MICROSAMPLE CRYOSTORAGE SYSTEMS AND METHODS
A multi-vial assembly for containing a plurality of samples in a cryostorage system includes a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly. The vials are independently removable from the integral vial assembly to permit selective access to the respective samples.
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This application claims the benefit of U.S. Provisional Application No. 61/430,292, filed Jan. 6, 2011, the disclosure of which is incorporated by reference herein in its entirety.
BACKGROUND OF THE INVENTIONSmall vials commonly referred to as cryovials, cryotubes, microcentrifuge tubes or microfuge tubes are often employed for storing samples at very low temperatures (e.g., at temperatures below −60° C.). Typically, microfuge tubes take the form of small, cylindrical plastic containers with conical bottoms and an integral snap cap or screw-on cap. They may be used by chemists and biologists as convenient sample vials in lieu of glass vials. Microfuge tubes may be particularly helpful for storing small sample contents and microcentrifugation can be used to collect the sample at the bottom of the tube. Microfuge tubes come in different nominal volumes, generally ranging from 250 μl to 2.0 ml.
SUMMARY OF THE INVENTIONAccording to embodiments of the present invention, a multi-vial assembly for containing a plurality of samples in a cryostorage system includes a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly. The vials are independently removable from the integral vial assembly to permit selective access to the respective samples.
In some embodiments, the multi-vial assembly is sized to removably and replaceably fit within a microfuge tube slot of a freezer box.
According to some embodiments, each of the vial chambers of the vials has a capacity in the range of from about 100 to 200 μl.
According to some embodiments, the multi-vial assembly has a height in the range of from about 25 to 48 mm, and a width in the range of from about 8 to 12 mm.
According to some embodiments, the multi-vial assembly includes a sleeve removably surrounding the integral vial assembly. Identification indicia may be provided on the sleeve. The multi-vial assembly may further include identification indicia on each of the vials.
According to some embodiments, the multi-vial assembly includes a support assembly supporting and coupling the vials, the support assembly including at least one support member to receive and hold the vials.
The support assembly may hold the vials in fixed relation to one another. In some embodiments, the support member includes a plurality of first mounting features, the vials each include a second mounting feature configured to engage a respective one of the first mounting features to positively position the vial on the support member, the first mounting features are one of plugs and sockets, and the second mounting features are the other of plugs and sockets. In some embodiments, the support assembly includes a top support member and a bottom support member engaging upper and lower ends of the vials, respectively, and the top member serves as a closure for the vial chambers of the vials. In some embodiments, the support assembly includes a locking member selectively operable to secure the support assembly to the vials and release the support assembly from the vials.
According to some embodiments, the multi-vial assembly includes a sleeve removably surrounding the integral vial assembly and the support assembly.
According to some embodiments, the vials are stacked on one another to form the integral vial assembly. In some embodiments, the stacked vials are directly coupled to one another. According to some embodiments, the vials each include an integral inner screw thread and an integral outer screw thread, and the stacked vials are directly coupled to one another by threaded engagement between their respective inner and outer screw threads. In some embodiments, at least one of the stacked vials serves as a closure for the vial chamber of another, immediately adjacent one of the stacked vials.
According to some embodiments, each of the vial chambers includes an upper main subchamber and a tapered lower subchamber.
The vials can be formed of polypropylene.
According to method embodiments of the present invention, a method for storing and handling a plurality of samples in a cryostorage freezer includes: providing a multi-vial assembly including a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly. The vials are independently removable from the integral vial assembly to permit selective access to the respective samples. The method further includes: placing the samples in respective ones of the vial chambers; placing the multi-vial assembly in a freezer chamber of a cryostorage freezer; and selectively removing one or more of the vials from the multi-vial assembly to selectively access the samples placed in the vial chambers of the removed vials.
In some embodiments, the method includes: providing a freezer box defining a plurality of microfuge tube slots; seating the multi-vial assembly in one of the microfuge tube slots; removing the multi-vial assembly from the microfuge tube slot; and thereafter removing the one or more of the vials from the multi-vial assembly to selectively access the samples placed in the vial chambers of the removed vials.
According to embodiments of the present invention, a microsample cryostorage system for containing a plurality of samples includes a cryostorage freezer having a freezer chamber and a multi-vial assembly disposed in the freezer chamber. The multi-vial assembly includes a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly. The vials are independently removable from the integral vial assembly to permit selective access to the respective samples.
In some embodiments, the microsample cryostorage system of includes a freezer box disposed in the freezer chamber and defining a plurality of microfuge tube slots. The multi-vial assembly is removably seated within one of the microfuge tube slots.
Further features, advantages and details of the present invention will be appreciated by those of ordinary skill in the art from a reading of the figures and the detailed description of the preferred embodiments that follow, such description being merely illustrative of the present invention.
The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which illustrative embodiments of the invention are shown. In the drawings, the relative sizes of regions or features may be exaggerated for clarity. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.
It will be understood that when an element is referred to as being “coupled” or “connected” to another element, it can be directly coupled or connected to the other element or intervening elements may also be present. In contrast, when an element is referred to as being “directly coupled” or “directly connected” to another element, there are no intervening elements present. Like numbers refer to like elements throughout. As used herein the term “and/or” includes any and all combinations of one or more of the associated listed items.
In addition, spatially relative terms, such as “under”, “below”, “lower”, “over”, “upper” and the like, may be used herein for ease of description to describe one element or feature's relationship to another element(s) or feature(s) as illustrated in the figures. It will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as “under” or “beneath” other elements or features would then be oriented “over” the other elements or features. Thus, the exemplary term “under” can encompass both an orientation of over and under. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.
The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and this specification and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
The smallest available cryostorage devices are typically suitable for liquid volumes of 1 to 2 milliliters (ml). If smaller tubes were created (for example PCR tubes for DNA testing) they would likely lack adequate surface area for labeling, and would not fit efficiently in currently available storage systems (i.e., the boxes and racks used in ultra-low temperature freezers and liquid nitrogen storage tanks). Conventional devices are difficult to re-label without freeze-thaw of contents (which degrades the samples). If they are used to create numerous small aliquots of samples to allow different tests to be done at different times in the future (considered a good laboratory practice for clinical studies), such “daughter aliquots” take up just as much freezer space as full 1 to 2 ml samples.
Microsample storage systems as disclosed herein can be used to store small or micro samples or specimens in ultra-low temperature freezers (i.e., −70 to −86° C.) or liquid nitrogen storage tanks. The inventive microsample storage systems include multi-vial assemblies that can be effectively stored and handled in freezer boxes, liquid nitrogen canes or sleeves, or other organizing devices in a freezer or storage tank. The samples may be any suitable samples such as liquid (e.g., serum or plasma) or solid (e.g., tissue or paper strips) samples.
With reference to
The freezer 20 may be any suitable low or ultra-low temperature freezer and defines a storage chamber 22. In some embodiments, the freezer 20 is operable to maintain the storage chamber 22 at a temperature less than about −70° C. and, in some embodiments, between about −70 and −86° C. Exemplary freezers include the REVCO™ brand Ultima Freezer™ freezer available from Thermo Electron Corp. of Asheville, N.C.
One or more of the racks 28 may be optionally provided in the freezer chamber 22 to support the freezer boxes 30. Exemplary racks include the 6112-1 racks available from Thermo Electron Corp. of Asheville, N.C. In addition to or in place of the rack 28, the freezer 20 may be provided with shelves.
The freezer 20 may be provided with one or more of the freezer boxes 30. With reference to
The multi-vial assembly 100 (
The support assembly 102 includes a top plate or member 110, a bottom plate or member 120, and a coupling member or lock pin 130. The top member 110 has a lower surface 112 and a coupling hole 114 extending therethrough. The hole 114 is surrounded by an upstanding flange 114A. The bottom plate 120 has an upper surface 122 and a lower surface 123. A plurality of vial slots 124 are defined in the upper surface 122 and a cam feature 128 is located on the lower surface 123. Indicia may be provided in or adjacent each vial slot 124 to identify or index the vial slot locations. A coupling hole 126 extends through the bottom member 120.
The locking pin 130 includes a shaft or body 132 having a handle 134 on one end and a latch feature 136 on an opposing end. The locking pin 130 may be formed of bent wire of a suitable metal such as stainless steel.
The sleeve 140 is tubular and, in the illustrated embodiment, is square in cross-section. The sleeve 140 may include readable or visible indicia 142 representing data relating to the assembly 100 so that the sleeve 140 serves as a label for the assembly 100. The indicia 142 may include a one- or two-dimensional bar code, for example. According to some embodiments, the sleeve 140 is formed of a polymeric material. Suitable materials for the sleeve 140 may include any suitable material such as a clear, thin material of the type used for shrink wrap tubing. According to some embodiments, the sleeve 140 is formed of TEFLON (PTFE) or polyvinyl chloride (PVC). According to some embodiments, the sleeve 140 has a thickness T5 (
The vials 150A-H may be substantially identical to one another or of different configurations. An exemplary vial 150A is shown in detail in
The vials 150 may be formed of any suitable material. According to some embodiments, the vials 150 are formed of a polymeric material. According to some embodiments, the vials 150 are formed of polypropylene.
Each vial 150 has a width W1 (
The multi-vial assembly 100 may be assembled as follows. Samples as desired are deposited in the chamber 152 of each vial 150. Each vial 150A-H is seated in a respective vial slot 124 by its base plug 156, before or after receiving a sample. The top member 110 is placed over the top ends of the vials 150A-H. The locking pin 130 is inserted through the holes 114, 124 and the central void defined by the vial array 151. The handle 134 is notated to force the latch feature 136 against the cam 128 to thereby load or compress the top and bottom members 110, 120 together and against the vials 150A-H. In this way, the components 110, 120, 130, 140 and 150 can be secured together as an integral or unitary vial assembly 153 as shown in
The assembled multi-vial assembly 100 may then be slid lengthwise into a slot 36 of the freezer box 30 as shown in
When it is desired to access a sample, the assembly 100 is withdrawn from the freezer box slot 36. The locking pin handle 134 may be used to assist in removal, such as by grasping or engaging the handle 134 with a hook. The locking pin 130 is counter-rotated and withdrawn from the members 110, 120. The top member 110 can then be lifted and the selected vial or vials 150 can be independently removed from the bottom member 120. The top member 110, locking pin 130 and sleeve 140 can be reinstalled to reassemble the assembly 100, after which the assembly 100 can be re-inserted in the freezer box slot 36 and re-stored in the freezer chamber 22.
According to some embodiments, the width W2 and length L2 (
According to some embodiments, the width W2 and length L2 are each less than 12 mm and, according to some embodiments, are each in the range of from about 8 to 12 mm. According to some embodiments, the height H2 is in the range of from about 25 to 48 mm.
According to some embodiments and as illustrated, the multi-vial assembly 100 is substantially rectangular or square in cross-section so that the shape thereof is complementary in size and shape to the freezer box slot 36. In this manner, the assembly 100 can ensure that the vials 150 are maintained upright and the available volume of the slot 36 can be used more efficiently. However, in some embodiments, the multi-vial assembly 100 may have a different cross-sectional shape, such as a round or square shape with beveled or rounded corners.
With reference to
With reference to
The vials 210 may be substantially identical or may vary in sample capacity, for example. An exemplary vial 210A is shown in detail in
The vials 210 may be formed of the same materials as described above with regard to the vials 150.
Each vial 210A-E may have indicia 217 corresponding to the indicia 157.
The vial chamber 214 includes a main vial chamber 214A and an annular lower subchamber 214B. According to some embodiments, each vial chamber 214 has a volume in the range of from about 100 to 400 μl.
The sleeve 240 is tubular and, in the illustrated embodiment, circular in cross-section. The sleeve 240 may include indicia 242 corresponding to the indicia 142 described above. Additionally, indicia may also be fabricated on or affixed to the individual vials themselves, in which case, the sleeve 240 could be optional. The sleeve 240 may be formed of the same materials as described above with regard to the sleeve 140.
The multi-vial assembly 200 may be assembled and used as follows. A respective sample A (
Once the unit 204 is assembled (
When a user desires to access a sample, the assembly 200 is withdrawn from the freezer box slot 36. The sleeve 240 is removed from the unit 204. The user may then unscrew and independently remove a selected vial 201A-D from the remaining vials of the unit 204 to access the contents of the removed vial. Typically, the user will remove the lower endmost vial; however, other removal sequences may be employed.
After the desired vial or vials 210A-D have been removed, the sleeve 240 can be re-placed on the unit 204 and the assembly 200 can be re-installed in the freezer box slot 36 and the freezer 20.
According to some embodiments, the outer diameter D4 (
According to some embodiments, the assembly 200 occupies at least 50% of the horizontal cross-sectional area of the freezer box slot 36. According to some embodiments, the diameter D4 is in the range of from about 6 to 12 mm. According to same embodiments, the height H4 (
The vials 210A-E may have heights and outer diameters appropriate to provide the above-described dimensions and to fit snugly within the sleeve 240. According to some embodiments, the assembly 200 includes at least three vials 210, according to some embodiments, at least five vials 210, and, according to some embodiments, at least nine vials. For example,
Optionally, seal members may be provided between the adjacent vials 210A-E. For example, parafilm, a cap liner, O-rings or Teflon seals may be provided to resist leakage, evaporation or “freezer burn”. In some cases (not shown) a separate plug or stopper may be provided for each vial 210 and may include a pull tab to assist in removal.
With reference to
As further alternatives, the multi-vial assemblies 100, 200, 300 may be constructed without sleeves 140, 240. In this case, the dimensions of the remaining components may be selected to provide overall dimensions for the assemblies 100, 200, 300 in the above-described ranges.
According to some embodiments, the vials 210, 310, 410 may be provided with texturing or features such as fins that facilitate grasping and rotating the vials to screw and unscrew the vials.
According to some embodiments, the individual vials 150, 210, 310, 410 may each include respective label indicia directly secured to or embedded therein to identify the vial. Similarly, the sleeves 140, 240 can be provided with identifying indicia 142, 242. The indicia may comprise two or three dimensional barcodes representing serial numbers on each vial in case the aliquots or samples are not identical or to maintain identification during sample processing. For example, as shown in
Because the bottom of each vial 210, 310, 410 is flat and the height is greatly reduced, the center of gravity of the vial is very low in comparison to conventional microfuge tubes and the vial provides a stable base. These vials 210, 310, 410 may thus permit pipetting without a rack and/or the vials may be mounted in a “stocks”-type frame to enable easy organization similar to 96-well plate configurations and to facilitate use of automated sample handing systems.
Multi-vial assemblies and cryostorage systems as described herein can enable the storage of multiple solid (e.g., paper strips or tissue) or liquid (e.g., serum or plasma) biological samples in the same space currently required for storage of a single specimen in a conventional microfuge tube. Each multi-vial assembly may be configured to fit into an individual slot of a commercially available cryostorage “freezer box” designed for 2 ml cryovials (i.e., of the type typically stored in −80° C. freezers or liquid nitrogen tanks). For example, each multi-vial assembly may have a nominal diameter of about 12 mm and a height of about 47 mm, consistent with current cryostorage devices. Liquid samples captured in the individual vials (e.g., each having a capacity of 100 to 400 microliters) of a multi-vial assembly can be stored and removed from storage independently, without thawing the remaining samples in the multi-vial assembly.
A removable plastic sleeve supporting a barcode label or other identification label can serve to maintain the orientation of the vials, protect users from liquid nitrogen-related vial ruptures, and/or allow exchange of the labeling without sample freeze-thaw.
Multi-vial assemblies and cryostorage systems of the present invention can not only conserve valuable cryogenic storage space, but can also provide more sample aliquots that have not been repeatedly freeze-thawed, and can provide storage volumes more consistent with testing devices that increasingly are designed for smaller sample volumes.
The foregoing is illustrative of the present invention and is not to be construed as limiting thereof. Although a few exemplary embodiments of this invention have been described, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the claims. Therefore, it is to be understood that the foregoing is illustrative of the present invention and is not to be construed as limited to the specific embodiments disclosed, and that modifications to the disclosed embodiments, as well as other embodiments, are intended to be included within the scope of the appended claims. The invention is defined by the following claims, with equivalents of the claims to be included therein.
Claims
1. A multi-vial assembly for containing a plurality of samples in a cryostorage system, the multi-vial assembly comprising:
- a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly;
- wherein the vials are independently removable from the integral vial assembly to permit selective access to the respective samples.
2. The multi-vial assembly of claim 1 wherein the multi-vial assembly is sized to removably and replaceably fit within a microfuge tube slot of a freezer box.
3. The multi-vial assembly of claim 1 wherein each of the vial chambers of the vials has a capacity in the range of from about 100 to 200 μl.
4. The multi-vial assembly of claim 1 wherein the multi-vial assembly has a height in the range of from about 25 to 48 mm, and a width in the range of from about 8 to 12 mm.
5. The multi-vial assembly of claim 1 including a sleeve removably surrounding the integral vial assembly.
6. The multi-vial assembly of claim 5 including identification indicia on the sleeve.
7. The multi-vial assembly of claim 5 further including identification indicia on each of the vials.
8. The multi-vial assembly of claim 1 including a support assembly supporting and coupling the vials, the support assembly including at least one support member to receive and hold the vials.
9. The multi-vial assembly of claim 8 wherein the support assembly holds the vials in fixed relation to one another.
10. The multi-vial assembly of claim 9 wherein:
- the support member includes a plurality of first mounting features;
- the vials each include a second mounting feature configured to engage a respective one of the first mounting features to positively position the vial on the support member; and
- the first mounting features are one of plugs and sockets, and the second mounting features are the other of plugs and sockets.
11. The multi-vial assembly of claim 9 wherein:
- the support assembly includes a top support member and a bottom support member engaging upper and lower ends of the vials, respectively; and
- the top member serves as a closure for the vial chambers of the vials.
12. The multi-vial assembly of claim 9 wherein the support assembly includes a locking member selectively operable to secure the support assembly to the vials and release the support assembly from the vials.
13. The multi-vial assembly of claim 8 including a sleeve removably surrounding the integral vial assembly and the support assembly.
14. The multi-vial assembly of claim 1 wherein the vials are stacked on one another to form the integral vial assembly.
15. The multi-vial assembly of claim 14 wherein the stacked vials are directly coupled to one another.
16. The multi-vial assembly of claim 15 wherein:
- the vials each include an integral inner screw thread and an integral outer screw thread; and
- the stacked vials are directly coupled to one another by threaded engagement between their respective inner and outer screw threads.
17. The multi-vial assembly of claim 15 wherein at least one of the stacked vials serves as a closure for the vial chamber of another, immediately adjacent one of the stacked vials.
18. The multi-vial assembly of claim 1 wherein each of the vial chambers includes an upper main subchamber and a tapered lower subchamber.
19. The multi-vial assembly of claim 1 wherein the vials are formed of polypropylene.
20. A method for storing and handling a plurality of samples in a cryostorage freezer, the method comprising:
- providing a multi-vial assembly including: a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly; wherein the vials are independently removable from the integral vial assembly to permit selective access to the respective samples;
- placing the samples in respective ones of the vial chambers;
- placing the multi-vial assembly in a freezer chamber of a cryostorage freezer; and
- selectively removing one or more of the vials from the multi-vial assembly to selectively access the samples placed in the vial chambers of the removed vials.
21. The method of claim 20 including:
- providing a freezer box defining a plurality of microfuge tube slots;
- seating the multi-vial assembly in one of the microfuge tube slots;
- removing the multi-vial assembly from the microfuge tube slot; and thereafter
- removing the one or more of the vials from the multi-vial assembly to selectively access the samples placed in the vial chambers of the removed vials.
22. A microsample cryostorage system for containing a plurality of samples, the microsample cryostorage system comprising:
- a cryostorage freezer having a freezer chamber; and
- a multi-vial assembly disposed in the freezer chamber and including: a plurality of vials each defining a vial chamber to hold a respective sample and coupled together to form an integral vial assembly; wherein the vials are independently removable from the integral vial assembly to permit selective access to the respective samples.
23. The microsample cryostorage system of claim 22 including a freezer box disposed in the freezer chamber and defining a plurality of microfuge tube slots, wherein the multi-vial assembly is removably seated within one of the microfuge tube slots.
Type: Application
Filed: Dec 14, 2011
Publication Date: Jan 16, 2014
Applicant: The University of North Carolina at Chapel Hill (Chapel Hill, NC)
Inventor: David A. Barrow (Chapel Hill, NC)
Application Number: 13/977,878
International Classification: B65D 25/04 (20060101);