Abstract:
Formation of a sterile connection includes inserting a first aseptic coupling device into a second aseptic coupling device, removing a first membrane from the first aseptic coupling device and a second membrane from the second aseptic coupling device, and rotating a locking clip on the first aseptic coupling device to compress a first seal member of the first aseptic coupling device with a second seal member of the second aseptic coupling device to form a sterile fluid passageway.

Description:
RELATED APPLICATIONS 
     This application claims the benefit of U.S. Patent Application Ser. No. 61/160,603 filed on Mar. 16, 2009, the entirety of which is hereby incorporated by reference. 
    
    
     BACKGROUND 
     Aseptic coupling devices can be used to connect two or more sterilized pathways. For example, aseptic coupling devices can be used to couple a fluid pathway from a first piece of processing equipment or container to a fluid pathway from a second piece of processing equipment or container to establish a sterile pathway for fluid transfer therebetween. 
     Typical aseptic coupling devices require a “dry-to-dry” or “dry connection” that is created using one or more pathway clamping devices placed upstream of the aseptic coupling devices so that the aseptic coupling devices are kept free of fluid while the connection between the aseptic coupling devices is made. Once the sterile connection between the aseptic coupling devices is made, the clamping devices are removed to allow fluid to flow through the aseptic coupling devices. 
     SUMMARY 
     According to one aspect, an aseptic coupling device includes an inner member defining a fluid passage therethrough, a seal member coupled to a front surface of the inner member, a membrane coupled to the front surface of the inner member to cover the seal member, and a locking ring positioned to rotate about the inner member. The inner member is sized to be received in a member of another aseptic coupling device to form a pre-coupled state. When the membrane is removed, the seal member engages a second seal member of the other aseptic coupling device, and, upon turning of the locking ring, the seal member and the second seal member are compressed to form a coupled state in which a sterile flow path is created between the aseptic device and the other aseptic device. 
     According to another aspect, an aseptic coupling device includes a main body defining a fluid passage therethrough, a front portion coupled to the main body, the front portion defining a plurality of channels therein, a seal member coupled to a front surface of the main body, a membrane coupled to the front surface of the main body to cover the seal member, and a slot defined in the main body sized to receive a clip. The front portion is sized to receive a portion of another aseptic coupling device so that the clip engages the other aseptic coupling device to form a pre-coupled state. When the membrane is removed, the seal member engages a second seal member of the other aseptic device, and, upon turning of a locking ring on the other aseptic coupling device, barbs of the locking ring are received within the channels of the front portion to compress the seal member with the second seal member to form a coupled state in which a sterile flow path is created between the aseptic coupling device and the other aseptic coupling device. 
     In yet another aspect, a method for forming a sterile connection includes: inserting a first aseptic coupling device into a second aseptic coupling device; removing a first membrane from the first aseptic coupling device and a second membrane from the second aseptic coupling device; and rotating a locking clip on the first aseptic coupling device to compress a first seal member of the first aseptic coupling device with a second seal member of the second aseptic coupling device to form a sterile fluid passageway. 
    
    
     
       DESCRIPTION OF THE DRAWINGS 
       Non-limiting and non-exhaustive embodiments are described with reference to the following figures, which are not necessarily drawn to scale, wherein like reference numerals refer to like parts throughout the various views unless otherwise specified. 
         FIG. 1  is a schematic view of an example system including first and second pieces of processing equipment and an aseptic coupling device forming a sterile connection therebetween. 
         FIG. 2  is a perspective view of an example aseptic coupling arrangement in a pre-coupled state. 
         FIG. 3  is a top view of the aseptic coupling arrangement of  FIG. 2 . 
         FIG. 4  is a cross-sectional view of the aseptic coupling arrangement of  FIG. 3 . 
         FIG. 5  is an end view of the aseptic coupling arrangement of  FIG. 2 . 
         FIG. 6  is another end view of the aseptic coupling arrangement of  FIG. 2 . 
         FIG. 7  is a cross-sectional view of the aseptic coupling arrangement of  FIG. 2  in a coupled state. 
         FIG. 8  is a perspective view of the aseptic coupling arrangement of  FIG. 2  in an uncoupled state. 
         FIG. 9  is a perspective view of an inner member of the male aseptic coupling of  FIG. 2 . 
         FIG. 10  is a side view of the inner member of the male aseptic coupling of  FIG. 9 . 
         FIG. 11  is a perspective view of the locking ring of the male aseptic coupling of  FIG. 2 . 
         FIG. 12  is a side view of the locking ring of the male aseptic coupling of  FIG. 11 . 
         FIG. 13  is an end view of the locking ring of the male aseptic coupling of  FIG. 11 . 
         FIG. 14  is a perspective view of a female aseptic coupling of  FIG. 2 . 
         FIG. 15  is a side view of the female aseptic coupling of  FIG. 14 . 
         FIG. 16  is a bottom view of the female aseptic coupling of  FIG. 14 . 
         FIG. 17  is an end view of the female aseptic coupling of  FIG. 14 . 
         FIG. 18  is a perspective view of an example clip. 
         FIG. 19  is an example method for connecting the aseptic coupling device. 
         FIG. 20  is a first perspective view of another aseptic coupling arrangement in a pre-coupled state. 
         FIG. 21  is a first exploded perspective view of the male coupling device of the arrangement of  FIG. 20 . 
         FIG. 22  is a second exploded perspective view of the male coupling device of the arrangement of  FIG. 20 . 
         FIG. 23  is a perspective view of another aseptic coupling arrangement having a coupler attached thereto. 
         FIG. 24  is a side view of the aseptic coupling arrangement of  FIG. 23 . 
         FIG. 25  is a cross-sectional view of the aseptic coupling arrangement of  FIG. 23 . 
         FIG. 26  is a first perspective view of the male and female aseptic coupling devices of  FIG. 2  in an uncoupled state and with caps attached thereto. 
         FIG. 27  is a second perspective view of the male and female aseptic coupling devices of  FIG. 2  in an uncoupled state and with caps attached thereto. 
         FIG. 28  is an end view of the cap of the male aseptic coupling device of  FIG. 26 . 
         FIG. 29  is a side view of the cap of the male aseptic coupling device of  FIG. 26 . 
         FIG. 30  is a perspective view of the cap of the female aseptic coupling device of  FIG. 26 . 
         FIG. 31  shows a side view of the cap of the female aseptic coupling device of  FIG. 26 . 
         FIG. 32  is an end view of the cap of the female aseptic coupling device of  FIG. 26 . 
         FIG. 33  is another cross-sectional view of the aseptic coupling arrangement of  FIG. 2  in a coupled state. 
         FIG. 34  is a side view of another example membrane for an aseptic coupling device. 
         FIG. 35  is a front view of the membrane of  FIG. 34 . 
         FIG. 36  is a perspective view of the membrane of  FIG. 34 . 
     
    
    
     DETAILED DESCRIPTION 
     Various embodiments will be described in detail with reference to the drawings, wherein like reference numerals represent like parts and assemblies throughout the several views. Reference to various embodiments does not limit the scope of the claims attached hereto. Additionally, any examples set forth in this specification are not intended to be limiting and merely set forth some of the many possible embodiments for the appended claims. 
     As used herein, the term “sterilize” means a process of freeing, to a specified degree, a surface or volume from microorganisms. In example embodiments, the sterility of various components can be achieved using one or more sterilization techniques, including gamma irradiation, E-beam, ethylene oxide (EtO), and/or autoclave technologies. 
     As used herein, the term “aseptic” refers to any process that maintains a sterilized surface or volume. 
     As used herein, the term “fluid” means any substance that can be made to flow including, but is not limited to, liquids, gases, granular or powdered solids, mixtures or emulsions of two or more fluids, suspensions of solids within liquids or gases, etc. 
     Referring now to  FIG. 1 , an example system  100  is shown. System  100  includes a first piece of processing equipment  110  and a second piece of processing equipment  120 . In example embodiments, equipment  110  and  120  are bioreactors including biomaterial. In other embodiments, equipment  110  and  120  can be other apparatuses that require a sterile connection therebetween such as, for example, a bioreactor and a media bag or other receptacle. 
     Equipment  110  includes a fluid pathway  112  extending therefrom that is terminated by an aseptic coupling arrangement  121  including a first aseptic coupling device  114 . Likewise, equipment  120  includes a fluid pathway  122  extending therefrom that is terminated by a second aseptic coupling device  124  of the aseptic coupling arrangement  121 . In example embodiments, the environment within pathways  112  and  122  and aseptic coupling devices  114  and  124  are sterile. 
     Aseptic coupling device  114  can be connected to aseptic coupling device  124 . Once aseptic coupling device  114  is connected to aseptic coupling device  124 , a sterile fluid pathway is established between equipment  110  and equipment  120 . Once the sterile fluid pathway is established, fluid can be transferred from equipment  110  to equipment  120 , or vice versa. 
     Referring now to  FIGS. 2-6 , aseptic coupling devices  114  and  124  are shown in a pre-coupled state. In this state, the aseptic coupling devices  114 ,  124  are connected to one another. However, a sterile flow path has not yet been created because membranes associated with the aseptic coupling devices  114 ,  124  have not yet been removed. 
     In the example shown, aseptic coupling device  114  is a male coupling device, and aseptic coupling device  124  is a female coupling device. In the example shown, the devices  114 ,  124  are keyed so that the devices  114 ,  124  can only be coupled in one manner, as described below. In alternative embodiments, other configurations are possible. 
     In the example shown, the male aseptic coupling device  114  includes an inner member  201 , a locking ring  202 , and a membrane  204 . See  FIGS. 9-13 . 
     Inner member  201  defines a fluid passage  502  through aseptic coupling device  114 . Inner member  201  is coupled to a portion  214 . In the example shown, portion  214  is barbed so that portion  214  can be connected to a fluid pathway (e.g.,  112 ) such as a hose. Inner member  201  also includes a circular channel  504  that is formed to allow inner member  201  to be rotatably coupled to locking ring  202 , as described below. 
     Inner member  201  also defines a channel  304 . See  FIGS. 8-10 . Channel  304  is sized to receive a clip  212  (see  FIG. 18 ) that is used to couple aseptic coupling device  114  to aseptic coupling device  124 . 
     Membrane  204  is coupled, using, for example, an adhesive, to a front surface  802  of inner member  201 . As shown in  FIG. 9 , in example embodiments, front surface  802  includes an opening  804 . Opening  804  allows fluid flow through inner member  201 . Front surface  802  forms a generally “D” shape and surrounds the opening  804 . An upper portion  809  of the front surface  802  allows membrane  204  to extend beyond opening  804  so that as membrane  204  is removed, the sterility of opening  804  is maintained even if membranes  204 ,  206  are pulled at different rates, as described below. Recess portions  806  and  808  are relief areas that minimize excessive pull forces. 
     Inner member  201  also has stops  313  formed adjacent front surface  802 . As described further below, stops  313  engage complementary structures on the mating device to define a coupled position. 
     In example embodiments, a seal member  532  is positioned in a window  531  formed by the inner member  201 . Seal member  532  is positioned to engage a corresponding seal member  533  positioned in a window  535  on aseptic coupling device  124  when aseptic coupling devices  114 ,  124  are connected and membranes  204 ,  206  are removed, as described below. See  FIG. 7 . 
     As shown in  FIGS. 2 ,  4 ,  5 ,  8 ,  16 , and  17 , membrane  204  extends through an opening  313  formed in the device  124 . A handle portion  520  is coupled to an end  522  of membrane  204 . In example embodiments, the handle portion  520  includes one or more attachment members  208 , such as attachment members/apertures, that are positioned to engage attachment members  210  on corresponding membrane  206  of the aseptic coupling device  124 , as described further below. 
     Locking ring  202  includes a tab portion  506  that is positioned to be received in channel  504  formed by inner member  201 . See  FIGS. 4 ,  11 , and  12 . This allows locking ring  202  to be spun in a direction  508  (see  FIG. 5 ) to lock aseptic coupling device  114  to aseptic coupling device  124 , as described below. Knurls  507  formed on the locking ring  202  allow the user to easily grasp and rotate the locking ring  202 . 
     Locking ring  202  also includes barbs  203  (see  FIGS. 4 and 13 ) extending from and spaced about an inner periphery of locking ring  202 . As shown in  FIGS. 8-10  and described further below, barbs  203  are received in corresponding channels  306  formed by aseptic coupling device  124  to couple aseptic coupling device  114  thereto. In one embodiment, four barbs  203  are spaced radially about the inner periphery of locking ring  202 . 
     Aseptic coupling device  124  includes a front portion  540  configured to be coupled to aseptic coupling device  114 , and a barbed portion  216  configured to be coupled to a fluid source. A fluid passage  503  is formed therethrough. 
     Front portion  540  includes channels  306  that extend from a front edge  307  of front portion  540 . In the example show, each channel  306  includes an inlet portion  902  that extends generally axially, and a locking portion  904  that extends generally radially. The inlet portion  902  is sized to receive one barb  203  of locking ring  202  of aseptic coupling device  114 . When the locking ring  202  is rotated in direction  508 , barb  203  extends into and is captured by locking portion  904  of channel  306 . In example embodiments, three channels  306  are spaced axially about front portion  540  to correspond to barbs  203  of locking ring  202 . 
     Front portion  540  also defines slots  311  that are positioned to receive clip  212 . Barbs  1002  on clip  212  engage a bottom surface  317  of device  124  (see  FIG. 18 ). Ramped portions  1004  on each side arm  1006  of the clip  212  extend radially inward through slots  311  to engage channel  304  on aseptic coupling device  114 . The ramped surfaces of the ramped portions  1004  allow the device to ride along the ramped portions  1004  and push arms  1006  away from one another to clear the ramped portions  1004 . Upon clearance, the ramped portion  1004  move back into place within channel  304  to couple the devices  114 ,  124 . In one example, the ramped portions  1004  make a “clicking” noise as they clear and enter the channel  304  to provide the user with audible and/or tactile feedback of a positive coupling. 
     Membrane  206  is coupled to a front surface  910  of aseptic coupling device  124 . See  FIG. 17 . In examples, surface  910  is generally “D” shaped and surrounds opening  908 . Similar to front surface  802 , an upper portion  909  of front surface  910  allows membrane  206  to extend beyond opening  908  so that as membrane  206  is removed, the sterility of opening  804  is maintained even if membranes  204 ,  206  are pulled at different rates, as described below. 
     Adjacent front surface  910  are formed stops  913 . The stops  913  engage stops  313  on the device  114  when the device is positioned in the coupled state. The stops  313 ,  813  define the closes position that the devices  114 ,  124  can come together. See  FIG. 33 . In this manner, the stops  313 ,  813  define the amount of compression in seals  532 ,  533  when the devices  114 ,  124  are in the coupled state. The stops  313 ,  913  thereby maintain the desired compression and minimize the possibility of side load leakage. 
     An end  554  of membrane  206  includes a handle portion  552  that includes attachment members  210  that are positioned to engage attachment members  208  on the corresponding membrane  206  of the aseptic coupling device  124 , as described further below. 
     Referring now to  FIG. 19 , an example method  1100  for connecting aseptic coupling device  114  to aseptic coupling device  124  is shown. 
     First, at operation  1102 , front portion  530  of aseptic coupling device  114  is inserted into aseptic coupling device  124  along centerline  302 . During insertion, barbs  203  are received in inlet portions  902  of channels  306 . In addition, front portion  530  surrounds inner member  201 . When front portion  530  is fully inserted, barbs  1002  of clip  212  are received in channel  304  on aseptic coupling device  114 . In this position (referred to as “pre-coupled”), aseptic coupling device  114  is coupled to aseptic coupling device  124 . 
     Next, at operation  1104 , the attachment members  210  on handle portion  552  of membrane  206  are connected to attachment members  208  on handle portion  520  of membrane  204 . Once connected, handle portions  520 ,  552  are grasped, and a force in a direction  559  is applied. As membranes  204 ,  206  are pulled in direction  559 , membranes  204 ,  206  roll in on one another and seals  532 ,  533  in ends  201  and  540  of each of aseptic coupling devices  114 ,  124  engage to form a sterile connection. 
     Once membranes  204 ,  206  are removed, locking ring  202  is rotated (stage  1106 ) in direction  508  so that barbs  203  enter locking portions  904  of channels  306 . As barbs  203  move along locking portions  904 , aseptic coupling device  114  is pulled slightly closer to aseptic coupling device  124  to compress the seal members  532 ,  533  together. At this position (referred to as “coupled”), an aseptic pathway exists through passages  502 ,  503  of the aseptic coupling devices  114 ,  124 . See  FIG. 7 . As noted above, the stops  313 ,  913  define the level of compression for the seal members  532 ,  533 . See  FIG. 33 . 
     Referring now to  FIGS. 20-22 , an alternative embodiment of an aseptic coupling arrangement  1000  is shown. In the example shown, aseptic coupling device  114  is identical to that described above, and an aseptic coupling device  1124  is a male coupling that is similar to aseptic coupling device  124  describe above. 
     However, aseptic coupling device  1124  includes a separate inner member  1102  and outer member  1104 . Inner member  1102  is identical in shape to inner member  201  of aseptic coupling device  114 . This allows both components to be molded using the same machinery. 
     Outer member  1104  includes a tab portion  1106  with a plurality of members  1107  that are positioned to be received in a channel  1108  formed by inner member  1102 . This allows outer member  1104  to be coupled to inner member  1102  and spin relative thereto. Other configurations are possible. 
     Referring now to  FIGS. 23-25 , another example embodiment of an aseptic coupling arrangement  2124  is shown. 
     In this example, an aseptic coupling device  2152  includes a termination  2154  that is sized to be coupled to another coupling device, such as a quick disconnect coupler  1902 . Examples of such couplers are described in U.S. Pat. Nos. D357,307; D384,731; 5,316,041; and 5,494,074. The entireties of these patents are hereby incorporated by reference. Other types of couplers can be used. 
     As shown, an insert member  2156  is connected (e.g., by sonic welding) to the termination  2154 . The coupler  1902  is, in turn, connected to the insert member  2156 . 
     In the example shown, the coupler  1902  includes a valving structure  1906 , and the insert member  2156  includes a valving structure  2158 . These valving structures  1906 ,  2158  are normally open when the coupler  1902  is connected to the insert member  2156 , so that fluid can flow therethrough. In such an example, the entire device  2152  can be sterilized prior to use. 
     When fluid flow is complete, a latch  1908  of the coupler  1902  can be actuated to disconnect the coupler  1902  from the insert member  2156  positioned between the termination  2154  and the coupler  1902 . When disconnected, valving structure  1906  in coupler  1920  stops the flow of fluid through the coupler  1920 , and valving structure  2158  in the insert member  2156  stops the flow of fluid through the device  2124 . This can result in a disconnect that is also aseptic. The coupler  1902  can thereupon, in turn, be connected to other terminations as desired. 
     In other embodiments, coupler  1902  can be connected to aseptic coupling device  114 . In still further embodiments, both aseptic coupling devices  114  and  124  can each have a coupler connected thereto. In other examples, the coupler  1920  can be welded to the devices  114 ,  124 , and the insert member  2156  can be coupled to the coupler  1920 . Other configurations are possible. 
     Referring now to  FIGS. 26-32 , in example embodiments, a cap  3100  can be connected to aseptic coupling device  124 , and a cap  3200  can be connected to aseptic coupling device  114 . The caps  3100 ,  3200  function to protect the membranes  204 ,  206  prior to use. When ready for use, caps  3100 ,  3200  are removed from devices  114 ,  124  before devices  114 ,  124  are coupled. 
     As shown in  FIGS. 28 and 29 , the cap  3200  includes a body  3202  that is concave to surround the front surface  802  of inner member  201  of the device  114 . Tabs  3204  on the body  3202  are received in the channel  304  on the inner member  201  to releasably couple the cap  3200  to the device  114 . A bottom member  3206  guides and protects a lower portion of the membrane  204 . The handle portion  520  attached to the member  204  extends out of the bottom member  3206 . 
     As shown in  FIGS. 30-32 , the cap  3100  includes a body  3102  that extends into the device  124 . Slots  3113  on each side of the body  3102  are positioned to engage ramped portions  1004  of the clip  212  (see  FIG. 18 ) as the cap  3100  is inserted into the front portion  540  of the device  124  to releasably hold the cap  3100  to the device  124 . Tabs  3105  formed on the body  3102  allow the user to grasp and remove the cap  3100  prior to use. A bottom member  3106  guides and protects a lower portion of the membrane  206 . The handle portion  522  attached to the member  206  extends out of the bottom member  3106 . 
     Referring now to  FIGS. 34-36 , another example membrane  950  is shown. The membrane  950  is similar in construction to membranes  204 ,  206 , and can be used in conjunction with either or both of the aseptic coupling devices  114 ,  124 . In the example shown, the membrane  950  includes an enlarged portion  960  positioned at the end of the membrane  950  that is attached to the front surfaces  802 ,  910  of the devices  114 ,  124 . Specifically, the enlarged portion  960  is spherical in shape so that the portion  960  generally encompasses a larger part of the front surface  802 ,  910  to provide a better sealing between the membrane  950  and the front surfaces  802 ,  910 . Other configurations are possible. 
     In example embodiments, the aseptic coupling devices are made of a polymeric material. For example, in one embodiment, the aseptic coupling devices are made of polycarbonate and the seal members used therein are made of a silicone rubber. Other materials can be used. 
     In some embodiments, membranes  204 ,  206  are autoclavable and gamma stable for sterilization. In various embodiments, membranes  204 ,  206  are a composite design that consists of two components: 1 tag and 1 vent. The tag is a laminate including: a polyethylene terephthalate (PET) film, polyethylene (PE) foam, aluminum foil, and a sealing layer. The foam and/or foil may or may not exist in the final configuration. The sealing layer allows the tag to be bonded or welded to polycarbonate connectors (e.g., aseptic coupling devices  114  and  124 ). The vent is an expanded poly(tetrafluoroethylene) (ePTFE) membrane that will be bonded or welded onto the tag. Membranes  204 ,  206  are located over the center of the flow area of aseptic coupling devices  114  and  124 , respectively, when the tags and vents are bonded or welded to connectors. The vent allows air and steam to flow into the system  100  during sterilization. The pore size of membranes  204 ,  206  are such that membranes  204 ,  206  filter out microorganisms larger than 0.2 microns. 
     In another embodiment, membranes  204 ,  206  are a polyethersulfone (PES) and polyester laminate membrane. This membrane is hydrophobic and breathable. The pore size is such that microorganisms larger than 0.2 microns are filtered out. When bonded, the polycarbonate melts into the polyester fibers, so that the PES acts as the filter, and the polyester acts as the structure. 
     In other embodiments, membranes  204 ,  206  are a Tyvek membrane that is coated on one side to allow membranes  204 ,  206  to be bonded to polycarbonate connectors (e.g., aseptic coupling devices  114  and  124 ). Tyvek is breathable in nature, so there is no need for an additional vent. Tyvek is a non-woven polyethylene membrane. 
     The various embodiments described above are provided by way of illustration only and should not be construed to limit the claims attached hereto. Those skilled in the art will readily recognize various modifications and changes that may be made without following the example embodiments and applications illustrated and described herein, and without departing from the true spirit and scope of the disclosure.