Cryogenic Storage Container
20230247983 · 2023-08-10
Inventors
- Adam Shields (Noblesville, IN, US)
- Frank J. Fischer, Jr. (Bloomington, IN, US)
- Michael Pallotta (Carmel, IN, US)
- Sean Werner (Indianapolis, IN, US)
Cpc classification
A01N1/0263
HUMAN NECESSITIES
International classification
Abstract
Containers for cryopreservation of biological material are disclosed. Each container is configured to provide a substantially consistent freeze profile throughout a chamber of the container. Specific embodiments include containers having a uniform dimension between two opposing walls defining the chamber, and containers wherein a ratio of a sum of the interior surface areas to the volume of the chamber is at or between 1 to 5 and 2 to 5.
Claims
1. A cryostorage container, comprising: a first body defining a chamber, the first body including a plurality of walls, the plurality of walls including: a first wall extending along a first side of the chamber; and a second wall extending along a second side of the chamber, the second side opposite the first side relative to the chamber, the chamber having a volume in a range of 25 mL to 250 mL, the chamber having a uniform characteristic dimension extending perpendicular to the first wall and the second wall from the first wall to the second wall, the uniform characteristic dimension being uniform across a planar cross-section of the chamber parallel to the uniform characteristic dimension.
2. The cryostorage container of claim 1, wherein the uniform characteristic dimension is uniform for at least 90% of all distances extending from the first wall to the second wall and being perpendicular to the first wall and the second wall.
3. The cryostorage container of claim 1, further comprising: a vent opening in fluid communication with the chamber; and a drain opening in fluid communication with the chamber.
4. The cryostorage container of claim 3, further comprising a filter associated with the vent opening to filter air entering and/or exiting the chamber.
5. The cryostorage container of claim 3, further comprising heat-sealable tubing attached to at least one from the group consisting of the drain opening and the vent opening.
6. The cryostorage container of claim 3, wherein the vent opening is positioned at a first end of the chamber and the drain opening is positioned at a second end of the chamber.
7. The cryostorage container of claim 1, wherein the chamber follows a serpentine path.
8. The cryostorage container of claim 7, wherein the body further includes: a first end wall at a first end of the chamber, the first end wall connecting the first wall and the second wall; and a second end wall at a second end of the chamber, the second end wall opposite the first end wall relative to the chamber, wherein the serpentine path extends along a length between the first end wall and the second end wall.
9. The cryostorage container of claim 7, wherein the first wall includes a plurality of wall portions positioned at different angles with respect to each other, wherein the second wall includes a plurality of wall portions positioned at different angles with respect to each other, each wall portion of the first wall approximately parallel with and opposite one of the wall portions of the second wall.
10. The cryostorage container of claim 7, wherein the serpentine path is defined at least partially by a series of curves bending in alternating directions, the series of curves separated by straight wall portions.
11. The cryostorage container of claim 7, wherein the serpentine path is defined by a series of straight wall portions arranged in a chevron pattern.
12. The cryostorage container of claim 1, wherein the uniform characteristic dimension is at or between 5 mm and 10 mm.
13. The cryostorage container of claim 1, further comprising a hanger opening arranged to receive an IV bag hanger.
14. The cryostorage container of claim 13, wherein the hanger opening is positioned at an opposite end of the cryostorage container from the drain opening such that when the container hangs freely from the IV bag hanger, the drain opening is at a lowest portion of the serpentine chamber.
15. The cryostorage container of claim 14, wherein the hanger opening is off-center along the end of the cryostorage container.
16. The cryostorage container of claim 1, further comprising a nucleation site facilitating ice crystal formation.
17. The cryostorage container of claim 16, wherein the nucleation site comprises an indentation formed in the plurality of walls.
18. The cryostorage container of claim 1, wherein the plurality of walls comprise a mounting feature, and wherein the cryostorage container further comprises a thermocouple carried by the mounting feature.
19. The cryostorage container of claim 18, wherein the mounting feature comprises a recess.
20. The cryostorage container of claim 19, wherein the mounting feature further comprises a wire retention element.
21. The cryostorage container of claim 1, wherein the plurality of walls includes transparent wall portions.
22. The cryostorage container of claim 21, wherein the transparent wall portions are recessed.
23. The cryostorage container of claim 1, further comprising: a second body defining a second chamber, the second body including a second plurality of walls, the second plurality of walls including: a third wall extending along a first side of the second chamber; and a fourth wall extending along a second side of the second chamber, the second side of the second chamber opposite the first side of the second chamber relative to the second chamber, the second chamber having a second volume in a range of 25 mL to 250 mL, the second chamber having a second uniform characteristic dimension extending perpendicular to the third wall and the fourth wall from the third wall to the fourth wall, the second uniform characteristic dimension being uniform across a planar cross-section of the second chamber parallel to the second uniform characteristic dimension, the first chamber in fluid communication with the second chamber.
24. The cryostorage container of claim 23, further comprising: a third body defining a third chamber, the third body including a third plurality of walls, the third plurality of walls including: a fifth wall extending along a first side of the third chamber; and a sixth wall extending along a second side of the third chamber, the second side of the third chamber opposite the first side of the third chamber relative to the third chamber, the third chamber having a third volume, the third chamber having a third uniform characteristic dimension extending perpendicular to the fifth wall and the sixth wall from the fifth wall to the sixth wall, the third uniform characteristic dimension being uniform across a planar cross-section of the third chamber parallel to the third uniform characteristic dimension, the second chamber in fluid communication with the third chamber
25. A cryostorage container comprising: a chamber having a volume; and wall portions defining the chamber, the wall portions each having an interior surface facing the chamber and an exterior surface opposing the interior surface, each interior surface having a surface area, a ratio of a sum of the surface areas of the interior surfaces to the volume of the chamber being at or between 1 to 5 and 2 to 5.
26. The cryostorage container of claim 25, wherein the wall portions defining the chamber follow a serpentine path from a first end of the chamber to a second end of the chamber.
27. The cryostorage container of claim 26, wherein the chamber has a length extending from the first end to the second end and a uniform width along the length.
28. The cryostorage container of claim 27, wherein the width is at or between 5 mm and 10 mm.
29. The cryostorage container of claim 25, wherein the wall portions have a thermal conductivity at or between 0.16×10.sup.−3 watts per Kelvin and 0.32×10.sup.−3 watts per Kelvin at room temperature.
30. The cryostorage container of claim 25, wherein the wall portions comprise a material having a thermal conductivity at or between 0.10 to 0.20 W/m K at room temperature.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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DETAILED DESCRIPTION OF THE INVENTION
[0066] For the purpose of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It should nevertheless be understood that no limitation of the scope of the invention is thereby intended. Any alterations and further modifications in the described embodiments, and any further applications of the principles of the invention as described herein are contemplated as would normally occur to one skilled in the art to which the invention relates. One embodiment of the invention is shown in great detail, although it will be apparent to those skilled in the relevant art that some features that are not relevant to the present invention may not be shown for the sake of clarity.
[0067] The language used in the claims and the written description is to only have its plain and ordinary meaning, except for terms explicitly defined below. Such plain and ordinary meaning is defined here as inclusive of all consistent dictionary definitions from the most recently published (on the filing date of this document) general purpose Merriam-Webster dictionary.
[0068] The terms “fill”, “filling”, and “filled” as used herein include both partial and complete filling. The term “drain”, “draining”, and “drained” as used herein include both partial and complete draining. The term “vent” as used herein means an opening to allow equalization of gas pressure between the inside and outside of the cryostorage container. Vents may allow the passage of gas through the vent (e.g., through a filter) and/or include a flexible membrane (e.g., a bag and/or balloon) that allows for expansion and/or contraction of gas within the chamber of the cryostorage container. The term “chamber width” as used herein means the distance between inside surfaces on opposing sides of the chamber, measured along a vector normal (i.e., perpendicular) to at least one of the inside surfaces. The “tubes”, “tubing” and “flexible tubing” disclosed herein can comprise a material suitable for cryostorage at −196° C. or below. Further forms, objects, features, aspects, benefits, advantages, and embodiments of the present invention will become apparent from a detailed description and drawings provided herewith
[0069] With respect to the specification and claims, it should be noted that the singular forms “a”, “an”, “the”, and the like include plural referents unless expressly discussed otherwise. As an illustration, references to “a device” or “the device” include one or more of such devices and equivalents thereof. It also should be noted that directional terms, such as “up”, “down”, “top”, “bottom”, and the like, are used herein solely for the convenience of the reader in order to aid in the reader's understanding of the illustrated embodiments, and it is not the intent that the use of these directional terms in any manner limit the described, illustrated, and/or claimed features to a specific direction and/or orientation.
[0070] The terms “approximately” and “about”, when qualifying a quantity, size, or geometry, shall mean the given value with a tolerance plus or minus 10 percent of the value, unless otherwise specified.
[0071] All ranges disclosed herein, unless otherwise indicated, encompass any and all sub-ranges subsumed therein. For example, a range of “less than 10” can include any and all sub-ranges between (and including) the minimum value of zero and the maximum value of 10, that is, any and all sub-ranges having a minimum value of equal to or greater than zero and a maximum value of equal to or less than 10, e.g., 1 to 5. In certain cases, the numerical values as stated for the parameter can take on negative values. In this case, the example value of range stated as “less than 10” can assume negative values, e.g. −1, −2, −3, −10, −20, −30, etc.
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[0073] The first wall 120, the second wall 124, and the chamber 110 follow a serpentine path along a length L of the body 102. Each of the first wall 120 and the second wall 124 include a plurality of wall portions positioned at differing angles with respect to each other, or at alternating angles moving from the first end 132 to the second end 136. Along the serpentine path, the first wall 120 and the second wall 124 have a uniform characteristic dimension therebetween, which is a uniform distance 156 therebetween, as measured along a direction perpendicular to an inside surface 150 of the first wall 120. The uniform distance 156 is uniform across a planar cross-section parallel with the distance D. For example, the distance 156 between the second wall 124 and the first wall 120, as measured along a vector normal to the inside surface 150 of the first wall 120, can be at or between 5 mm and 7 mm. The first wall 120 can be parallel to the second wall 124 along the serpentine path.
[0074] The first wall 120 and the second wall 124 can also have the uniform distance 156 between them along the height of the body. Accordingly, the first wall 120 and the second wall 124 can be separated by the uniform distance 156 across the length L and/or the height H. Advantageously, having the uniform characteristic dimension between the first wall 120 and the second wall 124 along the length L and/or the height H of the body 102, wherein the value of the uniform characteristic dimension is relatively small, aids in maintaining a substantially uniform freeze profile along the length L and/or the height H of the body 102.
[0075] In practicality, an exact uniformity of the uniform characteristic dimension is difficult to manufacture, so some tolerance is acceptable. Further, in some embodiments, an indentation, recess, protrusion, or other nonuniform structural feature can be useful or necessary, for example, to facilitate manufacturing. These nonuniform structural features can affect the uniform characteristic dimension over a portion of a wall of the chamber 110. Accordingly, in some embodiments, the uniform characteristic dimension can range, e.g., within 0.01 mm, 0.1 mm, 0.5 mm, 1.0 mm, or 2.0 mm. In some embodiments, the uniform characteristic dimension can range, for example, to deviate 0.1%, 0.5%, 1%, 2%, 5%, 10%, 20%, or 25% from the uniform characteristic dimension's target value or median value. Generally, higher uniformity of the uniform characteristic dimension is desirable to increase uniform cooling and/or thawing rates of the contained biological samples/materials.
[0076] In some embodiment, the uniform characteristic dimension can be uniform, within any of the ranges of the above-described tolerances, for 90% or more, 95% or more, or 99% or more of the perpendicular distances between the first wall 120 and the second wall 124.
[0077] In some embodiments, the walls can slightly diverge from one another along a direction extending from a bottom 140 of the body 102 to a top 160 of the body 102. This divergence can facilitate releasing the body 102 from a mold during manufacturing while having no significant impact on varying the freeze profile along the height H of the body 102.
[0078] Advantageously, serpentine chambers having a width between inner walls, a height, and an overall length can provide a greater volume for liquid storage than linear chambers of the same width, height, and overall length. Accordingly, serpentine chambers arranged for a cryostorage box can store more liquid than a linear container of similar dimensions (that is, having equal overall lengths).
[0079] The thermal resistance of the first wall 120 and the second wall 124 is preferably uniform along the length L and height H. For example, the first wall 120 and/or the second wall 124 can have a uniform material thickness along the length L and the height H. The first wall 120 and the second wall 124 can have the same thermal resistance to promote uniform thermal transfer during freeze/thaw cycles.
[0080] Referring additionally to
[0081] Referring to
[0082] One or more of the openings 202, 204, 206 can be arranged for filling and/or draining liquid from the chamber 110. In some embodiments, one or more of the openings 202, 204, 206 can be high throughput fill ports. In some embodiments, at least one of openings 202, 204, 206 communicating with the chamber 110 can be arranged to vent air into and/or out of the chamber 110. For example, when liquid is being drained from the chamber 110, a vent opening arranged to vent air allows air to enter the chamber 110 and when liquid is being filled into the chamber 110, the vent opening allows air to exit the chamber 110. In the illustrated embodiments, the first opening 202 at the first end of the chamber 110 is arranged for venting, the second opening 204 at the second end of the chamber is arranged for draining, and the third opening 206 is arranged for filling the chamber with liquid.
[0083] In some embodiments, the cryostorage container 100 can include a lid.
[0084] A bottom side 302 of the lid 300 may include a wall 310 extending between the vent opening (e.g., first opening 202) and the fill opening (e.g., third opening 206). The wall 310 prevents fluid entering through the fill opening from being immediately drawn out the vent opening, particularly when a negative pressure is applied to the vent opening to draw gas out the chamber 110.
[0085] Referring to
[0086] The cryostorage container can include a hanging element 230, which can be a loop, as shown in
[0087] The cryostorage container 100 can be arranged to support itself on a level surface in various positions. For example, the cryostorage container 100 can be arranged to support itself in a filling configuration.
[0088] To support itself in one or more configurations (e.g., filling and/or draining configurations), the cryostorage container 100 can include one or more stands. For example, referring to
[0089] In some embodiments, the cryostorage container 100 can have a height of about 80 mm, a length of about 125 mm, a width of about 20 mm, and a volume of about 48 ml. In some embodiments, the cryostorage container 100 has a volume in a range of 100 ml to 250 ml.
[0090] As described briefly above, cryopreservation containers with relatively large capacities according to the present invention are provided with uniform characteristic dimensions and high dimensional aspect ratios to facilitate consistency and uniformity of freeze/thaw rates. Such containers can have serpentine chambers, such as the cryostorage container 100 described above. Alternatively, such containers can have other shapes. Several exemplary shapes of chambers of such containers are illustrated in
[0091] Referring now to
Surface areas of the chamber 400 relate to the aspect ratios as follows:
[0092] For relatively high aspect ratios, or relatively high ratios of SA1 to SA2 or SA1 to SA3, the characteristic dimension R significantly affects, and provides substantial consistency of, the freeze profile of the chamber 400. Such relatively high aspect ratios may be, for example, between 1 to 1 and 2 to 1, preferably between 2 to 1 and 5 to 1, and more preferably between to 1 and 20 to 1.
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[0094] Surface areas of the chamber 500 relate to the aspect ratios as follows:
[0095] For a relatively high aspect ratio, or a relatively high ratios of SA1 to SA2, the characteristic dimension R significantly affects, and provides substantial consistency of, the freeze profile of the chamber 500. Such a relatively high aspect ratio may be, for example, between 1 to 1 and 2 to 1, preferably between 2 to 1 and 5 to 1, and more preferably between to 1 and 20 to 1.
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[0108] Illustratively, the upper wall 1702 includes one recess 1706 and the lower wall 1704 includes two recesses 1708. In some embodiments, the upper wall 1702 and the lower wall 1704 define an optical path length 1710 therebetween, and the optical path length 1710 may be uniform across a set of containers of various volumes. The one recess 1706 and the two recesses 1708 can be deep enough to fulfill their intended purpose of reducing or preventing damage to the walls 1702, 1704 while also being shallow enough to maintain sufficient uniformity of the uniform characteristic dimension D1 (e.g., within the tolerances discussed above) and sufficient consistency/uniformity of the freeze/thaw rates in the chamber.
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[0111] While the invention has been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes, equivalents, and modifications that come within the spirit of the inventions defined by following claims are desired to be protected. All publications, patents, and patent applications cited in this specification are herein incorporated by reference as if each individual publication, patent, or patent application were specifically and individually indicated to be incorporated by reference and set forth in its entirety herein.