Patent Publication Number: US-2005142041-A1

Title: System for multiple sterile sample collection and isolation

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
      This non-provisional application claims priority under 35 U.S.C. § 120 on U.S. application Ser. No. 09/919,836, filed on Aug. 2, 2001. This non-provisional application also claims priority under 35 U.S.C. S 119(e) on U.S. Provisional Application No. 60/222,610, filed on Aug. 2, 2000. The entirety of each of the above applications is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION  
      1. Field of the Invention  
      The present invention is directed to a system for multiple sterile sample collection and isolation. In particular, the present invention is directed to a sample collection apparatus, wherein a sample can be taken from within a sealed housing, while the sample and the inside of the housing are isolated from the outside ambient environment.  
      2. Description of Background Art  
      The pharmaceutical and biotechnology industry, the food and beverage industry, and the industrial enzyme and chemical industries all use processes that are conducted to a greater or lesser degree in isolation from the surrounding environment. While instrumentation exists for in-situ monitoring of many variables of a process, the monitoring of some variables still requires that physical samples be removed from the process for analysis elsewhere. It is frequently desirable that these samples be obtained without exposing the surrounding environment to the process, without exposing the sample material to the technician or the surrounding environment, or some or all of the above. One example of a case involving the desire to isolate the process, the surrounding environment, the technician and the sampled process material (once removed from the process) all isolated from each other is in the production of some toxic and hazardous chemotherapeutic agents or vaccines. The invention described herein provides a means through which such sampling can be accomplished. It should be understood that not all of the features of the system described need to be applied or incorporated into the system for it to be essentially the same system since, to have read this description and to have eliminated elements not necessary in a given application would be obvious to one knowledgeable in the field.  
     SUMMARY OF THE INVENTION  
      The present invention is directed to a device for sampling, wherein it is possible to isolate the process, the surrounding environment, the technician and/or the sampled process material in a simplified and more complete manner than the in the background art. In order to accomplish the above, the present invention provides a housing with an internal cavity containing a mechanism or set of mechanisms for maneuvering a single or multiple receptacles to a position where material may be filled into them before they are stopped or otherwise closed. The housing may mate with one or more containers holding one or more unfilled receptacles, which can be transferred into the housing to be filled. The housing and the mating surfaces between the housing and the container (or containers) may be cleaned, sterilized or otherwise decontaminated before the environment within the housing and the container holding the unfilled receptacles are brought into communication with each other, while being kept segregated from the outside surrounding environment. Likewise, the housing may mate with one or more closable containers capable of receiving one or more filled receptacles such that, once inside the container, the receptacles may be removed from the housing without exchange occurring between the environment within the container holding the filled receptacle, and the outside ambient environment. The housing and the mating surfaces between the housing and the container for receiving the filled receptacles may be cleaned, sterilized or otherwise decontaminated before the environment within the housing and the container for receiving the filled receptacles are brought into communication with each other while being kept segregated from the outside surrounding environment.  
      A primary object of the present invention is to receive one or more clean receptacles prepackaged in a clean outer package or container equipped with an access port which can be form a seal with the device and through which the clean receptacles can be transferred to be filled. Once filled, the receptacles can be removed through a second port (or through the same port, particularly if only one receptacle or group of receptacles is involved) into a package which can then be removed from the device while preserving the integrity of the environment within the device and within the package containing the receptacles from the ambient environment outside of the device.  
      Another primary object of the present invention is to provide a device which is capable of carrying out multiple material transfers from a source to a receptacle, wherein an exchange between the environment where the transfer takes place and the outside ambient environment can be largely inhibited.  
      Yet another primary object of the present invention is to provide a device, wherein the transfer can be made and the individual receptacles be stoppered before the housing is reopened. Furthermore, exchange between the environment within the invention and containing the filled, stoppered receptacles is prevented from exchange with the outside ambient environment.  
      Still another primary object of the present invention is to provide a series of steps by which empty receptacles may be filled and stoppered without exposing the ambient environment to the environment where the receptacles are filled.  
      Another object of the present invention is to provide a device by which exchange between the environment within the device and the outside ambient environment can be inhibited.  
      Another object of the present invention is to enable an operator to collect a single or multiple samples into individual unstoppered or stoppered receptacles and to seal the receptacles and package them individually or in groups. Furthermore, the packaged receptacles can be removed from the system without breaking the system&#39;s containment integrity from the surrounding environment or with the source of the material being filled into the receptacles.  
      The system according to the present invention can be used to transfer large volumes of material into smaller packages (vials, bottles, bags, etc.) and to place the packages into a secondary package, wherein material released during the filling operation and resting on the primary container can be sealed and be kept isolated from the surrounding environment when the secondary package containing the primary container filled with the material is detached from the system.  
      In the device and system according to the present invention, it is possible to collect samples of various types of materials that are capable of flowing. Accordingly, samples materials can be liquids, solids or gases.  
      The system may include a valved feed port for feeding a material into the interstitial space between the primary container or receptacle and the secondary package or bag in order to neutralize any toxic or hazardous materials resident on the primary container or within the secondary package.  
      The system may be fitted with a 2 nd  feed line which will direct material (such as a preservative or neutralizing agent, for example) into the primary container at the filling station before, during or after the primary container is filled but before it is recapped.  
      It should be noted that although the device of the present invention is designed for filling and sealing containers in a contained fashion, the system might be operated in an opened fashion.  
      In addition, all feed lines, vents and drains may be valved. Accordingly, when taken in combination with the sealed housing and the gasketed septum at the mouth of a bag or container from which empty primary receptacles are fed into the system and the gasketed septum at the mouth of a bag or container into which the filled primary receptacles are ejected, the system is a closed system from the outside surrounding environment. Accordingly, the entire process of sampling can be performed within a closed system.  
      The system according to the present invention includes a corer to core the septa sealing mouths of the bags or containers for holding the empty and filled receptacles, allowing them to open into the housing interior.  
      The system of the present invention includes a primary container clasp assembly, which can be lowered to capture the primary container, in this case, a receptacle. When raised, this assembly brings the receptacle stopper into contact with a stopper clasp assembly. When rotated, the combination of the primary container clasp assembly and the stopper clasp assembly can hold the receptacle still while the stopper is rotated off. The receptacle can then be lowered under the feed ports and filled. The stopper can then be replaced by reversing the process.  
      The system of the present invention also includes an ejector rod, which can be used to push the filled primary container out of the ejection port. This rod can be rotated, raised and lowered.  
      Although not shown, a similar injector rod can be included to capture the first (or any) unfilled primary container and bring it up to a position where the primary container clasp may engage it.  
      The system of the present invention may be cleaned and sterilized in place and may be made to be maintained and operated under pressure or under vacuum.  
      Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The present invention will become more fully understood from the detailed description given hereinbelow and the accompanying drawings which are given by way of illustration only, and thus are not limitative of the present invention, and wherein:  
       FIGS. 1A and 1B  are side views of the outside of one embodiment of the device of the present invention;  
       FIGS. 2A, 2B ,  2 C and  2 D are vertical center cross sections through the device illustrated in  FIG. 1 ;  
       FIGS. 3 and 4  are detail views of portions  3  and  4  of  FIG. 2C ;  
       FIG. 5  is a vertical cross section of the lower half of the device shown in  FIGS. 1A-2D  illustrating the condition where a receptacle package (or receptacle pack) and a receptacle tube sack assembly are attached but not cored so as to bring the internal environments of the device, the receptacle pack and the receptacle tube sack assembly in communication with each other;  
       FIG. 6  is a vertical cross section of an alternative embodiment of the device of the present invention, wherein all of the operations of the first embodiment may be accomplished with a single manipulator mechanism;  
       FIG. 7  is a cross-section of an alternative embodiment of the device of the present invention; wherein single receptacles may be filled and removed from the environment in which they were filled without allowing exchange between the outside ambient environment and the environment within the device where the receptacle was filled or the environment within the closed container holding the filled receptacle;  
       FIG. 8  is a cross-section of the device shown in  FIG. 5  with the plunger in the stopper of the filled receptacle depressed into a closed position, the lower portion of the housing removed, the receptacle tube sack extended and sealed over the upper material exposed portion and separated from the housing to which the upper portion of the sealed receptacle tube sack remains attached;  
       FIG. 9  is a cross-section of an alternative embodiment, wherein an individual receptacle can be attached to a housing for filling and the filled receptacle can be removed from the housing through the top of the housing rather than through the bottom of the housing as is illustrated in  FIGS. 5 and 6 ;  
       FIGS. 10A and 10B  are cross-sections of alternative embodiments of the present invention; and  
       FIG. 11  is a cross-section of an alternative embodiment of the present invention. 
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENTS  
      The present invention will now be described with reference to the accompanying drawings. It should be noted that the same references have been used throughout the several views to identify the same or similar elements.  
      The Main Housing:  
      Referring to  FIGS. 1A, 1B  and  2 A- 2 D, the device of the present invention includes a main housing  2  with an internal cavity  2   a.  The housing is depicted as having a removable cover plate  3  and a base plate  4 . The removable cover plate  3  and base plate  4  include flanges  21  and  24 , respectively. Furthermore, the main housing  2  includes an upper flange  22  and a lower flange  23 , which mate with the flanges  21  and  24  of the cover plate  3  and base plate  4 , respectively. Furthermore, the lower surface  21   a  of the flange  21  of cover plate  3  is sealed with the upper surface  22   a  of flange  22  of main housing  2  by a gasket  3   a,  and the upper surface  24   a  of flange  24  of base plate  4  is sealed with the lower surface  23   a  of flange  23  of main housing  2  by a gasket  4   a.  The main housing  2  is removably attached to the cover plate  3  and base plate  4  using sanitary clamps  14  and  15 , respectively.  
      Although the cover plate  3  and base plate  4  are illustrated as plates attached using sanitary clamps  14  and  15 , these elements could be attached by various other means of attachment. Furthermore, although the cover plate  3  and base plate  4  provide greater ease of access into the main housing  2 , these elements may be formed as fixed parts of the main housing  2 . In addition, should an alternate port or additional access port be desired, other ports may be formed in the main housing  2 , depending on the application.  
      The main housing  2  has a supply port  5  for receiving flowable material therethrough. The supply port  5  is connected upstream to at least one source of flowable material supply  5   a.  Materials supplied through port  5  include materials intended to be filled into an open empty receptacle  51 . Normally, opened receptacles are positioned under opening  6  of supply port  5  located within internal cavity  2   a  of housing  2  before the material supply  5   a  is turned on so that supplied material flows into the receptacle  51 . Once enough material is collected (including what might be resident in the supply line from the source to the opening  6  of supply port  5 ), supply  5   a  may be turned off. It should be noted that supply port  5  may also be connected to a manifold  5   b  for controlling the feeding of various other materials. In this way, supply port  5  could also be used to supply various other materials into the main housing, including desiccating, fixing, cleaning and sterilizing agents as well as other materials. Alternatively, other ports may be introduced into the main housing  2  for the purpose of supplying materials to the main housing  2  in independent fashion. For example, although not required, supply port  7  illustrated in  FIG. 2  is such a port and is intended to supply small amounts of fixative agent into the receptacle  51  before, during or after the receptacle is filled with material from the supply port  5  and before the receptacle is stoppered. Supply port  7  has an opening  8  within internal cavity  2   a.    
      It should be noted that the supply port  5 , supply port  7  and any other ports could also be used to supply materials to the housing as well as to draw materials out of the housing, such as in the case of a vent. In the embodiment illustrated in  FIGS. 2A-2D ; however, cover plate  3  is shown with a dedicated valved vent port  11  for venting purposes. Accordingly, it is unnecessary to provide a vent in the main housing  2 . It should also be noted that an intent of the device of the present invention is to control untreated material from being directly exchanged with the ambient environment outside the housing. Accordingly, material vented or drained from the housing would normally pass through closed piping or tubing to point where the material would be treated before being release to the ambient environment. In some cases physical treatment, such as filtration or heat-treating may be sufficient while in other cases, chemical or physical chemical treatments may be necessary.  
      Cover Plate:  
      Cover plate  3  in  FIG. 2A  includes a bore  16  with a tubular lower extension  19 . A cam  139  (discussed later) is mounted for rotation on the tubular lower extension  19 . A tube-clasp manipulator rod  101  is mounted within the bore  16 . The manipulator rod  101  is sealed with the bore  16  by an o-ring  135  and an o-ring grove  136  mounted within the walls of the bore  16  in a lower portion of the lower extension  19 .  
      Cover plate  3  also includes a bore  17  through which a receptacle ejector rod  160  (discussed later) is mounted. Ejector rod  160  is sealed with the cover plate  3  by an o-ring  17   a  and an o-ring grove  17   b  located within the walls of the bore  17 .  
      Additionally, cover plate  3  includes a bore  18  through which a coring rod  74   a  is mounted. Coring rod  74   a  is sealed with the cover plate  3  by an o-ring and groove combination  18   a  mounted in the wall of bore  18 .  
      Although not illustrated in the above embodiments, the device of the present invention may be fitted with viewing windows in order to aid the operator with the use of the system.  
      Base Plate:  
      Base plate  4  may be attached to the bottom of the main housing  2  in a similar or alternative fashion to the cover plate  3 . Likewise, either of the base plate  4  and cover plate  3  may be formed as a part of the main housing  2  while the other is detachable.  
      The base plate  4  illustrated in  FIGS. 2B and 2C  include three vertical through bores and one side bore. A drain opening (not visible) for valved drain port  12  is located at a lowest point so as to enhance drainage. Other bores include an injection bore  30   a  for receptacle injection port  30  and an ejection bore  170   a  for receptacle ejection port  170 . A supply port  9  for adding a cleaning, disinfecting, sterilizing, neutralizing or otherwise decontaminating agent into portions of the receptacle tube sack before it is closed is shown. Supply port  9  has an opening  9   a  located in the base plate  4  above the septum  190   a  (discussed later) of the receptacle tube sack assembly  190  (also discussed later). It should be noted at this time that the elements of the device could be rearranged so that all of the openings currently illustrated in the cover plate could also be located in the base plate. Likewise, all of the openings that currently appear in the base plate could also be relocated in the cover plate with the exception of drain port  12 , since the opening  12   a  should remain at the low point of the base plate.  
      It should be noted that although adding a cleaning, disinfecting, sterilizing, neutralizing or otherwise decontaminating agent through a supply port  9  and an opening  9   a  located within cover plate  3  would be more difficult (a tube feeding into a fold or lower section of the receptacle tube sack before it is sealed off would be one example), it can be accomplished and therefore should be considered to be within the scope of the present invention.  
      Injector Port Assembly:  
      Referring to  FIGS. 2C and 2D , the injector port assembly will now be described. Injection port  30  includes an outer tubular section  31  that extends down beyond the bottom of the base plate  4  and is shown terminating in a sanitary clamp flange  33 . Injection bore  30   a  is counterbored from the bottom up to form a seal face  36  relieved on the outer edge by an annular alignment recess  37  so that the internal bore of tubular section  31  is flush internally with the outside diameter wall of the alignment recess  37 .  
      Insert  32  nests inside the inner bore of tubular section  31 . The insert  32  includes a mirror image relieved seal face  38  with the outer edge also being relieved to form annular alignment recess  39 . At the opposite end, insert  32  is shown with a sanitary clamp flange  34  that mates with flange  33 . A sanitary clamp  46  is used to removably attach the sanitary flanges  33  and  34  to each other.  
      Receptacle Pack or Empty Receptacle Holder:  
       FIG. 2A-2D  illustrate a device that is designed to accept single or multiple receptacles, to fill the receptacles and then to have the capacity to expel all of the receptacles without losing the integrity of the system relative to the surrounding ambient environment. In order to accomplish this an individual receptacle or a group of receptacles are prepackaged into an empty receptacle holder in the form of a receptacle package  40  or a receptacle magazine  40   a  (not shown). Although  FIG. 2C  illustrates the receptacles being completely enclosed in the receptacle package  40 , it is only necessary that an access into the receptacle be enclosed in the package  40  such that, when the package is opened, the receptacle may be filled through the exposed access. Once filled, the access may be reclosed. In the case where the package  40  includes several receptacles, access to individual receptacles may be closed off after each receptacle is filled. Additionally,  FIGS. 2C and 2D  shows the receptacles with screwed on stoppers in place. It should be noted that this illustrates only one of many possible types of stoppers that might be used and further illustrates only one of many way these stoppers may be affixed to the receptacles. Furthermore, it is not necessary that the supplied receptacles have stoppers fixed in place; receptacles may be supplied in the opened condition as well.  
       FIGS. 2C and 2D  show receptacle package  40  as a flexible tubular structure with a tube wall  41  and a lumen  41   a  that is closed at both ends with flanged package septum  44  at the front end and terminating in a blind end  44   a  to the back of the receptacle package  40 . Although the receptacle package  40  may have one or more receptacles which do not have to be pre-stoppered and do not have to be of any particular level of cleanliness or sterility, the receptacle package  40  illustrated in  FIG. 2  is filled with several pre-stoppered receptacles stoppered with threaded stoppers. The stoppers&#39; tops are each shown with a raised sprue  56 , the sprue  56  having a hollow cavity  57  with a narrow slotted opening  57   a.  Receptacles are shown with bottoms tipped with a thread  59  ending in a blunt tip  58 . The pre-stoppered receptacles are positioned linearly within lumen  41  a in linked fashion head-to-toe (receptacle bottom tip to stopper top), similar to linked sausages. With the exception of the first stopper, pre-stoppered receptacles are linked to each other by having the blunt tip  58  of the receptacle inserted through the slotted opening  57   a  into the cavity  57  of the stopper that follows. The stopper of the first receptacle, shown in  FIG. 5 , is linked to the bottom of the septum  44  as will be described below.  
      Continuing with  FIG. 3 , receptacle package  40  is shown topped by a flanged package septum  44  with sprue  56  of the first stopper affixed to a bottom surface thereof. Attaching the first stopper to the portion of the septum  44  which will later be cored exemplifies a method by which septum core  44   b  may be carried through the device and ejected on the other side as part of the first stopper, thus, removing it from the system and eliminating it as a possible mechanical hazard. This represents one manner in which to remove core  44   b  is prevented from interfering with later device operations. It should be understood that other methods of removal are possible but it also is not necessary to remove the core  44   b  from the system at all but, rather, simply position it or system components so as not to interfere with the system&#39;s operation.  
      In this embodiment the outer edge of the flanged portion of flanged package septum  44  extends above and below the adjacent inner radial portion  42   c  of the flange to form two short tubular sections  42   a  and  42   b.  When the flanged package septum  44  is inserted up through the internal bore  35  of insert  32  and insert  32  is itself inserted up into tubular section  31 , tubular sections  42   a  and  42   b  become nested in alignment recesses  37  and  39  as the upper and lower surfaces of radial portion  42   c  mate with seal surfaces  36  and  38 . When sanitary clamp  46  is affixed to flanges  33  and  34 , insert  32  is firmly clamped in place and flanged package septum  44  firmly fixed and sealed above and below.  
      Cleaning the Housing:  
      One of the values of the device of the present invention is that it can fill receptacles in an environment isolated from the ambient surrounding environment. This device has particular value in processes where hazardous materials are handled and preventing release to the ambient environment is critical. Furthermore, the device of the present invention is valuable when obtaining uncontaminated samples from a process are important of where both of the above are important. The device of the present invention is also of value in other instances where sampling or subdividing, mixing or combining material in isolation is important.  
      Although the receptacles and their stoppers may be protected from the outside ambient environment and remain uncontaminated when prepackaged in a closed receptacle magazines  40  or receptacle tube sack assembly  190 , the exterior of the receptacle package  40  and receptacle tube sack assembly  190  are exposed to the outside environment. Therefore, the exterior of the receptacle package  40  and receptacle tube sack assembly  190  are contaminated by the outside ambient environment. In the same way, the internal cavity  2   a  of the main housing  2 , including the internal surfaces of each passage opening into the internal cavity  2   a  all the way back to the point where a closure or seal is formed, may become contaminated when exposed to the ambient environment. It is, therefore, standard practice to wash, clean, sterilize, neutralize or otherwise decontaminate the interior of the equipment once the equipment is assembled and closed to the outside ambient environment. Thus, once the receptacle package  40  and the receptacle tube sack assembly  190  are fixed in place and the housing is closed, washing, cleaning, sterilizing, neutralizing or other wise decontaminating agents may be applied to the interior of the system to wash, clean, sterilize, neutralize or other wise decontaminate the interior, including the upper surfaces of the flanged septa of receptacle package  40  and receptacle tube sack assembly  190 , which are also exposed to the interior. Once this has been accomplished, coring of the septa can be carried out to open the lumen of the receptacle package  40  and of the receptacle tube sack assembly  190  and their contents to the inside cavity of main housing  2 . Accordingly, the contents of the receptacle magazine and the receptacle tube sack assembly become part of the same isolated environment, separate from the outside surrounding ambient environment. Individual receptacles from the receptacle package  40  may be withdrawn from the package, conveyed into the internal cavity  2   a  of the main housing  2 , unstoppered (if supplied in stoppered condition), filled, stoppered (if desired), ejected through the receptacle ejection port  170  and into the lumen  191   a  of the receptacle tube sack assembly  190  into the a blind section of tube sack  191   b.  As will be described later, a section of the tube wall  193  can be individually sealed and pinched off from the portion remaining attached and continuous with the internal cavity  2   a  of the main housing  2 , allowing the integrity of the environment around the filled receptacle  51  a and that of the internal cavity  2   a  to both be preserved separate from that of the surrounding ambient environment. If a hazardous material is being processed within the main housing  2 , the main housing  2  may be washed, cleaned, sterilized, neutralized or otherwise decontaminated before being reopened to the ambient environment. In a similar fashion, a washing, cleaning, sterilizing, neutralizing or otherwise decontaminating material may be added to individual tube sacks before they are sealed off and separated from the environment within the housing. Alternatively, the individual section of tube sack may have incorporated in one or more pouches or spaces which may be released into the lumen of the tube sack once it is removed from the system, confining exposure to the agent only to the lumen of the tube sack holding the filled receptacle, keeping it separate from the internal cavity and connected environments.  
      Coring of the Septa:  
      The procedure for coring the septa will now be described. In this embodiment the receptacle injection port  30  and the receptacle ejection port  170  are both fitted with septa and both are cored at the same time. Since the coring procedure and the structure of the septa are similar for both the injection and ejection ports  30  and  170 , the procedure will be described for the injection port  30  with the understanding that the same happens for the ejection port  170 .  
      The coring assembly consists of an L-shaped coring rod  71 , cross bar  71  a and two cylindrical blades  72 , each with 360° bottom cutting edges  73 . The lower portion of one of the blades  72  rests in the upper portion of injection bore  30   a  while the lower portion of the other of the blades  72  rests in the counterpart upper portion of the ejection bore  170 . As pressure is applied down on coring rod handle  74 , coring rod  71  transfers the pressure through cross bar  71   a  and to the two blades  72 , forcing their cutting edges  73  to core out a cylindrical core section of both the flanged package septum  44  and the flanged receptacle sack septum  190  (described later). Ridged or semi-ridged inserts  197  and  43   a  may be included in the structure to add rigidity to the septa in the area adjacent to where the cut is made. While the septum core  44   b  from the package septum  44  remains attached to the stopper of the first receptacle  51 , the septum core  190   b  of the sack septum  190  will freely drop (or be pushed by the passage of the first filled receptacle  51  a through the ejection port  170 ) into the lumen  191   a  of the receptacle tube sack assembly  190 . Once cored, the opening through the septum  44  held in the injection port  30  and the septum  190  held in the ejection port  170  are both large enough so as to allow passage of receptacles or stoppers or receptacles with stoppers attached.  
      Instead of the vertical motion of the coring rod, the coring motion could be provided by extending cross bar  71   a  to mate with a rotating lever arm through the side wall of the housing. A cam on the lever arm could impart the motion to cross bar  71   a.    
      Cross bar  71   a  could also be attached to the lever arm. Although the arm motion would trace an arc, cutting could be effectively accomplished even though wider tolerances might be required. One of the added benefits of this approach would be that the blades could be withdrawn with the lever arm, allowing the upper portion of the blades to be solid and also allowing them to be fitted with an outer annular shoulder that could be brought into sealing communication with the septa shoulder about where the core was removed. Because the blades are solid and do not have a through bore in this case, when forming a seal with the septa shoulder it would facilitate resealing and repressurizing of the housing internal cavity at some time after coring should that be desired. Inserts  197  and  43   a  in the flanged septa  44  and  190 , respectively would add structural rigidity against which the outer annular shoulders of the blades could seal. Lastly, cores could be captured and removed from interfering with operations by including barbed pre-puncture needles mounted in the center of the coring blades. The needles would puncture the septa before being cored and the barbs on the needles would retain and withdraw cores after being cored as the lever arm is rotated back out of the way.  
      Many other methods for coring the septa are possible. The selection and description of these particular methods are not intended to limit the range of devices for coring that could be used with this device. These methods and descriptions are only intended to be illustrative of some methods for gaining access to the unfilled receptacles and for gaining access for filled receptacles to the empty receptacle sacks.  
      Conveying the Receptacle Through the Device:  
      Within the main housing  2  is a means for conveying the unfilled receptacle  51  up from the injection port  30  to the unstoppering station, the filling (and fixing) station, the restoppering station down through the ejection port  170 . This device for conveyance may consist of a single device or system or a set of systems (subsystems) working in cooperation to convey the receptacle  51  into the main housing  2  to the various stations and back out of the main housing  2 . To illustrate the concept, two embodiments are described below. These embodiments are chosen as examples and are merely representative of two of the many methods by which the receptacle could be conveyed into, through and back out of the main housing  2 . It should be noted here that device  1  may be designed so that receptacles  51  are supplied from and supplied to a ridged or semi-ridged magazine  40   a  and  200   a  or flexible walled package  40  or receptacle tube sack assembly  190 . Furthermore, the supply and destinations of receptacles could be located within the housing itself. The disadvantage of this approach is the larger space necessary to house the receptacles within housing  2  and, without additional features such as a transition port, access to filled receptacles would only be possible when the device is opened.  
      1. Embodiment of Conveyance Device: A Set of Systems (or Subsystems) Working in Cooperation:  
      Staging Clip Assembly:  
      Once package septum core  44   b  is severed from flanged package septum  44 , the first receptacle  51  in the series illustrated in device  1  is intended to be manually fed up into internal cavity  2   a  of main housing  2  until stopper  53  affixed to receptacle  51  is engaged by spring-loaded staging clip assembly  80  and captured. If receptacle  51  were not the first receptacle, the receptacle preceding it in the train would be pulled into the housing by the receptacle conveyance system  50  which would, in turn, pull receptacle  51 , attached to the preceding receptacle  51  by the combination thread  59  and tip  58  to sprue  56 , cavity  57  and opening  57   a  up into internal cavity  2   a  of main housing  2  until its stopper is captured by staging clip assembly  80 . As receptacle  51  moves up, the rest of the attached receptacles in the train within receptacle package  40  would also move up. As receptacle  51  is captured and held at the staging clip assembly  80 , receptacle conveyance system  50  pulls on its predecessor until tip  58  is pulled free from cavity  57  and opening  57   a  of stopper  53  or thread  59  breaks or is otherwise cut. It should be noted that stopper  53  and receptacle  51  could be molded as one piece, joined by thread  59  with the intention that thread  59  be broken or cut by an element of the staging clip assembly  80  or receptacle conveyance system  50  as one receptacle  51  is held while its predecessor advances through device  1 .  
      Staging clip assembly  80  has a detent  83  designed to capture receptacles  51  by the stopper  53  as they rise. Staging clip assembly  80  could be modified to capture many other sizes and designs of receptacles or exchanged for other assemblies. The assembly could, in fact, be modified or changed to one which more encircles and confines the movement of the receptacles into the housing. Versatility is the reason that staging clip assembly  80  is removably mounted on pedestal  81 .  
      Staging clip assembly  80  includes angled arms  82  and  84  designed to cause the clip to be deflected to the side and release the receptacle stopper  53  as the receptacle clasp assembly  100  engages and captures the receptacle  51 .  
      Receptacle Conveyance System:  
      The receptacle conveyance system  50  is illustrated in  FIGS. 2A and 2B . In general terms, the system captures the unfilled receptacle  51  from staging clip assembly  80  at the opening of the injection port  30 , moves the unfilled receptacle  51  up to the stopper clasp assembly  140  where the stopper  53 , if present, is removed. Receptacle conveyance system  50  then moves the open empty receptacle to the opening  6  of supply  5  where it is filled. After being filled, the receptacle  51   a  is brought back up to be restoppered by the stopper clasp assembly  140  before receptacle conveyance system  50  moves the filled, stoppered receptacle  51   a  back down and over to the ejection port  170 . There the receptacle clasp  100  disengages the receptacle  51   a,  allowing it to slip down into ejection port  170 . If the receptacle  51   a  is stoppered, the ejector rod tip  160   a  may engage the top of the stopper  53  before, during or after the receptacle clasp  100  releases the receptacle  51   a  into the ejection port  170 . In any case, the ejector rod  160  can be used to help manipulate the receptacle  51   a  down through the ejection port  170  into a receptacle tube sack assembly  190  (if employed) and out of the device  1 . If tube sacks are used, after the filled receptacle  51   a  clears the bottom of the ejection port assembly, a seal or closure  188  may be formed along the tube wall  193  using a variety of devices for sealing or closing  189 , thereby cutting off communication between environment in the sealed or closed portion of the tube wall  193  containing filled receptacle  51   a  and the internal cavity environment of the main housing  2 . At the same time, the integrity of the environment around the filled receptacle  51   a  within the section of tube wall  193  and the integrity of the environment within the main housing  2 , is maintained both separate and isolated from that of the outside ambient environment. A detailed description of the operation of the conveyance system  50  follows.  
      As illustrated in  FIG. 2B  and as described earlier, staging clip assembly  80  captures the stopper  53  of the stoppered unfilled receptacle  51  in detent  82  and holds it.  
      Handle  101   a,  located outside main housing  2 , is mounted on one end of the manipulator rod  101  and receptacle clasp assembly  100 , located inside the internal cavity  2   a  of the main housing  2 , is mounted onto the other end of the manipulator rod  101 . Thus, receptacle clasp assembly  100  can be raised and lowered vertically and rotated 360° from the outside by doing the same with handle  101   a.  As mentioned above, manipulator rod  101  extends up through bore  16  in lower extension  19  and cover plate  3 . It is sealed to the outside by combination o-ring  135  and o-ring groove  136  located in the lower portion of extension  19 .  
      Using handle  101   a,  receptacle clasp assembly  100  can be brought down and into engagement with the side of unfilled receptacle  51 , below stopper  53 . Receptacle clasp assembly  100  includes clasp arm  102   a,  linear bearing arm  102   b,  liner bearing  104 , spring loaded clasp arms  102   c,  spring arms  110  and  111 , grip rods  114   a - 114   d  and grip sleeves  118   a - 118   d.    
      Clasp arm  102   a  is mounted directly onto the base of manipulator rod  101  and has a rear extension. Linear bearing arm  102   b  houses linear bearing  104  which is mounted on subassembly alignment rod  105 . Alignment rod  105  is fixed onto stopper clasp assembly  140 . This arrangement permits receptacle clasp assembly  100  to slide freely up and down subassembly alignment rod  105 , independent of vertically fixed stopper clasp assembly  140  but which cause the two assemblies to be in locked rotational position relative to each other so that, as receptacle clasp assembly  100  is rotated, stopper clasp assembly  140  rotates by the same amount. As a result, any receptacle  51  or stopper  53  held by either always maintains their relative rotational alignment, regardless of position.  
      In addition, two spring-loaded clasp arms  102   c  are fitted with vertical grip rods  114   a - 114   d  to grip the side of the receptacle. In order to improve gripping capability on very smooth and wet receptacles, these rods may be covered with grip sleeves  118   a - 118   d  designed to enhance the clasp&#39;s ability to grip the receptacle. Sleeves with elastomeric, adhesive or abrasive exteriors are examples of materials that may aid gripping. For instances where stopper removal includes the application of strong rotational forces, vertical grip rods prove much more effective than radial grip rods. This is because a vertical grip rod would wipe across a wide exposed area of the receptacle at one time as opposed to other approaches such as radial grip rods that would not. Spring arms  110  and  111  or similar tensioners may be added to provide added pressure on the grip rods to improve gripping.  
      Receptacle clasp assembly  100  can be moved down and/or rotated around near base plate  4  so as to engage wedge-shaped release jams  109  (not visible in  FIG. 2 ) located adjacent to injection port  30  and ejection port  170  at the junction of the two spring loaded clasp arms  102   c,  forcing them apart to facilitate grasping or releasing receptacle  51 .  
      Captured receptacle  51  with stopper  53  in place can be raised vertically so that stopper  53  is engaged and captured by stopper clasp assembly  140  by raising handle  101   a  vertically. Stopper clasp assembly  140  includes clasp body  121 , clasp gear  121   a,  main gear  121   b,  grip rods  141   a - 141   d,  grip sleeves  145   a - 145   d,  cam  133  with lobe  139  and its bore  139   a  and lobe  131  with its bore  131   a,  upper pinion  122   a  and lower pinion  122   b.  The grip rods  141   a - 141   d  are attached to clasp body  121 , are slightly tapered and may be tension mounted so as to receive the stopper  53  and hold it firmly as it is forced up between the rods on top of the receptacle  51 . As with receptacle clasp assembly  100 , these rods may include grip sleeves  145   a - 145   d  to assist in tightly securing stopper  53  when it is engaged. Clasp gear  121   a  is nonrotatingly fixed to clasp body  121  by lower pinion  122   b.  The Clasp body  121 , clasp gear  121   a,  grip rods  141   a - 141   d  and sleeves  145   a - 145   d  are all attached as one rotatable element cam  133  by means of upper pinion  122   a  positioned in bore  131   a  of lobe  131  of cam  133 . Bore  137  of cam  133  is mounted rotationally free in recess  138  of lower extension  19 . Subassembly alignment rod  105  is fixed into bore  139   a  of lobe  139  of cam  133 . As described earlier, fixing the position of subassembly alignment rod  105  on cam  133  forces receptacle clasp assembly  100  to remain in fixed rotational alignment with stopper clasp assembly  140  attached to cam  133 . Main gear  121   b  is fixed to the wall  2   b  of internal cavity  2   a  of main housing  2 . With cover plate  3  in place, main gear  121   b  is fixed in the same horizontal plane as clasp gear  121   a  so that the two always remain meshed. If handle  101   a  is rotated, receptacle clasp assembly  100  and stopper clasp assembly  140  both rotate about manipulator rod  101 . Because clasp body  121  and its fixed parts are also fixed to clasp gear  121   a  which is meshed with main gear  121   b,  besides causing receptacle clasp assembly  100  and stopper clasp assembly  140  to rotate, turning handle  101   a  will also cause clasp gear  121   a  and clasp body  121  and its associated fixed parts to spin on their own axis about upper pinion  122   a.  With receptacle  51  captured in receptacle clasp assembly  100  and stopper  53  captured in stopper clasp assembly  140 , rotating handle  101   a  in one direction will cause a threaded stopper  53  to unscrew from the receptacle being held fixed on its own axis in the receptacle clasp assembly  100  while rotating handle  101   a  in the other direction would cause it to thread back on to the receptacle  51  or  51   a.  In this way stoppers  53  may be removed and reattached to receptacles  51  or  51   a.  Spring loaded clasps in combination with the rotational motion of either the stopper  53  or the receptacle  51  or  51   a  relative to the other in combination with applied vertical pressure is the commonly used method for opening stopper-receptacle combinations, even if they are friction tight and not held by threads.  
      In the manner described above, a receptacle  51  may have the stopper  53  temporarily removed. With the stopper  53  removed, handle  101   a  can be used to rotate and position the mouth  52  of the receptacle  51  under openings  6  and  8  of supplies  5   a  and  7   a,  respectively, or any other supply opening into internal cavity  2   a.  Once filled, handle  101   a  may again be used to maneuver filled receptacle  51   a  into communication with the stopper  53  still held in stopper clasp assembly  140  by, first, rotating receptacle  51   a  out from under openings  5   a  and  7   a  and then raising the receptacle clasp assembly  100  until the top of the receptacle  51   a  mates with the bottom of the stopper  53 . Rotating handle  101   a  in the opposite direction as before will reattach stopper  53 .  
      Filled, stoppered receptacle  5 la may be rotated so that it is over ejection port  170  and lowered down into it. Filled receptacle  51   a  may be dislodged from receptacle clasp assembly  100  by rotating receptacle clasp assembly  100  in the direction opposite the opening in the clasp while the lower half of the receptacle  51   a  is in the ejection port, by mating the clasp arms  102   a  with the release jam  109  adjacent to ejection port  170 , by pressing down on the top of stopper  53  with ejector rod  163  or some combination of the above. Once dislodged, receptacle clasp assembly  100  may be rotated back to a position ready to capture the next unfilled receptacle  51  and the process begins again.  
      Gravity may be sufficient to move filled receptacle  51   a  through ejection port throughbore  170   a  however, as mentioned above, ejector rod  163  may also be used.  
      Ejection Port Assembly:  
      Ejection port  170  has the same general arrangement as injection port  30 . The rejection port  170  includes an outer tubular section  171  that extends down beyond the bottom of base plate  4  and is shown terminating in a sanitary clamp flange  173 . Ejection port through bore  170   a  is counterbored from the bottom to form counter bore  171   a  terminating at the top in seal face  174  with a relieved outer annular edge forming alignment recess  175  so that the internal bore of tubular section  171  is flush internally with the outside diameter wall of alignment recess  174 .  
      Like injection port  30 , ejection port  170  also has an insert  177  whose forward or upper portion  177   a  nests inside the inner bore of tubular section  171  which has a seal face  178  also with a relieved outer annular edge forming alignment recess  179 . Insert  177  is also shown with a sanitary clamp flange  176  to mate with flange  173  of tubular section  171 , much as injector port  30  does. A sanitary clamp  172  fits over flanges  173  and  176  to hold them together. Many methods may be used to secure mating elements together. The flange clamp combination shown here is used only by way of example. Many other combinations may be employed, including bolt flanges, threaded collars, etc.  
      Although insert  177  could be substantially the same length or even shorter than insert  32 ,  FIGS. 2C and 2D  show a tubular extension  177   b  on insert  177  that extends substantially further down and which terminates with an external threaded portion  177   d  and, interiorly, in a truncated conical opening  177   c.  External threaded portion  177   d  may receive a threaded blind end cap  201  to protect the exposed blind end of receptacle tube sack assembly  190  that will be discussed below.  
      Tube Sacks or Filled Receptacle Holder:  
       FIGS. 2A-2D  illustrates a device that is designed to allow filled receptacles  51   a  to be removed from the device  1  as single unit receptacles, multiple receptacles as a single group or multiple receptacles as individual receptacles, all without losing the integrity of the environment around the receptacle (or receptacles) and without losing the integrity of the environment within the device  1 . This may be accomplished by attaching a length of empty blind ended sealed tubing constructed similarly to the receptacle package already described (except without any receptacles), allowing access to be gained into one end of the blind tube, the end with the septum, by the same coring means described earlier for the receptacle package, thereby opening the interior to receive filled receptacles as they are ejected through the ejection port  170 . Although illustrated in  FIGS. 2A-2D  as a soft sided tubular structure, like the receptacle package, the tube sack or filled receptacle holder may also be constructed as a semi-ridged or ridged container or magazine. Also like the receptacle package, rather than a septum, the access into the structure might also be structured in other ways, such as a valve.  
      As the first filled receptacle  51   a  is fed out of the ejection port  170  into the receptacle tube sack assembly  190 , whether rolled, folded or pleated, the first length of tube wall  193  that has been sealed at the distal end to form a blind length of tube sack, the blind end tube sack  191 , can be fed out. After the portion of the blind end tube sack  191  with the filled receptacle extends out beyond the lower conical portion  177   c,  the sack may be sealed in single or multiple seal fashion, segregating the internal environment of the housing from that within the length of blind end tube sack  191  now containing filled receptacle  51   a  to form a compartment. Before the length of tube wall  193  is sealed; however, an agent may be added into the length of blind end tube sack  191  now containing filled receptacle  51   a  to protect, stabilize, clean, sterilize, neutralize or otherwise decontaminate or treat the material still on the outside of the receptacle  51   a  and any residing within the blind end tube sack  191 . With the filled receptacle  51   a  in the blind end tube sack  191  a seal or closure  188  may then be made by a device for sealing or closing  189 . This device could be any appropriate means, including twisting, crimping, heat sealing, sonicating, gluing, tieing-off, zipping, clamping or any other pressure, temperature, chemical, physical or biological device. Furthermore, the seal or closure  189  could consist of single or multiple seals or closures formed in between sections of tube wall used to form a blind end tube sack  191  to receive the next filled receptacle  51   a.  It should be noted here as stated elsewhere in this disclosure that agents may be added into the sections of tube wall between seals of closures or into the section where a seal or closure will be made in order to promote cleaning, sterilizing, neutralizing, decontaminating or otherwise treating the material in that area so that when the tube wall is cut through to separate the distal sealed or closed section of tube wall containing the filled receptacle from the section of tube wall ending in a blind end tube section still attached to the device, material or residue won&#39;t be released into the outside ambient environment.  
      Whether or not an agent is added, the sealed sack containing the filled receptacle may be separated from the remaining sealed blind end section of tube sack still attached to the device. Ends of the cut tube wall may be treated after cutting as well in order to further limit the exchange of the contents with the ambient environment. Seals along the tube sack may be formed in many ways, including, but not limited to zip locks, heat sealing, tying off and crimping. A detailed description of other aspects of removing and detaching the filled receptacle from the device follows.  
      Referring again to  FIGS. 2A-2D , tube wall  193  is shown as being a flexible tubular structure with a straight, folded, rolled, pleated or nested tube wall with an interior space or lumen  193   a.  The distal end of tube wall  193  is sealed or closed to form a blind end while the end proximal to the device  1  is shown fused into the bottom of flanged sack septum  195  at a position radially inward from the bottom annular sealing surface  193   c  (annular sealing surface  193   b  being the top sealing surface). Also fused to the bottom of flanged sack septum  195  and extending downward but positioned slightly radially inward is sack support cylinder  196 . When cored, the bore through flanged sack septum left after it has been cored, called septum bore throughhole  190   c,  opens into the lumen  196   a  of sack support cylinder  196  so that, when a filled receptacle  51   a  is expelled through ejection port  170 , it passes through lumen  196   a.  Sack support cylinder  196  is not required but does keep tube sack  191  from collapsing and, since sack support cylinder  196  terminates proximally to truncated conical section  177   c,  it helps to control the playout of tube sack  191 . Tube sack  191  is therefore, positioned in the space between the outside wall of sack support cylinder  196  and the inside wall of insert  177 .  
      Flanged sack septum  195  is captured in the upper portion of ejection port  170  in the same manner as flanged package septum  44 , as can be seen in  FIGS. 2A-2D .  
      2. Embodiment of Conveyance Device: A Single Device or System:  
       FIG. 6  shows an embodiment of the device in which a single arm mechanism, working in cooperation with a reversible ratchet equipped stopper clasp, can destopper thread stoppered receptacles, fill the receptacle, restopper the receptacles and place the receptacles in the ejection port  170  as described earlier. One of the benefits of this arrangement is that the arm mechanism is completely isolated from the internal environment within the housing by a flexing (up/down and rotating) necked conical diaphragm  18   b.  The neck portion allows for most of the rotational movement while the neck and cone section combine to provide the up/down movement. While this embodiment shows coring of the injector septum and the ejector septum performed by two separate arms  74   a,  the action could be performed by a single arm. In either case, these coring devices could be equipped with flexing diaphragms to isolate the source of motion outside the housing from the action of the motion within the internal cavity of the housing.  
      Another feature of this embodiment is the reversible ratchet equipped stopper clasp to destopper and restopper receptacles. While the function could be performed by a fixed position stopper clasp in combination with the flexing, rotating necked conical diaphragm (thus eliminating any seals associated with the ratchet mechanism), this ratchet mechanism allows unlimited rotation in either direction without the need to first disengage and reengage the stopper from the clasp. Like other rotation devices capable of unlimited rotation in a direction, a significant amount of rotation in one direction limits the seal from the possibility of being a twistable sleeve or diaphragm to one that must allow sealing against a freely rotating surface, such as in the case of o-rings, bushings or other mechanical-type seals, all of which do not provide the level of isolation that a sleeve or diaphragm is capable of. The system integrity loss risk associated with the ratchet mechanism may be limited; however, by placing the portion of the ratchet with unlimited rotational capabilities within the housing while allowing communication through more effective flexing isolating seals (of diaphragm type, for instance) to easier-to-seal limited rotational portion components such as the directional switch mechanism to the ratchet.  
      The injection and ejection ports in  FIG. 6  both include staging clip assemblies  80   a  and  80   b,  two in each case. Furthermore, while the staging clip assemblies shown in the injection port  30   a  function similarly to that shown in  FIGS. 2A-2D , they extend up into the injection port. Also, those shown on the ejection port  170  do not include detents but, rather end with straight edges  82   c  or edges that tend to grip the sides of the receptacle and inhibit its being pulled back into the main housing  2  as the receptacle clasp is pulled back into the main housing  2  in order to clasp the next unfilled receptacle. That receptacle, once captured, can be used to assist the ejection of the previous filled receptacle by pushing it from behind.  
      This embodiment can perform the same functional operations as the embodiment of  FIGS. 2A-2D  described above. As mentioned in the description of the embodiment in  FIGS. 2A-2D , a cover plate  3  or base plate  4  can be attached to the main housing  2 . Furthermore, as mentioned previously, components shown located in cover plate  3  or base plate  4  could be switched or combined into one plate or the other. As such, receptacle injection port  30  and receptacle ejection port  170 , shown installed in base plate  4  in  FIGS. 2A-2D  are now shown installed as a part of the new fixed cover plate of  FIG. 6 . Also, receptacle conveyance system, formerly shown located through cover plate  3  in the embodiment of  FIGS. 2A-2D  is now shown installed through base plate  4  in the embodiment of  FIG. 6 . Because the receptacles need to be re-stoppered in the up-right condition, stopper clasp assembly  140  remains located in the upper portion of the housing. Likewise, because drainage flows down, drain port  12  and its opening  12   a  remain located in the lower portion of housing  2 . Whereas manipulator rod  101  with its attached receptacle clasp assembly  100  was shown entering through a o-ring groove seal combination ( 135 ,  136 ) located in cover plate  3  in the previous embodiment, In  FIG. 6 , it is shown entering through base plate  4  through a different type of seal; specifically, a necked conical diaphragm seal  18   b  with two parts, upper portion  18   c  and lower portion  18   d.  The outer radial lip  18   f  is captured between the top surface  4   c  of an upper tubular extension  4   b  of base plate  4  and a top face  2   c  of a counter bore up into side wall  2   b  of main housing  2 . Upper seal  18   c  of necked conical diaphragm seal  18   b  is formed by the capture of the radially inward extension of lip  18   g  between a lower surface  100   a  of receptacle clasp assembly  100  and an upper surface  101   b  of manipulator rod  101 . While lip  18   f  is shown being captured through the attachment of clamp  15  onto flanges  23  and  24 , the seal at lip  18   g  is shown being created when male threaded section  100   c  of receptacle clasp assembly  100  is threaded down into a female threaded section  101   c  of manipulator rod  101 . The mating of flanges under a clamp and the mating of threads are two ways described by way of example that the seals  18   c  and  18   d  may be formed. Many other arrangements are possible for these seals and these would be known and understood by one knowledgeable in the art and, now that the concept has been described, should be considered as being included within the scope of this description.  
      In  FIG. 6 , as in  FIGS. 2A-2D , receptacle clasp assembly  100  is shown attached to the end of manipulator rod  101  and assembly  100 . It includes spring arms ( 110 ,  111 ) as well as grip rods  114   a - d  which may, again, be covered by grip sleeves  18   a - d.  The assembly, however, is shown as being mounted so as to be a direct linear extension of manipulator rod  101 . By mounting the assembly thus, if a rotary motion is necessary to remove or attach a stopper, the rotary motion must come from either rotation assembly  100  by means of manipulator rod  101  in combination with a fixed stopper manipulator assembly (not shown) equipped with a fixed stopper clasp assembly (not shown). The device shown in  FIG. 6  is equipped with a stopper manipulator clasp assembly  120   b  capable of rotary motion by means of a reversible-direction ratchet mechanism  140   b.  While rotary motion in this case is still supplied by rotation of the manipulator rod, the total range of rotation capability required of the manipulator rod is limited to increments with the assistance of the ratchet mechanism. It is also possible to equip the device with more sophisticated ratchet mechanisms that are self-rotating, thus eliminating the need for the manipulator arm to be rotatable at all.  
       FIG. 6  illustrates another arrangement of staging clip assembly  80 , staging clip assembly  80   a,  where the angled arms  82   a  and  84   a  are recurved and extend up into receptacle injection port throughbore  30   a.  The detent  83  is the same but pedestal  81  is shown reduced, and identified as pedestal  81   a  in  FIG. 6 . Angled arms  82   a  and  84   a  can be caused to retract and release captured stopper  53  by the recurved extensions of grip rods  114   a - d,  clip release arms  115   a - d.  This can be accomplished when manipulator rod  101  and receptacle clasp assembly  100  are pushed up to capture an unfilled receptacle  51  and, at the same time, force angled arms  82   a  and  84   a  apart.  
      Receptacle ejection port  170  in  FIG. 6  is also shown with a clip assembly  80   b  designed to allow the filled receptacles to be extricated from the receptacle clasp assembly  100  as it is retracted from delivering the filled receptacle into receptacle ejection port  170 . This clip assembly  80  is equipped with angled arms  82   b,  which terminate in an edge  82   c  designed to grip the outside of the receptacle.  
       FIG. 6  also illustrates a modified version of coring assembly  70 , coring assembly  70   a,  in which the receptacle injection port and the receptacle ejection port both have their own coring assembly  70 . Each assembly includes a bent coring rod handle  74   a,  which is fitted rotatably through side wall  2   b  of housing  2  and attached, rotatably, to a cylindrical blade  72   a.  As with the angled arms of staging clip assembly  80   a,  these blades also extend further into the ports in order to show that the function of the device may still be performed even thought the these ports may be formed in many different ways.  
      It also should be noted that in the embodiment shown in  FIG. 6 , the cover plate is formed as a part of main housing  2  with receptacle injection port  30  and receptacle ejection port  170  located at the lateral margins. As mentioned above, elements of the system may be modified and reoriented without losing the functionality of the system so long the receptacles can be received, manipulated, have material collected in them and then have them transferred or made ready to be transferred from the device.  
      As with the device illustrated in  FIGS. 2A-2D , the device shown in  FIG. 6  can be used with single receptacles, unprestopper receptacles, receptacles using other types of stoppers than threaded ones as well as many other types of stoppered and non-stoppered arrangements.  
       FIG. 7  through  11  illustrate how a stoppered receptacle can be filled into a single tube sack.  FIGS. 7 and 8  illustrate that the tube sack need not cover the entire receptacle stopper combination.  
       FIGS. 7 and 8  illustrate one example of many types of possible stopper-receptacle arrangements that could be used. In this case, the stopper consists of two parts, threaded cap  53   a  and plunger  53   b.  This arrangement could be supplied in the plunger up or down condition and could be used in any of the embodiments presented (including that of  FIG. 9 , if supplied in the plunger up condition). Material can be supplied through the bore  53   c  in the plunger  53   b.  Once filled, the plunger can be depressed and held in place by one of the sets of ribs  53   d.    
       FIGS. 7-9  all illustrate embodiments of the device wherein a receptacle is equipped with an individual receptacle tube sack which will allow that receptacle to be removed from a dedicated receptacle filling station, either through the cover of the device or through the base of the device. If removed through the cover, the receptacle is pulled up causing the tube sack to be pulled down around the materials-exposed areas. The tube sack can then be closed and/or sealed below, thereby enclosing the exposed surfaces within the tube sack. If the receptacle is removed through the base; however, its removal causes the receptacle tube sack to be pulled up over the material-exposed surfaces. The tube sack can then be closed and/or sealed over the material-exposed areas.  
      One of the benefits of the stopper arrangement in  FIGS. 7 and 8 , particularly when the plunger  53   b  is supplied in an opened state, either as a package of many or as a single unit as shown  FIG. 7 , is that no threading mechanism is required to seal the receptacle after filling, only a ram plunger mechanism. While the one depicted in  FIG. 7  is o-ring sealed, the seal could also be a flexing diaphragm or sleeve which, although not as long lived or able to withstand the stresses of high pressure operation, would provided a greater degree of sealing effectiveness.  
      There are many possible receptacle designs and  FIG. 7  also illustrates another receptacle design wherein material may be filled into it and it may be closed without requiring rethreading a cap onto the receptacle. While in this case illustrated in this figure the plunger is shown installed in a threaded cap, it could also be installed into a fixed top or even onto the vertical sidewalls of the receptacle.  
       FIG. 7  also illustrate how an individual receptacle may be equipped with its own dedicated tube sack, allowing it to be removed from the device individually while preserving the environment of the filling areas immediately around the receptacle and within the housing largely separate from that of the surrounding ambient environment;  
       FIG. 8  illustrates the filled, sealed receptacle with the tube sack sealing over a top of the plunger stopper/threaded stopper combination but not over the receptacle itself. In this case the filled receptacle is removed down. In  FIG. 9 ; however, an arrangement is illustrated in which the tube sack is attached to the top of an individual stopper (as also was the case in  FIGS. 7 and 8  as opposed to the independent multiple tube sack arrangements of  FIGS. 1A-2D ,  5  and  6 ) wherein the individual filled stoppered receptacle is removed upward and, in this case, the stopper and receptacle combination would both be captured within the tube sack once it was sealed (not shown sealed). In each case the housing is left with the other portion of the tube sack that has the flange. It is important to note that this portion also has a blind seal so that the integrity of the internal housing environment is maintained and the materials released into the housing during the receptacle filling operation also contained and kept isolated from the surrounding ambient environment. By so doing the housing can be recapped and internally cleaned, sterilized, neutralize or otherwise decontaminated before being reopened to the ambient environment and refitted with another unfilled receptacle.  
       FIG. 10   a  and  10   b  illustrate a tube sack with ring or dot shaped pouches. These pouches may be filled with an agent that can be released into tube sacks once the filled receptacle is sealed within the sack. The agent could be a neutralizing, sterilizing, decontaminating or any other type of desirable agent. Furthermore, the pouches may be positioned between double seals in cases where the process of sealing itself may not effectively neutralize the materials present within the sack, receptacle or housing so that when a cut is made across the middle of the seal those exposed ends may release undesirable materials. Also, a seal may be made across the pouches so as to entrain agent into the seal.  
      Because any area within the tube sack will contain residue of material filled into the receptacle (because the internal surface of the tube sack was also exposed to the housing&#39;s internal environment where the filling operation was performed), a first unbroken seal may be made in the tube sack above the filled receptacle (or below, if the receptacle is removed through an upper port) before a cleaning, sterilizing, neutralizing or otherwise decontaminating agent is added into the tube sack. A second unbroken seal may then be made above the reservoir of added agent thereby segregating the agent containing area into a pouch within the tube sack, between the portion of the tube sack holding the filled receptacle and the portion still connected and exposed to the environment within the housing. After allowing the agent to work, the portion of the tube sack containing the filled receptacle may be removed from that still connected to the housing by cutting through the now decontaminated pouch. The second concept is that of preincorporating the agent into the structure of the tube sack, shown here as annular pouches.  Figure 10B  also illustrates how the decontaminating agent may be added into the portion of the tube sack containing the filled receptacle so as to act on residue within that environment before it is opened. The agents also could be added into the housing for the same purposes.  
       FIG. 11  illustrates the basic elements of yet another embodiment of the device, as well as a sealing device necessary for sealing the tube sack as a filled receptacle is withdrawn and segregated from the internal housing environment.  
      The information contained herein will make many other combinations and permutations of the embodiments apparent to one knowledgeable in the art. These combinations and permutations are, therefore, considered part of this disclosure and are covered by the claims that follow. Some of the alternatives of the present invention which should be considered as a part of the present invention are as follows.  
      For example, although o-rings may be deemed insufficient to seal sliding and/or rotating shafts in some instances, the shafts of the system according to the present invention can be equipped with elastomeric sleeves which include a first static seal anchored to the housing and a second static seal anchored on a corresponding shaft. This will allow the shafts to be slipped and/or rotated while maintaining an absolute seal between the inside of the housing and the surrounding outside environment.  
      In addition, the system may be automated.  
      Although the embodiment of the present invention is directed to receiving a sealed container containing one or more precleaned and/or presterilized receptacles, the device of the present invention can accept non-precleaned and non-presterilized receptacles and that are supplied into the system from a non-sealed container.  
      Although the embodiment of the present invention is directed to filling multiple receptacles, the device can be used to fill single receptacles.  
      Although the embodiment of the present invention is directed to filling receptacles without losing the integrity of the system, filling can be performed within the system while it is opened to the outside environment  
      Although the embodiment of the present invention is directed to stoppering receptacles after filling, the system can be used to fill receptacles only, without stoppering them before releasing them  
      Although the embodiment of the present invention is directed to the more complicated situation of first requiring the removal of screwed on caps from individual receptacles before filling them, it should be understood that the simpler case of supplying receptacles for filling with non-screwed on caps or un-stoppered receptacles would be within the present invention, since a simpler situation than that of the more demanding capture, unscrewing and separation of the cap from the receptacle before filling can be accomplished with the device according to the present invention.  
      Although the embodiment of the present invention is directed to the more complicated situation of re-stoppering receptacles with screwed on type stoppers after filling, it is understood that the simpler case of re-stoppering with non screwed on type stoppers or not restoppering at all after filling would be within the present invention, since this presents a simpler situation than that of the more demanding re-mating of a threaded cap with a threaded portion of the receptacle.  
      Although the embodiment of the present invention is directed to the release of the filled receptacle into a sack or container that can be sealed against the surrounding environment, allowing maintenance of the internal integrity of the device and that these seals may be single or multiple in nature, it is understood that the simpler case of providing over pressure to the system using purified (higher quality than the ambient) air or the still simpler situation of providing no barrier between the interior of the device of that surrounding the receptacle would also be within the present invention.  
      Although the embodiment of the present invention is directed to receiving receptacles from a container outside of the device, a reservoir of receptacles could be harbored within and supplied for filling from within. In this case, not having to provide a system to introduce the receptacles into the system would tend to simplify the device of the present invention. Furthermore, since the receptacles would then be housed within the system, they could be cleaned and/or sterilized in place, thereby further simplifying the system.  
      The description of this device also mentions the possibility of a fixative being added to the receptacles sometime before they are released to the outside environment. The requirement for the addition of one or more agents into the receptacle should be considered an extension covered by this description. In the same way, the addition of one or more agents into the housing and/or into the sack or container into which the receptacles are placed should be considered direct extensions of the above described fixative addition and should also be covered by this disclosure.  
      Lastly, each of the motions described may be automated and may be sealed such that exchange between the internal system environment and the ambient environment outside the system are substantially isolated from one another.  
      The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.