Abstract:
A connector cap for a reagent bottle which can be pre-attached to a fully assembled synthesis cassette allows greater control in the assembly of the cassette and simpler operation for the end user. The connector cap may be incorporated onto reagent bottle or on vials to be used with automated synthesis cassettes.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention is relates to the field of fluid connectors. More specifically, the present invention is directed to a container connector which may be employed in automated chemistry systems 
       BACKGROUND OF THE INVENTION 
       [0002]    Radiotracer synthesis has benefited from increased reliance on automated synthesizers and synthesis cassettes. Synthesis cassettes may be manufactured in a controlled environment and is shipped pre-assembled. For the end user this makes meeting GMP requirements simpler and radiotracer production more reliable than for platforms for which the cassette and reagents are supplied separately and are assembled by the end user. In this respect, minimizing the required number and complexity of connections made to the cassette prior to synthesis is desirable. 
         [0003]    The FASTlab® system, sold by GE Healthcare of Liege, Belgium, is a synthesizer/cassette system which is able to perform multi-step radiochemistry and on-cassette cartridge based purification. Such processes may fully utilize the capacity of the FASTlab cassette and require additional reagent bottles to be connected thereto, especially for cartridge based purification where greater volumes of solvent are needed than can fit into the cassette casing. This has led to the use of additional reagent bottles that are connected to the cassette by piercing the bottle stopper with large diameter needles. Once the bottles stoppers are pierced by the needles, the reagent is available for use. It is not desirable to have the stoppers pre-pierced prior to shipping of a commercial cassette since the reagent is then not confined to the regent bottle and may contaminate the cassette or deform the bottle septum such that fluid integrity is lost. This prohibits shipping a fully assembled cassette and means that there must be some final assembly by the end user. The needle tops and tubing connections can be color-coded to simplify assembly by the end user but there is still potential for operator error which could lead to failed production. One such user error could be failing to push a needle into the bottom of the reagent bottle which would make the reagent inaccessible. Also, the use of needles results in the risk of stab injuries. 
         [0004]    There is therefore a need for a means for connecting a conduit to a container in a manner that allows both to be shipped in an inactivated condition, that is, mechanically connected without establishing fluid communication therebetween, so as to then be placed in an activated condition the conduit and the container in fluid communication. 
       SUMMARY OF THE INVENTION 
       [0005]    In view of the needs of the art, the present invention provides a connector cap for a reagent bottle which can be pre-attached to either a partially-assembled or a fully-assembled synthesis cassette. This will allow greater control in the assembly of the cassette and simpler operation for the end user. This type of reagent bottle should be particularly suited to delivery of volumes of solvent for on-cassette cartridge-based purification of radiotracers. 
         [0006]    In an exemplary embodiment, the present invention provides a container connector for a container having an annular neck defining a container aperture and a pierceable septum spanning the container aperture. The container connector includes a connector cap and a septum piercing unit. The connector cap includes an annular cap body having opposed first and second ends and an elongate annular wall extending therebetween. The first end defines a first aperture, the annular wall includes an annular interior surface defining a cap cavity in fluid communication with the first aperture, and the interior surface is sized and shaped sized to engage the annular neck so that the cap can be moved from a first position with respect to the neck to a second position with respect to the neck. The septum piercing unit includes an elongate unit body including longitudinally opposed transversely-extending first and second end surfaces. The first and second end surfaces support a first cannula extending therefrom. The first cannula and unit body define a first and second fluid port respectively, wherein the first cannula and unit body further defines an elongate fluid passageway extending in fluid communication between the first and second fluid ports. The unit body is sized to span the container aperture such that the unit body is urgeable by the cap from the first position wherein the second cannula is positioned in overlying registry with the septum, to the second position wherein the second cannula has pierced the septum. 
         [0007]    The reagent bottle can be pre-filled and attached to the cassette and is ‘activated’ by a simple operation by the end user prior to use. This should lead to fewer production failures due to incorrectly connected reagent bottles and safer operation due to reduced usage of sharp needles. 
         [0008]    The connector cap may also be mated to bottles or vials providing sources of other fluids, or to a bottle or vial used for product collection or dispensing. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0009]      FIG. 1  depicts an exploded view of a bottle incorporating a container connector of the present invention. 
           [0010]      FIG. 2  depicts a cap and septum-piercing unit of the present invention. 
           [0011]      FIG. 3  depicts a cross-sectional view of the container connector in a first position, before ‘activation’ 
           [0012]      FIG. 4  depicts a cross-sectional view of the container connector in a second position, after ‘activation’ 
           [0013]      FIG. 5  depicts an automated synthesis cassette incorporating a container connector of the present invention between the cassette and a reagent container. 
           [0014]      FIG. 6  depicts a support member which may be employed with a container connector of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0015]    The present invention provides a connector cap for allowing quick connection between a conduit and a container. The present invention also provides a container, such as a bottle or vial, configured to engage or incorporate the connector cap of the present invention. The connector cap of the present invention allows:
   i) additional reagent to be used with a fully pre-assembled automated synthesis cassette;   ii) simplified operation by the end user with reduced chances of production failure;   iii) maintaining integrity of a reagent container until ‘activation’ before use;   iv) connection to be made without exposing the operator to sharp needles; and   v) other applications where connection between a container and a fluid conduit are required, including, e.g., source vials and or product collection vials.   
 
         [0021]    The bottle body has a threaded top and a septum which keeps the reagent contained within the cavity until ‘activation’. The septum piercing unit is pushed downwards by the action of tightening the cap. The cap has an open top to allow access to the fittings on the septum piercing unit. The septum is pierced by the two spikes (or needles or cannulas, etc.) on the septum piercing unit. This constitutes ‘activation’. Before activation the reagent is sealed with the bottle cavity. After activation the reagent is accessible and may be provided through the septum piercing unit to, e.g., a FASTlab cassette. The bottle includes dip tube which makes sealing connection with fluid cannula, or needle, of the piercing unit so as to effect deeper penetration of the fluid cannula into the bottle cavity. 
         [0022]    Desirably, the piercing unit and the bottle cooperatively engage each other so as to prevent rotation of the piercing unit by the rotation of the cap. Additionally, the dip tube may be fluted at one end to allow for some rotational displacement of the fluid cannula, the septum being contemplated to assist in the fluid-tight connection between the cannula and dip tube. 
         [0023]    Similarly, the piercing unit provides a vent cannula which pierces the septum to thus allow for airflow into the bottle cavity and assist in evacuation of the reagent through the fluid cannula. The bottle may include a vent tube which, like the dip tube for the fluid cannula, provides sealed engagement with the vent cannula. The present invention further contemplates that both the dip tube and the vent tube may depend from a planar substrate supported below the septum in the bottle. 
         [0024]    The reagent bottle might be constructed mainly from polypropylene which would have compatibility with water/organic mixtures. Other materials could be considered. Glass is also a possible material for the main bottle body. 
         [0025]    Referring now to  FIG. 1 , an exploded view of a reagent bottle  5  defining an open container cavity  6  employing a container connector  10  of the present invention is shown. Container connector  10  includes a connector cap  12  and a septum piercing unit  14  which cooperatively engage bottle  5 . Bottle  5  includes an annular neck  16  supporting a pierceable elastomeric septum  18  spanning across an open container aperture  20  defined by neck  16 . Septum is desirably formed from an elastomeric material which may be pierced by either a needle or cannula but will self-seal up removal of the needle or cannula for applications requiring the contents within cavity  6  to remain after removal of the needle or cannula. Bottle  5  includes a concave bottom  9  facing cavity  6  so as to provide a ‘low point’ within cavity  6  in which fluid will collect when bottle  5  is upright. 
         [0026]    With additional reference to  FIGS. 2-4 , connector cap  12  includes an annular cap body  22  having opposed first and second ends  24  and  26  and an elongate annular wall  28  extending therebetween. First end  24  includes an inwardly-extending annular rim  25  which defines a first aperture  30 . Annular wall  28  includes an annular interior surface  32  defining a cap cavity  34  in fluid communication with first aperture  30 . Interior surface  32  is sized and shaped sized to engage the annular neck  16  so that the cap can be moved from a first position with respect to the neck to a second position with respect to the neck. Septum piercing unit  14  includes an elongate unit body  40  including longitudinally opposed transversely-extending first and second end surfaces  42  and  44 . The first and second end surfaces  42  and  44  support first cannula  46  extending therefrom. First cannula  46  and unit body  40  define a first and second fluid port,  50  and  52 , respectively and an elongate fluid passageway  54  extending in fluid communication between first and second fluid ports  50  and  52 . Unit body  40  is sized to span container aperture  20  so that second end surface  44  is engaged by rim  25  such that unit body  40  is urgeable by cap  12  from the first position, depicted in  FIG. 3 , wherein the first cannula  46  is positioned in overlying registry with septum  18 , to the second position, depicted in  FIG. 4 , wherein second cannula  46  has pierced septum  18 . 
         [0027]    Unit body  40  of said septum piercing unit  14  may be configured to include opposing first and second major surfaces  54  and  56 , respectively, which extend in facing opposition to interior surface  32  as container connector  10  is assembled. Septum piercing unit  14  may further include an elongate hollow needle  60  extending through unit body  40  thereof, where needle  60  includes a first end  62 , a second end  64 , and an elongate tubular body  66  extending therebetween. First end  62  defines a first needle aperture  68 , second end  64  defines a second needle aperture  70 , and tubular body  66  defines an elongate needle passageway  72  extending in fluid communication therebetween, such that said first end  62  of needle  60  is first cannula  46  which pierces septum  18 . Second end  64  of needle  60  supports a connector  74  thereon, such as a female luer connector. As depicted in the example shown in  FIG. 5 , connector  74  engages a mating connector at one end of an elongate conduit  75  having an elongate tubular body defining an open conduit passageway therethrough. Connector  74  is thus able to place the conduit passageway in fluid communication with needle passageway  72 . The present invention contemplates that conduit  75  may be connected to a synthesis cassette  100  as shown in  FIG. 5 , or to any source of a fluid to deliver to container  5 . 
         [0028]    While first cannula  46  is depicted as being the first end  62  of needle  60 , the present invention further contemplates that cannula  46  may be formed from as a unitary member with unit body  40 . Additionally, first cannula  46  may have either a sharp or blunt first end for piercing septum  18 . It is known that blunt cannulas may be designed to pierce septums. As some embodiments of the present invention will not be concerned with the integrity of septum  18  after fluid withdrawal from cavity  6 , it will be apparent to those of ordinary skill in the art how to thus select the design of cannula  46  for the particular application. 
         [0029]    The present invention further contemplates that container connector  10  further includes an elongate second cannula  48  projecting from unit body  40 . Second cannula  48  provides for piercing septum  18  for venting. In the embodiment shown in  FIG. 1-4 , a vent needle  80  extending through unit body  40  provides both the second cannula  48  as well as the vent passageway through unit body  40 . Vent needle  80  includes a first end  82 , a second end  84 , and an elongate tubular vent body  86  extending therebetween. First end  82  defines a first vent aperture  88 , second end  84  defines a second vent aperture  90 , and tubular body  86  defines an elongate vent passageway  92  extending in fluid communication therebetween. The present invention contemplates that vent needle  80  provides the second cannula  48 . Desirably, vent body  86  supports a porous filtration media  94  across second aperture  90 . Media  94  defines porous passageways  96  therethrough in fluid communication with vent passageway  92  so as to limit the passage of contaminants therethrough but still allows air to vent therethrough from container  5 . As unit body  40  is urgeable by cap  12  from the first position wherein the second cannula  48  is positioned in overlying registry with septum  18 , to the second position wherein second cannula  48  has pierced septum  18 . The present invention further contemplates that filtration media  94  may be supported within any housing such that the filter passageways  96  are in sealed fluid communication with vent passageway  92 . For example, as shown in  FIG. 5 , vent needle  80  may include provide a media housing  81  suspended above cap  12  such that vent body  86  includes bend to accommodate the particular geometry of housing  81  about other components or connections of container connector  10 . 
         [0030]    The present invention contemplates that cap  12  and neck  16  include mating helical threads  13  and  17 , respectively, which guide movement of the cap between the first and second positions. Desirably, cap  12  and neck  16  further include cooperating detents for resisting movement of cap  12  from the first position. Additionally, cap  12  and neck  16  desirably include cooperating detents for resisting movement of cap  16  from the second position. 
         [0031]    Additionally still, septum piercing unit  14  engages neck  16  so as to prevent rotation of the septum piercing unit along its axis of travel as cap  16  is moved from the first to the second position. Towards this goal, that neck  16  may provide opposing guide slots  21  and  23  into which opposing edges  41  and  43  of planar unit body  40  are received so as to allow the linear displacement towards septum  18 , although any mating engagement between unit body  40  and neck  16  will be configured to allow such linear displacement. For example, should unit body  40  have substantially cylindrical shape, neck  16  could support one or more inwardly-extending rails which are received in corresponding grooves formed in unit body  40 . 
         [0032]    The present invention further contemplates providing an elongate tubular dip tube  102  supported in bottle cavity  6  for use with container connector  10 . Dip tube  102  includes a first end  104 , an opposed second end  106 , and an elongate tubular dip tube body  108  extending therebetween. First end  104  defines a first dip tube aperture  110 , second end of dip tube  102  defines a second dip tube aperture  112 , and dip tube body  108  defines an elongate dip tube passageway  114  extending in fluid communication therebetween. Desirably, second end  106  of dip tube  102  is positioned adjacent septum  18  in underlying registry with the first end  62  of needle  60 . First end  104  of dip tube  102  extends towards the bottom of cavity  6 , desirably centered above the concave bottom  9 . The present invention contemplates that when cap  12  is moved to the second position, first end  62  of needle  60  will be in fluid-tight engagement with first end  104  of dip tube  102 , as that portion of septum  18  about needle  60  will be compressed therebetween, while still placing dip tube passageway  114  in fluid communication with needle passageway  72 . In one embodiment of the present invention shown in  FIG. 6 , a dip tube support member  120  positions second end  106  of dip tube  102  adjacent to septum  18 . Dip tube support member  120  spans container aperture  20 , and is desirably held in place between an annular container shoulder  7  and septum  18 . Support member  120  includes an outer annular ring  122  with a segment  124  extending to support second end  106  of dip tube  102 . Annular ring  122  is sized and shaped to rest on an annular shoulder  7  of container  5 . Septum  18  sealingly engages interior surface  32  while adjacent to or on rim  122  Support member  120  may be designed so as to hold second end  106  of dip tube either abutting against septum  18  or slightly spaced thereabove. As the tip of needle  60  is pushed through septum  18  into dip tube  102 , the material of septum  18  can serve as a gasket between needle  60  and dip tube  102  so as to ensure fluid from to or from needle  60  all passes out of or in through dip tube  102  at aperture  110 . The present invention further contemplates that annular ring  122  of support member  120  may take other shapes such as substantially planar or substantially conical where the second end  106  of dip tube  120  opens therethrough. 
         [0033]    Moreover, the present invention contemplates alternatively providing an elongate tubular vent tube  130  supported by support member  120  in bottle cavity  6 . Vent tube  130  including a first end  132 , an opposed second end  134 , and an elongate tubular vent tube body  136  extending therebetween. First end  132  defines a first vent tube aperture  138 , second end  134  defines a second vent tube aperture  140  and vent tube body  136  defines an elongate vent tube passageway  142  extending in fluid communication therebetween. As second end  134  is positioned adjacent septum  18  in underlying registry with first end  82  of vent needle  80 , vent tube  130  is able to receive the first end of vent needle  80  as it is inserted through septum  18  upon movement of cap  12  to the second position. In the second position, passageway  92  is placed in fluid communication with vent tube passageway  142 . Fluid delivered through needle  60  into cavity  6  will cause the gas within cavity  6  to be pushed out through vent needle passageway  92 . Similarly, as fluid is withdrawn from cavity  6  through dip tube  102  and needle  60 , gas may be reintroduced into cavity  6  through vent tube passageway  142 . 
         [0034]    As described, the provision of dip tube  102  and vent tube  130  allows for a fluid to be delivered into cavity  6  without requiring deep penetration of needle  60  or vent needle  80  through septum  18 . Additionally, if needle  60  and dip tube  102  sealingly-engage each other as described, the contents of cavity  6  may also be withdrawn therefrom. The present invention thus provides for a container to which fluid may be delivered and withdrawn, providing for the possibility of mixing a fluid to the contents of the container, such as a reagent provided within cavity  6 , so that the mixture may be withdrawn from the container. 
         [0035]    The present invention further contemplates that both the dip tube and the vent tube may be supported below the septum in the bottle. With additional reference to  FIG. 6 , support member  120  may then include segment  126  inwardly extending from rim  122  to second end  134  of vent tube  130 . Again, it may be desirable to provide some clearance between second aperture  140  and septum  18  so as to allow some deflection of septum  18  towards the first openings of the dip tube and vent tube as the cannulas are urged through the septum. 
         [0036]    As shown in  FIG. 1 , the present invention may alternatively include a removable key  200  which prevents unintended movement of cap  12  and septum piercing unit  14 . Key  200  includes opposed deflecting tangs  201  and  202  which define a neck receptacle  204  therebetween. Key  200  includes a grip  205  for ease of pulling key  200  laterally away from neck  16 . Key  200  may be positioned such that neck  16  is received in neck receptacle  204  with tangs  201  and  202  extending between cap  12  and bottle  5 . Tangs  201  and  202  prevent cap  12  from being tightened down on neck  16  until key  200  is removed from about neck  16 . Key  200  thus prevents unintended movement of cap  12  which could pre-maturely pierce septum  18 . 
         [0037]    Further enhancements to the design could include the provision of some kind of rip off tab which would prevent accidental activation prior to use. This could be similar in design to those seen commonly on food containers. There could also be some kind of locking mechanism whereby once the bottle has been activated, it cannot be un-activated. This could be similar in operation to the mechanism commonly used on medicine bottles. 
         [0038]    Referring now to  FIG. 5 , the present invention also contemplates providing a synthesis cassette  100  incorporating the container connector  10  of the present invention. Cassette  100  is a version of a FASTlab synthesis cassette, although the present invention contemplates that the present invention can be applied to the cassettes for other synthesizers. Cassette  100  includes an elongate manifold  302  which incorporates a number of actuation valves  301 - 325  which are connected to either an activity inlet reservoir  330 , syringe pumps  332 ,  334 ,  336 , cartridges  340 ,  342 , conduits  350  and  352  leading to a reaction chamber  326 , or conduits  354  and  356  leading to cartridges  340  and  342  respectively. Valves  308 ,  309 ,  317  and  320  are capped so as to provide connection to nothing. Manifold  300  is further connectable to a waste vial (not shown), a dispense vial (not shown), as well as to internal reagent vials (at valves  302 ,  312 - 314  and  316 , not shown). The actual design of cassette  100  is not essential to the present invention, so long as it provides most or all of the fluid path used for the synthesis of a product fluid, such as a radiotracer for PET or SPECT imaging and so long as it provides for connection to a container connector  10  of the present invention. An active isotope is provided to an inlet reservoir at valve  306  and operation of the cassette may then direct it through a synthesis procedure. Valve  315  is connected to a source  360  of water for injection. Manifold  300  further provides ports for connection to a pneumatic system to further provide a motive force through manifold  300 . 
         [0039]    Using container connector  10 , the cassette  100  may be shipped connected to an external reagent bottle  5  having a neck  16 , as described hereinabove, which cooperatively engages the cap  12  of connector  10  and the septum piercing unit  14 . The present provides that cassette  100  may be shipped with the connections made between reagent bottle  5  and cassette  100  with connector cap  12  in the first, inactivated, position. Key  200  is provided about neck  16  so as to prevent cap  12  from inadvertently causing unit body  40  from piercing septum  18 . Alternatively, the present invention provides a kit of parts including a cassette  100  and reagent vial  5  adapted to be connected to cassette  100  by connector cap  10  and conduit  75 . The kit of parts may be shipped in a sterile package, such as a plastic bag, allowing the kit components to be loaded into the sterile package in environmentally clean conditions where the container is then sealed so as to maintain the clean or sterile condition experienced by the kit components until the package is opened. It is contemplated that the package is opened in a clean environment so that the kit components may be assembled and put to use without requiring further sterilization. Cassette  100  when assembled, may then be connected to an automated synthesizer, in the present illustration a FASTlab synthesizer, as well as connected to a waste vial, a dispense vial, and optionally to an HPLC purification system (shown at valves  318  and  319 ). Cassette  100  may thus be operated to include a reagent included within vial  5  in the synthesis process it performs. The actual synthesis process is not considered essential to the instant invention, just the provision of an external reagent bottle  5  which may be connected to manifold  300  either a time just prior to synthesis or even just prior to packaging. 
         [0040]    While the particular embodiment of the present invention has been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the teachings of the invention. The matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation. The actual scope of the invention is intended to be defined in the following claims when viewed in their proper perspective based on the prior art.