Abstract:
A connector apparatus designed for use in a bioprocessing assembly, and a method for coupling a piece of bioprocessing equipment to a media source in a sterilized environment. The connector apparatus includes a coupler including an end and at least one outlet, and a connector valve connectable at a first end to a fluid source, the connector valve including a valve member, the valve member being partially disposed within the coupler. The connector apparatus further includes a flow passage being actuatable from a closed configuration to an open configuration when the coupler and the connector valve are engaged, as well as being actuatable from an open configuration to a closed configuration. A clip member attached to the coupler allows the valve member to be moved from the closed configuration to the open configuration, and from the open configuration to the closed configuration.

Description:
RELATED APPLICATION 
   This application claims the benefit of U.S. Patent Provisional Application Ser. No. 60/501,357, filed Sep. 9, 2003, and entitled “Connector Apparatus and Method of Coupling Bioprocessing Equipment to a Media Source,” the entirety of which is hereby incorporated by reference. 

   TECHNICAL FIELD 
   This invention relates to a connector apparatus and a method for implementing the same. More particularly, this invention relates to a connector apparatus for coupling a media source to a bioreactor in a sterilized environment. 
   BACKGROUND 
   Bioprocessing systems are widely used for culturing biomaterial or producing and designing drugs used in pharmaceutical applications. Typically, these systems employ bioreactors and media dispensers connected by tube and valve assemblies. Multiple steam traps and a flow hood are often incorporated to sterilize the system from contaminants. Typically, bioreactors or culture environments and media dispensers have consisted of large vats for producing such biomaterials. Typically, the components used in the assembly were reusable stainless steel components. However, this can require a complex and time consuming coupling procedure. In addition, flow hoods, such as laminar flow hoods, can be cumbersome and inconvenient as they are moved in and out of the processing environment. As more specific cultures and designer drugs are being produced, and as more specific growth media provided to a bioreactor are being developed, there is a need for an improved and less complex bioprocessing system. 
   Furthermore, present designs using multiple steam traps and complex tube/valve assemblies create a bioprocessing system that is difficult to operate and may allow for increased margin of error with respect to sterilization of the system. Therefore, there is a need for a less complex system that is more convenient to handle, and that can simplify the more specific pharmaceutical designs associated with particular biomaterial production. 
   The present invention, as described herein, provides improvements upon one or more of the above described and other shortcomings of existing bioprocessing systems and their valve assemblies. 
   SUMMARY 
   In accordance with the present invention, the above and other problems were solved by providing a connector apparatus and a sterilized assembly for bioprocessing using the connector apparatus. In addition, a method for implementing a connector apparatus is provided. 
   In one embodiment of the present invention, a connector apparatus includes a coupler and a connector valve having a valve member. In example embodiments, the connector apparatus can be coupled to bioprocessing equipment and a media source to allow flow therebetween. 
   In example embodiments, the connector apparatus can be used once or multiple times to allow flow between bioprocessing equipment and a media source. 
   An advantage of the present invention is that the employment of a connector apparatus can greatly simplify the parts of a coupling mechanism in a bioprocessing system. Further, it can minimize the need for cumbersome laminar flow hoods and complex valve assemblies that may use multiple steam traps. Further, multiple exchanges can be accomplished between a piece of bioprocessing equipment and several media sources while maintaining the sterility of the bioprocessing equipment and connector apparatus. 
   These and other various advantages and features are pointed out in the following detailed description. For a better understanding of the disclosed embodiments and their advantages, reference should also be made to the drawings which form a further part hereof, and to accompanying descriptive matter, in which there are illustrated and described specific examples of an apparatus in accordance with the invention. 

   
     DESCRIPTION OF THE DRAWINGS 
     Referring now to the drawings in which like reference numbers represent corresponding parts throughout: 
       FIG. 1  is a perspective view of one embodiment of a connector apparatus in a closed state in accordance with the principles of the present invention; 
       FIG. 2  is a side view of the connector apparatus of  FIG. 1 ; 
       FIG. 3  is an end view of the connector apparatus of  FIG. 1 ; 
       FIG. 4  is a top view of the connector apparatus of  FIG. 1 ; 
       FIG. 5  is a cross-sectional view taken along line  5 — 5  of the connector apparatus of  FIG. 3 ; 
       FIG. 6  is a cross-sectional view of taken along line  6 — 6  of the connector apparatus of  FIG. 4 ; 
       FIG. 7  is a perspective view of the connector apparatus of  FIG. 1  in an open state; 
       FIG. 8  is a side view of the connector apparatus of  FIG. 7 ; 
       FIG. 9  is an end view of the connector apparatus of  FIG. 7 ; 
       FIG. 10  is a top view of the connector apparatus of  FIG. 7 ; 
       FIG. 11  is a cross-sectional view taken along line  11 — 11  of the connector apparatus of  FIG. 9 ; 
       FIG. 12  is a cross-sectional view taken along line  12 — 12  of the connector apparatus of  FIG. 10 ; 
       FIG. 13  is a perspective view of one embodiment of a coupler in accordance with the principles of the present invention; 
       FIG. 14  is a side view of the coupler of  FIG. 13 ; 
       FIG. 15  is a perspective view of one embodiment of a valve member in accordance with the principles of the present invention; 
       FIG. 16  is a side view of the valve member of  FIG. 15 ; 
       FIG. 17  is a cross-sectional view taken along line  17 — 17  of the valve member of  FIG. 16 ; 
       FIG. 18  is a perspective view of one embodiment of a connector valve in accordance with the principles of the present invention; 
       FIG. 19  is a top view of the connector valve of  FIG. 18 ; 
       FIG. 20  is an end view of the connector valve of  FIG. 18 ; 
       FIG. 21  is a cross-sectional view taken along line  21 — 21  of the connector valve of  FIG. 20 ; and 
       FIG. 22  is a flow diagram of an embodiment of a method of coupling a media source to a piece of bioprocessing equipment in accordance with the principles of the present invention. 
   

   In the following description of the illustrated embodiments, reference is made to the accompanying drawings that form a part hereof, and in which is shown by way of illustration of the embodiments in which the invention may be practiced. It is to be understood that other embodiments may be utilized as structural changes may be made without departing from the spirit and scope of the present invention. 
   DETAILED DESCRIPTION 
   Embodiments of the present invention relate to a connector apparatus for coupling a media source to a piece of bioprocessing equipment. Embodiments of the connector apparatus disclosed herein are similar to those disclosed in U.S. patent application Ser. No. 10/097,073, entitled “Connector Apparatus and Method of Coupling a Bioprocessor to a Media Source” and filed on Mar. 12, 2002, the entirety of which is hereby incorporated by reference. 
   Referring now to  FIGS. 1–12 , one embodiment of a connector apparatus  50  is illustrated connecting a media source  70  to a piece of bioprocessing equipment  90 . In  FIG. 1 , the connector apparatus  50  includes a coupler  20  (see  FIGS. 13 and 14 ) and a connector valve  10  (see  FIGS. 18–21 ). The connector valve  10  includes a valve member  40  (see  FIGS. 15–17 ) disposed therein. 
   As shown in  FIG. 1 , the valve member  40  includes an end  112  suitable for attachment to the media source  70 . The end  112 , as depicted in  FIG. 1 , is shown as a barbed end for attachment to a media source, such as  70 . However, there may be other interfaces that can be used to achieve the same result. 
   The coupler  20  has an outlet  122  for passage of media and connection to the piece of bioprocessing equipment  90 , such as but not limited to a bioreactor. The outlet  122 , as depicted in  FIG. 1 , is shown as a sanitary flange. However, there may be other interfaces that can be used to achieve the same result. 
   Also depicted is a second outlet  124  of coupler  20  for allowing steam passage to a steam trap or a condensate outlet during, for example, sterilization as described below. A sanitary flange similar to that of outlet  122  is disposed at the second outlet  124 . However, it will be appreciated that an O-ring seal also can be used at the second outlet  124 . 
   Referring now to  FIGS. 13 and 14 , coupler  20  includes outlets  122  and  124  noted above as well as an opening  250  for receiving the connector valve  10 . Coupler  20  also includes flanges  252  defined by slots running through to the opening  250 , and each flange  252  defines an aperture  22  for receiving tabs  12  of the connector valve  10 , as described further below. 
   As shown more particularly in  FIGS. 5 and 6 , the connector valve  10  is disposed within the coupler  20 . Referring now to  FIGS. 18–21 , the connector valve  10  defines a passage  260  sized to receive valve member  40 . Tabs  12  on the connector valve  10  engage apertures  22  of the coupler  20  (see  FIG. 13 ) and retain the connector valve  10  in place within the coupler  20 . An O-ring seal  14  positioned in slot  262  (see  FIGS. 18 ,  19 , and  21 ) engages the inner diameter of the connector  20  to seal end  16  of the connector valve  10  with the coupler  20 . 
   Referring now to  FIGS. 15–17 , valve member  40  defines a passage  224  from end  112  to end  130 . While end  112  is open and in fluid communication with passage  224 , end  130  is closed. In addition, apertures  220  are formed adjacent end  130  and are in fluid communication with passage  224 . 
   Referring again to  FIGS. 5 and 6 , the valve member  40  is disposed within the connector valve  10 . O-ring seals  42  and  44  positioned in slots  272  and  274  (see  FIGS. 16 and 17 ) of the valve member  40  engage the inner diameter of the connector valve  10  to seal the outer diameter of the valve member  40  with the connector valve  10 . 
   In the illustrated embodiment, a clip member  13  is held in an aperture  18  formed in the connector valve  10  (see  FIGS. 18 and 19 ) and surrounds a portion of the valve member  40 . The clip member  13  can be configured as described in U.S. Pat. No. 5,052,725 to Meyer et al., the entirety of which is hereby incorporated by reference. The clip member  13  functions to maintain the valve member  40  in a fixed longitudinal position with respect to the connector valve  10 . 
   More specifically, the clip member  13  can be actuated to allow longitudinal displacement of the valve member  40  with respect to the connector valve  10  between a closed position ( FIGS. 1–6 ) and an open position ( FIG. 7–12 ). For example, in the closed position as shown in  FIGS. 1–6 , a portion  15  of the clip member  13  is positioned in a slot  46  formed in the valve member  40  to retain the valve member  40  in place. 
   The clip member  13  can be actuated by pressing tab portion  17 , which then allows the valve member  40  to be moved longitudinally with respect to the connector valve  10  to an open position. Tab  266  of the connector valve  10  (see  FIG. 18 ) functions to bias the clip member  13  into the closed position. With the clip  13  actuated, the valve member  40  can be moved longitudinally by, for example, exerting force on (i.e., pushing) winged portion  49  of the valve member  40 . When the fully open position is reached, portion  15  of the clip member  13  is positioned in a slot  48  formed in the valve member  40  to retain the valve member  40  in place. 
   Likewise, the valve member  40  can be moved back to the closed position by actuating the clip member  13  by pressing tab portion  17  and then moving the valve member  40  longitudinally back to the closed position by, for example, exerting force on (i.e., pulling) the winged portion  49 . When the fully closed position is reached, portion  15  of the clip member  13  is once again positioned in the slot  46  formed in the valve member  40  to retain the valve member  40  in place. 
   As illustrated in the example embodiment, portion  15  of the clip member  13  is angled from a leading to a trailing edge so that the valve member  40  can be moved from the closed to the open position without requiring actuation of the clip member  13 . This is accomplished by the angled surface of the portion  15  functioning as a ramp to allow the clip member  13  to be more easily moved out of slot  46  of the valve member  40  when moved from the closed to the open position (see  FIG. 5 ). However, once in the open position, the trailing edge of the portion  15  is fully seated within slot  48  (see  FIG. 11 ) so that it is difficult to move the valve member  40  from the open position to the closed position without actuating the clip member  13 . In alternative embodiments, the angle in portion  15  of the clip member  13  can be removed, so that it is difficult to move the valve member  40  from both the closed to the open position and the open to the closed position without actuation of the clip member  13 . 
   Referring to  FIGS. 6 and 12 , the valve member  40  is slidingly retained in the connector valve  10  by arms  100  of the connector valve  10 . The arms  100  are moveable radially with respect to the connector valve  10  and include tips  102  that extend beyond the outer diameter of the connector valve  10  that is inserted into the coupler  20 . Therefore, when the valve member  40  is positioned in the coupler  20 , the tips  102  of the arms  100  contact the inner diameter of the coupler  20  and the arms  100  are radially biased inwardly. In such an arrangement, an inner end  104  of each arm  100  is positioned within a slot  106  formed on the valve member  40 . With the inner ends  104  positioned in the slot  106 , the valve member  40  can therefore only move longitudinally between ends  108  and  110  of the slot (see  FIGS. 16 and 17 ). Therefore, the valve member  40  cannot be pulled beyond the fully closed position (see  FIG. 6 ) because the arms  100  contact the end  110  of the slot. 
   When the valve member  40  is in the closed position as shown in  FIG. 6 , material can flow from outlet  122  of the coupler  20 , through passage  120 , into junction  121 , and through passage  222  to outlet  124  (reverse flow is also possible). However, because inner end  16  of the connector valve  10  is sealed by O-ring seal  14  against the coupler  20  and end  130  of the valve member  40  is sealed by O-ring seal  44  against the connector valve  10 , no material can flow into passage  224  and to end  112  of the valve member  40 . 
   Conversely, when the valve member  40  is in the open position as shown in  FIG. 12 , end  130  of the valve member  40  has been longitudinally displaced through junction  121  and into passage  222  of the coupler  20  such that O-ring seal  44  engages an inner diameter of the passage  222  of coupler  20 . In addition, O-ring seal  42  now seals the valve member  40  against the connector valve  20  adjacent to the junction  121  such that passage  224  in valve member  40  is fluidly connected to junction  121  through apertures  220  formed in valve member  40  (see  FIGS. 15–17 ). 
   In this open configuration for valve member  40 , material can flow from outlet  122  of the coupler  20 , through passage  120 , into junction  121 , through aperture  220  formed in valve member  40  (see  FIGS. 15–17 ) and through passage  224  to outlet  112  of the valve member  40  (reverse flow is also possible). However, because end  130  of the valve member  40  is sealed by O-ring seal  44  against the inner diameter of passage  222  of coupler  20 , no material can flow into passage  222  and to end  124  of the coupler  20 . 
   In a like manner, valve member  40  can be longitudinally displaced back into the closed position (see  FIG. 6 ) to reestablish fluid communication between passages  120  and  222 , and to foreclose communication with passage  224  of valve member  40 . 
   In example embodiments, the connector apparatus  50  can withstand steam and autoclave conditions. In addition, the connector apparatus  50  can be made of a material such as polycarbonate, or a polysulphone, or a polyphenylsulfide and including other high temperature thermoplastics or materials, which can be injection molded. 
   The media source can be a media bag or other like media vessel. The piece of bioprocessing equipment may be a bioreactor and can include a steam source for sterilization. The dimensions for a bioreactor and media source are specific to the needs of the biomaterial being processed and are further not described here. 
     FIG. 22  illustrates an example flow diagram of a method for coupling a bioreactor with a media source using an example connector apparatus disclosed herein. The method includes, at  901 , providing a connector apparatus, a media source, and a piece of bioprocessing equipment as detailed in the above descriptions. The connector apparatus is then connected to the bioprocessing equipment at  903 . 
   Next, the bioprocessing equipment and the connector apparatus are sterilized at  905 . In one embodiment, the bioprocessing equipment and the coupler are steam sterilized, and outlet  124  of coupler  20  functions as a steam trap or condensate outlet. 
   Next, the media source is coupled to the connector apparatus at  907 , and the media source and connector apparatus are sterilized at  909  using, for example, gamma sterilization. After this sterilization is completed, the entire assembly including the media source, connector apparatus, and piece of bioprocessing equipment are ready for use. 
   Next, the connector apparatus is opened at  911  by moving the valve member  40  from the closed position to the open position as described above. In this position, media can flow from the bioprocessing equipment to the media source, or vice versa. 
   Next, the flow of media between the bioprocessing equipment and the media source can be stopped at  913  by closing the connector apparatus through actuation of the valve member  40  from the open position to the closed position as described above. Once flow has been terminated, the media source can be disconnected from the connector apparatus at  915 . 
   If desired, the connector apparatus can then be reused. For example, the bioprocessing equipment and connector apparatus can be sterilized again at  905 , and a media source can be connected to the connector apparatus and sterilized at  907  and  909 . Next, the connector apparatus can be opened at  911 , allowing media to flow between the bioprocessing equipment and media source. Next, the connector apparatus can be closed at  913 , and the media source can be disconnected at  915 . 
   In this manner, the connector apparatus can be used once or multiple times, as desired. Further, multiple exchanges can be accomplished between a piece of bioprocessing equipment and several media sources while maintaining the sterility of the bioprocessing equipment and connector apparatus. 
   Further, the connector apparatus provides a more convenient and practical way of connecting bioprocessing equipment with a media source. In addition, the connector apparatus provides a versatile means for coupling that can be easily modified to accommodate a range of needs with respect to particular biomaterials processed. 
   Various modifications can be made to the example embodiments disclosed herein. For example, although the coupler  20  and connector valve  10  are illustrated herein as separate pieces, they can also be formed as one integral piece. Having described the embodiments of the present invention, other modifications and equivalents may occur to one skilled in the art. It is intended that such modifications and equivalents shall be included with the scope of the invention.