Abstract:
A tissue-sample container assembly including a container defining a cavity configured to store a tissue sample and a lid connectable to the container to close the cavity. The lid has a receptacle adapted to contain a preserving agent, a seal forming at least a portion of a bottom of the receptacle, and a puncturing member arranged above the seal and actuatable to break the seal. A preserving agent is disposed in the receptacle.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a continuation of U.S. application Ser. No. 14/125,477 filed Feb. 8, 2014, now U.S. Patent No. ______, issued ______, which is the U.S. National Phase of PCT Application No. PCT/DK2011/050434 filed on Nov. 11, 2011, which claims priority to DK Patent Application No. PA 2011 70297, filed on Jun. 14, 2011, the disclosures of which are incorporated in their entirety by reference herein. 
     
    
     TECHNICAL FIELD 
       [0002]    The present disclosure relates to a container assembly for storing a tissue sample and to a method of preserving a tissue sample. 
       BACKGROUND 
       [0003]    Container assemblies for releasing an agent into a container at a desired point in time are well known and come in many shapes and sizes, both within the industry as well as within consumer goods. 
         [0004]    In hospitals and clinics containers or Petri dishes are used for collecting and storing tissue samples, such that after a tissue sample has been taken from a patient, the tissue sample is placed in a container, and a preserving agent, often formalin, is subsequently filled in the container before the container is closed and sent off to a laboratory for analysis. Here the container is usually opened in a fume cupboard as formalin and other preserving agents are toxic to inhale. The problem with this is that in the hospital the personnel taking the tissue sample, have to handle a preserving agent on a daily basis when filling the container. Usually a formalin dispenser station or a dispenser mountable on the container temporarily is used. After the formalin has been dispensed into the container, the lid is mounted on the container. Handling of a preserving agent this way may result in spillage and inhalation. Inhalation and other exposures constitute is a health hazard and handling of formalin and other preserving agents should be carried out with great care. 
         [0005]    W02004/000678 describes different embodiments of mixing vials, in particular the embodiment depicted in  FIGS. 6A-B  show a mixing vial where a rigid rod is pressed through a supplemental container and the dilutant is entered into the container. 
         [0006]    U.S. Pat. No. 5,152,965 describes an assembly of containers, comprising a reagent vial and a container adapted to engage with an adapter assembly positioned between the two. The reagent vial contains a reagent to be mixed with a reagent diluent in the container. The adapter assembly comprises a coupler and a hollow plunger. The reagent vial is engageable with the coupler in a first position and is advanceable into a second position relative to the adapter assembly such that the hollow plunger thereof displaces the seal of the reagent vial permitting the reagent to flow through the hollow plunger to mix with diluent in the container. 
         [0007]    The advancement of the coupler results in an increased pressure in the container, which is undesirable as the increased pressure might result in a spillage of the content in the container, when the adapter assembly is removed from the container. 
         [0008]    W02008/040812 describes a receptacle configured to receive a volume of preserving agent, and a lid containing the preserving agent and being adapted to be coupled to a tissue storage container. The preserving agent is entered into the lid through a one way valve. The lid further comprises a membrane with a number of holes. A plastic disc containing an equal amount of holes is placed between the receptacle and the membrane in the lid. When the holes are brought into alignment, e.g. by twisting the lid, the preserving agent flows into the receptacle. This requires that the container assembly is oriented such that the cover facing upwards, thereby allowing the preserving agent to flow into the container assisted by gravity. 
       SUMMARY 
       [0009]    The object of the present invention is to provide a container assembly where the risk of spillage and evaporation is considerably reduced and risk of the sample getting stuck to the cover is eliminated. 
         [0010]    In a first aspect, this is achieved by providing a container assembly comprising a separator positioned between the seal and the bottom of the container, and the separator is provided with at least one aperture adapted to provide a fluid passage between the receptacle and the container. 
         [0011]    By positioning the separator between the receptacle and the bottom of the container, it is ensured that the tissue sample does not get stuck to the top member or the puncturing means and at the same time that the seal does not interfere with the tissue sample. The tissue sample will usually be positioned at the bottom of the container. 
         [0012]    According to a preferred embodiment the container assembly further comprising a space between the separator and the seal, the separator being provided with a conduit adapted to provide a fluid passage between the space and the container. This enables air from the container to travel upwards and thereby making it easier for the preserving agent to enter the container through the separator. 
         [0013]    The conduit may have an opening positioned above the level of the preserving agent after the seal has been broken. Thereby the air in the container below the separator bypasses the preserving agent, making it easier for the preserving agent to enter the container below the separator. 
         [0014]    The cover may constitute a lid. Instead of having to remove the cover after having released the content in the receptacle, the cover may stay on the container and function as a lid, making it easy to transport. 
         [0015]    The cover may comprise a membrane having a substantially convex shape in the first position and a substantially concave shape in the second position. This membrane preferably covers the puncturing member. The different shapes of the membrane in the first and second position, makes it possible for the personnel to see from above if the seal has been broken. 
         [0016]    The cover is preferably adapted to be fluid tightly sealed to the container. This contributes to reducing the risk of spillage. 
         [0017]    The cover may comprise a protective cap for covering the membrane. Thereby it is ensured that the membrane and thereby the puncturing member is not pressed accidentally and the seal is not broken when it is not intended to. 
         [0018]    The container assembly may comprise a tracking device, such that the tissue sample can be tracked from where it was taken all the way to the laboratory. The container assembly may also comprise a temperature tracker, such that it is possible to see if the tissue has been subjected to heat or cold, which may affect the tissue sample and consequently the results of a test. 
         [0019]    The puncturing member may be provided with at least one aperture, for providing a passage between the space and the container. This eases the flow of the preserving agent into the container. The preserving agent may flow around the puncturing member as well. 
         [0020]    The separator may comprise a bottom and, engagement means for engagement with corresponding engagement means of the cover, such that the bottom of the separator is prevented from contacting the bottom of the container. The tissue sample does therefore not risk being pressed or squashed when in the container and when the cover is removed for entering or taking out the tissue sample, the separator stays connected to the cover and does not get in the way when handling the tissue sample. The engagement means may for example be threads or a snap closure. 
         [0021]    An outer diameter of the separator may be substantially equal to an inner diameter of the container, such that the separator and the container substantially fit together and little fluid may bypass the separator. 
         [0022]    The seal may be selected from a group consisting of a film, a foil, a membrane and a polymer. These are all materials that are suitable to be either punctured or cut or in any way penetrated, such that the preserving agent may escape. 
         [0023]    A part of the container assembly may comprise a transparent part for viewing inside the container. This enables the user of the container assembly to visually inspect the sample to see if a proper preservation has been carried out or whether the preserving agent has been released from the receptacle into the container. 
         [0024]    The assembly may be provided with an indicator for indicating whether the seal has been broken. This can be seen as an indicator of whether the content of the receptacle has been compromised, if the seal has been damaged contaminants might enter the receptacle, or whether the content of the receptacle has been released and thereby alert the user. If the content has been released, the user knows that the container should not be opened without taking different safety measures, such as opening the container in a fume cupboard. 
         [0025]    The separator is preferably a contrast colour, such as blue, to a colour of the tissue. This makes it easier the see the tissue sample if it gets stuck to the separator during transport e.g. to the laboratory. 
         [0026]    The puncturing member may be provided with at least two projections for breaking the seal, such that more holes are created it the seal and the preserving agent may more easily leave the receptacle and enter the container. 
         [0027]    By providing the puncturing member with teeth, the seal may be broken or pierced in several places easing the flow of preserving agent into the container. 
         [0028]    The cover may be adapted to be locked to the container. This secures that there cannot be any tampering with the tissue samples. 
         [0029]    According to another embodiment the container assembly may comprise a container for storing a tissue sample, a cover adapted to engage with the container, wherein the cover comprises: a top member comprising a receptacle, wherein the receptacle is adapted to contain a preserving agent, a seal for sealing off said receptacle, a punching or puncturing member for breaking said seal wherein the seal is broken by displacing the punching or puncturing member, a volume where the volume is defined by the interior of the outer walls of the container assembly, wherein the punching or puncturing member is provided with engagement means adapted to engage with corresponding engagement means provided on the top member, such that the position of the punching or puncturing member is adjustable independently of the orientation of the container assembly, the container assembly has a first and a second position, wherein in the first position the container is separate from the receptacle, and in the second position fluid communication is provided between the receptacle and the container, wherein the volume in the first position is the same as the volume in the second position. By not changing the volume of the container assembly, the pressure inside the container remains the same and thereby the risk of spillage when opened is considerably reduced. 
         [0030]    The punching or puncturing member may be adapted to support the seal after the seal has been broken. By letting the punching or puncturing member support the seal the risk of parts of the seal slipping into the container after the seal has been broken, and mixing with the content here, is reduced. 
         [0031]    The cover may further comprise a ring member adapted to engage with said container. This ensures that the cover is connectable to the container. 
         [0032]    The seal may be broken from outside of the receptacle. By not having to mount any punching or puncturing means within the receptacle, the risk of spillage during mounting of the cover is reduced and the risk of any contaminants getting into the receptacle is reduced, and the shelf life of the assembly is increased. 
         [0033]    The punching or puncturing member and the receptacle may be adapted to substantially fit together. This means that they are shaped such that they leave minimum room for anything being positioned between the two, except for the broken seal, when the punching or puncturing member has been displaced to its terminal position. The terminal position is defined as a position where the punching or puncturing member cannot be displaced further from its initial position. This reduces the risk of any preserving agent flowing from the container back into the receptacle behind the punching or puncturing member, thereby separating the tissue sample from the preserving agent. 
         [0034]    At least a part of the space in the receptacle may form part of the space in the container, when the cover is mounted on the container and the seal has been broken. This means that the punching or puncturing member is displaced such that when the seal has been broken, the punching or puncturing member functions as a new separator between the receptacle and the container and at least some of the space in the receptacle now forms part of the container where the tissue sample may be present. 
         [0035]    The punching or puncturing member may only be able to advance when the cover is mounted on the container. This secures that the seal is not accidentally broken, and the preserving agent may leak. 
         [0036]    The punching or puncturing member may only be able to advance when the top member is pushed down simultaneously with being turned. This secures that even when the top member is mounted on the container, the seal is not accidentally broken. 
         [0037]    The cover may comprise resilient means for urging the punching or puncturing member away from the receptacle. This enables the opening of the cover by simultaneously pushing and turning of the cover. Additionally it contributes to ensuring that the seal does not rest on the punching or puncturing member and thereby increasing the risk of unintentionally breaking the seal. 
         [0038]    The receptacle may comprise an opening and a bottom, wherein the receptacle may be tapered towards the bottom. By making the receptacle tapered, a faster release of the preserving agent is obtained and it is not possible for any of the preserving agent to not be released into the container when the seal is broken. The receptacle may also be straight or cylindrical. 
         [0039]    According to a second aspect a method of preserving a tissue sample, comprises the steps of: providing a container, filled with a preserving agent and sealed off by a seal, a puncturing member and a separator , placing a tissue sample in said container, engaging said cover with the container thereby positioning said separator between the seal and the bottom of the container, displacing the puncturing member whereby said seal is broken and the preserving agent is allowed to enter into the container through the separator. 
         [0040]    The puncturing member is preferably displaced by pressure on the puncturing member. 
         [0041]    A different method of providing a container assembly for containing a tissue sample may be provided, comprising the steps of: providing a container, providing a cover including a top member with a receptacle and punching or puncturing member, filling said receptacle with a preserving agent, sealing said receptacle with a seal, placing a tissue sample in said container, engaging said cover with the container, displacing the punching or puncturing member by engaging engagement means of the punching or puncturing member with engagement means on the top member of the cover, whereby the seal is broken and the preserving agent is entered into the container. 
         [0042]    Any features from the first aspect may be incorporated into the second aspect, and vice versa. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0043]    In the following, the invention will be described in further detail with reference to the drawings in which: 
           [0044]      FIG. 1  shows a perspective view of the container assembly in a first embodiment, 
           [0045]      Fig. 2  shows an exploded view of the container assembly shown in  FIG. 1 , 
           [0046]      FIG. 3  shows a detailed view of a cross section of the cover in the first embodiment, 
           [0047]      FIG. 4  shows a cross section of the container assembly in a first position in the first embodiment, 
           [0048]      FIG. 5  shows a cross section of a first embodiment of the container assembly in a first position with the lid slightly pushed down, 
           [0049]      FIG. 6  shows a cross section of a first embodiment of the container assembly in a second position where the seal has been broken, and 
           [0050]      FIG. 7  shows a view corresponding to  FIG. 3  of the container assembly in a second embodiment, 
           [0051]      FIG. 8  shows a perspective view of the container assembly in a third embodiment, 
           [0052]      FIG. 9  shows a cross section of the container assembly in a first position in the third embodiment, 
           [0053]      FIG. 10  shows a cross section of the container assembly in a second position in the third embodiment, 
           [0054]      FIG. 11  shows a cross section of the container assembly in the third embodiment, 
           [0055]      FIG. 12  shows a perspective view of the container assembly in a fourth embodiment, 
           [0056]      FIG. 13  shows a cross section of the container assembly in a first position in the fourth embodiment. 
           [0057]      FIG. 14  shows a cross section of the container assembly in a first position in a fifth embodiment. 
           [0058]      FIG. 15  shows a cross section of the container assembly in a second position in a fifth embodiment. 
           [0059]      FIG. 16  shows a cross section of the container assembly in a first position in a sixth embodiment. 
           [0060]      FIG. 17  shows a cross section of the container assembly in a second position in a sixth embodiment. 
           [0061]      FIG. 18  shows an exploded view the container assembly in a sixth embodiment as well as the container assembly in an assembled state. 
           [0062]      FIG. 19  shows an exploded view the container assembly in a seventh embodiment as well as the container assembly in a perspective view in an assembled state. 
           [0063]      FIG. 20  shows the container assembly in an assembled state in a seventh embodiment. 
           [0064]      FIG. 21  shows a cross section of the container assembly in a first position in a seventh embodiment. 
       
    
    
     DETAILED DESCRIPTION 
       [0065]    Like reference numbers refer to like features throughout the drawings. 
         [0066]      FIG. 1  shows a container assembly generally designated  100  and comprising a container  1  for containing a tissue sample and a cover  2  in an assembled state. In the embodiment shown the cover  2  comprises a ring member  26 , which is grooved for a firmer grip, and a top member  21 . The ring member  26  may be provided with a rubber surface or simply with a smooth surface instead. The top member  21  is provided with projection(s)  214  for making it easier to get a hold on the top member  21 , when the top member  21  is to be turned. The cover constitutes a lid, making the container assembly easy to transport. In the embodiment shown the container assembly is in an assembled state maximum 35 mm thick or deep or long on one of its sides, which makes it possible to send it in a letter. The container assembly may also be a maximum of 20 mm on one of its sides, 25 mm on one of its sides or 50 mm on one of its sides. The container assembly may be larger on one of its sides, or even smaller on one of it sides. The receptacle in this embodiment is adapted to contain 10 ml of preserving agent, such as formalin. The receptacle may be able to contain a different amount of preserving agent, such as less than 15 ml, less than 20 ml, less than 25 ml, less than 50 ml, less than 100 ml or less than 10 ml preserving agent or more than 100 ml of preserving agent. The container  1  is at least able to contain the corresponding amount of preserving agent as well as a tissue sample. A tissue sample may take up up to 1 cm 3 , but is likely to be smaller, down to 1 mm 3 . The tissue sample may be able to be covered by the preserving agent no matter the orientation of the assembly. 
         [0067]      FIG. 2  shows the different parts of the container assembly  100  in a first embodiment. In addition to the top member  21 , the cover comprises a seal  22  in the form of a foil. The seal may also be a film, a membrane, a polymer, a composite material or glass. The top member  21  is made of a polymer material, but may be made of other materials such as glass. In the embodiment shown the cover  2  further comprises a packing  24  in the form of an O-ring for sealing the connection between the ring member  26  and the top member  21 . Other sealing means may be used. 
         [0068]    Between a punching or puncturing member  23  and the top member  21  is resilient means  25  in the form of a spring positioned, for urging the punching or puncturing member  23  away from the seal  22 . In other embodiments the resilient means  25  may be made of another resilient material such as rubber or it may be in the form of flexible rods positioned around the circumference of the punching or puncturing member  23  or inside the top member  21  along the circumference of the receptacle  211 . The rods may be made of a polymer or a metal. The resilient means  25  may be integrated with either the top member  21  or the punching or puncturing member  23 . 
         [0069]    In this embodiment the punching or puncturing member  23  in the form of a punch or a plunger is provided with apertures  232  in an area of the punching or puncturing member  23  that is adapted to enter the receptacle  211 . The apertures  232  contribute to facilitating a fluid communication between the receptacle and the container  1 . The punching member or puncturing  23  may also, or alternatively, be provided with apertures along flange  233 , which is not intended to enter the receptacle  211 . The punching or puncturing member  23  is hollow but it may also be solid and provided with one larger aperture or several smaller apertures for facilitating a fluid communication between receptacle  211  and the container  1 . By making the punching or puncturing member  23  solid and making it fit together in shape with the receptacle  211  or only providing the punching or puncturing member  23  with aperture(s) along the flange  233 , the receptacle  211  is either almost filled by the punching or puncturing member  23  or the connection between the receptacle  21  and the container  1  is sealed off when the punching or puncturing member  23  has reached its terminal position. This prevents the preserving agent from becoming separated from the tissue sample. Only a minimal part or nothing of the preserving agent can flow back into the receptacle  211  and into a space that is not reachable to the tissue sample, because the tissue sample may be larger than the provided apertures. 
         [0070]    Finally, the container assembly  100  comprises the container  1  adapted to engage with ring member  26 . The engagement between the two can either be done via threads or via a press on cover, by pressing a resilient circumferential flange on the ring member  26  over a flange or other projections on the container  1  or vice versa. The ring member  26  is in this embodiment used for holding the container  1  and the top member  21  together and it contributes to controlling how far the top member  21  may be pushed down. 
         [0071]    The container  1  and/or the cover  2  may be provided with a transparent part for viewing inside the container  1  to see if a tissue sample is in the container  1  or if the seal  22  has been broken and the preserving agent is in the container  1 . The container  1  and the cover  2  may be provided with a locking mechanism to prevent tampering with the tissue sample on the way from the hospital to the laboratory. The locking mechanism may be of a kind that may only be opened by the laboratory personnel or it may be an indicator showing if the assembly  100  has been opened. 
         [0072]      FIG. 3  shows a close up view of an embodiment of the cover  2  in an assembled state. 
         [0073]    As shown in detail in this figure, the top member  21  is provided with the receptacle  211  inside the top member  21  in the embodiment shown. The top member  21  is further provided with engagement means in the form of indentations  213 . These are adapted to engage with projections  261  provided on the ring member  26 . The engagement between the two retains the top member  21  in position as well as provides a safety margin of how far down the top member  21  may be pushed. If such movement limiting means was not present it would be possible to accidentally press the top member  21  and break the seal  22 . Additionally, the ring member  26  is provided with projection(s)  262  that keep(s) the punching or puncturing member  23  in place. In the embodiment shown the punching or puncturing member  23  is provided with threads  231  that are adapted to engage with threads  212  inside the top member  21 . These make sure that the punching or puncturing member  23  cannot merely be pushed from below, such that the seal  22  breaks unintentionally. When it is desired to break the seal  22 , the top member  21  is advanced such that the seal  22  breaks. In this embodiment the top member  21  must be turned at the same time the top member  21  is being pushed from above simultaneously with the punching or puncturing member  23  being pushed from below. The punching or puncturing member  23  is being pushed from below by the container  1 . Before breaking the seal  22  the cover  2  and the container  1  is preferably fluid tightly coupled. 
         [0074]    In the embodiment shown, the receptacle  211  is tapered such that the opening of the receptacle  516  is wider than the bottom  215 . The receptacle may be other shapes such as cylindrical, pyramid shaped polygonal or other shapes. Correspondingly the punching or puncturing member may have the same shape. 
         [0075]    In all of the embodiments the receptacle in the cover may be filled with a preserving agent at the site where the cover is being manufactured or at least before the cover is delivered to the user. The receptacle may be filled with a preserving agent through the opening, which is later sealed off by the seal. 
         [0076]    From the embodiment in  FIG. 4  it can be seen how the punching or puncturing member  23  rests on the edge of the container  1  and by mounting the cover  2  on the container  1  the punching or puncturing member  23  is pushed slightly upwards. This makes sure that the punching or puncturing member  23  is only able to advance when the cover  2  is mounted on the container  1 . The engagement means  231  and  212  is still not able to engage if the top member  23  were turned. In this embodiment the top member  21  must be pushed down as well. This added security that the top member  21  must be pushed down as well to break the seal  22  may be left out. 
         [0077]    Instead of advancing the engagement of the engagement means on the top member  212  with the engagement means on the punching or puncturing member  231 , by turning the top member  21 , it may be possible to have a sudden release of the preserving agent, where the seal  22  is broken by pushing the top member  21  down without turning the top member  21 . In this case the indentation  213  extends further upwards and does not stop the projection  261  until after the seal  22  has been broken. 
         [0078]    Between the ring member  26  and the container  1  a further packing (not shown) may be provided for added sealing between the two. 
         [0079]    The broken line encircles the volume  110  that does not change during breaking of the seal  22 . The volume  110  is defined by the interior of the outer walls of the container assembly  100 . This is the interior wall of the top member  21 , the ring member  23  and the container  1 . Where the parts overlap, it is the parts being the most interior that define the volume. 
         [0080]    In  FIG. 5  the top member  21  has been pushed down as can be seen on the engagement between the projection  261  and the indentation  213 . The punching or puncturing member  23  is ready to engage with the top member  21 . By turning the top member 180-360 degrees the punching or puncturing member is forced through the seal and the seal is broken. The seal  22  is broken from below meaning that the punching or puncturing member  23  is outside the receptacle  211  before the seal  22  is broken. The top member may be turned more or less to break the seal  22  and to reach its terminal position. 
         [0081]      FIG. 6  shows the punching or puncturing member  23  in the terminal position. The top part of the punching or puncturing member  23  above the flange  233  fits exactly into the receptacle  211 . The top part of the punching or puncturing member may be smaller or bigger than the receptacle  211 . After the seal has been broken, it is positioned between the top member  21  and the punching or puncturing member  23 , and the seal  22  is prevented from entering into the container  1 . The punching or puncturing member  23  supports the seal  22  after the seal  22  has been broken. The seal  22  might also be of such a kind that upon puncturing the seal draws out to the sides, leaving nothing but a ring of sealing material along the edge of the opening of the receptacle  216 . The space that is left when the punching or puncturing member  23  has reached its terminal position is preferably less than 1/20 of the space in the receptacle from opening  216  to bottom  215  or the distance from the bottom of the receptacle  215  to the punching or puncturing member  23  is less than 1 mm. 
         [0082]    The  FIGS. 1-6  show the different positions or states that the container assembly may have. 
         [0083]    In  FIGS. 1-3  a container, a cover is provided including a top member with a receptacle and punching or puncturing member. In  FIG. 3  the receptacle is filled with a preserving agent and the receptacle is sealed. In  FIG. 4  a tissue sample (not shown) is placed in the possibly empty container and the cover is brought into engagement with the container. In  FIG. 5  the top member is pushed down and in  FIG. 6  the punching or puncturing member is displaced by engaging engagement means of the punching or puncturing member with engagement means on the top member. The seal is consequently broken or punctured and the preserving agent is allowed to enter into the container. 
         [0084]      FIG. 7  shows a container assembly in a second embodiment. The second embodiment works as described for the first embodiment and the features with the same reference number are the same. The difference here is that the container  10  is extending up into the punching or puncturing member  23 . The punching or puncturing member  23  thereby has the option to rest on the projection  262  on the container or on the edge of the container. So that it is either the projection  262  that pushes the punching or puncturing member  23  up, or it is the edge of the container. By making the container extend into the punching or puncturing member the personnel opening the container assembly is better protected from spillage as the wall above the level of preserving agent in the container is higher. 
         [0085]      FIGS. 8-11  shows a third embodiment of the invention. Referring to  FIG. 8 , the assembly comprises a container  1  and a cover  2 , the cover  2  comprising a protective cap  27  and a top member  21 . The purpose of the protective cap  27  is to secure that the membrane (see  FIGS. 9 and 10 ) is not pressed unintentionally. The protective cap  27  may be pivotable or removable. The top member  21  is provided with projections  29  for an easy grip and is removed from the container  1  by turning. The diameter Ø of this embodiment is 33 mm, but may be smaller or bigger. The height H is 47 mm, but may be smaller or bigger. The receptacle  211  may be higher such that more preserving agent may be contained. The receptacle  211  and the container  1  should preferably be able to contain about 20 ml preserving agent, respectively. 
         [0086]    In  FIG. 9  the assembly is in the first position and in  FIG. 10  in the second position. The cross section in  FIGS. 9-10  is taken along the line A-A as shown in  FIG. 8 , and  FIG. 11  is a cross section along the line B-B also shown in  FIG. 8 . The container  1  is adapted to receive a tissue sample  45 , and the cover comprises a top member  321 . A separator  31  is provided between the seal  22  and the bottom  13  of the container. In this way, in a mounted state with the cover attached the container  1 , the container  1  is separated into two spaces, a first  11  and a second  12  space. Even though the spaces  11 ,  12  are separated does not necessarily mean that the separator  31  and the container  1  are fluid tightly sealed. Fluid may be prevented from bypassing the separator  31 . Fluid may also bypass the separator  31  instead of traveling though the separator  31 . The inner circumference of the container  1  is of substantially same size as the outer circumference of the separator  31 , but the inner circumference of the container  1  may be slightly bigger than the outer circumference of the separator  31 . 
         [0087]    Referring to  FIGS. 9-10 , the top member  321  is provided with engagements means  324 , such as threads, for engagement with the container  1 . The container  1  is likewise provided with engagement means  325 , here in the form of threads for engagement with the corresponding threads on the top member  321 . The engagement between the top member  321  and the container  1  may alternatively be accomplished by means of a snap closure. Furthermore, the top member  321  is provided with engagement means  326  for engagement with the puncturing member  323 . The engagement means  326  is in the form of four slits in a hollow cylindrical shape that is adapted to receive the puncturing member  323 . The cylindrical shape may be solid and/or the number of slits may be varied. Engagement means in the form of a snap lock may be provided instead. Furthermore, the top member  321  may be provided with engagement means  327  for engagement with engagement means  328  provided on the inner side of the separator  31 . Hereby the separator  31  stays attached to the cover  2  when the cover  2  is removed from the container  1 , e.g. for taking out a tissue sample. The engagement means  327 , 328  may be in the form of threads or a snap closure. 
         [0088]    On top of the top member  321  the membrane  28  is positioned. In  FIG. 9  it has a substantially convex shape and in  FIG. 10  it has a substantially concave shape. When the pressure is removed from the membrane  28 , the membrane  28  will keep its concave shape. This allows personnel to see from above if the preserving agent has been released. As the container  1  is preferably see-through, it may also be seen through the container  1  if the preserving agent has been released. The membrane  28  may be a spring membrane that automatically bounces back to its first position. The puncturing member  323  is activated by pressing the membrane  28 . Thereby the puncturing member  323  is displaced along the longitudinal axis of the assembly, and the seal  22 , separating the receptacle  211  from the container  1 , is ruptured or broken. 
         [0089]    In the embodiment shown, the puncturing member  323  is provided with teeth  329  for piercing the seal  22 . The puncturing member  323  is made of a polymer material, but may also be made of metal or other suitable materials. An additional piercing element  330  for breaking through the seal  22  is provided, but may be dispensed with. 
         [0090]    The seal  22  may be a foil, a film or a polymer membrane. 
         [0091]    The separator  31  is adapted to hang from the cover  2 . At the bottom  13  of the separator  31  a grid is provided. The separator  31  should be able to let the preserving agent through, and while at the same time ensuring that the seal  22  does not enter the container  1  and securing that the tissue sample  45  does not migrate into the receptacle  211  during transport. 
         [0092]    Referring to  FIG. 11 , the apertures  291  in the grid in the separator  31  are squares, each approx. 1 mm in transverse size, but may be smaller or bigger, circular or polygon-shaped. The grid is permeable for a liquid with a surface tension similar to that of water. Another kind of permeable membrane may also be used. The separator  31  may be provided with apertures elsewhere, such as in the walls of the separator  31 . The separator  31  is not a container for the tissue sample such as a cassette, but instead separates the container  1  in two interconnected spaces. The second space  12  and/or the bottom of the container  1  is adapted to receive the tissue sample  45 . The first space  11  may also be positioned in the cover  2 . Referring to  FIGS. 9-11  the separator  31  is furthermore provided with a conduit  30  with an opening or air inlet at the bottom of the separator  31  and an opening or an air outlet positioned at a distance from the air inlet. The air outlet is positioned such that when the seal  22  has been broken and the preserving agent has left the receptacle  211 , the preserving agent may not pass the grid due to the smallness of the apertures and the surface tension of the agent, without for example shaking the assembly. The permeability of the grid can be increased by means of the conduit  30  that allows air in the container  1  to bypass the preserving agent through the conduit  30  and thereby letting the preserving agent pass through the apertures  291  in the grid. The opening or air outlet is therefore positioned such that it is above the level of the preserving agent when the seal  22  has been broken. Two conduits  30  are provided in this embodiment, but one of more than two conduits  30  and other shapes of conduits may be provided instead. The separator  31  or at least the grid is blue or another colour of contrast to a tissue sample. This makes it easier to see a tissue sample in case it clings to the separator  31 . The separator may be other colours. The space  12  for the tissue sample  45  is positioned below the separator  31 . The assembly may be provided with a tracking device such as an RFID (radio frequency identification) tag, such that the sample can be tracked from collection to test in a laboratory. The sample  45  need not be covered by the preserving agent at all times, since the fumes in the container  1  will usually be enough to preserve the sample  45 . 
         [0093]      FIGS. 12 and 13  show a fourth embodiment of the invention in the form of container assembly  400 .  FIG. 13  shows a cross section of the assembly along the line A-A as shown in  FIG. 12 . All the features and functions present in the third embodiment are likewise present in the fourth embodiment where the same reference numbers indicate similar features. The difference between the third and the fourth embodiment is that the fourth embodiment is higher and is able to contain around 20 ml of formalin or other preserving agent both in the receptacle  211  and in the container  1 . The conduit(s)  30  has in this embodiment not been made longer as it takes some time before the preserving agent passes the separator  31  and thereby the conduit(s)  30  will still be above the level of the preserving agent when the seal  22  has been broken. The conduit(s)  30  may be made longer, such as between 2-5 cm long. Any size of container able to contain between about 5-50 ml of preserving agent can be imagined. 
         [0094]      FIGS. 14 and 15  show a fifth embodiment of the invention in the form of container assembly  500 . All the features and functions present in the third and fourth embodiments are likewise present in the fifth embodiment where the same reference numbers indicate similar features. In  FIG. 14  the assembly  500  is in a first position and in  FIG. 15  the assembly is in a second position. In addition to similar features as those described in the third and/or fourth embodiments, the container assembly  500  further comprises a removable cap  528  provided with gripping parts  548 . The cap  528  protects the membrane  28  from pressure during transport. 
         [0095]      FIGS. 16-18  show a sixth embodiment of the invention in the form of container assembly  600 . The container assembly  600  differentiates itself among others from the third embodiment in that the top member  621  is taller and is able to contain more preserving agent. The punching or puncturing member  323  is also taller and is provided with a cross shaped or T-shaped projection  626  at the top. The projection  626  rests at a circumferential flange  627  provided on the top member  621 . Thereby when the membrane  28  is pushed down, the projection is forced pass the circumferential flange  627  upon which it rested in its initial position. The circumferential flange  627  or the projection  626  may have resilient properties, which allow the projection  626  to pass the circumferential flange  627 . The projection  626  may be tapered such that it can be pressed pass the flange  627  more easily. The circumferential flange  627  may also be in the form of circumferential projections that are not connected along the whole circumference. The top member  621  is connectable to the container  1  such that the exterior of the top member  621  engages with the interior of the container  1 . It may also be vice versa. The top member  621  and container  1  may be provided with engagement means in form of threads. 
         [0096]    Furthermore, the separator  31  is provided with conduit(s)  31  in the form of segments. By extending the wall of the conduit(s) across the separator  31  as a chord, the separator  31  gets more rigid. The conduit(s)  30  do(es) not extend above the top edge of the separator  31 , but may do so in other embodiments. 
         [0097]    The top member  621  extends above the highest point of the membrane  28  in a first position, thereby protecting the membrane  28  from pressure when no protective cap is provided. The highest point in this embodiment is the center of the membrane. 
         [0098]    The sixth embodiment may further comprise any of the features from the third, fourth and fifth embodiment. 
         [0099]      FIGS. 19-21  show a seventh embodiment of the invention. In addition to the features in the sixth embodiment the container assembly  700  is additionally provided with a cap  728 . The top member  721  does not extend beyond the highest point of the membrane  28  as it does in the sixth embodiment. The seventh embodiment may contain any of the features from the third, fourth, fifth and sixth embodiment. 
         [0100]    By “broken” is meant that a hole has been created in the film or seal where either the preserving agent may flow out or particles or contaminants from the outside may enter. 
         [0101]    The term “cover” as used herein includes all means that cover the opening of a container. The term “separator” is used for a member used to separate the seal from a potential tissue sample placed in the container. In some embodiments the separator also functions as the punching or puncturing member, such that the separator and the punching member form one element, while in other embodiments the puncturing member and the separator are separate elements. 
         [0102]    The word “container” is generally used about the container or space that is adapted to contain the tissue sample. 
         [0103]    Furthermore, it is conceivable to make use of other configurations of the container assembly. It may be of industrial size where the container is able to contain at least 1 L or less than 5 L, 10 L, 100 L, 1000 L or more. The container may contain a substance which is to be mixed with a second substance with less of a volume. The cover or lid may be able to contain the second substance, with a volume of less than 5 ml, 10 ml, 30 ml, 50 ml, 100 ml or more than 100 ml, which is to be mixed with the substance in the container. The second substance may be a toxic or volatile substance or a substance where it is important that the exact amount of substance is entered into the container. This larger sized container assembly may have the same features as the first, second, third or fourth embodiment. Any feature of these embodiments may be applied independently of each other to this larger sized container assembly. 
         [0104]    In general, the features of the embodiments shown and described may be combined freely and no feature should be seen as essential unless stated in the independent claims.