip or integrated circuit, which may further include a temperature sensor and memory. In some variations, the temperature sensor can operate in a range from approximately -40°C to 45°C, allowing measurement of the frozen plasma temperature and providing data storage and input/output capabilities.

[0276] In some variations, the system can be adapted to extend the temperature sensing range to between approximately -150°C or -196°C (for liquid nitrogen freezing) and +45°C, thus accommodating the needs of cell and gene therapy applications. In some variations, this extended- range temperature label may be placed on a disposable bag or similar container, which can then be processed by the same machine as blood or plasma samples, thus enabling a single platform for both applications.

[0277] In some variations, the system may use an antenna and associated circuitry for both RFID communication and temperature sensing, where the only suitable sensor for extremely low temperatures may be coupled to. In some variations, the system may include a chamber structure that is configurable to house one, two, or four chambers, each with independent temperature

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 control and sensing. In some variations, the current implementation may support up to two chambers, but the architecture allows scalability.

[0278] In some variations, the temperature control of the chamber can be managed using cushions, which may consist of a plastic frame filled with a liquid such as water in volumes up to 350 mL. In some variations, heating elements may be present behind the cushion, and sensors can be used to maintain and monitor the temperature. In some variations, the cushions can be replaced with those made from contaminated or doped silicone material, such as silicone mixed with ceramic or carbon dust, to provide up to 10 times higher thermal conductivity than water.

[0279] In some variations, the system may incorporate a thermoelectric module, such as a Peltier element, for both heating and cooling, enabling precise thermal regulation. In some variations, the chamber design can be horizontal rather than vertical to allow parallel, squeeze-type motion, and may include two temperature sensors — one for measuring internal temperature and one for safety cutoff at temperatures above 37°C (or another preset value).

[0280] In some variations, the system may accommodate both blood/plasma bags and vials, enabling a hybrid architecture. In some variations, vials of varying internal volume (e.g., from 1 mL up to 50 mL) may be used, with adapters (vial gaps) to fit a fixed external diameter (e.g., 26 mm) to maintain compatibility with the processing chamber. In some variations, vials can be customized with graduated internal volumes or used with a sensor-integrated adapter, depending on whether temperature sensing is required for the specific process.

[0281] In some variations, temperature sensors for these adapters may be placed in the bottom of the adapter and may include either a thermistor (NTC or PTC) or a thermocouple. In some variations, the system may further incorporate a load cell under the chamber or hook to measure the weight of the substance and dynamically adjust processing parameters based on sample volume.

[0282] In some variations, the software can include a proportional-integral-derivative (PID) control algorithm for maintaining temperature by modulating heating and cooling power in response to real-time temperature measurements. In some variations, the frequency and speed of measurement and control may be determined by analog or digital elements, with adaptive averaging or low-pass filtering used to stabilize temperature data and avoid spikes.

[0283] In some variations, the system may include a user interface with a touchscreen, a barcode reader, communication modules, battery backup, and may support up to four chambers for simultaneous sample processing. In some variations, the system can be configured to automatically detect when to discard contaminated components, drain collected liquid, and signal for replacement of disposables.

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[0284] In some variations, the system may enable processing and infusion of samples for both plasma and cell/gene therapy, maintaining end-stage infusion temperatures between 30°C and 37°C as required for clinical safety and cell viability. In some variations, the process may be staged with an "ice-free" stage at 5-6°C, followed by inline warming to the target infusion temperature. [0285] In some variations, the system can accommodate multiple temperature sensor types (e.g., thermistor for continuous measurement and thermocouple for on-off or alarm conditions) to provide redundancy and flexibility for different processing scenarios. In some variations, the hybrid machine may be configured to process either bags or vials, or both, and may include provisions for future expansion or adaptation to new disposable types or sensing technologies. [0286] In some variations, the platform may be used to thaw and warm a standard blood plasma bag for transfusion. In some variations, the base unit includes a main control unit (MCU) and a chamber fitted with a water-based cushion. In some variations, the plasma bag is placed inside a Bag as an example such as an overwrap bag disposable, which is comprised of a thin, leakproof polymer and incorporates a first-generation sensor such as a sensor label. In some variations, this label can include an integrated antenna operating at 13.5 MHz, a microchip with memory, and a temperature sensor capable of measuring from -40°C to +40°C. During operation, the chamber’s heating plate heats the cushion, while temperature readings from the sensor are transmitted wirelessly to the control unit. In some variations, if a crack in the plasma bag is detected by the Bag as an example such as an overwrap bag’s containment, leaked fluid drains into a removable chamber drawer for safe disposal. In some variations, the system maintains the plasma at 37°C until ready for use.

[0287] In some variations, the platform is configured for thawing cryogenically stored cell therapy samples, such as CAR-T or stem cell vials. In some variations, a commercial or proprietary vial containing the cell therapy product is first inserted into an adapter according to some embodiments, which includes a second-generation sensor (as sensor II) such as a sensor label. In some variations, the sensor II contains two or more temperature sensors, such as one thermistor and one thermocouple, which unexpectedly is enabling temperature measurement from -196°C up to +45°C. In some variations, the loaded vial/adapter assembly is frozen and subsequently inserted into a Thawing Chamber Module (TCM) in the base unit. In some variations, the chamber features cushions made from silicone doped with carbon dust for high thermal conductivity, and utilizes a Peltier thermoelectric element for rapid heating and cooling. Real-time temperature data from the sensor II is received wirelessly, which can enable PID-controlled temperature ramping and safe warming to the target temperature for clinical administration.

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[0288] In some variations, the platform is used in a hybrid mode to process both a blood plasma bag and a cell therapy vial simultaneously. One chamber is loaded with a plasma bag inside a bag as an example such as an overwrap bag, while another chamber is loaded with a proprietary cell therapy vial inside an adapter according to some embodiments of the present disclosure . In some variations, both chambers are equipped with doped-silicone cushions and Peltier heating/cooling elements. In some variations, the main control unit receives temperature data wirelessly from both a first-generation sensor (for the bag) and a sensor II (for the vial). In some variations, each chamber independently uses its own PID controller to maintain the appropriate temperature. In some variations, load cells beneath each chamber provide real-time volume information, which the system uses to automatically adjust the heating profile for each sample type.

[0289] In some variations, an adaptor according to some embodiments of the present disclosure can be provided with commercial vials of variable volume.

[0290] In some variations, the system processes commercial vials of differing internal volumes using an adaptor according to some embodiments of the present disclosure. In some variations, the adaptor according to some embodiments of the present disclosure can be constructed from thin, rigid plastic or aluminum and accommodates vials of 1-5 ml, 1-15 ml, or 1-50 ml, maintaining a constant outer diameter for chamber compatibility. In some variations, a commercial vial of a varying size can be inserted into the appropriate adaptor according to some embodiments of the present disclosure, which may contain a bottom-placed thermocouple or sensor II for temperature monitoring. The assembled unit is then placed into the chamber, where a cushion provides conductive heating or cooling, and temperature data is transmitted wirelessly or via direct contact. The platform may agitate the chamber using both vertical and lateral movement for sample mixing as needed.

[0291] In some variations, a commercial bag with integrated overwrap and label can be provided. [0292] In some variations, the system accommodates a commercial cryo-bag that includes an overwrap for additional sterility. In some variations, the cryo-bag can be placed inside a bag as an example such as an overwrap bag that is disposable, which includes a sensor II such as a sensor label on the bottom surface. In some variations, the assembled unit is loaded into the chamber, where thermal contact is made with the cushion and the temperature is maintained according to a user-set program. In some variations, a bag as an example such as an overwrap bag together provide an additional layer of leak protection and facilitate safe thawing of the sample, while the integrated label enables real-time wireless temperature monitoring.

[0293] In some variations, automated thawing with PID and alarm can be provided.

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[0294] In some variations, the system provides automated thawing with advanced PID temperature control and redundant safety sensors. Both thermistor and thermocouple sensors are integrated in the disposable or chamber to provide continuous and threshold monitoring. If the thermocouple detects an over-temperature condition (e.g., above 42°C), the chamber module automatically disables heating and triggers an alarm on the UI. The system logs all temperature data and sensor status for quality assurance.

[0295] In some variations, a proprietary vial with integrated bottom thermocouple can be provided. [0296] In some variations, a proprietary vial is designed with a heat-conductive body, durable caps, and an integrated thermocouple in the bottom cap. In some variations, the thermocouple can be electrically interfaced with a guide tooth, enabling direct temperature measurement via contact with the chamber’s sensor interface. In some variations, this design allows the system to accurately monitor the internal temperature of the sample even at ultra-low temperatures, ensuring optimal warming and minimizing risk to the sample integrity.

[0297] In some variations, the platform can include both a reusable system and a disposable element, such as a combination of a system and replaceable container, where the disposable may be a bag (e.g., an overwrap bag) or vial adapter used for biological sample processing.

[0298] In some variations, the disposable bag, such as different types of overwrap containers, can serve at least two primary functions: directly measuring the temperature of the contents (e.g., frozen plasma) using an integrated temperature sensor, and containing any leaks resulting from cracked or damaged bags, thereby preventing contamination of the system during thawing or warming operations.

[0299] In some variations, the invention provides a disposable containment and sensor system, herein referred to as ZipSleeve™, for the controlled thawing or warming of biological samples, such as blood or plasma. In some variations, the ZipSleeve™ is comprised of a thin amorphic bag constructed from a leakproof polymeric material. The bag has an amorphic shape and is made to be sufficiently thin to allow optimal heat transfer, while maintaining a thickness adequate to prevent leakage and provide mechanical protection. In addition, the bag material is selected to avoid radio-frequency (RF) blocking, enabling wireless data transmission from embedded sensors. [0300] In some variations, the ZipSleeve™ incorporates a sensor label, hereinafter ZipLabel™, which is affixed to the bag and configured to monitor the temperature of the contained sample in real time. The ZipLabel™ includes a yellow substrate supporting an integrated antenna, which operates at approximately 13.5 MHz and is capable of both transmitting and receiving information via RF communication. In some variations, the antenna is also configured to absorb energy from RF transmission for the purpose of wirelessly charging the onboard electronic components. These

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 components may include an integrated circuit (IC) or chip with memory and processor capabilities, as well as at least one temperature sensor.

[0301] In some variations, the temperature sensor built into the ZipLabel™ can operate in a range from approximately -40°C to +45°C, or from -40°C to +40°C as required for clinical thawing applications. The temperature sensor and supporting electronics are configured for two principal functions: (1) wireless communication of temperature data to an external controller, and (2) wireless power harvesting and management. The sensor label may also include one or more domes filled with thermal insulation material (such as Puron or Styrofoam), positioned to allow a high temperature gradient between the ambient environment and the frozen bags or containers.

[0302] In some variations, the system is capable of detecting and containing leaks resulting from damaged or cracked blood/plasma bags during the thawing process. The ZipSleeve™ is designed such that, if a leak occurs, the leakage is contained within the sleeve and does not contaminate the reusable chamber or associated equipment, thereby preventing cross-contamination and simplifying post-use disposal.

[0303] For example, FIG. 20 illustrates an example container as a bag (e.g., ZipSleeve™ Technology) showing bag construction, leak containment, RF antenna integration, and wireless sensor placement in some variations. In some variations, referring to FIG. 20, a disposable bag (Bag as an example such as an overwrap bag) is constructed from a thin, amorphic, leakproof polymer (e.g., EVA, PET, or proprietary blends), dimensioned for optimal heat transfer and configured to accept a standard blood, plasma, or cell/gene therapy bag. An integrated sensor label (e.g., a first generation sensor) is fixed to the surface or bottom, incorporating a 13.5 MHz antenna for RF data transmission and wireless power transfer. The sensor circuitry may include a memory, processor, and temperature sensor, offering real-time, wireless temperature data. The sensor may measure from -40°C to +40°C, and also functions to contain leaks and prevent system contamination . In some variations, showing an amorphic bag constructed from a thin, leakproof material, with integrated sensor label (ZipLabel™) attached to the bag. The figure includes an inset showing the internal layout of the sensor label, including the yellow substrate, the RF antenna loop, the electronic module (comprising memory, processor, and temperature sensor), and at least one dome of thermal insulation material. The schematic also indicates the wireless communication pathway and the functional operation of the sensor label for real-time temperature monitoring.

[0304] For example, FIG. 21 shows schematic illustrating a multi-sensor (e.g., sensor II, e.g., ZipLabel™-II) as a wireless label, dome-shaped thermal insulators, RFID circuitry, and temperature range extension to -196°C in some variations. In some variations, referring to FIG. 21, a second-generation sensor in a label form (, which can a sensor II) includes an expanded sensor

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 array capable of operation from -196°C up to +45°C, with at least one primary temperature sensor and one or more secondary sensors. In some variations, as shown in fig. 21, the sensor II module (e.g., ZipLabel-II) provides a wireless temperature-sensing platform configured for integration with biological containers that are subjected to extreme thermal conditions, including cryogenic freezing and physiological warming. The sensor II comprises one or more temperature sensors capable of operating across a wide measurement range of approximately -150 °C to +45 °C. This enables precise thermal monitoring of both deep-frozen samples — such as cell and gene therapy materials stored in liquid nitrogen vapor or liquid — and biological substances like blood and plasma that require warm delivery near body temperature.

[0305] In some variations, sensor II includes an antenna coil encircling a microelectronic substrate. This antenna is operative to receive and transmit data using radio-frequency identification (RFID) communication, and simultaneously harvests power via inductive coupling from an external RF reader, typically operating at 13.75 MHz. The harvested RF energy eliminates the need for onboard batteries and supplies power to an integrated circuit that incorporates memory, temperature sensing logic, and a data interface.

[0306] In certain configurations, the sensor II includes two separate temperature sensing elements. The first is a thermocouple (e.g., Type T or Type C) that provides accurate thermal readings in cryogenic conditions, such as -150 °C to -196 °C. The second may be a thermistor, providing high-resolution thermal monitoring in the moderate range of approximately 0 °C to +45 °C. These sensors are thermally coupled to one or more insulation domes that may be filled with materials such as Puron™, styrofoam, or other thermal insulators. The domes serve to maintain a thermal gradient across the sensor region while minimizing heat exchange with the external environment, thus preserving sensor accuracy and signal stability during freeze-thaw cycles. In some embodiments, the sensor II module is embedded in or affixed to a disposable sleeve or adapter — such as a ZipSleeve or a ZipVial adapter — that houses a blood bag, plasma container, or CGT vial. In some variations, the sensor II module supports monitoring for (i) blood and plasma units ranging from approximately 100 mL to 500 mL, and (ii) cell and gene therapy containers ranging from 50 mL to 100 mL. Despite differences in starting conditions — ranging from room temperature to cryogenic freezing — both product types are typically administered at or near 37 °C. The sensor II module enables continuous monitoring from frozen storage through warming and final delivery. The sensor II is designed for compatibility with a multi-purpose processing machine configured to accommodate both vials and bags. This platform includes a control system, user interface, chamber hardware, and wireless reader module. By standardizing the sensing interface and providing extended-range thermal detection, sensor II facilitates interoperable use across

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 workflows that otherwise require distinct and dedicated equipment. In various implementations, the system may also incorporate weighing modules (e.g., load cells) to dynamically assess sample volume and adjust thermal profiles accordingly. Through its extended thermal range, wireless and battery-free operation, and modular physical integration, sensor II provides a robust and scalable solution for real-time temperature tracking of biologies across a range of clinical applications. Whether used for thawing cryopreserved cell therapies or warming transfusable plasma, the system ensures accurate control and traceability while simplifying hardware integration and reducing contamination risks.

[0307] FIG. 22A illustrates an embodiment of a container (e.g., ZipSleeve™-B) configuration comprising a sensor II (ZipLabel™-II) integrated into the lower portion of the sleeve in some variations. This embodiment is optimized for accommodating frozen biologies such as blood or plasma bags and is designed to measure thermal profiles during thawing, storage, or warming. The sensor II is enclosed within or adjacent to a thermal insulation dome to provide measurement stability in the presence of steep thermal gradients.

[0308] FIG. 22B illustrates an embodiment of a container (e.g., a ZipSleeve™-V) configuration adapted for vials in some variations. This embodiment includes an internal funnel structure that guides a vial to align precisely with the sensor II embedded in the sleeve. The configuration ensures consistent thermal contact and measurement regardless of vial positioning. The sensor II supports extended-range temperature measurement and integrates wireless power and communication via RFID.rnal funnel structure that guides a vial to align precisely with the sensor II embedded in the sleeve. The configuration ensures consistent thermal contact and measurement regardless of vial positioning. The sensor II supports extended-range temperature measurement and integrates wireless power and communication funnel structure that guides a vial to align precisely with the sensor II embedded in the sleeve.

[0309] FIG. 22C shows an embodiment of a container (e.g., a ZipSleeve™-S) configuration, similar in purpose to the V variant in some variations, with a different funnel geometry and an integrated retention structure or insert (shown in red) that maintains vial alignment against the sensor II. This embodiment is configured for single-use or variable vial volumes and maintains high thermal conductivity and sensing fidelity.

[0310] In some variations, as illustrated in FIGS. 22A to 22C, the disclosed system comprises a modular series of container sleeves each configured to house a biological payload and integrate a second-generation temperature sensing label, herein referred to as sensor II (e.g., ZipLabel™-II). Sensor II is a wireless, battery-free, RFID-enabled sensing device operable across a temperature range from approximately -196°C to +45°C, depending on the configuration.

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[0311] As shown in FIG. 22A, the ZipSleeve™-B variation is configured for blood or plasma bags and includes one or more thermal insulation domes surrounding sensor II. The sensor is embedded at the base of the sleeve, positioned for direct contact with the lowest region of the bag, where freezing or thawing initiates. The dome may be filled with thermal insulation material such as Puron™ or Styrofoam™ to buffer environmental heat exchange and preserve accurate temperature readings.

[0312] In some variations, as illustrated in FIG. 22B, the ZipSleeve™-V configuration includes an internal guiding funnel structure designed to receive vials of variable volume. The funnel centers the vial and maintains alignment of its bottom surface with the embedded sensor II. This alignment ensures that the thermal profile of the vial contents is consistently and accurately measured, regardless of operator handling. The sensor II remains embedded within the insulation dome at the base of the funnel. Wireless sensing, inductive charging, and bi-directional data exchange are achieved via the same RFID interface as in other embodiments.

[0313] In further variations, as depicted in FIG. 22C, the ZipSleeve™-S configuration is similarly adapted for vial use but may include a fixed cavity or bracket insert to secure and thermally isolate vials. This bracket, shown in red, may be fabricated from an elastomeric or semi-rigid polymer that holds the vial in place during transport, thawing, or warming. The bracket further ensures that the vial base maintains direct thermal contact with sensor II. This configuration is particularly useful for automated systems or workflows requiring reproducible vial alignment and minimal human intervention. Each configuration in FIG. 22A-22C provides environmental buffering and structural containment while allowing high-resolution temperature measurement at the point of thermal exchange. The sensor II is universally compatible across all three sleeve types and provides continuous, real-time, and contact-based thermal monitoring from cryogenic storage through active thawing to final clinical use. These designs enable multi-format handling with a standardized sensing approach, facilitating manufacturing efficiency and clinical safety.

[0314] FIG. 23A illustrates an embodiment of a chamber concept comprising two vertically oriented heating cushions, each filled with approximately 300 mL of sealed, water-based gel in some variations. The heating cushions are positioned along opposite interior walls of a tiltable enclosure and are affixed to heating plates regulated by independent temperature sensors. The system incorporates RFID-based sample identification, a chamber module controller (CMC), and dual temperature sensors (thermocouple and thermistor, labeled TC + NTC PUCK) for active control and safety shutoff. The chamber supports tilt-based agitation and is designed to accommodate an encased plasma bag.

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[0315] FIG. 23B shows an embodiment of the Gen II chamber system incorporating advanced cushions formed from thermally conductive silicone doped with carbon or ceramic particles in some variations. These cushions are affixed to both heating plates and thermoelectric (TE) modules, enabling both heating and cooling with precise control to maintain a constant temperature (e.g., 37 °C). The chamber features load cells mounted on hooks for automatic weight-based identification of frozen plasma bag mass, allowing dynamic thawing profiles. The chamber also integrates RFID readers, horizontal agitation via a motorized retraction assembly, and upgraded control systems. The TE modules replace traditional resistive plates and are regulated through both thermistor and thermocouple inputs for real-time safety and performance monitoring.

[0316] FIG. 23 C provides a detailed sectional view of a Gen II cushion assembly compatible with the chamber shown in FIG. 23B in some variations. The cushion body is fabricated from multidurometer silicone (e.g., Shore 5/10 and 80), molded around integrated temperature sensors. These sensors are housed in a thermally isolated tunnel located approximately midplane along the vertical axis of the cushion. The cushion is configured to receive heat and/or cooling from an affixed TE module and to transfer that thermal energy efficiently to an inserted sample. Mechanical dimensions, mounting points, and insulation profiles are shown to illustrate integration with standard chamber architectures. The use of impure silicone significantly increases heat conductivity relative to water-based gels, while also reducing fluid leakage risk.

[0317] In some variations, as shown in FIGS. 23 A-23C, the disclosed device comprises a thermal conditioning chamber configured to house biological samples such as plasma bags within a ZipSleeve™ format and to modulate sample temperature through a pair of opposing heating cushions. The Gen I architecture, illustrated in FIG. 23A, uses gel-based cushions heated via planar resistive elements. Each heating element is thermally coupled to a cushion and is independently controlled by a chamber module controller. A tilt actuator facilitates mechanical agitation. Temperature sensing is provided by a combination of thermocouple and NTC thermistor (PUCK configuration), and safety shutdown is triggered above a defined threshold (e.g., 42 °C). This architecture is suitable for thawing 250 mL plasma bags within 15 minutes and 450 mL bags within 30 minutes (±20%).

[0318] In more advanced embodiments, as shown in FIG. 23B, the Gen II architecture replaces the gel cushions with cushions molded from impure silicone doped with thermally conductive particulates, such as carbon or ceramic. These cushions are affixed to both a heating plate and a Peltier-based thermoelectric (TE) module, which allows for both heating and active cooling. The cushion assembly maintains a target thermal environment (e.g., 37 °C), while minimizing

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 overshoot and energy waste. Load cells at the top of the chamber determine sample mass, allowing dynamic tuning of thermal input during thawing. The agitation mechanism is implemented as a horizontal motorized retraction system, replacing the earlier tilt-based motion, and enhancing mechanical reliability and precision.

[0319] As illustrated in FIG. 23 C, each Gen II cushion includes a central tunnel for embedding sensor assemblies. The cushion structure comprises multiple silicone durometers, where the external wall material provides structural rigidity, and the inner surfaces ensure compliant contact with the sample. This configuration allows for enhanced thermal transfer and durability. In some implementations, the thermocouple is used for binary safety control (on/off), while the NTC thermistor provides continuous feedback for PID regulation. The sensors are encapsulated in thermally conductive but electrically insulated materials and are shielded from environmental interference. The design facilitates easy replacement, low maintenance, and compatibility with existing ZipSleeve™ configurations across multiple formats. mal wall material provides structural rigidity, and the inner surfaces ensure compliant contact with the sample. This configuration allows for enhanced thermal transfer and durability. In some implementations, the thermocouple is used for binary safety control (on/off), while the NTC thermistor provides continual wall material provides structural rigidity, and the inner surfaces ensure compliant contact with the sample.

[0320] In some variations, the chamber may include heating cushions comprising a plastic frame on two sides and filled with approximately 350 mL of fluid. In some variations, the cushions can be positioned adjacent to heating plates that deliver thermal energy for warming biological containers. In some variations, each heating plate may be coupled to a thermoelectric module, such as a Peltier unit, which can provide both heating and cooling functions depending on the direction of electrical current.

[0321] In some variations, the Peltier module can operate on the principle that current flowing in one direction causes one side of the unit to cool while the opposite side heats, and reversing the current reverses the thermal flow. In some variations, this allows the chamber to maintain a stable temperature (e.g., 37 °C) during warming procedures. In some variations, the cushions may be thermally regulated using a PID-based control loop (Control Rate Point, CRP), which can provide analog, continuous sampling and real-time feedback to adjust temperature with high precision.

[0322] In some variations, the system may operate at approximately 52 Hz frequency, allowing rapid thermal modulation during the thawing process. In some variations, the control system can be configured to prevent temperature overshoot or undershoot, maintaining a tight tolerance around the setpoint.

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[0323] In some variations, each cushion may be equipped with two types of temperature sensors. In some variations, a first sensor can be a thermistor, which may be either a positive or negative coefficient device that changes resistance based on temperature. In some variations, this thermistor can provide accurate continuous measurement over a limited range. In some variations, a second sensor may be a thermocouple, formed from two dissimilar metals joined together, which can serve both as a precise temperature sensor and as a binary trigger for events such as overheating alerts (e.g., cutoff above 42 °C).

[0324] In some variations, the system may include a drain port and liquid collection drawer positioned below the chamber floor. In some variations, this container drawer can collect fluid in the event of cushion rupture or leak, allowing safe removal and minimizing risk of contamination or device damage.

[0325] In some variations, the developer may seek to replace the water-gel-based cushion technology with cushions molded from contaminated silicone. In some variations, this silicone can be doped with heat-conductive additives such as carbon or ceramic dust. In some variations, the doped silicone may exhibit thermal conductivity in the range of 10 W/m K, which is 10-20 times higher than water gel (approximately 0.59 W/m K). In some variations, this higher conductivity can reduce the time required to transfer thermal energy between the heating elements and the biological sample.

[0326] In some variations, a distinction can be drawn between heat conductivity and heat capacity: while the doped silicone may heat and cool more quickly, the overall thermal inertia may differ from water-based materials. In some variations, the system may be configured to compensate for this through continuous PID control and real-time sensing. In some variations, the chamber mechanism may shift from a vertical tilting motion to a horizontal parallel movement. In some variations, this can improve uniformity of heat distribution and reduce mechanical complexity. In some variations, this horizontal motion may allow for integration with load cells that measure the mass of frozen samples and automatically adjust thawing profiles accordingly. In some variations, the provisional application may describe earlier cushion-based chamber architectures without referencing the integration of the extended-range sensor (sensor II). In some variations, inclusion of the sensor II can enable enhanced performance, broader temperature sensing range (e.g., -196 °C to +45 °C), and wireless monitoring throughout the thawing process.

[0327] FIG. 24A illustrates a simplified cryo-freeze to thawing workflow for cell and gene therapy substances prepared in standard commercial vials, in some variations. In some variations, the therapeutic substance can be filled into a vial ranging from approximately 1 mL to 50 mL in volume. In some variations, the vial may be placed into a modular adapter configured to

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 standardize outer dimensions regardless of internal volume variation. In some variations, a temperature sensor may be affixed to or integrated at the bottom of the adapter to enable direct monitoring of the thermal state during storage and thawing. In some variations, the assembled unit can be removed from cryogenic storage and inserted into a thawing device designed to accept vial- based payloads. In some variations, the device may provide controlled heating, real-time sensor feedback, and agitation functions to raise the substance temperature to a clinically acceptable range, such as 37 °C.

[0328] FIG. 24B illustrates a variant of the process supporting multiple vial formats and container geometries, in some variations. In some variations, a patient-specific therapeutic substance can be placed in either a commercial or proprietary vial, and each may be fitted into a standardized adapter unit. In some variations, this adapter can accept various vial shapes while maintaining a uniform interface for the thawing device. In some variations, the adapter may include an embedded or surface-mounted sensor located at its lower portion. In some variations, the frozen unit can be thawed using a thermal control system that accommodates the adapter geometry. In some variations, the system may perform heating cycles dynamically adjusted to the vial’s shape and volume, enabling compatibility across a wide range of clinical packaging formats. In some variations, this configuration allows facilities to maintain workflow uniformity even when the original containers exhibit structural variation.

[0329] FIG. 24C demonstrates an integrated dual-format thawing procedure that supports both vials and cryogenic bags, in some variations. In some variations, the frozen therapeutic payload can be housed in a container selected according to clinical needs — either a bag or a vial. In some variations, a compatible thermal sleeve or adapter can be used to interface the frozen container with the temperature control system. In some variations, sleeves or adapters may be equipped with embedded temperature sensors to enable direct and continuous thermal monitoring. In some variations, the thawing process may include gradual warming via heated cushions or thermoelectric elements, assisted by sensor-based feedback control to prevent thermal overshoot. In some variations, once the thawed product reaches the target temperature range (e.g., between 15 °C and 37 °C), it can be extracted and transferred for further clinical or processing steps, such as cell reconstitution or infusion preparation.

[0330] FIG. 25 illustrates a modular thawing chamber architecture designed to accommodate a standardized outer-diameter well with internal adapters for variable vial formats, in some variations. In some variations, the chamber may utilize a fixed well size and rely on gap-filling adapters to accommodate vial volumes ranging from approximately 5 mL to 50 mL. In some variations, these adapters can maintain thermal alignment while standardizing the geometry of

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 non-uniform vial containers. In some variations, the adapter (e.g., shown as ZipVial 2) may include an embedded temperature sensor affixed to its bottom surface, configured to align with an RFID reader embedded at the base of the chamber. In some variations, each chamber well may incorporate at least two thermoelectric (TE) modules (e.g., Peltier elements), positioned symmetrically on opposite walls. In some variations, these elements can be controlled by one or more temperature sensors positioned within the wall structure and connected to a central control unit. In some variations, the Peltier modules may enable both active heating and cooling to maintain precise temperature control around the inserted vial. In some variations, each heating element may include an independent sensor for overheating protection. In some variations, the chamber may include a vertical lift or elevator that enables rapid insertion and removal of the vial assembly. In some variations, the lift can also rotate left and right by approximately ±30°, enabling mechanical agitation or sample mixing during thermal processing. In some variations, the well has a nominal inner diameter of approximately 27 ± 0.5 mm and a depth of approximately 120 ± 0.5 mm, allowing compatibility with vials up to 50 mL. In some variations, the top of the lift may include an integrated load cell mounted on a printed circuit board (PCB) for real-time weight measurement. In some variations, the load cell assembly may include front-end electronics and a connector routed through the hollow central axis of the lift. In some variations, this configuration enables dynamic sensing of frozen sample mass for adaptive thermal profile selection. In some variations, the system allows for precise thermal conditioning of CGT vials with minimal manual intervention and supports automated feedback based on RFID sensor input and real-time temperature and mass data.

[0331] FIG. 26 illustrates a thermal chamber configuration utilizing a fixed-diameter cylindrical well with thermoelectric elements and multiple temperature sensors, in some variations. In some variations, the chamber may support vials of various sizes (e.g., 5 mL, 15 mL, 50 mL) by incorporating adapters that match vial profiles to a standardized outer diameter. In some variations, the chamber wall may include at least two thermoelectric modules (e.g., Peltier devices) and at least one wall-mounted temperature sensor for heating and cooling control. In some variations, each thermoelectric module can be equipped with a separate overheating protection sensor. In some variations, three or more thermocouple sensors can be positioned vertically on the well wall to directly contact the inserted adapter (e.g., ZipVial or VialGap) for real-time thawed substance monitoring. In some variations, the internal diameter of the well may be approximately 27 ± 0.5 mm, with a depth of approximately 120 ± 0.5 mm, which can accommodate vial volumes up to 50 mL. In some variations, a motorized lift system can lower and raise the vial assembly, enabling fast insertion and extraction. In some variations, the lift can

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 also rotate ±30° for sample agitation or mixing during thawing. In some variations, the lift assembly may contain an interfacing plate (PCB1) at its top surface, which includes a load cell mounted to the front side and a connector routed through the lift axis. In some variations, this allows real-time mass detection of the inserted vial and may be used to adjust thawing profiles based on the frozen content's weight. In some variations, the well may be constructed from aluminum or silicone material, and the adapter may be designed to ensure thermal continuity between the vial contents and the surrounding thermoelectric modules.

[0332] FIG. 27A illustrates a sectional view of a thermal well containing a vertically aligned set of temperature sensors and an integrated lift mechanism, in some variations. In some variations, the thermal well may include a cylindrical cavity, with temperature sensors (e.g., thermocouples or thermistors) embedded along the wall to monitor the thawing profile at various vertical locations. In some variations, a lift mechanism may be located beneath the well and include a hollow shaft that allows electrical or signal routing. In some variations, the lift can provide vertical movement to position the vial for loading and unloading and can also support lateral oscillation (e.g., ±30° rotation) for sample agitation or mixing during thawing.

[0333] FIG. 27B depicts the load position of the system, in some variations. In some variations, the lift may be raised upward to bring the vial into alignment with the thermal well opening, allowing manual or automated insertion. In some variations, once the vial is inserted, the lift may lower it into the thermally regulated region between opposing thermoelectric modules (e.g., Peltier devices). In some variations, this loading motion facilitates rapid exchange of sample containers with minimal thermal disruption.

[0334] FIG. 27C shows the home position, in some variations. In some variations, the vial and adapter assembly (e.g., Zip Vial) is fully seated in the well, with the lift returned to its default position. In some variations, this position establishes contact between the bottom of the adapter and the load cell mounted to the interfacing plate within the lift. In some variations, the load cell can detect the mass of the inserted frozen sample and enable the control system to determine an appropriate thawing profile. In some variations, this configuration ensures that both vertical alignment and sensor contact are optimized for real-time thermal feedback during processing.

[0335] FIG. 28 illustrates multiple structural variations of a cryogenic-compatible vial device with outer diameter, configured for sterile use in cell and gene therapy workflows, in some variations. In some variations, the vial may be constructed as a sterile, disposable container optionally incorporating an embedded temperature sensor for thermal tracking. In some variations, the vial can accommodate a wide volume range, from approximately 1.0 mL to 50 mL, while maintaining a standardized outer diameter compatible with an external thermal adapter or thawing device. In

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 some variations, the vial is suitable for cryogenic storage at temperatures down to -196 °C and controlled thawing up to approximately 37 °C.

[0336] In some variations, the vial may include a snap-fit or press-fit top cap, which may contain a septum and O-ring to maintain sterility. In some variations, filling or emptying of the vial may occur through both top and bottom ports, enabling flexible sterile fluid handling. In some variations, connection to syringes or closed-loop systems may be achieved using a Luer- compatible port. In some variations, the vial body may be constructed from high-performance polymers such as PTFE, PF A, PVC, PE, ABS, or PVDF, chosen for their thermal durability and chemical compatibility at extremely low temperatures.

[0337] In some variations, the vial may be integrated into a modular system in which the fixed outer diameter enables direct compatibility with a standard thermal interface device, eliminating the need for custom chamber reconfiguration. In some variations, fill volume markings may be molded or printed onto the inner wall to facilitate dosing and monitoring. In some variations, each structural variation shown may be optimized for a particular fill method, connector type, or downstream integration, allowing the same outer form factor to be used across a range of CGT applications.

[0338] FIG. 29 illustrates a modular gapping system used to adapt commercial vial diameters to a fixed-diameter thermal well, in some variations. In some variations, the system includes a family of sterile, thermally conductive sleeves — referred to as gap adapters — that fit between commercial vials and a standardized chamber wall. In some variations, the adapters may be open or closed at the bottom, and constructed from aluminum or rigid plastic with good heat transfer characteristics. In some variations, different adapter sizes may be implemented to accommodate a range of vial formats, such as an adaptor configured for vial volumes ranging from 1 mL to 5 mL, with an inner diameter of approximately 8 mm, an adaptor configured for vial volumes from 1 mL to 15 mL, with an inner diameter of approximately 13 mm, and an adaptor configured for vial volumes up to 50 mL, with an inner diameter of approximately 24 mm.

[0339] In some variations, all three adapters may maintain a common outer diameter of approximately 26 mm and a length of approximately 120 mm to match the fixed well dimensions. In some variations, this gapping system allows different vial sizes to be used within a single thawing chamber architecture without requiring modifications to the chamber hardware. In some variations, the high thermal conductivity of the adapter materials supports efficient heat transfer between the thermoelectric elements and the sample vial, improving thawing accuracy and speed. [0340] FIG. 30 illustrates a disposable chamber structure configured for thawing biological vials to temperatures up to 37 °C, using water gel or silicone-based thermal transfer materials, in some

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 variations. In some variations, the chamber may be constructed with two vertical thermal walls filled with either water/gel or silicone doped with conductive additives such as silver, graphene, carbon nanotubes, or ceramic dust. In some variations, the use of doped silicone enhances thermal conductivity for more efficient and uniform thawing. In some variations, the vial is positioned between the two thermal elements and seated within a cylindrical adapter — referred to as a vial adaptor or vial gap — which standardizes the interface geometry. In some variations, this adaptor ensures compatibility with a fixed-diameter chamber well, regardless of the original vial size. In some variations, a second-generation sensor (label II) is mounted at the bottom of the adaptor to enable real-time temperature tracking and RFID-based monitoring throughout the thawing cycle. [0341] In some variations, thermistors may be embedded in the thermal cushion structure to measure and regulate wall temperature. In some variations, the chamber may be constructed with a modular design to allow for disposable use while maintaining sterility and process consistency across batches.

[0342] FIG. 31 illustrates a thawing chamber module (TCM) configured for thermal processing of cryogenically stored vials using a disposable adapter system and Peltier-based thermoelectric control, in some variations. In some variations, the chamber may include a cylindrical aluminum well surrounded on two or more sides by Peltier elements capable of active heating and cooling. In some variations, the chamber may be designed to process samples across a wide thawing range, from < -196 °C up to 4-8 °C and/or 37 °C. In some variations, a vial is inserted into a disposable thermal adapter (e.g., ZipVial 2) that includes a fixed outer diameter and standardized height. In some variations, the bottom of the adapter may include an embedded label II temperature sensor, which communicates with an RFID reader located at the bottom of the chamber for real-time thermal monitoring. In some variations, a thermistor may also be embedded in the chamber wall or base to control feedback for the Peltier elements. In some variations, the chamber well includes fixed and movable sides to ensure proper alignment and thermal contact. In some variations, the internal diameter (d2) is fixed and set larger than the inserted vial diameter (dl), to ensure snug yet adaptable thermal coupling. In some variations, the vial and adapter assembly can be inserted using an elevator mechanism that moves vertically to position the sample and retracts following thermal processing. In some variations, this configuration provides modular compatibility with multiple vial types and volumes while maintaining efficient thawing through tight sensor integration and symmetric thermoelectric control.

[0343] FIG. 32A illustrates a cryo-compatible vial structure incorporating a bottom-mounted thermocouple for precise temperature sensing, in some variations. In some variations, the vial body may be made of a thermally conductive plastic such as PTFE, PCTFE, or FEP, with a

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 threaded interface for attaching top and bottom caps. In some variations, the top cap may optionally include a septum or luer-lock for sterile fluid access, and the bottom cap may house the thermocouple interface, which aligns via a mechanical guide tooth. In some variations, the thermocouple may be electrically connected through contacts embedded within the bottom cap, allowing closed-loop communication with a reader or control circuit during thermal processing.

[0344] In some variations, the vial body may be cylindrical or square in cross-section and have a total capacity of different volumes such as approximately 30 mL plus 0.75 mL for the lower chamber extension. In some variations, the thermocouple may offer high-precision sensing over a range from -200 °C to +50 °C, and more than one sensor may be included for redundancy or vertical distribution along the container wall.

[0345] FIG. 32B shows a variant with similar material construction and thermal profile but with a modified tapering vial body and bottom housing for enhanced heat transfer and sensor contact. In some variations, this configuration may include tapping or other mechanical interfaces for downstream docking. In some variations, both top and bottom caps are durable between -200 °C and +50 °C and form tight seals under cryogenic conditions.

NON-LIMITING EMBODIMENTS

[0346] The present disclosure is also described by way of the following non-limiting embodiments. However, the use of these and other embodiments anywhere in the specification is illustrative only and in no way limits the scope and meaning of the disclosure. Likewise, the disclosure is not limited to any particular preferred embodiment or aspect described herein. Indeed, modifications and variations may be apparent to those skilled in the art upon reading this specification, and such variations can be made without departing from the disclosure in spirit or in scope.

1. A container enclosure for use in thawing a biological substance comprising: a cavity configured to receive a container comprising the biological substance; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing.

2. A container enclosure for use in thawing a biological substance comprising: a cavity configured to receive a container comprising the biological substance; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing; and an identifier for the biological substance.

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3. A container enclosure for use in thawing a biological substance comprising: a cavity configured to receive a container comprising the biological substance, wherein the container has a volume of up to about 50 mL; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing; and an identifier for the biological substance.

4. The enclosure of any of Embodiment(s) 1-3, further comprising a ratio of a diameter of the container to a width of the cavity between about 1 : 1 and about 5:32.

5. The enclosure of any of Embodiment(s) 1-4, wherein the biological substance comprises one or more of an mRNA vaccine, DNA vaccine, exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, and cell therapy product.

6. The enclosure of any of Embodiment(s) 1-5, wherein the cell therapy product comprises one or more of stem cells and T-cells.

7. The enclosure of any of Embodiment(s) 2-6, wherein the identifier receives the temperature measurement from the temperature sensor.

8. The enclosure of any of Embodiment(s) 1-7, wherein the cavity comprises a shape configured to funnel the container to a predetermined position and location within the enclosure.

9. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -80°C.

10. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -80°C or lower.

11. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -100°C or lower.

12. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -120°C or lower.

13. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -140°C or lower.

14. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -150°C or lower.

15. The enclosure of any of Embodiment(s) 1-8, wherein the container enclosure is configured to receive a container with a temperature of down to about -190°C or lower.

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16. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -100°C or lower.

17. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -120°C or lower.

18. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -140°C or lower.

19. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -150°C or lower.

20. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -190°C or lower.

21. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -100°C or lower and up to about 25 °C or higher.

22. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -120°C or lower and up to about 30 °C or higher.

23. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -140°C or lower and up to about 35 °C or higher r.

24. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -150°C or lower and up to about 35 °C or higher.

25. The enclosure of any of Embodiment(s) 1-15, wherein the temperature sensor is configured to measure a temperature of down to about -190°C or lower and up to about 45 °C or higher.

26. The enclosure of any of Embodiment(s) 1-25, wherein the temperature sensor comprises a plurality of temperature sensors.

27. The enclosure of any of Embodiment(s) 1-26, wherein the temperature sensor comprises a plurality of temperature sub-sensors.

28. The enclosure of any of Embodiment(s) 1-27, wherein the temperature sensor comprises a plurality of temperature sensors respectively configured to measure different temperature ranges.

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29. The enclosure of any of Embodiment(s) 1-28, wherein the temperature sensor comprises a thermocouple sensor, thermistor sensor, IR sensor, RFID-integrated sensor, and a combination thereof.

30. The enclosure of any of Embodiment(s) 1-29, wherein the temperature sensor comprises a thermistor and a thermocouple.

31. The enclosure of any of Embodiment(s) 1-30, wherein the temperature measured by the temperature sensor is processed to provide complementary temperature monitoring and safety cutoff.

32. The enclosure of any of Embodiment(s) 1-31, further comprising an antenna configured for both energy harvesting and RF communication.

33. The enclosure of any of Embodiment(s) 1-32, wherein the container is selected from a group consisting of: a commercial cryogenic vial, a disposable cryo-vial with fixed outer dimensions, and a custom vial having variable inner volume.

34. The enclosure of any of Embodiment(s) 1-33, wherein the container comprises one or more of a vial and cuvette.

35. The enclosure of any of Embodiment(s) 1-34, further comprising a gap adapter configured to receive the container and maintain a fixed outer diameter.

36. The enclosure of any of Embodiment(s) 35, wherein the gap adapter comprises a rigid body with high thermal conductivity, fabricated from aluminum, PTFE, or doped silicone.

37. The enclosure of any of Embodiment(s) 35-36, wherein the temperature sensor is affixed to the base of the gap adapter, and aligned with an RFID reader embedded in a chamber base.

38. The enclosure of any of Embodiment(s) 1-37, wherein the enclosure comprises a thermally conductive material configured to transfer thermal energy to regulate a temperature of the biological substance.

39. The enclosure of any of Embodiment(s) 1-38, wherein the enclosure is configured for single use.

40. A container enclosure for use in thawing a biological substance comprising: an adapter configured to receive a container comprising the biological substance; and a housing comprising: a thermal conductor defining a cavity configured to receive the adapter; and a temperature sensor configured to measure the temperature of the biological substance.

41. A container enclosure for use in thawing a biological substance comprising:

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 an adapter configured to receive a container comprising the biological substance; and a housing comprising: a thermal conductor defining a cavity configured to receive the adapter; a temperature sensor configured to measure the temperature of the biological substance; and an identifier for the biological substance.

42. A system comprising the container enclosure of any of Embodiment s) 1-41, further comprising a temperature control device comprising a chamber and a thermal source, wherein the temperature control device is configured to receive the container enclosure in the chamber and the thermal source is configured to control the temperature of the biological substance.

43. The system of any of Embodiment s) 42, further comprising a controller including a processor and memory, the controller configured to control the thermal source.

44. The system of any of Embodiment s) 42-43, wherein the thermal source comprises a Peltier element.

45. The system of any of Embodiment s) 42-44, wherein the temperature control device further comprises an agitator configured to agitate the container enclosure.

46. The system of any of Embodiment s) 42-45, wherein the temperature control device further comprises a reader configured to receive one or more of biological substance data and the measured temperature from one or more of the identifier and the temperature sensor.

47. The system of any of Embodiment s) 42-46, wherein the system is configured to perform temperature-controlled thawing based on approximately real-time wireless monitoring during thawing.

48. The system of any of Embodiment s) 42-47 wherein the system is configured to perform temperature-controlled thawing from cryogenic to physiologic range based on approximately real-time wireless monitoring during thawing.

49. The system of any of Embodiment s) 42-48, further comprising a thermal chamber comprising a thermal conductor, wherein the thermal chamber comprises a pair of opposed thermoelectric modules for simultaneous heating and cooling.

50. The system of any of Embodiment s) 42-49, wherein the thermal chamber further comprises at least one embedded thermistor and at least one thermocouple.

51. The system of any of Embodiment s) 49, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling.

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52. The system of any of Embodiment s) 49, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling at frequencies up to 50 Hz.

53. The system of any of Embodiment s) 42-52, wherein the temperature control device operates based on a filtering algorithm configured to perform adaptive averaging on temperature readings to reduce noise.

54. The system of any of Embodiment s) 42-53, wherein the system includes a thermal protection logic that disconnects power if the sensed temperature exceeds a threshold.

55. The system of any of Embodiment s) 42-54, wherein the system is configured to execute a thawing protocol comprising ice-free thawing from about -196 °C or higher, warming a target temperature between 30-37 °C.

56. The system of any of Embodiment s) 42-55, further comprising a hybrid platform configured with a first chamber adapted for cryo-bags and a second chamber adapted for cryo- vials.

57. A container enclosure for use in thawing a biological substance comprising: an adapter configured to receive a container comprising the biological substance, the adapter comprising: an adapter temperature sensor configured to measure the temperature of the biological substance.

58. A container enclosure for use in thawing a biological substance comprising: an adapter configured to receive a container comprising the biological substance, the adapter comprising: an adapter temperature sensor configured to measure the temperature of the biological substance; and an identifier for the biological substance.

59. The enclosure of any of Embodiment(s) 57-58, wherein the container enclosure is configured to receive a container with a temperature of down to about -80°C or lower.

60. The enclosure of any of Embodiment(s) 57-58, wherein the container enclosure is configured to receive a container with a temperature of down to about -100°C or lower.

61. The enclosure of any of Embodiment(s) 57-58, wherein the container enclosure is configured to receive a container with a temperature of down to about -120°C or lower.

62. The enclosure of any of Embodiment(s) 57-58, wherein the container enclosure is configured to receive a container with a temperature of down to about -140°C or lower.

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63. The enclosure of any of Embodiment(s) 57-58, wherein the container enclosure is configured to receive a container with a temperature of down to about -150°C or lower.

64. The enclosure of any of Embodiment(s) 57-58, wherein the container enclosure is configured to receive a container with a temperature of down to about -190°C or lower.

65. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -100°C or lower.

66. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -120°C or lower.

67. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -140°C or lower.

68. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -150°C or lower.

69. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -190°C or lower.

70. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -100°C or lower and up to about 25 °C or higher.

71. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -120°C or lower and up to about 30 °C or higher.

72. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -140°C or lower and up to about 35 °C or higher r.

73. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -150°C or lower and up to about 35 °C or higher.

74. The enclosure of any of Embodiment(s) 57-64, wherein the temperature sensor is configured to measure a temperature of down to about -190°C or lower and up to about 45 °C or higher.

75. The enclosure of any of Embodiment(s) 57-74, wherein the temperature sensor comprises a plurality of temperature sensors.

76. The enclosure of any of Embodiment(s) 57-75, wherein the temperature sensor comprises a plurality of temperature sub-sensors.

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77. The enclosure of any of Embodiment(s) 57-76, wherein the temperature sensor comprises a plurality of temperature sensors respectively configured to measure different temperature ranges.

78. The enclosure of any of Embodiment(s) 57-77, wherein the temperature sensor comprises a thermocouple sensor, thermistor sensor, IR sensor, RFID-integrated sensor, and a combination thereof.

79. The enclosure of any of Embodiment(s) 57-78, wherein the temperature sensor comprises a thermistor and a thermocouple.

80. The enclosure of any of Embodiment(s) 57-79, wherein the temperature measured by the temperature sensor is processed to provide complementary temperature monitoring and safety cutoff.

81. The enclosure of any of Embodiment(s) 57-80, further comprising an antenna configured for both energy harvesting and RF communication.

82. The enclosure of any of Embodiment(s) 57-81, wherein the container is selected from a group consisting of: a commercial cryogenic vial, a disposable cryo-vial with fixed outer dimensions, and a custom vial having variable inner volume.

83. The enclosure of any of Embodiment(s) 57-82, wherein the container comprises one or more of a vial and cuvette.

84. The enclosure of any of Embodiment(s) 57-83, further comprising a gap adapter configured to receive the container and maintain a fixed outer diameter.

85. The enclosure of any of Embodiment(s) 84, wherein the gap adapter comprises a rigid body with high thermal conductivity, fabricated from aluminum, PTFE, or doped silicone.

86. The enclosure of any of Embodiment(s) 84-85, wherein the temperature sensor is affixed to the base of the gap adapter, and aligned with an RFID reader embedded in the chamber base.

87. The container enclosure of any of Embodiment s) 84-86, wherein the adapter comprises a protrusion configured to releasably contact the container.

88. The container enclosure of any of Embodiment s) 84-87, wherein the adapter comprises a connector coupled to the temperature sensor and disposed on an outer surface of the adapter.

89. The container enclosure of any of Embodiment s) 84-88, wherein the adapter comprises a sleeve.

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90. A system comprising the container enclosure of any of Embodiment s) 57-89, further comprising a temperature control device comprising a thermal source, a thermal conductor, and a chamber configured to receive the container enclosure.

91. The system of any of Embodiment s) 90, wherein the system is configured to perform temperature-controlled thawing based on approximately real-time wireless monitoring during thawing.

92. The system of any of Embodiment s) 90-91 wherein the system is configured to perform temperature-controlled thawing from cryogenic to physiologic range based on approximately real-time wireless monitoring during thawing.

93. The system of any of Embodiment s) 90-92, further comprising a thermal chamber comprising the thermal conductor, wherein the thermal chamber comprises a pair of opposed thermoelectric modules for simultaneous heating and cooling.

94. The system of any of Embodiment s) 90-93, wherein the thermal chamber further comprises at least one embedded thermistor and at least one thermocouple.

95. The system of any of Embodiment s) 93, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling.

96. The system of any of Embodiment s) 93, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling at frequencies up to 50 Hz.

97. The system of any of Embodiment s) 90-96, wherein the temperature control device operates based on a filtering algorithm configured to perform adaptive averaging on temperature readings to reduce noise.

98. The system of any of Embodiment s) 90-97, wherein the system includes a thermal protection logic that disconnects power if the sensed temperature exceeds a threshold.

99. The system of any of Embodiment s) 90-98, wherein the system is configured to execute a thawing protocol comprising ice-free thawing from about -196 °C or higher, warming a target temperature between 30-37 °C.

100. The system of any of Embodiment s) 90-99, further comprising a hybrid platform configured with a first chamber adapted for cryo-bags and a second chamber adapted for cryo- vials.

101. The system of any of Embodiment s) 90-100, wherein the thermal source is configured to control a temperature of the biological substance.

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102. The system of any of Embodiment s) 90-101, wherein the thermal conductor comprises a thermal conductor temperature sensor configured to measure the temperature of the thermal conductor.

103. The system of any of Embodiment s) 90-102, wherein the thermal source comprises a Peltier element.

104. The system of any of Embodiment s) 90-103 wherein the temperature control device further comprises an agitator configured to agitate the container enclosure.

105. The system of any of Embodiment s) 90-104, further comprising a controller including a processor and memory, the controller configured to control the thermal source.

106. The system of any of Embodiment s) 90-105, wherein the temperature control device further comprises a reader configured to receive one or more of biological substance data and the measured temperature from one or more of the identifier and the temperature sensor.

107. The system of any of Embodiment s) 90-106, wherein the housing comprises a handle.

108. The system of any of Embodiment s) 90-107, wherein the housing is configured to transition between an open configuration and a closed configuration, wherein the closed configuration is configured to hold the container enclosure within the chamber.

109. The container enclosure of claims 57-89, wherein the adapter comprises a thermally conductive material.

110. The container enclosure of any of Embodiment s) 57-89, wherein the adapter comprises a sleeve.

111. The system of any of Embodiment s) 90-107, wherein the thermal conductor comprises one or more of a fluid, gel, metal, ceramic, polymer, and silicone.

112. The container enclosure of claims 57-89, wherein the adapter comprises one or more of a metal, ceramic, polymer, and silicone.

113. The container enclosure of claims 57-89, wherein the adapter comprises a rigid material.

114. The container enclosure of claims 57-89, wherein the temperature sensor comprises a thermocouple.

115. The system of any of Embodiment s) 90-107, wherein one or more of the thermal conductor and the adapter are configured for single use.

116. A system, comprising: a plurality of temperature control devices configured to control a temperature of a biological substance, wherein each device comprises:

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 a container enclosure configured to receive a container comprising a biological substance; a temperature sensor configured to measure a temperature of the biological substance; an identifier for the biological substance; and a controller coupled to the plurality of temperature control devices, the controller comprising a processor and memory, and configured to: receive the temperature corresponding to one or more of the biological substances from one or more of the temperature control devices; and control the temperature of one or more of the biological substances using one or more of the temperature control devices based on its respective temperature sensor.

117. The system of any of Embodiment s) 116, wherein each temperature control device comprises an agitator, and the controller is configured to control agitation of one or more of the temperature control devices based on its respective temperature sensor.

118. The system of any of Embodiment s) 116-117, wherein controlling the temperature of one or more of the biological substances comprises controlling the temperature of the biological substance between down to about -80°C and up to about 37°C.

119. The system of any of Embodiment s) 116-117, wherein controlling the temperature of one or more of the biological substances comprises controlling the temperature of the biological substance between down to about -100°C and up to about 37°C.

120. The system of any of Embodiment s) 116-117, wherein controlling the temperature of one or more of the biological substances comprises controlling the temperature of the biological substance between down to about -120°C and up to about 37°C.

121. The system of any of Embodiment s) 116-117, wherein controlling the temperature of one or more of the biological substances comprises controlling the temperature of the biological substance between down to about -150°C and up to about 37°C.

122. The system of any of Embodiment s) 116-117, wherein controlling the temperature of one or more of the biological substances comprises controlling the temperature of the biological substance between down to about -190°C and up to about 37°C.

123. A system for controlling a temperature of a biological substance, comprising: an adapter configured to receive a container comprising the biological substance; a thermal conductor in thermal communication with the adapter; a thermal source in thermal communication with the thermal conductor; a temperature sensor configured to measure the temperature of the biological substance; and an identifier for the biological substance.

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124. The system of any of Embodiment s) 116-123, wherein the system is configured to perform temperature-controlled thawing based on approximately real-time wireless monitoring during thawing.

125. The system of any of Embodiment s) 116-124 wherein the system is configured to perform temperature-controlled thawing from cryogenic to physiologic range based on approximately real-time wireless monitoring during thawing.

126. The system of any of Embodiment s) 116-125, further comprising a thermal chamber comprising a thermal conductor, wherein the thermal chamber comprises a pair of opposed thermoelectric modules for simultaneous heating and cooling.

127. The system of any of Embodiment s) 126, wherein the thermal chamber further comprises at least one embedded thermistor and at least one thermocouple.

128. The system of any of Embodiment s) 126, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling.

129. The system of any of Embodiment s) 126, wherein the thermoelectric modules are regulated by a PID-based analog controller that performs continuous sampling at frequencies up to 50 Hz.

130. The system of any of Embodiment s) 116-129, wherein the temperature control device operates based on a filtering algorithm configured to perform adaptive averaging on temperature readings to reduce noise.

131. The system of any of Embodiment s) 116-130, wherein the system includes a thermal protection logic that disconnects power if the sensed temperature exceeds a threshold.

132. The system of any of Embodiment s) 116-131, wherein the system is configured to execute a thawing protocol comprising ice-free thawing from about -196 °C or higher, warming a target temperature between 30-37 °C.

133. The system of any of Embodiment s) 116-132, further comprising a hybrid platform configured with a first chamber adapted for cryo-bags and a second chamber adapted for cryo- vials.

134. A method for thawing a biological substance, the method comprising: positioning a container comprising a biological substance in an adapter, wherein the biological substance is in a frozen state; positioning the adapter with the biological substance in a chamber of a thawing device such that the biological substance is in thermal communication with a first heating assembly located within a housing of the thawing device; and

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 activating the heating assembly to heat and thereby thaw the enclosed biological substance, wherein the enclosed biological substance comprises mRNA, and the mRNA has a postthaw cycle threshold (Ct) value below about 30.

135. The method of any of Embodiment s) 134, wherein the post-thaw Ct value is between about 27.0 and about 29.0.

136. The method of any of Embodiment s) 134, wherein positioning the container in the adapter further comprises positioning the container such that a side portion of the adapter overlaps a sidewall portion of the container and a bottom portion of the adapter overlaps and a bottom portion of the container.

137. The method of any of Embodiment s) 134, wherein a top portion of the container remains uncovered.

138. The method of any of Embodiment s) 134, wherein at least one of a neck and a lip of the container remains uncovered.

139. The method of any of Embodiment s) 134, wherein positioning the container in the adapter further comprises positioning the container in the adapter with an interference fit.

140. The method of any of Embodiment s) 134, wherein positioning the adapter in the chamber further comprises positioning the adapter such that a longitudinal axis of the container is about parallel to a longitudinal axis of the chamber.

141. The method of any of Embodiment s) 134, wherein positioning the adapter further includes positioning the adapter in a cavity of a container enclosure and positioning the container enclosure in the chamber.

142. The method of any of Embodiment s) 139, wherein after positioning the adapter in the cavity of the container enclosure, a portion of the container overlaps with a temperature sensor of the container enclosure.

143. The method of any of Embodiment s) 134, wherein positioning the container in the adapter includes positioning the container such that the adapter holds the container in an upright position.

144. A method of heating a biological substance, comprising: positioning a container comprising a biological substance in an adapter, wherein the biological substance is in a frozen state; positioning the adapter with the container in a container enclosure, wherein the container enclosure comprises a temperature sensor configured to measure a temperature of the biological

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132631-000IPGEN/9785637 4 Attorney Docket No. 132631-0008W001 substance, and wherein positioning the adapter results in at least a portion of the container overlapping the temperature sensor; placing the container enclosure into a chamber of a thawing device; heating the enclosed biological substance to an endpoint temperature using the thawing device; and removing the container enclosure from the chamber of the thawing device after the biological substance has reached the endpoint temperature.

145. The method of any of Embodiment s) 142, wherein heating the biological substance further comprises heating a thermal conductor positioned in the chamber.

146. The method of any of Embodiment s) 142, wherein the biological substance comprises mRNA and the endpoint temperature is 4°C.

147. The method of any of Embodiment s) 142, wherein the biological substance comprises blood plasma and the endpoint temperature is 15°C.

148. The method of any of Embodiment s) 142, wherein positioning the adapter in the container enclosure includes positioning the adapter such that the adapter holds the container in alignment with the temperature sensor.

149. The method of any of Embodiment s) 142, wherein the adapter holds the container in an upright position in the container enclosure.

150. The method of any of Embodiment s) 142, wherein the adapter maintains the container in a position in which a longitudinal axis of the container is parallel to a longitudinal axis of the chamber when the container enclosure is positioned within the chamber.

151. A system for thawing a biological substance, comprising: an adapter configured to receive a container comprising the biological substance; a container enclosure comprising a cavity configured to receive the adapter and a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity; and an identifier for the biological substance.

152. The system of any of Embodiment s) 151, wherein the adapter is configured to maintain a position of the container relative to the temperature sensor during thawing.

153. The system of any of Embodiment s) 151, wherein the adapter is configured to maintain the container in an upright position during thawing.

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154. The system of any of Embodiment s) 151, wherein the adapter comprises a thermally conductive material.

155. A container configured to be received in a temperature control device to control a temperature of a biological substance contained therein, the container comprising: a body portion comprising a first proximal connector, a first distal connector, and a fluid reservoir configured to receive the biological substance; a top portion comprising an opening for transferring biological substance into the fluid reservoir and a second proximal connector configured to couple with the first proximal connector of the body portion; and a bottom portion comprising a temperature sensor configured to measure the temperature of the biological substance and a second distal connector configured to couple with the first distal connector of the body portion.

156. The container of any of Embodiment s) 155, wherein the fluid reservoir is configured to hold a volume of about 1 mL and about 26 mL of the biological substance.

157. The container of any of Embodiment s) 155, wherein the fluid reservoir is configured to hold a maximum volume of about 26 mL to about 30 mL of the biological substance.

158. The container of any of any of Embodiment s) 155, wherein the body portion comprises a diameter or width between about 5 mm and about 30 mm.

159. The container of any of Embodiment s) 155, wherein the fluid reservoir comprises a length of between about 15 mm and about 100 mm.

160. The container of any of Embodiment s) 155, wherein the fluid reservoir comprises a proximal diameter or width between about 5 mm and about 10 mm, and a distal diameter or width between about 10 mm and about 15 mm.

161. The container of any of Embodiment s) 155, wherein a diameter or width of the fluid reservoir varies along a longitudinal axis of the container.

162. The container of any of Embodiment s) 155, wherein the cross-sectional shape of the fluid reservoir along a longitudinal axis of the container is different than a cross-sectional shape of the container along the longitudinal axis.

163. The container of any of Embodiment s) 155, wherein the fluid reservoir has a trapezoidal cross-sectional shape.

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164. The container of any of Embodiment s) 155, wherein the body portion comprises a proximal end with a first diameter or width and distal end with a second diameter or width, and wherein the fluid reservoir has a third diameter or width and the third diameter or width is greater than both the first and second diameters or widths.

165. The container of any of Embodiment s) 155, wherein the temperature sensor is configured to measure temperatures between about -200°C and about 40°C.

166. A system for use in controlling the temperature of the biological substance comprising: the container of any of Embodiment(s) 155; and the temperature control device comprising a thermal source and a chamber configured to receive the container, wherein one or more of the top portion and the bottom portion are configured hold the container upright within the chamber.

[0347] The specific examples and descriptions herein are exemplary in nature and variations may be developed by those skilled in the art based on the material taught herein without departing from the scope of the present invention, which is limited only by the attached claims.

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Claims

Attorney Docket No. 132631-0008W001 CLAIMS WHAT IS CLAIMED IS:

1. A container enclosure for use in thawing a biological substance comprising: a cavity configured to receive a container comprising the biological substance; a temperature sensor configured to measure a temperature of the biological substance, wherein the temperature sensor overlies a portion of the cavity configured to hold the container during thawing; and an identifier for the biological substance.

2. The enclosure of claim 1, wherein the biological substance comprises one or more of an mRNA vaccine, DNA vaccine, exosome, liquid biopsy, blood, cryo-preserved tissue, therapeutic, prophylactic, and cell therapy product.

3. The enclosure of claim 1, wherein the identifier receives the temperature measurement from the temperature sensor.

4. The enclosure of claim 1, wherein the cavity comprises a shape configured to funnel the container to a predetermined position and location within the enclosure.

5. The enclosure of claim 1, wherein the container enclosure is configured to receive a container with a temperature of down to about -90°C or lower.

6. The enclosure of claim 1, wherein the container enclosure is configured to receive a container with a temperature of down to about -140°C or lower.

7. The enclosure of claim 1, wherein the container enclosure is configured to receive a container with a temperature of down to about -190°C or lower.

8. The enclosure of claim 1, wherein the temperature sensor is configured to measure a temperature of down to about -100°C or lower and up to about 25 °C or higher.

9. The enclosure of claim 1, wherein the temperature sensor is configured to measure a temperature of down to about -150°C or lower and up to about 35 °C or higher.

10. The enclosure of claim 1, wherein the temperature sensor comprises a plurality of temperature sensors respectively configured to measure different temperature ranges.

11. The enclosure of claim 1, wherein the temperature sensor comprises a thermocouple sensor, thermistor sensor, IR sensor, RFID-integrated sensor, and a combination thereof.

12. The enclosure of claim 1, wherein the temperature sensor comprises a thermistor and a thermocouple.

13. The enclosure of claim 1, wherein the temperature measured by the temperature sensor is processed to provide complementary temperature monitoring and safety cutoff.

14. A system comprising the container enclosure of claim 1, further comprising a temperature control device comprising a chamber and a thermal source, wherein the temperature Attorney Docket No. 132631-0008W001 control device is configured to receive the container enclosure in the chamber and the thermal source is configured to control the temperature of the biological substance.

15. The system of claim 14, wherein the thermal source comprises a Peltier element.