Abstract:
Fluid transfer device and method that allows for sterile wet connections, allows the connection to be reversed, and allows the connection to be reconnected, while leaving the connectors sterile and reusable under pressure. In certain embodiments, the device includes a first member and a second member, the latter adapted to receive the former in locking engagement upon actuation of the device to create fluid communication between the two in a sterile manner. Each of the members include a door that when opened, allows the first member to be linearly displaced into the second member to allow fluid to be transferred. When fluid transfer is complete, the first member can be retracted from the second member, and the doors closed.

Description:
[0001]    This application claims priority of U.S. Provisional Application Ser. No. 61/806,442 filed Mar. 29, 2013, the disclosure of which is hereby incorporated by reference. 
     
    
     BACKGROUND 
       [0002]    The embodiments disclosed herein relate to the transfer of media, such as liquids, into or from a container or the like. For example, the embodiments disclosed herein relate to a fluid transfer device in the form of a connector or valve, enabling good sterile fluid transfer between two systems. 
         [0003]    When conducting complex and/or delicate fluid processes within a “closed” fluid system, it is often necessary to connect or link unit operations of the manufacturing process or to monitor the progress of the process it is often desirable to transfer the fluid without disturbing the process, such as may occur upon “opening” the receptacle or unit operation. For example, in the study and/or manufacture of biochemical products (e.g., biopharmaceuticals), biochemical fluid is often contained in an aseptically “closed” fermenting tank, bioreactor, or like fluid receptacle, wherein the fluid is processed over comparatively long periods of time, under diverse and changing chemical and environmental conditions. By withdrawing and analyzing samples of the fluid intermittently in the course of the process, one can learn more about the progress of the process, and if called for, take prophylactic measures to change the outcome thereof. There also exists a need to connect multiple unit operations together or draw from or add to multiple vessels into a common flow conduit in a sterile manner without “opening” the vessel or flow conduit and disrupting the process. 
         [0004]    Similar issues arise also in instances wherein fluid is conducted through a conduit, or a pipe, or other like fluid receptacle. Sampling of said fluid is often difficult because in many industrial systems, said receptacles are not easily opened or disassembled to allow one to withdraw fluid samples, especially in a sterile manner. While several fluid sampling techniques are known, certain technical issues can be noted. For example, certain integrated fluid sampling fixtures comprise stainless steel valves and piping which, for biopharmaceutical applications, often require laborious steam sterilization and cleaning prior to use. Other fluid sampling devices are difficult to integrate into extant fluid processing systems, for example, by requiring the installation of custom-fitted ports onto a host fluid receptacle. Still other devices, although adapted for use in standard industrial ports, are complex and costly instruments comprising valves, inlets, outlets, seals, needles, and other components, all precisely arranged, but capable of only a single aseptic sample per sterilization cycle. Finally, the majority of fluid sampling devices—as is the case in many of those already mentioned—require in their operation the piercing of a septum using a hypodermic needle 
         [0005]    There is a need for the introduction or removal of materials from the process stream in order to add components of the product, such as media or buffers to a bioreactor; withdraw samples from the process stream to check for microbial contamination, quality control, process control, etc; conduct unit operations such as mixing, filtration, cell culture, etc., and to fill the product into its final container such as vials, syringes, sealed boxes, bottles, single use storage containers such as film bags, single use mix bags/mixers, and the like. 
         [0006]    In light of the above, a need exists for a fluid transfer device that can provide a sterile wet connection, under pressure, provide a dripless disconnection, and completely reverse the connection leaving the flow path sterile and reusable. 
       SUMMARY 
       [0007]    Embodiments disclosed herein provide a fluid transfer device that allows for wet connections under pressure, allows the connection to be reversed, and allows the connection to be reconnected, while leaving the connectors sterile and reusable. In certain embodiments, the device is in the form of a connector or valve. In certain embodiments, the device includes a first member or housing and a second member or housing, one adapted to receive the other in locking engagement upon actuation of the device to create fluid communication between the two in a sterile manner. Each of the members or housings includes a door that when opened, allows a valve sleeve of one member to be displaced into the other member to allow fluid to be transferred. When fluid transfer is complete, the valve sleeve can be retracted, and the doors closed. 
         [0008]    In accordance with certain embodiments, disclosed is a fluid transfer device comprising a first member or housing, the first member or housing comprising a first body member having a port and a grooved surface, and a first base having an outlet. The device also includes a second member or housing, the second member or housing comprising a second body member, a second member valve sleeve member having at least one thread configured to be engaged in the grooved surface of the first body member, and a second inner body having an inlet. The second member valve sleeve member is linearly displaceable into and out of the first body member to create (and eliminate) fluid communication between the inlet and the outlet. 
         [0009]    Drip-free connection and disconnection are achieved. 
         [0010]    In certain embodiments, the fluid transfer device includes first and second members or housings, which can be engaged or coupled and locked together. The act or acts of engagement or coupling, and locking of the two members or housings, also creates sterile fluid communication between the two members or housings, and thus between valve members carried by the two members or housings. In certain embodiments, the act or acts of engaging or coupling, and locking the two members or housings creates sterile fluid communication by actuating one or more doors within the device to open positions. In certain embodiments, the act or acts of engaging and coupling, and locking the two members or housings is carried out by relative movement of one member or housing with respect to the other. In certain embodiments, the relative movement includes rotational movement. In certain embodiments, the rotational movement includes rotating the first and second members or housings in opposite directions. In certain embodiments, the relative movement includes linear movement. In certain embodiments, the linear movement includes moving the first and second members or housings in the same direction. 
         [0011]    In certain embodiments, once the members are engaged or coupled, locked, and fluid communication is achieved, relative displacement of a valve member carried by one of the members or housings into a valve member carried by the other member or housing is effectuated, such as by applying a rotational and/or axial force to one of the valve members. 
         [0012]    Suitable materials of construction include materials capable of withstanding the conditions typically encountered by such devices, including those of sterilization. Suitable materials include but are not limited to plastic, stainless steel and aluminum. Suitable plastic materials may include but are not limited to polysulfone, glass filled polysulfone, polyphenylene sulfide, glass filled polyphenylene sulfide, polyphenyl sulfone and glass filled polyphenyl sulfone are all acceptable materials due to their biocompatibility, chemical, heat and creep resistance. The plastic components of said connector may be formed by machining or molding. The seals used in the embodiments disclosed herein can be made of but not limited to silicone, rubber, including natural and synthetic rubbers, thermoplastic elastomers, polyolefins, PTFE, thermoplastic perfluoropolymer resins, urethanes, EPDM rubber, PDDF resins etc. Fluids to be transferred include liquids and gases. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0013]      FIG. 1  is a perspective exploded view of a first member of the device in accordance with certain embodiments; 
           [0014]      FIG. 2  is a side view of a first member of the device in an assembled condition in accordance with certain embodiments; 
           [0015]      FIG. 3  is a cross-sectional view of the first member taken along line A-A of  FIG. 2 ; 
           [0016]      FIG. 4  is a perspective bottom view of the first member of the device of  FIG. 1 ; 
           [0017]      FIG. 5  is a perspective exploded view of a second member of the device in accordance with certain embodiments; 
           [0018]      FIG. 6  is a side view of a second member of the device in an assembled condition in accordance with certain embodiments; 
           [0019]      FIG. 7  is a cross-sectional view of the second member taken along line A-A of  FIG. 6 ; 
           [0020]      FIG. 8A  is a front view of an overmolded inner sleeve in accordance with certain embodiments; 
           [0021]      FIG. 8B  is a cross-sectional view taken along lines B-B of  FIG. 8A  in accordance with certain embodiments; 
           [0022]      FIG. 9  is a perspective view of a first alternative embodiment of a fluid transfer device; 
           [0023]      FIG. 10A  is a perspective view of the first alternative embodiment of a fluid transfer device in a pre-engaged or coupled position; 
           [0024]      FIG. 10B  is a perspective view of the first alternative embodiment of a fluid transfer device in a partially engaged or coupled condition; 
           [0025]      FIG. 10C  is a perspective view of the first alternative embodiment of a fluid transfer device in an engaged or coupled position; 
           [0026]      FIG. 10D  is a top view of a portion of the first alternative embodiment of a fluid transfer device; 
           [0027]      FIG. 11A  is an exploded view of a portion of the first alternative embodiment of a fluid transfer device; 
           [0028]      FIG. 11B  is an exploded view of another portion of the first alternative embodiment of a fluid transfer device; 
           [0029]      FIG. 12  is a cross-sectional view of a portion of the first alternative embodiment of a fluid transfer device; 
           [0030]      FIG. 13A  is an exploded view of a first valve member in accordance with certain embodiments; 
           [0031]      FIG. 13B  is a side view of the valve member of  FIG. 13A ;  FIG. 13C  is a cross-sectional view of the valve member taken along line A-A of  FIG. 13B ; 
           [0032]      FIG. 14A  is an exploded view of a second valve member in accordance with certain embodiments; 
           [0033]      FIG. 14B  is a side view of the valve member of  FIG. 14A ;  FIG. 14C  is a cross-sectional view of the valve member taken along line B-B of  FIG. 14B ; 
           [0034]      FIG. 14D  is a cross-sectional view of section C of  FIG. 14C ; 
           [0035]      FIG. 14E  is a cross-sectional view along line D-D of  FIG. 14A . 
           [0036]      FIG. 15  is a perspective view of another alternative embodiment of a fluid transfer device; 
           [0037]      FIG. 16  is a perspective view of a portion of the fluid transfer device of  FIG. 15 ; 
           [0038]      FIG. 17  is a perspective view of a valve isolator bellows assembly in accordance with certain embodiments, showing a portion of the assembly in an exploded view; 
           [0039]      FIG. 17A  is a perspective view of a bellows retainer in accordance with certain embodiments; 
           [0040]      FIG. 17B  is a top view of a door and bottom view of a cam in accordance with certain embodiments;  FIG. 18A  is a perspective view of a portion of the bellows assembly in accordance with certain embodiments; 
           [0041]      FIG. 18B  is a perspective view of the bellows assembly of  FIG. 17  showing motion of various elements thereof in accordance with certain embodiments; 
           [0042]      FIG. 19A  is a perspective view of a portion of the bellows assembly showing motion of various elements thereof in accordance with certain embodiments; 
           [0043]      FIG. 19B  is a perspective view of the bellows assembly of  FIG. 17  showing motion of various elements thereof in accordance with certain embodiments; 
           [0044]      FIG. 20  is an exploded view of the bellows assembly of  FIG. 17  and portions of the fluid transfer device housing in accordance with certain embodiments; 
           [0045]      FIG. 21A  is a perspective view, in partial cross-section, of one housing of a fluid transfer device in the closed position in accordance with certain embodiments; 
           [0046]      FIG. 21B  is cross-sectional view of the closed position of  FIG. 21A ; 
           [0047]      FIG. 22A  is a perspective view, in partial cross-section, of one housing of a fluid transfer device in a partially open position in accordance with certain embodiments; 
           [0048]      FIG. 22B  is cross-sectional view of the partially opened position of  FIG. 22A ; 
           [0049]      FIG. 23A  is a perspective view, in partial cross-section, of one housing of a fluid transfer device in an almost fully open position in accordance with certain embodiments; 
           [0050]      FIG. 23B  is cross-sectional view of the almost fully opened position of  FIG. 23A ; 
           [0051]      FIG. 24A  is a perspective view, in partial cross-section, of one housing of a fluid transfer device in a fully open position in accordance with certain embodiments; 
           [0052]      FIG. 24B  is cross-sectional view of the fully opened position of  FIG. 24A ; 
           [0053]      FIG. 25  is a perspective view of a vent and vent membrane incorporated into a housing in accordance with certain embodiments 
           [0054]      FIG. 26  is an exploded view of an alternative door assembly in accordance with certain embodiments; 
           [0055]      FIG. 26A  is an exploded view of the alternative door assembly of  FIG. 26  shown partially assembled; 
           [0056]      FIG. 26B  is another exploded view of the alternative door assembly of  FIG. 26  shown partially assembled; and 
           [0057]      FIG. 26C  is a perspective view of the alternative door assembly of  FIG. 26  shown in the closed position. 
       
    
    
     DETAILED DESCRIPTION 
       [0058]    Turning first to  FIGS. 1-4 , there is shown a first member or housing  100  of the fluid transfer device in accordance with certain embodiments, comprising a first sterility housing plate  1  having a port  30 , which is preferably circular, that may be closed or blocked by a movable door  2 . Door  2  includes an axially extending shaft member  32  that fits into aperture  31  on first sterility housing plate  1  and about which the door  2  is pivotable to block or unblock the port  30 . The door  2 , when opened, can be moved inside an isolated pocket (not shown) within the device to protect the internal chamber of the device from anything that may be on the external face of the door. 
         [0059]    The first member or housing  100  also includes a first body member  3 , which includes an aperture  33  that receives an axially extending shaft member  32 ′ of door  2 , and is sealed with O-ring  10 . Thus, the door is pivotable about the axis defined by shaft member  32 ′, between the sterility housing plate  1  and the body member  3 , to allow or prohibit fluid communication from the port  30  in plate  1 , through port  303 , to the cylindrical member  304  of first body member  3 . In accordance with certain embodiments, the first body member  3  has a base  300 , an axially extending annular shoulder  41 , and an outer annular rim  302  formed radially outwardly from the shoulder  41  and extending axially. The member  3  also includes a port  303  that leads to cylindrical member  304  extending axially from the base  300  in a direction opposite that of axially extending rim  302 . The cylindrical member  304  includes an internal groove or grooves  305  formed in the inner cylindrical wall of the cylindrical member  304 . As best seen in  FIG. 3 , the groove or grooves  305  terminate prior to the free end of the cylindrical member  304 . A door lever  5  sits on top of base  300  of the body member  3 . The door lever  5  has an axially extending end portion  5 ′ that sits in a slot defined by two spaced axially extending protrusions  80 ,  81  on the base  300  ( FIG. 2 ). In certain embodiments, the door lever  5  is attached to the door by an opening in the lever sliding over a feature on shaft member  32 ′. 
         [0060]    The first member or housing  100  also includes first bayonet ring  4 , which preferably has a knurled circumferential outer surface as shown, to facilitate the user grasping the ring and rotating it. The bayonet ring  4  has an inner annular shoulder  420  and a keyed locking mechanism coupled thereto for attaching to the second member  200  as discussed in greater detail below. In accordance with certain embodiments, the locking mechanism includes a plurality of slots  406  spaced along the perimeter of the shoulder  420 , each slot defined by an L-shaped member  409  that extends axially from the shoulder  420 . Positioned between the spaced slots is a plurality of spaced stopping members  407 . 
         [0061]    The first member or housing  100  also includes a cover  6  having a base  610  and an annular axially extending rim  612 . The cover  6  has an aperture  615 , preferably circular, that aligns with and receives cylindrical member  304  when in the assembled condition. 
         [0062]    The first member or housing  100  includes inner body member  7  that is surrounded by valve shutoff sleeve  8 , is positioned in the cylindrical member  304  and sits over wiper seal  12 . The sleeve  8  is generally cylindrical, and includes an outer circumferential radially extending flange  77  that serves as a seat for biasing member or spring  9 , which fits over the outer cylindrical wall of the sleeve  8 . 
         [0063]    The first member or housing  100  also includes first base member  13 , which includes an axially extending generally cylindrical member  113  terminating in a free distal end having distal opening or outlet  114 , and extending axially to a free proximal end having a proximal end  115 . The distal region of the member  13  tapers radially outwardly towards the proximal end, thereby forming a shoulder  118 . This creates a region of increase radial thickness that helps act as a barb-like fitting and facilitates connection to a tube or the like. The base member  13  includes a generally frusto-conical region  116  that surrounds cylindrical member  113 , the region  116  having a circumferential radially extending flange  117  that sits on the rim of the cylindrical member  304  when in the assembled condition ( FIG. 3 ). An annular groove  119  in the proximal region of the member  113  receives O-ring  11  to seal against the sleeve  8 , as best seen in  FIG. 3 . 
         [0064]    Turning now to  FIGS. 5-7 , there is shown a second member or housing  200  of the fluid sampling device in accordance with certain embodiments. The second member  200  includes a second sterility housing plate  19  having a port  23 , which is preferably circular, that may be closed or blocked by movable second door  22 . Door  22  includes an axially extending shaft member  24  that fits into aperture  21  on second sterility housing plate  19  and about which the door  22  is pivotable to block or unblock the port  23 . The door  22  is sealed in aperture  21  by door shaft seal  26 . 
         [0065]    The second member or housing  200  also includes a poppet  60 , which includes a base portion  61  and a plurality of spaced legs  62  extending axially from the base portion  61 . Those skilled in the art will appreciate that although four legs  62  are shown, the number of legs is not particularly limited. The legs  62  retain a biasing member or spring  800  that is positioned internally of the legs  62 , as best seen in  FIG. 7 . 
         [0066]    Overmolded inner sleeve  50  includes tubular member  50 A that is positioned around spring  800  and poppet  60 , and over-mold seal  50 B that seats in an annular groove at the base of the tubular member  50 A, as shown in detail in  FIGS. 8A and 8B . A connector body  70  has an annular radially extending flange  71  having a diameter greater than the inner diameter of the tubular member  50 A, allowing the flange  71  to sit on the free end rim of the tubular member  50 A a shown in  FIG. 7 . The portion of connector body  70  below the flange  71  has an outer diameter less than an inner diameter of the tubular member  50 A, allowing that portion to sit inside the tubular member  50 A. Similarly, the portion of connector body  70  above the flange  71  has an outer diameter less than the inner diameter of the lower free end of inner body  90 , which is reduced in thickness relative to the remainder of inner body  90 , allowing that portion to sit inside the inner body  90 . The inner body includes a lower cylindrical region  91 , an intermediate frusto-conical region  92 , and an upper cylindrical region  93 . The upper cylindrical region  93  includes a portion that extends radially outwardly towards the intermediate frusto-conical region  92 , thereby forming a shoulder  94 . This region of increase radial thickness helps acts as a barb-like fitting and facilitates connection to a tube or the like. 
         [0067]    The second member  200  also includes a generally cylindrical second member valve sleeve  110 , which includes a proximal free end  111  formed with an external thread or threads  112  configured to engage the groove or grooves  305  in the first member  100 . A circumferential groove  213  is provided to receive O-ring  127  that seals against cylindrical member  130  of the second body  150  as discussed below. Distal free end  216  of the sleeve  110  includes a plurality of spaced slots  217  that receive corresponding spaced projections  141  on nut  140 . As best seen in  FIG. 7 , the valve sleeve  110  is positioned over the inner sleeve  50 , the connector body  70 , and a portion of the lower cylindrical region  91  of the inner body  90 . 
         [0068]    The second member  200  includes a second body  150  having a base  151 , an axially extending annular shoulder  152 , and an outer annular rim  153  formed radially outwardly from the shoulder  152  and extending axially. The member  200  includes a port  203  that leads to cylindrical member  130  extending axially from the base  151  in a direction opposite that of axially extending shoulder  152 . The door  22  is pivotable about the axis defined by shaft member  24 , between the sterility housing plate  19  and the second body  150 , to allow or prohibit fluid communication from the port  23  in plate  19 , through port  203 , to the cylindrical member  130  of the second body  150 . Extending radially outwardly from the rim  153  is a plurality of spaced tabs  155  configured to be received in the slots  406  in the bayonet ring  4  of the first member  100 . 
         [0069]    In operation, the second member  200  and first member  100  are brought together such that the sterility housing plates  1  and  19  are in opposing relation. Relative rotation of the first and second members is created, such as by rotating the bayonet ring  4 , causing the tabs  155  in the second member to enter the slots  460  of the first member and lock the members together. This relative rotation also causes the alignment of the ports  30  and  23  in the sterility housing plates  1  and  19 , which are opposed. Fluid communication between the first and second members is created, as the relative rotation also causes the doors  2  and  22 , which were previously blocking the ports in the respective sterility housing plates and the ports in the respective body members, to pivot to an open position. Once the doors are in the open position, the second member valve sleeve  110  is axially displaced through the port  23  in sterility housing plate  19 , and through the port  30  in sterility housing plate  1 . The second member valve sleeve  110  is then rotated with nut  140 , and is further displaced axially, causing the thread or threads  112  to engage and mate with the groove or grooves  305  in cylindrical member  304  of base  300 . This causes the axial displacement of valve shutoff sleeve  8 , compressing spring  9 . A sterile connection is thus made, and fluid can be transferred. 
         [0070]    Once fluid transfer is complete, the second member or housing  200  is retracted from the first member or housing  100 . Thus, the nut  140  is rotated, causing the threads  112  in the second member valve sleeve  110  to disengage with the grooves  305  in the cylindrical member  304  of base  300 . Spring  9  is no longer compressed, and the valve shutoff sleeve  8  is retracted axially to its original position. Wiper seal  12  pushes against base portion  61  and seals and wipes across over-mold seal  50 B in tubular member  50 A. The seal wipes any liquid that may be present when device is being pulled apart. The second member valve sleeve  110  is then removed from the first member, and the bayonet ring  4  is rotated to cause the doors to block the respective ports, thereby maintaining a sterile environment in each member. The process can then be repeated. 
         [0071]    Due to its simplicity, the device can be obtained by simple molding of all the members that constitute it, thus being possible for the device to be a single-use (disposable) device for reasonable cost. The device may also be made from conventional machining of its components from the various plastic and metal materials previously listed. 
         [0072]      FIG. 9  illustrates a first alternative embodiment of the fluid transfer device in accordance with certain embodiments. The valve operation of this first alternative embodiment is similar to the earlier embodiment; upon connection of the first and second members, sterile fluid communication is established under pressure by causing displacement of one valve member into another. The primary difference is in the configuration of the body members or housings and the way the members are brought into engagement or are coupled together. For example, the embodiment of  FIG. 9  uses a hinged assembly to mate the first and second members or housings. 
         [0073]    More specifically,  FIG. 9  shows first member or housing  400  and second member or housing  320  in a partially assembled condition. First member or housing  400  includes body member  401  that has pins  402  on opposite sides of the bottom surface of body member  401  for engagement with a corresponding slot  313  in the body member  301  of second member  320 . Similarly, second member  320  includes body member  301  that has pins  312  on opposite sides of the bottom surface of body member  301  for engagement with a corresponding slot  403  in the body member  401  of first member  400 . Body  301  of second member  320  includes a slidable locking handle assembly  310 . Body  401  of first member  400  includes a slidable locking handle assembly  410 . 
         [0074]    Slidable locking handle assembly  410  is shown in greater detail in  FIG. 11A . It includes handle member  415 , spaced door shafts  416  (only one shown), door  425  and door stop  426 . The door shafts  416  are coupled to the handle member  415  and slide in respective apertures  323  in the body member  401  ( FIG. 12 ). The handle assembly  410  includes spaced radially projecting L-shaped flanges  417  (only one shown in  FIG. 11A ) that slide on respective opposite edges of the body member  401 . When in the closed position, the flanges  417  of handle assembly  410  fit in corresponding reduced in thickness regions in the body member  301 , which enables the first and second members to mate. Sliding the handle assembly  410  to the locked position moves the flanges  417  away from the reduced in thickness regions in the body member  301  and cooperatively with handle assembly  310 , clamps the first and second members together. 
         [0075]    In certain embodiments, door  425  is a generally flat member configured to block the port in the second member  320 , preventing fluid communication between the first and second members  400 ,  320 . In certain embodiments, the door  425  seals against overmolded gasket  429  that is positioned on the inside of the bottom sterile face  411  of the body member  401 . An overmolded sterile plate gasket  419  is a perimeter gasket that can be overmolded onto the housing beyond the edge of the sterile plate  411  to seal against the corresponding second member sterile plate when the first and second members are brought together, to keep out contaminants. 
         [0076]    Projecting upwardly from the door  425  is a door stop  426 , which when the door  425  is in the fully open position, abuts against a wall in the body member  401  to delimit the door open position. 
         [0077]    In certain embodiments, wiper seal  428  is positioned in the body member  401  so that as the door  425  is actuated from its closed to its open position, and vice versa, it contacts the wiper seal  428 . The wiper seal  428  isolates the door in the open position from the region of the device where fluid flows. This helps to maintain sterile the area where fluid flows. 
         [0078]    The handle assembly  310  of second member  320  has a similar construction, as shown in  FIG. 11B . It includes handle member  315 , spaced door shafts  316  (only one shown), door  325  and door stop  326 . The door shafts  316  are coupled to the handle member  315  and slide in respective apertures (not shown) in the body member  401 . The handle assembly  310  includes spaced radially projecting L-shaped flanges  317  (only one shown in  FIG. 11B ) that slide on respective opposite edges of the body member  301 . Sliding the handle assembly  310  to the locked position cooperatively with handle assembly  410  clamps the first and second members together. 
         [0079]    In certain embodiments, door  325  is a generally flat member configured to close the port in the second member  320 , preventing fluid communication between the first and second members  400 ,  320 . In certain embodiments, the door  325  seals against overmolded gasket  329  that is positioned on the inside of the bottom sterile face  311  of the body member  301 . Projecting upwardly from the door  325  is door stop  326 , which when the door  325  is in the fully open position, abuts against a wall in the body member  301  to delimit the door open position. 
         [0080]    In certain embodiments, wiper seal  328  is positioned in the body member  301  so that as the door  325  is actuated from its closed to its open position, and vice versa, it contacts the wiper seal  328 . The wiper seal  328  isolates the door in the open position from the region of the device where fluid flows. This helps to maintain sterile the area where fluid flows. 
         [0081]    In certain embodiments, a vent  625 , vent membrane  626  and vent cover  627  may be incorporated into the housing, to draw in ambient air as the valve member is retracted ( FIG. 25 ). A suitable membrane  626  is a  0 . 22  micron sterilizing membrane. The vent  626  may include a plurality of holes communicating with the housing interior, which provide a path for air to enter the device when the valve is retracted from the female housing which creates a syringe effect. Air that is pulled in flows through the vent  626  and is sterilized by the membrane  626 . In certain embodiments, the vent membrane  626  can be heat sealed to the housing, but gaskets could be used or a pre-existing filter could be attached to a port in the housing. 
         [0082]    To assemble the transfer device, the first member  400  and second member  320  are oriented at 90° as shown in  FIG. 10A , the members are brought into engagement such that the hinge pin  408  on body member  401  can be inserted into the slot  308  on body member  301  as shown in  FIG. 10B , the body members  301 ,  401  thereby forming a clamshell-like configuration. The clamshell is closed by bringing the ends opposite the hinge of members  320  and  400  together, rotating about the axis of the hinge pin  408  as shown by the arrows in  FIG. 10B . The closed, assembled position is shown in  FIG. 10C . In this position, the locking handle assemblies  310 ,  410  mate so that sliding actuation of one handle also actuates the other. In this position, the valve is closed by doors  425 ,  325 ; there is no fluid communication between the first member  400  and the second member  320 . 
         [0083]    Upon connection of first and second members or housings  400 ,  320 , each of the pins  312  enters a respective slot  403  in the first member  400 , and displaces locking member  405  axially, moving it out of the path of slidable handle assembly  410 . Similarly, each of the pins  402  enters a respective slot  313  in the second body member  320 , and displaces locking member  365  axially, moving it out of the path of slidable handle assembly  310 . In certain embodiments, each locking member  365 ,  405  is an elongated member having a free end that is axially displaceable. 
         [0084]    Once the first and second members or housings  400 ,  320  are in engaging relation, the locking handle assemblies  310 ,  410  are actuated by sliding them to the left as depicted in  FIG. 10C . This actuation simultaneously locks the members  320 ,  400  together, and moves the doors in each member to the open position, which establishes fluid communication between the first and second members  400 ,  320 . Once fluid communication is established, the valve member of the second member  320  can be displaced into the valve member of the first member  400 , as discussed in greater detail below. 
         [0085]      FIGS. 13A-13C  illustrate the first member valve member  450 . Fitting  413  includes an axially extending generally cylindrical member terminating in a free distal end having distal opening or outlet  414 , and extending axially to a free proximal end  435  that sits over the upper free end of cylindrical member  404  of first member  400  ( FIG. 12 ). The distal region of the fitting  413  tapers radially outwardly towards the proximal end, thereby forming a shoulder  418 . This creates a region of increase radial thickness that helps act as a barb-like fitting and facilitates connection to a tube or the like. The fitting  413  includes a generally frusto-conical region  436 , the region  436  having a circumferential radially extending flange  437  that sits on the rim of the cylindrical member  404  of first member  400  when in the assembled condition of  FIG. 10C . 
         [0086]    Wiper seal  442  is a generally cylindrical member, and includes an intermediate outer circumferential radially extending flange  477  that serves as a seat for biasing member or spring  479  which fits over the downwardly projecting member  439  in fitting  413 . 
         [0087]    Base member  480  has an upper cylindrical portion that seals inside wiper seal  442  with the aid of O-ring  486 . The lower region  484  of the base member  480  includes a downwardly facing depressor member  481  that in the embodiment shown extends axially from the member  480  and has a semispherical shape. It functions to displace the poppet  560  in the corresponding valve member  350  of the second member  320  upon actuation of the valve, as discussed in greater detail below. 
         [0088]      FIGS. 14A-14E  show the valve member  350  of the second member or housing  320 . The valve member  350  includes upper inner body  510 . Upper inner body  510  includes an axially extending generally cylindrical member terminating in a free distal end having distal opening or outlet  514 , and extending axially to a free proximal end having a proximal end opening  535 . The distal region of the inner body  510  tapers radially outwardly towards the proximal end, thereby forming a shoulder  518 . This creates a region of increase radial thickness that helps act as a barb-like fitting and facilitates connection to a tube or the like. 
         [0089]    The valve member  350  also includes a poppet  560 , which includes a solid base portion  561  and a plurality of spaced legs  562  extending axially from the base portion  561 . Those skilled in the art will appreciate that the number of legs is not particularly limited. The base portion  561  includes a centrally located detent  559  that receives projection  482  on the depressor member  481 , as discussed in greater detail below. The legs  562  retain a biasing member  580  such as a compression spring or the like that is positioned internally of the legs  562 . The opposite end of the biasing member  580  sits in inner body connector  594 , which is shown in greater detail in  FIG. 14D . Inner body connector  594  includes an intermediate annular ring  593  that seats between the gap between lower edge of upper inner body  510  and the upper edge of valve lower inner body  575 . The ring  593  extends radially inwardly to provide a seat for biasing member  580 . 
         [0090]    Valve outer sleeve  570  is a generally cylindrical member that has threads  571  at its lower end for engaging corresponding grooves  318  ( FIG. 12 ) in the generally cylindrical member  404  of first member  400 . The lower portion of upper inner body  510  sits inside the valve outer sleeve  570  as seen in  FIG. 14C , as does inner body connector  594 , biasing member  580 , poppet  560 , and lower inner body  578 . The lower inner body  578  is generally cylindrical, and as shown in  FIG. 14E , includes at its lower end radially inwardly extending flanges  577 , which hold an overmolded seal  579  to seals against poppet  560 . 
         [0091]    In certain embodiments, relative linear displacement of the valve members  350 ,  450  into each other is effectuated by applying an axial load. In certain embodiments, the valve member  350  of the second member  320  is linearly displaced into the valve member  450  of the first member  400 , and then further displacement of the valve member  350  into the valve member  450  is effectuated by relative rotation of the valve members, such as by rotating the valve member  350  of the second member  320  with knob  599 . This rotation causes the thread or threads  571  on the valve outer sleeve  570  to engage the corresponding groove or grooves  318  in the cylindrical member  404  of valve member  450 . Continued relative rotation further displaces the valve member  350  into valve member  450 , causing the depressor member  481  to contact and displace poppet  560  in a first direction against the bias of biasing member  580 . Still further rotation causes the threaded end of valve member  350  to engage the radial flange  477  of wiper seal  442 , causing the latter to displace in a second direction against the bias of biasing member  479 . In certain embodiments, the first and second directions are opposite directions. The displacements of the poppet  560  and of the wiper seal  442  create fluid communication between and through the valve members  350 ,  450 . 
         [0092]      FIGS. 15 and 16  illustrate a second alternative embodiment of the fluid transfer device in accordance with certain embodiments. The valve operation of this second alternative embodiment is similar to the first alternative embodiment; upon engagement and locking of the first and second members or housings, sterile fluid communication is established under pressure, and displacement of one valve member into another can be carried out. The primary difference is in the configuration of the body members or housings and the way the members are brought into engagement. For example, the embodiment of  FIGS. 15 and 16  involve the alignment of pin and hook features followed by engaging cam locks ( FIG. 16 ) on the faces of the body members or housings. 
         [0093]    More specifically,  FIGS. 15 and 16  show first member or housing  400 ′ and second member or housing  300 ′ in an assembled condition. The valve members  350 ′,  450 ′ are the same or essentially the same as the valve members  350  and  450  of the first alternative embodiment, and thus will not be discussed in detail here. 
         [0094]    The housing for the valve members (shown in  FIG. 16  without the valve members in place) includes a first member or housing  400 ′ having body member  401 ′ that has a shaped bottom region that corresponds to a similarly shaped bottom region of second member or housing  300 ′, allowing the first and second members to mate. Each member  400 ′,  300 ′ includes a top plate. In certain embodiments, each member  400 ′,  300 ′ includes a cam slot (only one shown at  490 ′ for first member  400 ′), that receives a respective cam member (only one shown at  391 ′ for second member  300 ′) on the other member, each cam member being received by the respective cam slot as the two members  400 ′,  300 ′ are engaged and twisted in opposite directions to lock them together. Each member  300 ′,  400 ′ carries a respective lever arm  303 ′,  403 ′ arm attached to a respective door  325 ′,  425 ′. Each lever arm is rotatable between a door open and a door closed position. Lever arm  403 ′ of first body member  401 ′ has an axially extending hollow leg  426 ′ that mates with a pin (not shown) that extends axially from the second member  301 ′. Similarly, lever arm  303 ′ of second body member  301 ′ has an axially extending hollow leg  326 ′ that mates with a pin (not shown) in the bottom of first body member  401 ′. 
         [0095]    In certain embodiments, each body member  401 ′,  301 ′ has a bottom plate having a valve port that is normally closed by a respective door  425 ′,  325 ′. When the members are in the assembled condition, the valve ports are aligned. 
         [0096]      FIG. 17  illustrates a valve isolator bellows assembly  700 . The assembly  700  includes a bellows  710  that is held by seal retainer member  711  ( FIG. 17A ). Seal retainer member  711  includes a first ring  711 A that secures bellows  710 , and a second ring  711 B that connects to cam member  720 . The first ring  711 A includes alternating top and bottom radially inwardly extending flanges  712 A,  712 B that serve to retain the bellows  710 . Door  325 ′ also has a ring that connects to cam member  720 . Both the door  325 ′ and seal retainer member  711  are moved by rotation of cam  720 . In certain embodiments, the cam  720  is generally cylindrical, and includes a plurality of cam slots or grooves  721  (one shown in each of  FIGS. 17 and 19A ) formed in its outer side surface. There are corresponding spaced pins  713  on the second ring  711 B of the seal retainer member  711  that extend radially inwardly, each of which travels in a respective cam slot  721  of the cam  720 . In certain embodiments, the second ring  711 B includes three such pins  713 , and the cam  720  includes three such cam slots  721 , each one corresponding to a respective pin. 
         [0097]    In certain embodiments, the door  325 ′ includes a pin (not shown) extending axially downwardly from its bottom to mate with an aperture  306 ′ ( FIG. 20 ) in base  307 ′ of the member  400 ′. As seen in  FIG. 17B , the door includes an axially extending button  327  and a plurality (three shown) of spaced axially extending wings  327 A that surround the button  327  but do not extend as high. The button  327  and wings  327 A fit into and are engaged by the open region  331  in the underside of the cam  720 , the open region  331  including spaced radially inwardly projecting prongs  332  that fit into the spaces  333  between the wings  327 A on the door  325 ′ as shown by the solid arrows in  FIG. 17B . In certain embodiments, cam  720  includes a keyed pin  723  extending upwardly axially from its top surface to mate with lever arm  303 ′. Rotation of lever arm  303 ′ causes a corresponding rotation of cam  720 . Rotation of the cam moves the door  325 ′ from the open to the closed position (and vice versa), and causes vertical movement of the bellows  710  as the retainer member  711  rides in the cam slots  721  of the cam, as discussed in greater detail below. 
         [0098]      FIG. 17  illustrates the door  325 ′ and bellows  710  in the closed position. In this position, the door  325 ′ prevents fluid communication between the valve members, and the bellows  710  is sealed against the door  325 ′. As lever arm  303 ′ rotates as shown in  FIGS. 18A and 18B , the cam  720  coupled to the lever arm also rotates, causing the door to open and the retainer member  711  to ride in the cam slots  721 , thereby first moving axially upwardly and then ultimately moving the bellows axially downwardly towards the port in the body member  301 ′ as the bellows seal breaks from the door. Continued rotation of lever arm  303 ′ moves the door to its fully open position, as shown in  FIGS. 19A and 19B , and causes bellows to reach its lowest, valve sealing position (as guided by travel in the cam slots  721 ). In this position, the bellows is over the valve port and seals against the bottom plate  380 ′, protecting the valve members from contamination. 
         [0099]    Although the bellows assembly is shown with respect to member or housing  320 , in certain embodiments both housings include bellows assemblies to isolate their respective valves during connection. 
         [0100]      FIGS. 21A and 21B  illustrate the fluid transfer device with the valve members in the closed position, i.e., the door  325 ′ is positioned over the valve port with the bellows  710  against the door  325 ′. As seen in  FIGS. 22A and 22B , as the first and second members or housings are twisted in opposite directions to lock them together, the door  325 ′ begins to rotate to the open position. The bellows seal retainer member  711  also begins to rotate as the pins ride in the cam slot, and the bellow seal  710  breaks from the door  325 ′. As rotation continues as shown in  FIGS. 23A and 23B , the door  325 ′ rotates past the bellow seal  710 . The pins in the seal retainer member  711  continue their travel in the cam slots to lower the bellows seal  710  towards the bottom plate  380 ′. The position of the door  325 ′ and bellows  710  upon completion of the rotation is shown in  FIGS. 24A and 25B . The door  325 ′ is in the full open position, and the valve port  395 ′ is unobstructed by the door. Similar door movement occurs at the same time in the other member or housing, allowing fluid communication between the two members or housings. The bellows  710  seals against the bottom plate  380 ′ of the housing. The housings are now locked together, the valve ports open, and the valve members can be engaged by relative axially displacement of one into the other. 
         [0101]      FIG. 26  illustrates an alternative embodiment where the doors are brought in close proximity to one another in the closed position, thereby reducing or eliminating dead volume between them. In certain embodiments, each door assembly includes a face plate member  910  that includes an opening  911  that may have a gasket  912  fitted about its perimeter. The face plate member  910  includes a pair of opposite elongated side track members  913 ,  914  that extend upwardly from the surface of the face plate member  910 . In certain embodiments, each track member  913 ,  914  includes an intermediate notch  915  which creates a cam for the plug pins  932 a-d to push the door flush to the face upon closing and retracting when opening. Each track member  913 ,  914  also includes an end ramp  960  on which two of the plug pins ride when the door cams down to its closed position or up to its open position. The notches and ramps cooperate with mating track of cam  624  ( FIG. 25 ), working together to trap the plug pins; one cam  624  bumps the door forward to close, and the mating rail on the cover bumps backward to open. In certain embodiments, each track  913 ,  914  is positioned slightly inwardly of a side edge of the face plate member  910  so that the region between each track member and the side edge forms, with a respective track member, an L-shaped track for the door assembly to ride on. In certain embodiments, a carrier member  920  is configured to carry plug  930 , and includes four upwardly extending side walls  931   a - d  as shown. Carrier member  920  also includes upwardly extending notched tab  923  which recites slotted shaft  940  as shown in  FIG. 26A . Plug  930  includes a solid downwardly projecting cylindrical portion  931  that is shaped to seal in opening  911  with the aid of gasket  912 . 
         [0102]    As shown in  FIG. 26B , handle  945  slides onto the housing and rides in the L-shaped track. A slot  946  ( FIG. 26 ) in the end face of the handle  945  engages shaft  940 . Bellows  947  may enclose shaft  940 . Actuation of the handle  945  to the closed position translates the plug  931  from the open position to the closed position over the opening  911  in the member  910 , as shown in  FIG. 26C . The plug  931  is now flush to the face of the connector housing, reducing or eliminating dead volume trapped between it and the plug of the other housing member (which is similarly designed).