Patent Publication Number: US-2007102393-A1

Title: Specimen enclosure apparatus and containers and closure devices for the same

Description:
RELATED APPLICATION  
      The present application claims the benefit of and priority from U.S. Provisional Application No. 60/718,655, (Attorney Docket No. 01072), filed Sep. 20, 2005, the disclosure of which is hereby incorporated herein in its entirety by reference. 
    
    
     BACKGROUND OF THE INVENTION  
      The present invention relates to apparatus for enclosing a specimen, reagants and components thereof. In particular, the present invention relates to an apparatus for enclosing a specimen that can be used in a microbial detection and/or characterization system.  
      Various apparatus for enclosing specimens are known in the art. Typically, such apparatus include a specimen container or bottle and a closure or stopper for the specimen container or bottle. Further, several types of closures are known for use with specimen containers or bottles. A standard closure, for example, for medical vials is a rubber stopper. A rubber stopper can seal a vial or bottle by either a plug seal or a flange seal. A plug seal may be provided by compressing the rubber stopper in the neck of a bottle.  FIGS. 1A and 1B  show a simple plug stopper  100  where the plug seal  106  is defined by contact between the cylindrical surface of the stopper  100  and the neck  108  of the bottle  102 . The closure holding the stopper in the bottle is not shown in  FIGS. 1A and 1B . The stopper  100  may be sealed in the neck  108  of the bottle  102  by radial R compression. This compression may be induced by the interference of the stopper  100  with the bottle neck  108 . The stopper plug  100  may, therefore, have an outer diameter greater than the inner diameter of the neck  108  of the bottle to cause the stopper  100  to be compressed. This plug seal  106  may also be referred to as a valve seal.  
      A flange seal  104  may be created by contact between a flange  104   a , which is the horizontal surface of the stopper, and a top horizontal surface  104   b  of the bottle  102 . The compression where these two surfaces mate may be provided by a closure member, which may be applied over the stopper  100  and onto the bottle  102 . Examples of these closures may be a crimp seal, a screw cap or a tear-off seal. The stopper  100  may seal to the top surface  104   b  of the bottle  102  by being compressed by the closure. In contrast to a plug seal, which typically relies on geometric interference with the bottle, a flange seal is generally compressed by the closure and this sealing force (compression) can generally be controlled by the equipment that applies the stopper.  
      Lyophilization stoppers are another known type of stopper used in the pharmaceutical industry. Typically, these stoppers  110  contain a slot  114  in the stopper legs  116  as seen in  FIGS. 2A through 2C . The stopper  110  may be held above the vial  112  by protruding nibs  118 , which position ( FIG. 2C ) allows gas to be evacuated from the vial  112  through the slots  114  in the stopper  110 . At the end of the degassing process, the stopper  110  may be pressed into the vial (bottle)  112  and seal the bottle  112  through a flange and/or a plug seal ( FIG. 2A ). A plug seal and flange seal have been described above. The limitations of a standard lyophilization stopper depend on the applications of the product. The standard lyophilization stopper typically has two legs  116  that deflect in towards the bottle  112  due to the compression of the stopper  110  into the bottle  112 . This can be seen in a finite element analysis model shown in  FIG. 3 . Due to the plug seal and the geometric interference, the legs  116  of the stopper  110  generally deflect in towards the center of the vial. The vial is not shown for clarity. The stopper and crimp shown above are modeled in a cross section in  FIG. 3 , because the boundary and load conditions in  FIG. 3  are symmetric about the center plane.  
      For aseptic product applications, which generally use autoclave terminal sterilization, the movement of the surface contact (interface) between the stopper and bottle or vial can make it difficult to sterilize this interface. In an autoclave process, the product is typically placed into an autoclave and steam heats the product for at least 15 minutes at 121° C. The steam outside the product transfers heat to the interior contents of the vial, which heat vaporizes moisture in the vial. This moist heat is then transferred to the inner surfaces of the bottle, which kill microorganisms and spores. The rate of kill for microorganisms (bacteria, molds etc) depends on the amount of time exposed to this moist heat. For an effective rate of lethality, the microorganisms typically are exposed directly to moist heat (steam).  FIG. 4  illustrates two zones where moist and dry heat may be transferred to the stopper/vial interface. As can be seen in  FIG. 4 , steam from the heated moisture inside the vial does not penetrate into first zone  124 , as the stopper  120  is compressed against the bottle  122  in the first zone  124 . Dry heat may still be transferred to this area  124  and this area  124  may still reach the temperature of the autoclave (standard cycle temperature 121° C.). However, dry heat is generally not as effective at killing microorganisms as moist heat. The second zone  126  is exposed directly with moist heat due to clearance between the stopper  120  and the bottle (vial)  122 .  
      In addition to lyophilization stoppers, which generally seal with a plug and a flange seal, septums may also be used to seal a vial. This type of stopper/seal may be a circular elastomeric material. An advantage of a septum (flange) seal is that there is no plug seal. The plug seal may move away from the bottle neck during shipping or rough handling. In addition, the contact area of a plug seal may change with pressure inside the bottle or vary with the crimping pressure on the stopper. If the contact area changes after the product is terminally sterilized in an autoclave, microorganisms trapped in the plug seal may come into contact with the product.  
      A septum stopper may eliminate the problems with a plug seal as no plug seal is provided. However, a plug seal may be beneficial to retaining the seal integrity of the product. In addition, a plug seal may be more stable in the vial than the flange only seal of a septum stopper. A septum stopper generally may move radially, as there is no plug seal preventing this radial movement. This radial movement may break the integrity of the flange seal between the septum and vial. Secondly, the plug seal may be more stable in the bottle during the assembly of the stopper to the vial. A crimp seal placed over the septum may move the septum and compromise the seal integrity.  FIG. 5  shows the cross-section of a septum  130  forming a flange seal with a bottle (vial)  132 . The illustrated flange seal is between the flat surface of the septum  130  and the top surface  134  of the vial  132 . A closure (not shown) compresses the septum  130  on top of the vial  132 .  
     SUMMARY OF THE INVENTION  
      Embodiments of the present invention include a specimen enclosure apparatus. The specimen enclosure apparatus includes a container having a cavity configured to receive the specimen and an opening extending through a neck of the container to the cavity. An internal flange is positioned intermediate the neck of the container. The specimen enclosure apparatus further includes a closure device configured to be received in the opening. The closure device has a flange seal portion configured to contact the internal flange to form a flange seal proximate the cavity and further has a radial travel limiter integrally formed with the closure device that is configured to contact the container in the opening to limit radial movement of the flange seal portion relative to the internal flange.  
      In further embodiments, the neck further includes a plug sealing cylindrical surface extending from proximate the internal flange away from the cavity. The radial travel limiter is a mating plug sealing cylindrical surface configured to form a plug seal with the plug sealing cylindrical surface of the neck. The flange seal is positioned between the plug seal and the cavity.  
      In other embodiments, the flange seal is an internal flange seal and the container further includes an external flange positioned at an end of the neck away from the cavity. The closure device further includes an external flange seal portion configured to contact the external flange to form an external flange seal at the end of the neck. The plug seal is positioned between the external flange seal and the internal flange seal.  
      In further embodiments, the closure device is positioned in the opening and the apparatus further includes a closure member extending over the closure device and coupled to the container that retains the closure device in the opening and compresses the flange seal. The closure member may be a crimp seal, a screw cap and/or a tear-off seal. An edge of the flange seal adjacent the cavity may be positioned to be directly exposed to moist heat during sterilization of the apparatus.  
      In other embodiments, the closure device further includes a degassing extension member extending from the flange seal portion into the cavity that is configured to retain the closure device in a degassing position in the opening defining a passage from the cavity through the opening through which a gas may be moved into and out of the cavity. The degassing extension member may include a plurality of tabs extending from an exterior surface thereof configured to engage the neck in the opening to retain the closure device in the degassing position and to displace the exterior surface of the degassing extension member from the neck to define the passage from the cavity through the opening.  
      In yet further embodiments, specimen enclosure apparatus include a container having a cavity configured to receive the specimen and an opening extending through a neck of the container to the cavity and a closure device. The closure device covers the opening and has a flange seal portion configured to contact an external flange seal portion on an end of the neck of the container displaced from the cavity to form a flange seal closing the opening. The closure device further has a radial travel limiter integrally formed with the closure device that contacts an exterior surface of the neck to limit radial movement of the flange seal portion of the closure device relative to the external flange seal portion of the container. The apparatus may further include a closure member coupled to the container that retains the closure device covering the opening and compresses the flange seal.  
      In other embodiments, the closure device further includes a degassing extension member extending from the flange seal portion along an exterior surface of the neck that is configured to retain the closure device in a degassing position defining a passage from the cavity through the opening through which a gas may be moved into and out of the cavity. The degassing extension member may include a tab extending from a surface thereof configured to engage the exterior surface of the neck to retain the closure device in the degassing position. The tab may be a circumferentially extending ridge and the degassing extension member may further include a slot extending past the ridge to define the passage along the exterior surface of the neck.  
      In further embodiments, the neck further includes a plug sealing cylindrical surface defined by the exterior surface of the neck and the radial travel limiter is a mating plug sealing cylindrical surface configured to form a radial seal with the plug sealing cylindrical surface of the neck, the flange seal being positioned between the radial seal and the cavity. The apparatus may further include a closure member coupled to the container that retains the closure device covering the opening and compresses the flange seal. The closure member may further compress the radial seal. The neck may further include a narrowed portion and an intermediate portion extending from the narrowed portion to the plug sealing cylindrical surface and the closure member may engage the intermediate portion to retain the closure device.  
      In yet other embodiments, containers for a specimen enclosure apparatus include a main portion including a cavity configured to receive the specimen and a neck extending from the main portion. An opening extends through the neck to the cavity. An internal flange is positioned intermediate the neck of the container that is configured to contact a flange seal portion of a closure device to form a flange seal proximate the cavity. A radial travel limiting contact surface is provided in the opening that is configured to contact the closure device to limit radial movement of the flange seal. The radial travel limiting contact surface may be a plug sealing cylindrical surface extending from proximate to the internal flange away from the cavity that is configured to form a plug seal with the closure device. The container may further include an external flange positioned at an end of the neck away from the cavity that is configured to contact the closure device to form an external flange seal, the plug seal being positioned between the flange seal formed by the internal flange and the external flange seal.  
      In further embodiments, closure devices for a specimen enclosure apparatus include a flange seal portion configured to contact an internal flange positioned intermediate a neck of a container configured to receive the specimen to form a flange seal proximate the cavity and further include a radial travel limiter. The radial travel limiter is integrally formed with the flange seal portion and is configured to contact the container in an opening extending through the neck to the cavity to limit radial movement of the flange seal portion relative to the internal flange. The radial travel limiter may be a mating plug sealing cylindrical surface extending from the flange seal portion that is configured to form a plug seal with a plug sealing cylindrical surface extending from the internal flange of the container away from the cavity of the container. The closure device may further include an external flange seal portion configured to form a further flange seal with an external flange of the container positioned at an end of the neck away from the cavity, the plug seal being positioned between the flange seal and the further flange seal.  
      In yet other embodiments, the closure device further includes a degassing extension member extending from the flange seal portion and away from the radial travel limiter that is configured to retain the closure device in a degassing position in the opening defining a passage from the cavity through which a gas may be moved into and out of the cavity. The degassing extension member may include a plurality of tabs extending from an exterior surface thereof configured to engage the neck in the opening to retain the closure device in the degassing position and to displace the exterior surface of the degassing extension member from the neck to define the passage.  
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       FIG. 1A  is a cross-sectional view illustrating the flange and plug areas of a conventional stopper in a specimen bottle.  
       FIG. 1B  is a bottom perspective view of the stopper of  FIG. 1A .  
       FIG. 2A  is a perspective view illustrating a conventional lyophilization stopper insert to a sealed position in a specimen bottle according to the prior art.  
       FIG. 2B  is a bottom perspective view illustrating the lyophilization stopper of  FIG. 2A .  
       FIG. 2C  is a perspective view illustrating of the arrangement of  FIG. 2A  with the stopper in a degassing position.  
       FIG. 3  illustrates a finite element analysis of the lyophilization stopper shown in  FIG. 2A .  
       FIG. 4  is a cross-sectional view illustrating the interface between a stopper and a vial including two areas of the interface of a plug seal therebetween according to the prior art.  
       FIG. 5  is a cross-sectional view of a conventional septum forming a flange seal with a vial according to the prior art.  
       FIGS. 6A through 6D  illustrate a closure device for a specimen container according to some embodiments of the present invention.  
       FIGS. 6E through 6F  illustrate a closure device for a specimen container according to other embodiments of the present invention.  
       FIG. 6G  is a perspective view of a closure device for a specimen container according to further embodiments of the present invention.  
       FIGS. 7A through 7D  illustrate a closure device for a specimen container according to yet further embodiments of the present invention.  
       FIG. 8  is a perspective view of a specimen container according to some embodiments of the present invention.  
       FIG. 9A  is a cross-sectional view of the neck of the specimen container of  FIG. 8 .  
       FIG. 9B  is a cross-sectional view of the neck of conventional specimen container.  
       FIG. 10  is a front elevational view of the specimen container shown in  FIG. 8 .  
       FIG. 11  is a cross-sectional view of the specimen container shown in  FIG. 8 .  
       FIG. 12  is a cross-sectional view of the closure device shown in  FIG. 6A  placed in the specimen container shown in  FIG. 8 .  
       FIGS. 13A and 14A  are cross-sectional views illustrating the closure devices of  FIGS. 6A and 7A , respectively, in the degassing position in the specimen container shown in  FIG. 8 .  
       FIGS. 13B and 14B  are cross-sectional views illustrating the closure devices of  FIGS. 6A and 7A , respectively, in the sealing/closed position in the specimen container shown in  FIG. 8 .  
       FIG. 15  is a perspective view illustrating a closure device according to further embodiments of the present invention.  
       FIG. 16A  is a cross-sectional view illustrating the neck area of a specimen enclosure apparatus in a degassing position according to further embodiments of the present invention.  
       FIG. 16B  is a front perspective view illustrating the neck area of a specimen enclosure apparatus of  FIG. 16A  in a sealed/closed position.  
       FIG. 16C  is a cross-sectional view illustrating the neck area of the specimen enclosure apparatus  FIG. 16B . 
    
    
     DETAILED DESCRIPTION OF EMBODIMENTS OF THE 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, although the terms first, second, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present invention.  
      Spatially relative terms, such as “beneath”, “below”, “lower”, “above”, “upper” and the like, may be used herein for ease of description to describe one element or feature&#39;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 “below” or “beneath” other elements or features would then be oriented “above” the other elements or features. Thus, the exemplary term “below” can encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90° or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.  
      As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless expressly stated otherwise. It will be further understood that the terms “includes,”“comprises,”“including” 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. It will be understood that when an element is referred to as being “connected” or “coupled” to another element, it can be directly connected or coupled to the other element or intervening elements may be present. Furthermore, “connected” or “coupled” as used herein may include wirelessly connected or coupled. As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items.  
      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.  
      Closure devices according to some embodiments of the present invention will now be described with reference to  FIGS. 6A through 6G .  FIG. 6A  is a perspective view of a closure device  200   a .  FIG. 6B  is a top plan view,  FIG. 6C  is a front view, and  FIG. 6D  is a bottom plan view of the closure device  200   a  of  FIG. 6A .  FIGS. 6E  and  6 F show a closure device  200   b  that differs in the number of tabs provided relative to the closure device  200   a  of  FIGS. 6A through 6D  (three versus four). The closure device  200   c  shown in  FIG. 6G  differs in that a depression  204  is not included in a top surface  202  of the closure device. The closure devices (stoppers) shown in  FIGS. 6A-6G  may be inserted into a container of a specimen enclosure apparatus (see  FIG. 8 ) to provide two flange seals and one plug seal.  
      Referring first to  FIGS. 6A through 6D , the closure device  200   a  is illustrated as an elastomeric stopper extending along a central axis A. As used herein, references to longitudinal will refer to a direction extending along the central axis A, circumferential will refer to extending around the central axis A, and radial will refer to a radial direction as illustrated by the arrow R in  FIG. 6A . The closure device  200   a  is configured to be received in an opening to a specimen container, such as illustrated in  FIG. 8 . The illustrated closure device  200   a  includes an internal flange seal portion  206  and an external flange seal portion  210 . The internal flange seal portion  206  is configured to contact an internal flange of a specimen container to form a flange seal proximate the specimen cavity of the container. The external flange seal portion  210  is configured to contact an external flange of the container to form an external flange seal at the end of a neck of the enclosure. The flange seal formed by the internal flange seal portion  206  has an edge positioned adjacent to the cavity, which is positioned to be directly exposed to moist heat during sterilization of the specimen in the container.  
      The closure device further includes a radial travel limiter  208 , integrally formed with the closure device  200   a , that is configured to contact the specimen container in an opening to the container to limit radial movement of the flange seal portion  206  relative to the internal flange of the container. More particularly, as illustrated in  FIGS. 6A through 6D , the radial travel limiter is a mating plug sealing cylindrical surface  208  configured to form a plug seal with a plug sealing cylindrical surface in the neck of the container. As such, the internal flange seal formed using the internal flange seal portion  206  is positioned between the plug seal formed by the mating plug sealing cylindrical surface  208  and the specimen-containing cavity of the container when the closure device  200   a  is inserted in the container. In other words, as seen in  FIG. 12 , the closure device  200   a  may be pressed into the opening in the neck of the container  400  to position an internal flange seal  450  between a cavity  402  and a plug seal  452 . As seen in  FIG. 12 , of the plug seal  452  is positioned between the internal flange seal  450  and an external flange seal  454 .  
      As also seen in the embodiments of  FIGS. 6A through 6D , the closure device  200   a  includes a degassing extension member  212 . The degassing extension member  212  extends longitudinally towards the cavity  402  as best seen in  FIG. 12 . The degassing extension member  212  is configured to retain the closure device  200   a  in a degassing position in the opening of the container and to define a passage  460  ( FIG. 13A ) from the cavity  402  through the opening through which a gas may be moved into and out of the cavity  402 . More particularly, as illustrated in the embodiments of  FIGS. 6A through 6D , the degassing extension member  212  includes a plurality of tabs  214  extending from an exterior surface thereof. The tabs  214  are configured to engage the neck of the container to retain the closure device  200   a  in a degassing position and to displace the exterior surface of the degassing extension member  212  from the neck to define a passage from the cavity through the opening.  
      In the embodiments illustrated in  FIGS. 6A through 6D , a top surface  202  of the closure device  200   a  includes a depression  204  in a central region thereof. The depression  204  may be used, for example, for insertion of a needle or the like through the closure device  200   a  to withdraw a specimen from the cavity  402 . Furthermore, as discussed above, the mating plug sealing cylindrical surface  208  may be used to form a plug seal. Accordingly, a diameter of the mating plug sealing surface  208  may be selected to provide an interference fit with a smaller diameter opening in the neck of the container to provide a desired compression of the closure device  200   a  in forming the plug seal. Similarly, a closure member  407  ( FIG. 13B ) as will be discussed further herein may extend over the closure device  200   a  and may be coupled to a container to retain the closure device  200   a  and to compress the closure device  200   a  longitudinally to form flange seals with the respective flange seal portions  206 ,  210 .  
      Referring now particularly to  FIG. 6D , it can be seen that a total of four tabs  214  are provided in the illustrated embodiments. More particularly, the tabs  214  extend circumferentially a length defined by the angle α. Similarly, the respective tabs  214  are displaced from each other (center to center) by an angle β 1 , appearing as 90° in  FIG. 6D  where each of the four tabs  214  are uniformly located around the circumference of the closure device  200   a . It will be understood that more or less tabs  214  may be used and that the tabs need not be uniformly spaced or sized in some embodiments. As also shown in  FIG. 6D , the degassing extension member  212  may include a longitudinally extending hollow core  220 . However, it will be understood that the degassing extension member  212  may be a solid elastomeric member and need not include the hollow core  220 .  
      Further embodiments of a closure device  200   b  are illustrated in  FIGS. 6E through 6G . As shown in the embodiments of  FIGS. 6E and 6F , three tabs  214  are provided, each uniformally displaced from the other tabs by an angle β 2 , shown as 120° in  FIG. 6F . Note that, as with the description of  FIG. 6D  above, a uniform spacing of the tabs  214  may not be provided in other embodiments of the present invention. The closure device  200   b  shown in  FIGS. 6E and 6F  may operate otherwise substantially as described with reference to the embodiments of  FIGS. 6A through 6D . The closure device  200   c  illustrated in  FIG. 6G  differs in that a top surface  202 ′ thereof does not include the depression  204  shown in  FIG. 6A . Various like numbered elements in  FIG. 6G  may otherwise be described substantially as previously described with reference to  FIGS. 6A through 6F .  
      A closure device according to further embodiments of the present invention will now be described with reference to  FIGS. 7A through 7D .  FIG. 7A  is a perspective view of a closure device  300 .  FIG. 7B  is a top plan view,  FIG. 7C  is a front view, and  FIG. 7D  is a bottom plan view of the closure device  300  of  FIG. 7A . The closure device (stopper)  300  shown in  FIGS. 7A-7D  may be inserted into a container of a specimen enclosure apparatus (see  FIG. 8 ) to provide one flange seal and one plug seal. In other words, the closure device  300  shown in  FIGS. 7A through 7D  eliminates the top (external) flange seal, i.e., the flange seal that mates with the top surface of the vial.  
      As seen in the embodiments of  FIGS. 7A through 7D , the closure device  300  extends longitudinally along a central axis A. The closure device  300  is shown as an elastomeric stopper for closing a specimen enclosure apparatus. A top surface  302  of the closure device  300  includes a depression  304  that may be used substantially as described with reference to the depression  204  of  FIG. 6A . A flange seal portion  306  is configured to contact the internal flange positioned intermediate a neck of a container configured to receive the specimen to form a flange seal proximate a cavity containing the specimen in the container. A radial travel limiter  308  is integrally formed with the flange seal portion  306 . The radial travel limiter  308  is configured to contact the container in an opening extending through a neck of the container to the cavity to limit radial movement of the flange seal portion  306  relative to an internal flange of the container. As more particularly shown in the embodiments of  FIGS. 7A through 7D , the radial travel limiter is a mating plug sealing cylindrical surface  308  extending from the flange seal portion  306  that is configured to form a plug seal with a plug sealing cylindrical surface extending from the internal flange of the container away from the cavity. This arrangement can be seen, for example, in  FIG. 14B  where the closure device  300  is shown inserted in a neck  406  of the container of the specimen and closure apparatus.  
      Also, shown in the embodiments of  FIGS. 7A through 7D  is a degassing extension member  312  extending from the flange seal portion  306  and away from the radial travel limiting mating plug sealing cylindrical surface  308 . The degassing extension member  312  is configured to retain the closure device  300  in a degassing position in the opening of the container to define a passage  460 ′ from the cavity  402  through which a gas may be moved into and out of the cavity as seen in  FIG. 14A . More particularly, in the illustrated embodiments, the degassing extension member  312  includes a plurality of tabs  314  extending from an exterior surface thereof configured to engage the neck in the opening to retain the closure device  300  in the degassing position and to displace the exterior surface of the degassing extension member  312  from the neck to define the passage  460 ′.  
      As more particularly seen in the view of  FIG. 7D , the illustrated embodiments of  FIGS. 7A through 7D  include a total of four uniformly circumferentially placed tabs  314  and the degassing extension member  312  includes a longitudinally extending hollow core  320 . However, as described previously with reference to the embodiments of  FIGS. 6A through 6G , more or less tabs  314 , which may be uniformly or non-uniformly spaced, may be used in some embodiments and the degassing extension member  312  may be solid without the hollow core  320  in some embodiments.  
       FIG. 8  illustrates a specimen container  400  or vial according to some embodiments of the present invention. As will be described herein, the neck  406  of the container  400  of  FIG. 8  includes an internal step, which forms a flange seal with a closure device as described with reference to  FIGS. 6A-6G  and  7 A- 7 D.  
      A container  400  for a specimen enclosure apparatus according to some embodiments of the present invention will now be further described with reference to  FIGS. 8, 10  and  11 .  FIG. 8  is a perspective view of the container  400 ,  FIG. 10  is a front plan view, and  FIG. 11  is a cross-sectional view of the container  400 . As seen in the embodiments of  FIGS. 8, 10  and  11 , the container  400  includes a main portion  408  including a cavity  402  configured to receive the specimen. A neck  406  extends upwardly longitudinally from the main portion  408 . An opening  404  extends through the neck  406  to the cavity  402  defined by the main portion  408 .  
      An internal flange  410  is positioned intermediate the neck  406  of the container  400 . The internal flange  410  is configured to contact the flange seal portion  206 ,  306  of the closure device  200   a ,  200   b ,  200   c ,  300  to form a flange seal proximate the cavity  402 .  
      Also shown in the embodiments of  FIGS. 8, 10  and  11  is a radial travel limiting contact surface  412  in the opening  404 . The radial travel limiting contact surface  412  is configured to contact the closure device  200   a ,  200   b ,  200   c ,  300  to limit radial movement of the flange seal  450  ( FIG. 12 ). More particularly, as shown in  FIGS. 8, 10  and  11 , the radial travel limiting contact surface is a plug sealing cylindrical surface  412  extending from proximate to the internal flange  410  away from the cavity  402  that is configured to form a plug seal with a closure device  200   a ,  200   b ,  200   c ,  300 .  
      The container  400  illustrated in  FIGS. 8, 10  and  11  further includes an external flange  414  including a raised portion  416  positioned at an end of the neck  406  away from the cavity  402 . The external flange  414  is configured to contact the closure device  200   a ,  200   b ,  200   c ,  300  to form an external flange seal  454  ( FIG. 12 ). As best seen in  FIG. 12 , the plug seal  452  is positioned between the internal flange seal  450  formed by the internal flange  410  and the external flange seal  454 . As such, the internal flange seal  450  is positioned between the plug seal  452  and the cavity  402 .  
      As also shown in the embodiments of the container  400  in  FIGS. 8, 10  and  11 , the container  400  is configured to mate with a closure member retaining a closure device  200   a ,  200   b ,  200   c ,  300  in the opening  404 . In particular, the neck  406  includes a narrowed portion  430  and an intermediate portion  432  extending from the narrowed portion  430  to the longitudinally extending member  420  defining the plug sealing cylindrical surface  412 . A closure member may, thus, be crimped or the like around the neck portion  406  to engage an intermediate portion  432  to retain the closure device  200   a ,  200   b ,  200   c ,  300  in the opening  404  and to apply longitudinal forces for forming respective flange seals  450 ,  454 . The narrowed portion  430  is further shown as having an internal surface  418  configured to engage the tabs  214 ,  314  to hold a closure device  200   a ,  200   b ,  200   c ,  300  in the degassing position as seen in  FIGS. 13A and 14A , respectively.  
      A standard vial  140  generally contains straight sides  144  in the neck of the bottle as shown in  FIG. 9B . As shown in  FIG. 9A , a neck  356  of a container  350  includes an internal step  360 . An opening  354  extends through the neck  356  to a cavity  352  defined by a main body  358  of the container  350 . Further, there are three surfaces  360 ,  362 ,  364 / 366  for sealing with a stopper of the present invention, such as the closure device of  FIGS. 6A-6F . Only two of these, the lower flange surface  360  and the plug surface  362 , may be used when a stopper, such as the closure device of  FIGS. 7A-7D  is used.  FIGS. 9A and 9B  differ in that the neck of the container  350  shown in  FIG. 9A  has a flange seal between the vial contents and the plug seal, whereas the neck of standard vial  140  as shown in  FIG. 9B  does not have such a flange seal, although the sides  144  may provide a plug seal and an external flange seal may be provided by the surface  142 .  
       FIG. 12  shows the placement of the closure device  200   a  of  FIG. 6A  in the container (vial) of  FIG. 8 , including a main body  408  defining a cavity  402  for receiving a specimen. There are three sealing surfaces in the vial as compared to two in a standard vial. The vial has an internal flange which mates with the stopper flange to form an internal flange seal  450 . An external flange seal  454  is also shown with a plug seal  452  between the flange seals  450 ,  454 . The crimp seal or closure is not shown for clarity.  
      As can be seen in  FIG. 12 , an edge of the internal flange seal  450  may be placed in direct contact with the product (specimen) contents. On top of the internal flange seal  450  is the plug seal  452 . This is the reverse of most standard stoppers, in which a plug seal is in direct contact with the product contents and a flange seal is behind this plug seal.  
      In the stopper shown in  FIG. 12 , the internal flange seal  450  is in direct contact with the product contents, which may allow for moist heat to penetrate the product contact surfaces. The flange seal  450  between the stopper and specimen container or vial may be a more controlled surface and may be less variable in contact than a plug seal. The stopper compression at this flange seal may be set by the closure force, which is in contrast to a plug seal that relies on the geometric interference to maintain compression. By also incorporating a plug seal, the seal integrity of the product may be more robust than if the flange seal were used alone.  
      In some embodiments of the present invention, the plug seal is isolated from the vial contents. This may result in a higher rate of lethality of microorganisms during a terminal sterilization process.  
      The degassing process using the closure devices of  FIGS. 6A-6G  and  7 A- 7 D will now be further described with reference to  FIGS. 13A-13B  and  14 A- 14 B, respectively. The illustrated closure devices (stoppers)  200   a ,  300  include four tabs (nibs)  214 ,  314  at the end of the stopper  200   a ,  300 , although fewer or more nibs can be used. These nibs  214 ,  314  have a geometrical interference with the neck  406  of a bottle. Further, these nibs  214 ,  314  are compressed into the inner neck  418  of a bottle and hold the stopper  200   a ,  300  above the surface of the bottle. Gases can be evacuated or added to the bottle through a passage  460 ,  460 ′ defined by the annulus between the stopper and the inner neck of the bottle, up between the stopper nibs  214 ,  314 . After the degassing process is complete, the stopper  200   a ,  300  may be pressed into the bottle and the sealing surfaces of the stopper seals the contents as seen in  FIGS. 13B and 14B , respectively.  
       FIG. 15  is a perspective view illustrating a closure device (stopper)  500  according to yet further embodiments of the present invention. The stopper  500  of  FIG. 15  does not have a large plug seal. The illustrated stopper  500  includes a cap part  507  defining a flange seal surface  506  and an extension part  512 . The extension part  512  includes 6 tabs (nibs)  508  defining a radial travel limiter. However, more or less tabs  508  may be provided. Furthermore, it will be understood that the cap part  507  may define a plug seal exterior circumferential surface that forms a plug seal with a mating surface of a receiving container, where a flange seal formed by the flange seal surface  506  will be positioned between the contents of the container and the plug seal.  
      A specimen enclosure apparatus  600  according to further embodiments of the present invention will now be described with reference to  FIGS. 16A through 16C .  FIG. 16A  is a cross-sectional view illustrating a degassing position while  FIG. 16C  is a cross-sectional view illustrating a closed or sealed position.  FIG. 16B  is a perspective view illustrating the closed position of  FIG. 16C . As seen in the embodiments of  FIGS. 16A through 16C , a container  408 ′ has a cavity  402 ′ configured to receive the specimen. An opening  404 ′ extends through a neck  406 ′ of the container  408 ′ to the cavity  402 ′. A closure device  601  covers the opening  404 ′. The closure device  601  has a flange seal portion  606  that is configured to contact an external flange seal portion  414 ′ on an end of the neck  406 ′ of the container  408 ′ displaced from the cavity  402 ′ to form a flange seal  450 ′ ( FIG. 16C ). The flange seal  450 ′ closes the opening  404 ′. The closure device further includes a radial travel limiter  608  integrally formed with the closure device  601  that contacts an exterior surface  420 ′ of the neck  406 ′ to limit radial movement of the flange seal portion  606  of the closure device  601  relative to the external flange seal portion  414 ′ of the container  408 ′.  
      As seen in  FIGS. 16B , a closure member  407 ,  407 ′,  407 ″ is coupled to the container  408 ′ that retains the closure device  601  covering the opening  404 ′ and compresses the flange seal  450 ′. The closure member  407 ,  407 ′,  407 ″ may be a crimp seal, a screw cap, a tear-off seal and/or the like with a septum liner. The closure member  407 ,  407 ′,  407 ″ may be metal and/or plastic. As seen best in  FIG. 16C , an edge  620  of the flange seal  450 ′ adjacent the opening  404 ′ is positioned to be directly exposed to moist heat during sterilization.  
      The illustrated closure device  601  of  FIGS. 16A through 16C  further includes a degassing extension member  612  extending from the flange seal portion  606  along an exterior surface of the neck  406 ′ that is configured to retain the closure device  601  in degassing position ( FIG. 16A ) defining a passage from the cavity  402 ′ through the opening  404 ′ through which a gas may be moved into and out of the cavity  402 ′. As more particularly shown in the embodiments of  FIGS. 16A through 16C , the degassing extension member  612  includes a tab  614  extending from a surface thereof configured to engage the exterior surface  420 ′of the neck  406 ′ to retain the closure device  601  in the degassing position shown in  FIG. 16A . More particularly, the illustrated tab  614  is a circumferentially extending ridge  614  and the degassing extension member  612  further includes a plurality of slots  615  extending past the ridge  614  to define the passage along the exterior surface of the neck.  
      As also shown in the embodiments of  FIGS. 16A through 16C , the neck  406 ′ includes a plug sealing cylindrical surface defined by the exterior surface  420 ′ of the neck  406 ′. The radial travel limiter is formed by a mating plug sealing cylindrical surface  608  of the closure device  601  that is configured to form a radial seal  652  ( FIG. 16C ) with a plug sealing cylindrical surface  420 ′ of the neck  406 ′. The flange seal  450 ′ is positioned between the radial seal  652  and the cavity  402 ′ as seen in FIG.  16 C. As such, the closure member  407 ,  407 ′,  407 ″ may serve to compress both the flange seal  450 ′ and the radial seal  652 . Note that references to a radial seal herein refer to the radial direction in which the seal forming forces are imparted by the closure member  407 ,  407 ′,  407 ″. In contrast, a plug seal, as discussed above, is formed by geometric interference of the fit of the closure device into an opening in the neck of the container. Thus, in the embodiments of  FIGS. 16A through 16C , a flange seal is positioned with an edge in direct contact to the cavity so as to be exposed to moist heat, while the radial seal is positioned outside the container  408 ′ forming a seal with an exterior surface thereof with a flange seal  450 ′ positioned between the radial seal  652  and the specimen contents of the cavity  402 ′.  
      Some embodiments of the present invention can be used in products other than those which require terminal sterilization, such as lyophilized products including pharmaceuticals. The process of degassing described above with various stoppers of the present invention is similar to that in a lyophilization process. Lyophilized products generally require that ambient moisture does not penetrate into the vial and cause melt-back of the lyophilized product. Some embodiments of the present invention provide stoppers having three sealing surfaces that may have a high level of seal integrity. Secondly, injectable pharmaceutical products generally must be sterile as the contents are injected into a patient. The flange seal in proximity to the sample contents may prevent specimens, such as microorganisms, on the plug seal surface from entering the vial contents. The flat surface of the stopper in some embodiments can typically be easily sterilized with UV or other sterilization, whereas the cylindrical plug surface may be more difficult.  
      Example stoppers such as illustrated in  FIGS. 6A and 7A  and a vial as illustrate in  FIG. 8  may be made from stereolithography models and cast into polyurethane models. The final polyurethane models may have  50  Shore A hardness that is a typical durometer of elastomer stoppers. A prototype model of the vial may be made by stereolithography and may be tested with the stopper prototypes for fit.  
      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. In the claims, means-plus-function clauses are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures. 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.