Abstract:
Containers that are suitable for long-term and efficient storage, tracking, and manual or robotic manipulation of cryopreserved biological materials, in particular human tissue samples, are disclosed herein. According to one exemplary embodiment disclosed herein, a container may include a receptacle and a plurality of projections. The receptacle may include a lower wall and a side wall. The side wall may have an inner surface. The plurality of projections may extend upward along and outward from the inner surface of the side wall. The plurality of projections may define a region for receiving a sample having an orientation and may be shaped and arranged to inhibit a change in the orientation of the sample when stored in the container.

Description:
REFERENCE TO RELATED APPLICATIONS  
       [0001]    This application claims priority to U.S. Provisional Application No. 60/254,239, filed Dec. 8, 2000, the contents of which are incorporated by reference herein. 
     
    
     
       BACKGROUND  
         [0002]    Cryopreservation or freezing at very low temperatures has been an effective method for long-term preservation of biological materials. The goal of cryopreservation is to preserve the structural integrity and viability of biological materials for an indefinite period of time.  
           [0003]    Cryopreservation typically involves enclosing biological material within a freezing medium to be frozen and preserved in an ampoule or a tube. Because of their shape, these ampoules or tubes are difficult to stack, thereby impeding efficient storage and retrieval of the biological materials contained therein. As a result, standard storage vials are often stored in freezers using ordinary plastic bags or cardboard boxes. These conventional approaches to storage have proven to be inadequate for maintaining and tracking a large inventory of specimens.  
           [0004]    Further, cataloging specimens in these standard storage vials is often difficult and time consuming. Usually, labeling of the specimens consists of writing notes on the side of an ampoule or tube by hand. Upon freezing and thawing several times, the writing can become illegible. Consequently, frozen specimens are sometimes misused, misplaced or even lost.  
           [0005]    Accordingly, there remains a need in the art for a cryopreservation container suitable for efficient long-term storage, tracking, and retrieval of biological materials, and that also overcomes the current difficulties associated with standard storage vials.  
         SUMMARY  
         [0006]    Containers that are suitable for long-term and efficient storage, tracking, and manual or robotic manipulation of cryopreserved biological materials, in particular human tissue samples, are disclosed herein. The containers disclosed herein can be used as a part of an automated inventory management system for frozen tissue samples.  
           [0007]    According to one exemplary embodiment disclosed herein, a container may include a receptacle and a plurality of projections. The receptacle may include a lower wall and a side wall. The side wall may have an inner surface. The plurality of projections may extend upward along and outward from the inner surface of the side wall. The plurality of projections may define a region for receiving a sample having an orientation and may be shaped and arranged to inhibit a change in the orientation of the sample when stored in the container.  
           [0008]    According to another exemplary embodiment disclosed herein, a container may include a base, a receptacle, a cover, a marking panel, and a plurality of projections. The base may have a top surface and a first end. The receptacle may extend upward from the top surface of the base and have an inner surface and a cross-section that has a substantially circular shape. The cover may threadably engage the receptacle and form a fluid-tight seal with the receptacle for confining a sample within the receptacle and inhibiting desiccation of the sample. The marking panel may extend from the first end of the base and may have a substantially planar surface for receiving identifying indicia. The plurality of projections may extend upward along and outward from the inner surface of the receptacle and upward from the top surface of the base. A projection may have at least a first side, a second side, and a third side, in which the first side faces the inner surface of the receptacle, the second and third sides are substantially planar, and the second side is oriented in a direction perpendicular to the third side. The plurality of projections may be shaped and arranged to inhibit a change in the orientation of a sample when stored in the container.  
           [0009]    According to another exemplary embodiment disclosed herein, a base may have a bottom surface. The bottom surface may have a plurality of protrusions projecting downward therefrom. The protrusions may be shaped and arranged to permit an identification panel containing identifying indicia to be removably and securely attached to the container. 
       
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]    These and other features of the containers disclosed herein will be more fully understood by reference to the following detailed description in conjunction with the attached drawings in which like reference numerals refer to like elements throughout the different views. While the drawings illustrate principles of the containers disclosed herein, they are not drawn to scale, but show only relative dimensions.  
         [0011]    [0011]FIG. 1A is a top perspective view of an embodiment of the cryopreservation container disclosed herein.  
         [0012]    [0012]FIG. 1B is a bottom perspective view of the cryopreservation container in FIG. 1A.  
         [0013]    [0013]FIG. 2A is a top view of a cover.  
         [0014]    [0014]FIG. 2B is a view of the underside of the cover in FIG. 2A.  
         [0015]    [0015]FIG. 2C is a sectional view of the cover of FIG. 2A along line C-C, showing internal threads.  
         [0016]    [0016]FIG. 3A is top view of the cryopreservation container of FIG. 1A.  
         [0017]    [0017]FIG. 3B is a sectional view of the bottom of the cryopreservation container of FIGURE 1A.  
         [0018]    [0018]FIG. 3C is a sectional view of the cryopreservation container of FIG. 3A along line C-C, showing external threads.  
         [0019]    [0019]FIG. 4 is a sectional view of the cryopreservation container of FIG. 3A along line A-A, illustrating a cover attached to the receptacle.  
         [0020]    [0020]FIG. 5 is a sectional view of the cryopreservation container of FIG. 1A, showing a flat marking surface.  
         [0021]    [0021]FIG. 6 is a top view of a receptacle, showing an alternative configuration of projections.  
         [0022]    [0022]FIG. 7A is a top perspective view of another embodiment of the cryopreservation container disclosed herein.  
         [0023]    [0023]FIG. 7B is a bottom perspective view of the cryopreservation container in FIG. 7A. 
     
    
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS  
       [0024]    Certain exemplary embodiments will now be described to provide an overall understanding of the principles of the containers disclosed herein. One or more examples of these embodiments are illustrated in the drawings. Those of ordinary skill in the art will understand that the containers described herein can be adapted and modified to provide instruments and methods for other suitable applications and that other additions and modifications can be made without departing from the scope of the containers disclosed herein. For example, the features illustrated or described as part of one embodiment or one drawing can be used on another embodiment or another drawing to yield yet another embodiment. Such modifications and variations are intended to be included within the scope of the present disclosure.  
         [0025]    An exemplary embodiment of a container for storing cryopreserved material is illustrated in FIGS.  1 - 7 . As shown in FIGS.  1 - 7 , the container  10  includes a base  12 , a receptacle  14 , a cover  16 , and a marking panel  18 .  
         [0026]    As shown in FIGS. 1A and 1B, the base  12  has a substantially rectangular shape. The base  12  may, however, have a variety of shapes. For example, the base  12  may have the shape of any type of polygon, including a square, a rectangle, and a triangle, or the shape of any type of oval, including an ellipse and a circle.  
         [0027]    As shown in FIGS. 1A and 1B, the base  12  has a substantially planar top surface  100  and a bottom surface  102  that has a recessed interior portion  104  and a raised exterior portion  106 . The top and bottom surfaces  100 ,  102  of the base may have a variety of other constructions, as provided below.  
         [0028]    An alternative construction of the base  12  is illustrated in FIGS. 7A and 7B. As shown in FIGS. 7A and 7B, the bottom surface  102  of the base  12  may include protrusions  112  shaped and arranged to permit an identification panel containing indicia identifying the contents of the container  10  to be securely and removably attached to the container  10 . The identification panel may be any structure known to one of ordinary skill in the art for containing indicia, including, but not limited to, impressions or protrusions in any type of surface, such as writing on paper, embossing on plastic, or a bar code designed to be read by an optical scanner.  
         [0029]    As shown in FIGS. 3A, 3B, and  3 C, the container  10  includes a receptacle  14 . The receptacle  14  may be formed integral with the base  12 , or the receptacle may be formed separately and attached to the base using any securing means known to one of ordinary skill in the art, including, but not limited to, an adhesive and a weld. Apart from being permanently attached to the container  10 , the receptacle  14  may be removably and replaceably attached to the container  10 .  
         [0030]    As shown in FIGS. 3A, 3B, and  3 C, the receptacle  14  is defined by a wall  36  that extends upward from the top surface  100  of the base  12 . The wall  36  may extend in a direction substantially perpendicular to the base  12 , and the receptacle  14  may have cross-section that is substantially circular and consistent in diameter throughout the upward extent of the wall  36 . The receptacle  14  may, however, have a variety of other constructions. The receptacle  14  may have the shape of a cylinder, a cone, a bowl, or a box. The receptacle  14  may have a cross-section that has the shape of any type of polygon, including a square, a rectangle, and a triangle, or any type of oval, including a circle and an ellipse. Moreover, the receptacle  14  may have a cross-section that has a first extent that varies over the upward extent of the wall  36 . For example, the receptacle  14  may have a circular cross-section characterized by a diameter that varies over the upward extent of the wall  14 . Additionally, the receptacle  14  may have a cross-section whose basic shape varies over the upward extent of the wall. For example, the receptacle  14  may have a square cross-section for a first portion of its height and a circular cross-section for a second portion of its height.  
         [0031]    In alternative embodiments, the container  10  may be constructed without a base  12 . In these embodiments, and other embodiments in which the receptacle  14  is separate or removable from the base  12 , the receptacle  14  is defined by a lower wall and a side wall. In those embodiments in which the receptacle  14  is attached to the base  12 , the top surface  100  of the base  12  provides the lower wall of the receptacle  14 .  
         [0032]    As shown in FIGS. 3A, 3B, and  3 C, projections  26  are enclosed within the wall  36  of the receptacle  14 . The projections  26  are shaped and arrange to inhibit a change in the orientation and position of a sample within the container  10 . The wall  36  has an inner surface  30  and an outer surface  32 . As shown in FIGS. 3A, 3B, and  3 C, the projections  26  may extend upward from the top surface  100  of the base  12  along the inner surface  30  of the wall  36 . The projections  26  may also have a variety of other positions. For example, the projections  26  may not be contiguous with the base  12 , but may simply project upward along and outward from the inner surface  30  of the wall  36 . Alternately, the projections  26  may not be contiguous with the wall  36 , but may simply project upward from the top surface  100  of the base  12 . The projections  26  may be formed integral with the base  12 , the wall  36 , or both the base  12  and the wall  36 . Alternately, the projections  26  may be formed separately and attached to the base  12 , the wall  36 , or both the base  12  and the wall  36  using any means known to one of ordinary skill in the art, including, but not limited to, an adhesive or a weld. Apart from being permanently attached to the container  10 , the projections  26  may be removably and replaceably attached to the container  10 .  
         [0033]    As shown in FIGS. 3A, 3B,  3 C and  6 , the projections  26  decrease the space within the receptacle  14 , thereby defining a region for receiving a sample. The projections  26  are shaped and arranged within the receptacle  14  to inhibit a sample from rotating from a desired orientation and moving from a desired position. The projections  26  may have a variety of shapes and arrangements in addition to those shown in FIGS. 3A, 3B,  3 C, and  6 . For example, the projections  26  may have cross-sections that are hemispherical. Additionally, the projections  26  may extend along the entire upward extent of the wall  36 , or the projections  26  may extend along only a portion of the upward extent of the wall  36  in order to accommodate samples having different shapes. For example, in one embodiment, as shown in FIG. 3C, the projections  26  may extend only partway along the upward extent of the wall  36  in order to accommodate samples that have mushroom-like shapes.  
         [0034]    As shown in FIGS. 1A and 1B, the container  10  includes a cover  16  removably attached to the container  10  for confining the sample within the container  10 .  
         [0035]    As shown in FIG. 2C, the cover  16  may threadably engage the container  10 . The cover  16  may have internal threads  24  that engage external threads  28  formed on the outer surface  32  of the wall  36  of the receptacle  14 . Rotation of the cover  16  relative to the base  12  and the receptacle  14  may be used for opening and closing the container  10 . Rotation may occur in either the clockwise or counter-clockwise direction. Preferably, rotation in one direction is used to open the container  10 , and rotation in the opposite direction is used to close the container  10 . Preferably, the rotation is not greater that 360° in either direction to open or close the container, and most preferably the rotation is 270°.  
         [0036]    Additionally, the cover  16  may engage the receptacle  14  to provide a fluid-tight seal, thereby inhibiting desiccation of the contents. Also, the cover may engage the receptacle so as to provide a seal that withstands at least approximately 80 kPa of internal pressure, and preferably at least approximately 95 kPa of internal pressure.  
         [0037]    The cover  16  may be removably attached to the receptacle  14  by using any structure known to one of ordinary skill in the art, including, but not limited to, a press-fit or a snap-on mechanism.  
         [0038]    The cover  16  may also have a variety of shapes, provided that it is mated to the receptacle  14  to confine the sample within the container  10 . The cover  16  may be shaped so as to have a portion that fits around the outer surface of the wall  36 , or the cover may be shaped so as to have a portion that fits inside the wall  36 . For example, as shown in FIG. 4, the cover  16  may have a lip  38  that engages the inner surface  30  of the wall  36  of the receptacle portion  14  in a substantially fluid-tight seal to inhibit degradation of a sample in the container  10 . As shown in FIGS. 1A and 1B, the outer surface of the cover  16  may contain serrations  40  to facilitate gripping or robotic manipulation.  
         [0039]    As shown in FIGS. 4 and 5, the container  10  includes a marking panel  18  for receiving indicia identifying the contents of the container  10 . The marking panel  18  may be formed integrally with the base  12 , or may be formed separately and attached to the base using any means known to one of ordinary skill in the art, including, but not limited to, an adhesive and a weld. Apart from being permanently attached to the container  10 , the marking panel  18  may be removably and replaceably attached to the container  10 . The marking panel  18  may include a substantially smooth surface to facilitate observation of identifying indicia positioned thereon. As shown in FIG. 4, in one embodiment, the marking panel  18  may form an angle  110  with the top surface  100  of the base  12 , and may be formed by a recess  46  in the underside of the base  12 . Alternative constructions of the marking panel  18  and alternative angles  110  are possible. For example, the marking panel may form any angle  110  with the top surface  100  that is greater than 90 degrees. Additionally, as shown in FIG. 5, in another embodiment, the marking panel  18  may be flat  48 , that is, may form an angle 110 of 180 degrees with the top surface  100  of the base  12 , and may be formed by extending one side of the base  12 .  
         [0040]    The base  12 , receptacle  14 , and cover  16  are constructed from polymeric material. The cover  16  may be constructed from a different polymeric material than the receptacle  14  to inhibit the binding of the receptacle  14  and the cover  16  at low temperatures. For example, the cover  16  may be made of polyethylene, and the receptacle  14  may be made of polypropylene. The container  10  may also be fabricated from any other material suitable for cryopreservation, including, but not limited to, glass, stainless steel, and any other inert metal.  
         [0041]    The base  12 , receptacle  14 , and cover  16  may be constructed to be transparent to facilitate observation and identification of a sample within the container  10 . Alternately, the base  12 , receptacle  14 , and cover  16  may be constructed to be opaque to prevent light from degrading a sample within the container  10  during storage.  
         [0042]    The receptacle  14  and the cover  16  may be coated with one or more layers of one or more biologically inert materials to facilitate cryopreservation in various chemical environments. The receptacle and the cover may also be coated with one or more layers of one or more biologically inert materials to enhance resistance to corrosion by substances used in cryopreservation.  
         [0043]    The containers disclosed herein are compatible with a variety of biological samples. Suitable biological samples for the containers disclosed herein include, but are not limited to, samples derived from human tissue, animal tissue, and plant tissue by any means known to one of ordinary skill in the art.  
         [0044]    While the containers disclosed herein have been particularly shown and described with reference to the exemplary embodiments thereof, those of ordinary skill in the art will understand that various changes may be made in the form and details herein without departing from the spirit and scope of the disclosure. Those of ordinary skill in the art will recognize or be able to ascertain many equivalents to the exemplary embodiments described specifically herein by using no more than routine experimentation. Such equivalents are intended to be encompassed by the scope of the present disclosure and the appended claims.