Abstract:
A seal cap assembly for use with a biological specimen container, the cap assembly including an integral ampoule that holds a pre-filled agent. A piercer is movably disposed in the cap assembly to pierce into the ampoule. When the cap assembly is attached to a biological specimen container, the ampoule is pierced, the pre-filled agent in the ampoule is mixed with the specimen, and the seal cap assembly seals the biological specimen container. The seal cap assembly, together with a biological specimen container, permits stabilization, storage, and transport of biological fluid samples.

Description:
RELATED APPLICATIONS 
       [0001]    The present application claims the benefit of U.S. Provisional Patent Application No. 61/548,473, filed Oct. 18, 2011, which application is incorporated by reference herein in its entirety. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The present invention relates generally to biological specimen containers. More particularly, the present invention relates to containers used for collecting, storing, and transporting biological specimens to be used in assays, and more particularly to containers that chemically enhance the biological specimen. 
       BACKGROUND 
       [0003]    Bodily fluids are collected for various reasons, including diagnosing illness, simple therapeutic removal, determining pregnancy, confirming or establishing levels of therapeutic agents, determining drug abuse, and profiling DNA composition. Blood, urine, and saliva are among the commonly collected bodily fluids for some or all of these purposes. 
         [0004]    A variety of methods are used to collect bodily fluids, depending on the fluid and the intended use, and a corresponding variety of bottles, tubes, and other containers are employed to store and transport the fluids. The containers for holding the specimens must be both sealed and conveniently accessed. Commonly, these containers are a specimen tube with a sealing cap. 
         [0005]    Often, immediately upon or shortly after their collection, bodily fluids must be chemically treated. Examples of required treatments are anticoagulants added to blood to prevent coagulation, lysing agents added to blood to burst cells, test reagents added to urine for drugs of abuse testing, and so on. Another example is saliva samples, for which preservative buffering solutions are often added to prevent destruction of components in the saliva. Saliva used for drugs of abuse testing or genetic testing often requires this treatment to maintain its composition for those purposes. 
         [0006]    Because of the parallel needs to 1) store or transport biological specimens, and 2) chemically treat them, there is a need for container devices that can accept, chemically treat, and seal a biological specimen in a simple, convenient, reliable way. 
         [0007]    One example of a container for collection of fluids is the BD Vacutainer® Blood Collection Tube produced by Becton, Dickinson and Company. These tubes are used to collect venous blood, and are an evacuated test tube with a rubber stopper. A conduit needle connects the test tube to venous blood through the rubber stopper. Blood is drawn into the test tube because the tube is evacuated and sealed with the rubber stopper during its manufacture. Appropriate chemicals, for example anticoagulants or preservatives, are pre-filled in the test tube to chemically treat the collected blood sample. 
         [0008]    However, not all bodily fluids are or can be collected using evacuated tubes. Saliva, for example, is often collected either by inserting a sponge into the mouth or by spitting into a funnel-like container. In those cases, mixing the sample with chemical treatments requires different devices and methods. For the former, it is common to drop the saliva-saturated sponge into a test tube that contains a liquid buffer. Because the tube must be opened to add the sponge, the liquid buffer can be lost, unless extra care is taken to avoid tipping the tube until it is resealed. For the latter, simply adding a liquid buffer to the bottom of a closed funnel would be unsuitable for most saliva donations due to the possibilities of spilling or ingesting the buffer. 
         [0009]    U.S. Pat. No. 5,335,673 to Goldstein, et al, discloses a device and method for collecting, chemically treating, and storing a saliva sample. The donor saturates a wand-mounted sponge with saliva by inserting the sponge into the mouth. The sponge is then inserted into a container which holds the required chemical treatment in liquid form. The wand is snapped off, leaving the sponge in the tube, after which the tube is sealed with a cap. Devices such as this are commercially available, including the Intercept® Oral Fluid Drug Test sold by OraSure Technologies of Bethlehem, Pa., and the Quantisal™ Oral Fluid Collection Device sold by Immunalysis Corporation of Pomona, Calif. Devices similar to these suffer from several drawbacks. First, collecting saliva with a mouth-inserted sponge is uncomfortable for the donor. Also, collecting and confirming an adequate volume of sample is not assured. Also, as previously mentioned, the liquid buffer can easily be lost if the tube is inadvertently tipped. 
         [0010]    US Patent Application No. 20090216213 to Muir, et al, and US Patent Application No. 20110212002 to Curry, et al, disclose saliva collection devices wherein the donor spits into a short, round collection vessel, and a funnel-like collection vessel, respectively. In neither application does the liquid chemical agent simply reside in the collection vessel, but is instead sealed in a cap. Once the donation is complete, the cap is affixed to the collection container, whereby the liquid chemical is released to mix with the saliva. This arrangement prevents the undesirable possibility that the liquid chemical can be spilled, or worse, ingested, during the donation process. In both of these devices, a liquid buffer is pre-filled in the cap and sealed with a membrane. The membrane is punctured by cutting elements disposed in the collection containers, or portions thereof. Nevertheless, the devices disclosed in these patent applications exhibit drawbacks as well. For example, direct expectoration into an open container is clumsy and unsanitary. Donors may miss the funnel or container when spitting, may dribble sputum onto themselves or the administrator, and may spill the container, all with negative consequences. The requirement for repetitious and sequential positioning and spitting is cumbersome and exhausting. Also, the arrangement of features designed to puncture the membrane and free the liquid from the cap requires that sharp cutting elements be disposed in close proximity to the donor. This can be hazardous to the donor. 
         [0011]    A specific drawback of Muir et al. includes the disclosed aspect ratio of the specimen container. The container diameter must be relatively large to accept the expectorated saliva, but this means that determining the actual volume of saliva accumulated is difficult. Curry et al. avoids that drawback by making the funnel separate and separable from the specimen container. But this arrangement suffers from increased complexity and additional parts. Once the donation is complete, the first cap, containing the liquid buffer, is affixed, which releases the buffer into the saliva. Next, that cap assembly must be removed, after which a seal cap is attached to the specimen container. Both of these applications disclose sample collection systems with pre-filled caps for which the cap puncturing features are disposed in the collection container or portions thereof. This arrangement leads to many drawbacks for these devices, including, for example, the aforesaid set of drawbacks. 
         [0012]    U.S. Pat. No. 4,723,687 to Kutterer and U.S. Pat. No. 5,505,326 to Junko are prior art examples of caps with piercing elements disposed in the cap. These piercing elements pierce liquid containers that have been sealed with membranes over their openings. Neither of these, however, has a receptacle or vessel for mixing two components. Neither do they have compartments in the cap itself to hold a chemical constituent. 
         [0013]    Additional prior art patents and applications include U.S. Pat. No. 4,150,950 to Takeguchi, et al., U.S. Pat. No. 5,283,038 to Seymour, U.S. Pat. No. 5,339,829 to Thieme, et al., U.S. Pat. No. 5,566,859 to Willis, et al., U.S. Pat. No. 5,567,309 to Classon, et al., U.S. Pat. No. 7,854,343 to Ellson, et al., U.S. Pat. No. 7,854,895 to Gallagher, et al., US Patent Application No. 20020015663 to Goldstein, et al. 
         [0014]    No prior art patents or available devices adequately address the need to collect, treat, and store a biological sample in a simple-to-use, convenient, low-cost device. Therefore, there remains a need for a biological collection system that employs a pre-filled cap assembly for which the pre-filled agent is held in an ampoule and is accessible by puncturing into the ampoule, and for which the puncturing elements are disposed in the cap assembly, and also for which the act of applying the cap assembly to the collection container substantially at once exposes the pre-filled agent, allows mixing of the pre-filled agent and the biological sample, and seals the mixture within the assembly. 
       SUMMARY OF THE INVENTION 
       [0015]    The present invention is a seal cap assembly for use with a biological specimen container. The cap includes an integral ampoule, or a vessel, that holds a pre-filled agent, such as a diluent, reagent, preservative, buffer solution, or the like, which is mixed with the specimen when the cap assembly is attached to the specimen container. Because of the pre-filled agent, which mixes into the biological specimen, the seal cap assembly permits stabilization, storage, and transport of biological fluid samples. 
         [0016]    The cap assembly comprises, in one preferred embodiment, a housing, which includes a vessel, a liquid chemical agent filled into the vessel, a pierceable sealing membrane covering the opening of the vessel, a piercer to penetrate the membrane for access to the liquid in the vessel, and appropriate connecting features, such as screw threads, to mate with a specimen container. 
         [0017]    In typical use, a biological sample is first collected into a collection tube. Then the cap assembly is inserted, advanced, and screwed onto the collection tube. This attachment action causes the piercer to advance, thereby penetrating the sealing membrane. Once this membrane is pierced, the liquid agent contained in the cap is free to flow into the collection tube and mix with the specimen contained therein. Simultaneous with advancing of the piercer (i.e. as the collection tube is inserted and screwed into the cap), seals are created between the cap assembly and the collection tube. This prevents either the specimen, the chemical agent, or the resultant mixture from coming out of the closed assembly, and allows for safe, secure transport or storage of the stabilized biological specimen. Whenever access to the specimen mixture is required, for example to remove some or all for a chemical assay, the cap assembly is removed from the collection tube. The specimen is then poured or pipetted out. 
         [0018]    One suitable application of the present invention is to stabilize, store, and transport an oral fluid, or saliva sample for subsequent laboratory testing of genetic composition or for drugs of abuse. In those cases, one suitable method for collecting saliva is described in U.S. patent application Ser. No. 13/214,722 for a SALIVA COLLECTION DEVICE, which is hereby incorporated by reference herein. The device disclosed in that application collects a neat saliva sample. Other methods of collecting the saliva sample may also be used with the present invention. For example, either an oral sponge device or a spit funnel device may be used to collect a saliva sample, and the corresponding specimen container can be used with the present invention. Saliva, due to its chemical nature, is not adequately stable for use in some tests with some time delays. Therefore the present invention can be used to stabilize the collected saliva sample, and to seal it in the collection tube, thus facilitating transport and stable storage until the desired laboratory test or assay can be completed. 
         [0019]    An object of the present invention is to provide a safe, convenient, inexpensive sealing cap that is pre-filled with a chemical agent, and that is used to stabilize, store, and transport a biological specimen in a specimen container. 
     
    
     
       DESCRIPTION OF THE DRAWINGS 
         [0020]      FIG. 1  is an overall assembly perspective drawing showing an ampoule cap assembly according to an embodiment of the present invention and a mating specimen collection tube. 
           [0021]      FIG. 2  is an exploded perspective view of an ampoule camp assembly according to an embodiment of the present invention. 
           [0022]      FIG. 3  is a cross-section view of an embodiment of present invention in a ready-to-use state. 
           [0023]      FIG. 4  is a cross section view showing an ampoule cap assembly of an embodiment of the present invention at the beginning position of engagement to a specimen tube containing a specimen. 
           [0024]      FIG. 5  is a detail cross-section view of an ampoule cap assembly of an embodiment of the present invention in partial engagement with a specimen tube, wherein access to the ampoule portion of ampoule cap assembly has begun. 
           [0025]      FIG. 6  is a detail cross-section view of an ampoule cap assembly of an embodiment of the present invention fully engaged with the specimen tube, and wherein the fill agent has exited from the ampoule cap assembly. 
           [0026]      FIG. 7  is a full cross-section view showing an ampoule cap assembly of an embodiment of the present invention fully engaged with the specimen tube, and the resulting mixture of pre-filled agent and specimen. 
           [0027]      FIG. 8  is a perspective view of the sealing membrane in the as-pierced configuration for one embodiment of the present invention. 
           [0028]      FIG. 9  is a perspective cross-section view of piercer showing the internal feature of one embodiment of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0029]      FIG. 1  shows one embodiment of an ampoule cap assembly  101  of the present invention. Ampoule cap assembly  101  can removably attach to a specimen tube  103  by way of external threads  105 , said threads in particular embodiments may be internally oriented. Ampoule cap assembly  101  has corresponding internal threads, as well as other suitable mating features to attach ampoule cap assembly  101  to specimen tube  103 . Specimen tube  103  will have been filled with a suitable volume of a biological sample fluid that needs chemical conditioning prior to storage, transport, or testing. 
         [0030]      FIG. 2  shows the constituent components of an embodiment of ampoule cap assembly  101 , starting with an ampoule cap housing  201 . The constituent components and their functions and characteristics are described in greater detail later in this disclosure. A pre-filled agent  203  is loaded into the ampoule cap housing  201  through vessel opening  205 . Pre-filled agent  203  is captured and sealed within ampoule cap housing  201  via sealing membrane  207 . Piercer  209  movably assembles into the ampoule cap housing  201 . Ampoule cap housing  201  may incorporate ribs  211  to aid the user in assembling and tightening of the ampoule cap assembly  101  to the specimen tube  103 . 
         [0031]    We now refer to the ready-to-use condition of an embodiment of the present invention, ampoule cap assembly  101 , which is shown in  FIG. 3 . Ampoule cap housing  201  can be injection molded out of any suitable thermoplastic, such as polycarbonate, styrene, polyester, or polypropylene. Ampoule cap housing  201  includes vessel walls  301 , which define a chamber or vessel  304 . Vessel  304  defines the contained volume for pre-filled agent  203  or further frangible capsule. 
         [0032]    Pre-filled agent  203  can be any liquid, powder, lyophilized cake, lyophilized pellet, gel, and so forth, that is intended to mix with the biological specimen contained in specimen tube  103 . Pre-filled agent  203  may, for example, be a preservative, a test reagent, or a buffering solution. One embodiment of the present invention uses a stabilizing buffer as pre-filled agent  203 , which combines with a saliva sample contained in specimen tube  103 . This stabilizes the saliva sample so it can be used some time later, for example, for genetic or drugs of abuse testing. 
         [0033]    Retention member  207  configured as a sealing membrane retains pre-filled agent  203  in the interior  303  of vessel  304  by bonding to a staking rim  305  of vessel walls  301 . Sealing membrane  207  must only meet requirements for the intended application, specifically environmental barrier properties, ability to seal to the selected substrate material, and frangibility, Many alternatives are commonly available as standard technology for packaging pharmaceuticals, food, and in-vitro diagnostics. Sealing membrane  207  can be, for example, a metal foil/thermoplastic co-extrusion commonly used in packaging technology. Sealing membrane  207  can be bonded to staking rim  305  using, for example, adhesives, RF heating, or direct heating. In other embodiments the retention member can be a frangible member or capsule. 
         [0034]    Actuating member  209  configured as a piercer movably assembles onto the vessel wall  209  portion of ampoule cap housing  201  via guide walls  307 . Piercer  209  includes seal lip  309  which sealingly rides along seal surface  311 , which is a portion of the outer side of vessel walls  301 . Piercer  209  includes piercing tip  313  and annulus  315 , which features are employed to pierce and guide sealing membrane  207 . Piercer  209  can be injected molded out of any suitable thermoplastic such as styrene or polypropylene. Actuating member can also have other configurations to break or sever the retention member releasing the prefilled agent. Ampoule cap housing  201  includes internal threads  317 , which engage with external threads  105  of specimen tube  103  ( FIG. 1 ). 
         [0035]      FIG. 4  shows the arrangement of ampoule cap assembly  101  and specimen tube  103  at a position wherein the specimen tube  103  has been initially inserted into ampoule cap assembly  101  just prior to when any internal actions or movements are initiated. Specimen  401  will have previously been collected directly or indirectly into specimen tube volume  403  of specimen tube  103 . For example, specimen  401  can be saliva collected using any suitable method, one such method being that disclosed in U.S. Patent Application Publication No. 2012/0046574, previously incorporated by reference herein. Other patents and patent publications, each of which is incorporated by reference herein, that show certain elements and features or functionality that may be combined with or used with aspects of the instant invention are as follows: U.S. Pat. No. 4,150,950 to Takeguchi, et al; U.S. Pat. No. 5,283,038 to Seymour; U.S. Pat. No. 5,339,829 to Thieme, et al; U.S. Pat. No. 5,566,859 to Willis, et al; U.S. Pat. No. 5,567,309 to Classon, et al; U.S. Pat. No. 7,854,343 to Ellson, et al; U.S. Pat. No. 7,854,895 to Gallagher, et al; US Patent Publication No. 20020015663 to Goldstein, et al; US Patent Publication No. 20090216213; US Patent Publication No. 20110212002; U.S. Pat. No. 4,723,687 to Kutterer; and U.S. Pat. No. 5,505,326 to Junko. 
         [0036]    Ampoule cap assembly  101  is shown in  FIG. 5  assembled to specimen tube  103  in an intermediate position between initial insertion and final position. Piercer  209  has moved so that its piercing tip  313  has punctured sealing membrane  207  and created a flap  501  out of a portion of sealing membrane  207 . Seal ring  503  has now sealingly engaged with seal surface  505  of specimen tube  103 . Tube end  509  of specimen tube  103  rests against flange  507 , thereby arresting further motion between specimen tube  103  and piercer  209 . Seal lip  309  has slid along seal surface  311  of ampoule cap housing  201 , also creating a seal. It is important to note that, despite the immediately preceding description, it is not necessary for tube end  509  of specimen tube  103  to rest against flange  507  at this intermediate position. In other words, the sequence of seal creation and motion arrest need not be unambiguously sequenced, and the sequence order is not important to proper device function, as long as appropriate seals exist at the final component stop positions. 
         [0037]    In  FIG. 6 , the ampoule cap assembly  101  is shown fully assembled to specimen tube  103 . Internal threads  317  of ampoule cap housing  201  have mated with external threads  105  of specimen tube  103 . Seal lip  309  is in sealing engagement with seal surface  311 , seal ring  503  is in sealing engagement with seal surface  505 , and tube end  509  contacts flange  507 , which in turn contacts stop  601  of ampoule cap housing  201 . All of this defines a final, arrested position in which the internal volume defined by vessel  304  and specimen tube  103  are sealed, which prevents leaking and loss of contents. 
         [0038]    Flap  501  of sealing membrane  207  has now been displaced as shown, so as to be substantially away from vessel opening  205  ( FIG. 2 ). Thus, vessel  304  is now in fluid communication with specimen tube volume  403  Annulus  315  of piercer  209  is sized and shaped to shear sealing membrane  207  into the geometry flap  501 , and to move it toward an internal surface of vessel wall  301 . 
         [0039]    Because vessel  304  is now in fluid communication with specimen tube volume  403 , its contents can be made to mix with specimen  401  to create a specimen mixture  701  as shown in  FIG. 7 . For example, if pre-filled agent  203  is a liquid, it may flow by gravity alone into specimen tube  103 . Or if pre-filled agent  203  is a dry component, specimen mixture  701  can be produced by agitation of the sealed assembly. 
         [0040]    Access to specimen mixture  701  is gained by unscrewing ampoule cap assembly  101  from specimen tube  103 , which simultaneously removes all its components as well, sans pre-filled agent  203 . Specimen mixture  701  can be pipetted or poured out for any desired subsequent use. 
         [0041]      FIG. 8  shows the geometry of flap  501 , which is formed from a portion of sealing membrane  207 , in the form created in an embodiment of the present invention. Although this is one embodiment, other pierced forms of sealing membrane  207  may also be employed. For example, sealing membrane  207  can be made to tear into an “X” pattern, starting at its center. In other words, the geometry of flap  501  in  FIG. 8  is a suitable result, but does not represent the only suitable geometry employable in the present invention. 
         [0042]      FIG. 9  shows piercing tip  313  and annulus  315  of piercer  209 . This feature, along with shearing edge  901  work together with the inner surface of vessel walls  301  ( FIG. 3 ) to form the flap  501  of  FIG. 8 . Shearing edge  901  acts with vessel walls  301  to create a manner of shearing action on sealing membrane  207 . Again,  FIG. 9  shows one embodiment of piercer  209 , but should not be taken to limit the scope of the present invention vis-à-vis its specific geometry for piercing membrane  207 . For example, piercing tip  313  need not be a point, and need not be aligned with annulus  315 . Piercing tip  313  can be positioned on the center axis of piercer  209 , and initiate piercing in the center of membrane  207 . 
         [0043]    The above disclosure is related to the detailed technical contents and inventive futures thereof. People skilled in this field may proceed with a variety of modifications and replacements based on the disclosures and suggestions of the invention as described without departing from the characteristics thereof. Nevertheless, although such modifications and replacements are not fully disclosed in the above descriptions, they have substantially been covered by the spirit and technical theory of the subject invention.