US20070102393A1

US20070102393A1 - Specimen enclosure apparatus and containers and closure devices for the same

Info

Publication number: US20070102393A1
Application number: US11/523,306
Authority: US
Inventors: Bruno Colin; Sylvain Baeyaert; Chris Ronsick; Mark Wilson; Ron Robinson
Original assignee: Biomerieux SA
Current assignee: Biomerieux SA; Biomerieux Inc
Priority date: 2005-09-20
Filing date: 2006-09-19
Publication date: 2007-05-10
Also published as: CA2622752A1; WO2007035746A3; JP2009508781A; WO2007035746A2; EP1926556A2; CN101287553A; AU2006292280A1; CN101287553B

Abstract

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. Containers and closure devices are also provided.

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'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 6F 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 β₁, 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 β₂, 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 7A-7D.
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 7A-7D will now be further described with reference to FIGS. 13A-13B and 14A-14B, 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. 16C. 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.

Claims

1. A specimen enclosure apparatus, comprising:

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 positioned intermediate the neck of the container; and

a closure device configured to be received in the opening, the closure device having a flange seal portion configured to contact the internal flange to form a flange seal proximate the cavity and having 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.

2. The apparatus of claim 1, wherein the neck further comprises a plug sealing cylindrical surface extending from proximate the internal flange away from the cavity and wherein the radial travel limiter comprises a mating plug sealing cylindrical surface configured to form a plug seal with the plug sealing cylindrical surface of the neck, the flange seal being positioned between the plug seal and the cavity.

3. The apparatus of claim 2, wherein the flange seal comprises an internal flange seal and wherein the container further comprises an external flange positioned at an end of the neck away from the cavity and wherein the closure device further comprises an external flange seal portion configured to contact the external flange to form an external flange seal at the end of the neck with the plug seal being positioned between the external flange seal and the internal flange seal.

4. The apparatus of claim 2, wherein the closure device is positioned in the opening and wherein the apparatus further comprises 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.

5. The apparatus of claim 4, wherein the closure member comprises a crimp seal, a screw cap and/or a tear-off seal.

6. The apparatus of claim 2, wherein the closure device is positioned in the opening and wherein an edge of the flange seal adjacent the opening is positioned to be directly exposed to moist heat during sterilization.

7. The apparatus of claim 2, wherein the closure device is positioned in the opening and wherein the closure device further comprises 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.

8. The apparatus of claim 7, wherein the degassing extension member includes 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.

9. The apparatus of claim 8, wherein an edge of the flange seal adjacent the opening is positioned to be directly exposed to moist heat during sterilization.

10. A specimen enclosure apparatus, comprising:

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 covering the opening, the closure device having 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 and having 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.

11. The apparatus of claim 10, wherein the apparatus further comprises a closure member coupled to the container that retains the closure device covering the opening and compresses the flange seal.

12. The apparatus of claim 11, wherein the closure member comprises a crimp seal, a screw cap and/or a tear-off seal.

13. The apparatus of claim 10, wherein an edge of the flange seal adjacent the opening is positioned to be directly exposed to moist heat during sterilization.

14. The apparatus of claim 10, wherein the closure device further comprises 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.

15. The apparatus of claim 14, wherein the degassing extension member includes 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.

16. The apparatus of claim 15, wherein the tab comprises a circumferentially extending ridge and wherein the degassing extension member further comprises a slot extending past the ridge to define the passage along the exterior surface of the neck.

17. The apparatus of claim 10, wherein the neck further comprises a plug sealing cylindrical surface defined by the exterior surface of the neck and wherein the radial travel limiter comprises 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.

18. The apparatus of claim 17, wherein the apparatus further comprises a closure member coupled to the container that retains the closure device covering the opening and compresses the flange seal.

19. The apparatus of claim 17, wherein the closure member further compresses the radial seal.

20. The apparatus of claim 17, wherein the neck further includes a narrowed portion and an intermediate portion extending from the narrowed portion to the plug sealing cylindrical surface and wherein the closure member engages the intermediate portion to retain the closure device.

21. The apparatus of claim 1, wherein the closure member comprises a crimp seal, a screw cap and/or a tear-off seal.

22. A container for a specimen enclosure apparatus, the container comprising:

a main portion including a cavity configured to receive the specimen;

a neck extending from the main portion;

an opening extending through the neck to the cavity;

an internal flange 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; and

a radial travel limiting contact surface in the opening that is configured to contact the closure device to limit radial movement of the flange seal.

23. The container of claim 22, wherein the radial travel limiting contact surface comprises 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.

24. The container of claim 23, further comprising 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.

25. A closure device for a specimen enclosure apparatus, the closure device comprising:

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

a radial travel limiter integrally formed with the flange seal portion that 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.

26. The closure device of claim 25, wherein the radial travel limiter comprises 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.

27. The closure device of claim 26, further comprising 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.

28. The closure device of claim 26, further comprising 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.

29. The closure device of claim 28, wherein the degassing extension member includes 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.