Abstract:
The present invention relates to a sterile transfer device for fluids, be they liquids or gases. It is comprised of a body having a bore formed through at least a portion of its interior. Preferably, it is a central bore formed through the entire length of the body. Contained within the bore is a movable plunger. The body has a first and a second end. The first end contains a face designed to be attached to the upstream component. The second end is connected to a downstream component such as a filter, pipeline, sample bag and the like. The plunger has corresponding first and second ends. The first end of the plunger when it the closed position is in alignment with the face of the body which combined form a steamable surface and a sterile barrier against the environment to the rest of the interior of the body, the plunger and downstream components.

Description:
[0001]     The present invention relates to a disposable, sterile fluid transfer device. More particularly, it relates to a disposable sterile fluid transfer device, preferably in the form of a connector or valve for use in the pharmaceutical and biopharmaceutical industry.  
       BACKGROUND OF THE INVENTION  
       [0002]     In the pharmaceutical, biotechnology and even food, beverage and cosmetics industries, it is often desired to provide a processing system that is capable of handling fluids in a sterile manner. This is designed to prevent unwanted, often dangerous organisms, such as bacteria as well as environmental contaminants, such as dust, dirt and the like from entering into the process stream and/or end product. It would be desirable to have a completely sealed system but this is not always possible with the processes that take place in production.  
         [0003]     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; and to fill the product into its final container such as vials, syringes, sealed boxes, bottles and the like.  
         [0004]     Typically, the systems have been made of stainless steel and the system is exposed to live steam before use and then cleaned with chemicals such as caustic solutions after use to ensure that all contaminants are removed.  
         [0005]     Steaming is the most effective means of sterilization. The use of steam in a set system is known as steaming in place or SIP. Saturated steam carries 200 times the BTU heat transfer capacity of heated air because of the latent heat released by the steam as it changes from vapor to liquid.  
         [0006]     Several disadvantages exist with the use of steam. Any connections to or openings of the system made after the system has been SIP&#39;d is an aseptic (but not sterile) connection or opening. This increases the risk of contamination of the entire system. One typically uses alcohol wipes or an open flame to clean the components to be connected, (e.g. connecting a sample collection bag to a system after SIP has occurred) and thus minimize the risk of contamination.  
         [0007]     Also the high temperatures and pressure differentials of the steam make the selection of filter materials and components very difficult and limited and even then an accidental pressure differential at high temperatures can cause a filter, membrane or other non-steel component to fail.  
         [0008]     Additionally, such systems that are reused need to undergo rigorous testing and validation to prove to the necessary authorities that the system is sterile before each use. The expense of validation as well as the cleaning regiment required is very high and very time consuming (typically taking 1 to 2 years for approval). In addition, some components are very difficult to adequately clean after use in preparation for their next use. Manufacturers are looking for ways to reduce both their costs and the time to market for their products, One possible approach is to adopt an all disposable system that is set up in a sterile fashion, used and then thrown away.  
         [0009]     The present invention provides a connector that can be used in either the traditional steel system or disposable system which provides both a means for steam sterilizing the mating point of the connector to the system as well as providing a sterile downstream area or component, in pre-sterile condition, that can be disposed of after use and not be recleaned.  
       SUMMARY OF THE INVENTION  
       [0010]     The present invention relates to a sterile transfer device for fluids, be they liquids or gases. It is comprised of a body having a bore formed through at least a portion of its interior. Preferably, it is a central bore formed through the entire length of the body. Contained within the bore is a movable plunger. The body has a first and a second end. The first end contains a face designed to be attached to the upstream component. The second end is connected to a downstream component such as a filter, pipeline, sample bag and the like. The plunger has corresponding first and second ends. The first end of the plunger when it the closed position is in alignment with the face of the body which combined form a steamable surface and a sterile barrier against the environment to the rest of the interior of the body, the plunger and downstream components.  
         [0011]     The downstream components are assembled to the device and it is placed in the closed position. The entire device and downstream components are sterilized, such as with gamma radiation. In use the device and downstream components are attached by the face to the upstream component such as a filter outlet, a tank outlet, a “T” of a pipe and secured in place. The system and the face of the device are then steam sterilized in place. The device is then selectively opened when needed establishing a sterile pathway through the device to the downstream components. 
     
    
     IN THE DRAWINGS  
       [0012]      FIG. 1  shows a cross sectional view of a first embodiment of the present invention in a closed position.  
         [0013]      FIG. 2  shows a cross sectional view of the first embodiment of the present invention of  FIG. 1  in an open position.  
         [0014]      FIG. 3  shows a cross sectional view of the first embodiment of the present invention of  FIG. 1  mounted to an upstream component.  
         [0015]      FIG. 4  shows a cross sectional view of a second embodiment of the present invention in a closed position.  
         [0016]      FIG. 5  shows a cross sectional view of a second embodiment of the present invention of  FIG. 3  in an open position.  
         [0017]      FIG. 6  shows a cross sectional view of another embodiment of the present invention.  
         [0018]      FIG. 7  shows a cross sectional view of another embodiment of the present invention.  
         [0019]      FIG. 8  shows a cross sectional view of another embodiment of the present invention.  
         [0020]      FIG. 9A  shows a perspective view of a locking mechanism of the present invention in unopened condition.  
         [0021]      FIG. 9B  shows a perspective view of the locking mechanism of  9 A of the present invention in the opened condition.  
         [0022]      FIG. 9C  shows a perspective view of the locking mechanism of  9 A of the present invention in the reclosed position.  
         [0023]      FIG. 10A  shows a perspective view of a locking mechanism of the present invention in unopened condition.  
         [0024]      FIG. 10B  shows a perspective view of the locking mechanism of  10 A of the present invention in the opened condition.  
         [0025]      FIG. 10C  shows a perspective view of the locking mechanism of  10 A of the present invention in the reclosed position.  
         [0026]      FIG. 11A  shows a perspective view of a locking mechanism of the present invention in unopened condition.  
         [0027]      FIG. 11B  shows a perspective view of the locking mechanism of  11  A of the present invention in the opened condition.  
         [0028]      FIG. 12A  shows a perspective view of a locking mechanism of the present invention in unopened condition.  
         [0029]      FIG. 12B  shows a perspective view of the locking mechanism of  12 A of the present invention in the opened condition.  
         [0030]      FIG. 12C  shows a perspective view of the locking mechanism of  12 A of the present invention in the reclosed position.  
         [0031]      FIG. 13  shows a perspective view of a locking mechanism of the present invention in unopened condition.  
         [0032]     FIGS.  14  shows an alternative design of the present invention.  
         [0033]     FIGS.  15  shows another embodiment of the device of the present invention.  
         [0034]     FIGS.  16 A-I show other embodiments of the device of the present invention in cross sectional view.  
         [0035]      FIG. 17  shows the device of the present invention in one potential application in which there is a sterile to nonsterile connection.  
         [0036]      FIG. 18  shows the device of the present invention in one potential application in which there is a sterile to sterile connection. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0037]     The present invention is a sterile fluid transfer device, preferably in the form of a connector or a valve.  
         [0038]     A first embodiment of the present invention is shown in  FIG. 1 . The device  2  is formed of a body  4  having a first end  6  and a second end  8 . The body  4  also has a bore  10  extending in this embodiment from the first end  6  to the second end  8 . The bore  10  as shown is formed of three sections each with a different diameter. There is the first bore section  12  which has a first set diameter, a transition bore section and a second bore section which has a second set diameter that is greater than the first set diameter of the first bore section  12 . The transition bore section  14  is arranged between the first and second bore sections  12 ,  16  and has an outwardly tapering diameter along its length with the diameter of the transition section  14  adjacent the first bore section  12  being equal to the first set diameter and the diameter of the transition section  14  adjacent the second bore section  16  being equal to the second set diameter. The diameter of the transition section between the first and second bore sections is preferably a linear outward progression between the two bore sections.  
         [0039]     Contained within the bore is a plunger  18  which has a shape corresponding to that of the bore  14 . The plunger has a first portion  20  having a diameter equal to or less than that of the diameter of the first bore section, a second plunger portion  22  having a diameter equal to or less than that of the second bore section and a transitional portion  24  between the first and the second plunger portions  20 ,  22  having an outwardly tapered diameter between the first and second plunger portions  20 ,  22  equal to or less than the diameter of the transition bore section  14 . The plunger  18  also contains one or more openings  26  in either the transitional portion  24  or the first or second portions  20 ,  22  as well as a fluid channel  27  that-forms a fluid connection to a downstream component or tubing (not shown).  
         [0040]     As shown, the farthest part  28  of the second portion  22  contains a barb design  30  to connect to the next downstream component. The plunger also contains several preferable elements that are useful but not necessary to the invention. Included among these are a cam  32  and a connector handle  34 . The cam  32  rides in a cam slot  36  formed in the body  4  and together is used to limit the length of travel of the plunger  18  in the bore  14 .  
         [0041]     The device is shown in  FIG. 1  in the closed position. One or more seals  38  are arranged along the length of the plunger  18  to form a liquid tight seal between various portions of the plunger  18  and the bore  14  when they are in the closed or open positions. As shown the seals  38  are contained in grooves  40 .  
         [0042]     The device  2  is attached to an upstream component or pipe by a sanitary flange  42  formed as part of the body  4 . In the closed position the flange  42  and the farthestmost end of the first portion of the plunger  44  form a face  46  against the rest of the system. The flange  42  can be attached to the upstream component or pipe by a clamp such as a Tri-Clover™ fitting, Ladish™ fitting, ClickClamp™ clamp or the like. This face  46  is capable of withstanding steam treatment when in the device is in the closed position as will be described in more detail below.  
         [0043]      FIG. 2  shows the device  2  of  FIG. 1  in the open position. To the extent that the same reference numbers apply to both  FIGS. 1 and 2  they have been kept the same.  
         [0044]     In  FIG. 2 , the plunger has been moved from the closed position of  FIG. 1  to an open position. The farthestmost end of the first portion of the plunger  44  has been moved back from the face  46  providing a passageway  48  to the bore  14  and the one or more openings  24  and the fluid channel  26  forming a fluid connection between the upstream  50  and downstream sides  52  of the device  2 . As shown, the plunger is moved rearward or downstream and rotated at the same time, as evidenced by the movement of the cams  32  in the cam slot  36 .  
         [0045]      FIG. 3  shows the device  2  of  FIG. 1  mounted to an upstream component  54 , in this instance a “T” pipe and a downstream component  56 , in this instance a piece of hose or plastic pipe. Also shown is liquid tight seal  58  formed between the flange of the device  2  and a flange  60  (clamp not shown).  
         [0046]      FIGS. 4 and 5  show an embodiment of the present device  61  in which there is no fluid passage formed in the plunger. Instead, the body contains a port  62  which provides the fluid connection to the downstream component  64 , in this instance a piece of plastic piping. As shown in the closed position, the farthestmost end  66  of the first portion  68  of the plunger  70  seals off the downstream side of the device  61  from the upstream component  72 . The port  62  is shown as being at a 90 degree angle to the length of the body, but it may be any other desired angle.  
         [0047]     As shown in  FIG. 5 , when the device of  FIG. 4  is opened, the farthestmost end  66  of the first portion  68  of the plunger  70  has been moved back from the face  72  providing a passageway  74  to the bore  76  and the port  62  so as to provide fluid communication between the upstream component  72  and the downstream component  64  through the device  61 .  
         [0048]     As shown in  FIGS. 1-5 , the seals may be mounted on the plunger of the device. Further, the seals shown in  FIGS. 1-5  are O-rings, either pre-formed and retained within grooves on the plunger or formed in place in the grooves of the plunger. However, if desired, different configurations of seals and their placements can be used. For example,  FIG. 6  shows some seals  80  formed on the plunger  82  with other seals  84  held in grooves  86  in the inner surface of the bore  88 .  
         [0049]      FIG. 7  shows an embodiment with a linear or gland seal  90  is retained within a groove  92  on the inner wall of the body  94  and other seals  96  attached to the plunger  98  in grooves  100 .  
         [0050]      FIG. 8  shows a similar design to that of  FIG. 7  except that the gland seal  90  is formed on the outer wall  91  of the plunger  98  and other seals  96  are attached to the plunger  98  in grooves  100 .  
         [0051]     As this is device is provided in a sterile condition, i.e. the interior of the system and any component connected downstream of the device is pre-sterilized such as with gamma radiation, ethylene gas or the like and shipped in a sterile condition, some type of use indicator would be helpful so one knows when a system has been used and should therefore be replaced.  
         [0052]      FIG. 9A  shows a first embodiment of an indicator useful on the present invention. As shown in the  FIG. 9A , the body section  102  distal from the steamable face  104  has a series of one or indentations or locking recesses or fixed pawls  106 . The plunger  108  has a mating detent  110  which is located in one of the recesses before the device is sterilized. The device is shipped in this sterile condition with the detent remaining in the recess. In fact, the detent/recess combination works to ensure that the device doesn&#39;t accidentally open due to vibration or handling during shipping.  
         [0053]     The device is then taken from its sterile container in the closed position of  9 A and attached by its face to the system. The face is then steam sterilized. The device is then opened by rotating the handle to an open position as shown in  FIG. 9B .  
         [0054]     When the device is closed after use, the handle  112  of the plunger  108  is capable of moving the detent  110  past the first recess and into the second recess  106  as shown in  FIG. 9C . This provides a visual indication to the user that the device is no longer sterile. In addition, it provides a manual indication to the user that the device has been used as the detent  110  has to be turned past the two recesses  106 , each with an affirmative clicking action before the device can be opened. Moreover, one can design the walls of the farthermost (used condition) recess  106  so that the movement out of the recess requires an extraordinary amount of force to again indicate to the user that the device has been used and shouldn&#39;t be reused.  
         [0055]      FIG. 10A  shows another embodiment of an indicator useful on the present invention. As shown in the  FIG. 10A , the body section  113  distal from the steamable face (not shown) has a series of one or indentations or locking recesses or fixed pawls  106  as well as one or more breakaway tabs  114 . The plunger  108  has a mating detent  110  which is located in one of the recesses  106  before the device is sterilized as well as a breaking bar  116 . The device is shipped in this sterile condition with the detent remaining in the recess and the breaking bar being positioned behind the breakaway tab.  
         [0056]     The device is then taken from its sterile container in the closed position of  10 A and attached by its face (not shown) to the system. The face is then steam sterilized. The device is then opened by rotating the handle  112  to an open position as shown in  FIG. 10B . In doing so the breaking barn  16  rotates past and over the breakaway tab  114 , causing it to be bent over or removed altogether.  
         [0057]     When the device is closed after use, the handle  112  is capable of moving the detent  110  past the first recess  106  and into the second recess  106 A as shown in  FIG. 10C .  
         [0058]      FIGS. 11A  and B show a plastic feature extending from the body that forms another breakaway (or bend-away) indicator.  FIG. 11A , shows the valve in its shipped (or pre-sterilized) position. It is intended that when the valve is opened, this protruding feature will break away or at least bend away from its original position, thereby indicating that the valve has been actuated and should not be used again once it has been subsequently closed.  FIG. 11B  shows the valve in the open position, showing the tab feature as being bent.  
         [0059]      FIG. 12A  shows another embodiment of an indicator useful on the present invention. As shown in the  FIG. 12A , the body section  113  distal from the steamable face (not shown) has a series of one or indentations or locking recesses or fixed pawls  106  as well as one or more tab retainers  120 . The plunger  108  has a mating detent  110  which is located in one of the recesses  106  before the device is sterilized as well as a breakaway or fold over tab  122 . The device is shipped in this sterile condition with the detent remaining in the recess and the breaking bar being positioned behind the breakaway tab.  
         [0060]     The device is then taken from its sterile container in the closed position of  12 A and attached by its face (not shown) to the system. The face is then steam sterilized. The device is then opened by rotating the handle  112  to an open position as shown in  FIG. 12B . In doing so the tab  122  in tab retainer  120  rotates out of the retainer  120 , causing it to be bent over or removed altogether.  
         [0061]     When the device is closed after use, the handle  112  is capable of moving the detent  110  past the first recess  106  and into the second recess  106 A as shown in  FIG. 12C  with the tab  122  if it remains being bent up and not being returning to the retainer  120 .  
         [0062]     As an alternative or in addition to any of the mechanisms discussed above, as shown in  FIG. 13  one may use a shrink wrap indicator  130  over the device or at least the handle portion  132  of the plunger  134  and the surrounding body  136  of the device to indicate that the device is in an unopened condition.  
         [0063]     As an alternative to the face of the device as shown in  FIG. 1 , one may use a foil  160 , metal or plastic, such as PEI, PEEK, polysulphones, aluminum, stainless steel and the like, adhered to the body portion  162  of the face  164  and used to form the sterile seal as shown in  FIG. 14 . It is then pierced or penetrated by the plunger  166  to establish a fluid flow. A rubber septum in lieu of the foil could also be used. A scored surface can also be used. The foil may be adhered in a variety of manners that are well known in the art such as heat sealing, vibration welding such as ultrasonic welding, solvent bonding and through the use of adhesives such as epoxies and urethanes.  
         [0064]      FIG. 15  shows another embodiment of the present invention. In this embodiment the body of the device is formed as an integral component of a pipe. Preferably the pipe is made of a steam resistant plastic (described below) or alternatively, it may be made of a metal such as stainless steel so long as it contains the necessary features of the present invention. The body can be formed as an arm of the piece as shown. The plunger (as shown being similar to that of  FIG. 1 ) is then inserted into the body of the piece.  
         [0065]     FIGS.  16  A-I show several other connectors devices that fall within the present invention.  FIG. 16A  is similar to the valve design of  FIG. 14A . It is comprised of a body  180 , and a plunger  181  contained with in a bore  182  of the housing. The plunger has a fluid channel 185  connecting it in fluid communication to the rest of the downstream side of the device and beyond. A face  183  is formed by the outermost portion of the body  180  and plunger  181 . Unlike the embodiment of  FIG. 1 , the bore  182  is essentially linear as is the plunger  181 . As shown, the device is in its open position. The plunger  181  rather than retracting into the bore  12 , is extended out from the bore to expose an opening or openings  184  so as to create fluid communication between one end and the other end of the device.  
         [0066]      FIG. 16B  shows a close up variant of the design of  FIG. 16A . In this variant, the opening  184 B is formed at a right angle to the fluid channel  185 B only on one side of the plunger.  
         [0067]      FIGS. 16C  and D show a close up cross-sectional view of another embodiment. In this variant, the upstreammost portion of the plunger  181 C is in the form of series of spring fingers  186 . The plunger  181 C is pulled back into the bore  182 C to open the device as shown in  FIG. 16D . Fluid then flows into the bore  182 C, into openings  184 C through the fluid channel  185 C to the downstream component.  
         [0068]      FIGS. 16E  and F show a close up cross-sectional view of another embodiment. In this variant, the upstreammost portion of the plunger  181 E is in the form of compression nut  187 . The plunger  181 E is pulled back into the bore  182 E to open the device as shown in  FIG. 16F . Fluid then flows into the bore  182 E, into openings  184 E through the fluid channel  185 E to the downstream component.  
         [0069]      FIG. 16G  shows another embodiment of the present invention. In this design, the plunger  181 G is actually mounted to move laterally within the bore  182 G of the housing  180 G in a push/pull fashion to open and close the device. The face  183 G is formed of the upstream end of the body and the plunger  181 G as shown.  
         [0070]      FIG. 16H  shows a rotatable device with the body  180 H being formed of two pieces  188 A and  188 B. The plunger  181 H is contained within a portion of the bore  182 H as shown. The plunger as shown is in the closed position. The face  183 H is formed by the upstreammost portions of the plunger  182 H and the body portion  188 B. Also as shown the upstream component is attached to the plunger  181 H. As the plunger is rotated from its closed to its open position, the fluid channel  185 H of the plunger aligns with a fluid channel  189  of body portion  188 B to establish fluid communication through the device.  
         [0071]      FIG. 16I  shows another variant of the rotational design. Here the Plunger  181 I is retained in the bore  182 I of the body  180 I by a groove  190  and abutment  191 . When the plunger  181 I is rotated to its open position, fluid may pass through the bore  182 I into the fluid channel  185 I through opening  184 I.  
         [0072]      FIG. 17  shows the device of the present invention in one potential application in which there is a sterile to nonsterile connection. As shown the fluid transfer device  200  of the embodiment shown in  FIG. 3  is attached by its face (not shown) to a connection point  204  such as a “T” fitting on a process pipe  206  as shown. A clamp  202  holds the adjoining and mating faces (not shown, but see  FIG. 3  for details of the mating assembly) of the device and the pipe  206  together in a liquid tight arrangement. The exit of the device  208  here in the form of a barb is connected to a tube  210  which in turn is connected to a collection bag  212 . In use, the device  200  is in a closed position and has the tube  210  and bag  212  connected to it. The device with the tube and bag are then gamma sterilized (i.e. by gamma irradiation) or otherwise sterilized.  
         [0073]     The device with the tube and bag is then attached to the pipe by the device face (not shown) by the clamp  202 . The face is then steam sterilized along with the remainder of the system and is ready for use. When it is desired to fill the bag  212 , one simply opens the device  200  by rotating the handle  214  which moves the plunger (not shown) away from the face creating an opening into the bore for the fluid to flow out the exit  208  through tube  210  and into the bag  212 . Once the bag  212  is full, the handle is rotated the opposite direction to close the bore to the fluid. The bag  212  can then be closed off via a clamp or hemostat (not shown) and removed for further processing or use.  
         [0074]      FIG. 18  shows a system using the device of the present invention wherein two sterile devices can be connected together. As shown, one can use a connector  300  formed of four interconnecting arms  302  A, B, C and D the end of each arm  302  A,B, C and D having a mating flange  304  A,B, C and D a first sterile transfer device  306  of the present invention in attached to arm  302 A and a second device  308  is attached to a second arm  302 B. A live steam line  310  is attached to arm  302 C and a steam/condensate trap  312  is attached to arm  302 D. Alternatively, one could attach a sterile barrier filter as taught by PCT/US01/47425, filed Dec. 3, 2001 and available from Millipore Corporation of Bedford, Mass. to arm  302 D to remove the condensate after steaming.  
         [0075]     Devices  306  and  308  are attached to other components of the system (not shown) and as with the embodiment of  FIG. 14  are presterilized such as with gamma radiation before assembly the connector  300 .  
         [0076]     After assembly, steam enters through line  310  to sterilize the entire interior of connector  300  and the steamable faces of the devices  306  and  308 . The steam then shut off and the steam/condensate is removed to the trap  312  which is then shut off from the connector  300 . Devices  306  and  308  are then opened to form a sterile to sterile connection between them.  
         [0077]     Other uses will be found for these devices. For example, they can be used to isolate a steam fragile component, such as some filters with steam sensitive membranes, in a process line. The filter especially in the form of a disposable capsule can be attached to the device and presterilized (such as by gamma). The device can then be connected to the line which is then steam sterilized and the device is then opened to provide fluid flow to the filter. If desired the inlet and outlet of the filter can contain such devices the outermost ends of which have the steam sterilizable face. Alteratively, a device can be attached to each end of a length of tube to form a sterile transfer pipe. Other uses can also be made of the present invention. Additionally, the connector of the present invention can be connected or actually molded into a disposable plastic container such as disposable process bag for the manufacture and transfer of biotech products. Such bags are readily available from companies such as Hyclone of Utah and Stedim of France.  
         [0078]     The device is formed a plastic material and may be formed by machining the body and plunger assemblies and then applying the necessary seals and the like, or preferably by molding the body and the plunger separately and assembling them together with the necessary seals and other components.  
         [0079]     The device may be made of any plastic material capable of withstanding in line steam sterilization. The temperature and pressure of such sterilization is typically about 121° C. and 1 bar above atmospheric pressure. In some instances, it may be desirable to use even harsher conditions such as 142° C. and up to 3 bar above atmospheric pressure. The body and at least the face of the plunger should be capable of withstanding these conditions. Preferably, the entire device is made of the same material and is capable of withstanding these conditions. Suitable materials for this device include but are not limited to PEI (polyetherimide), PEEK, PEK, polysulphones, polyarlysulphones, polyalkoxysulphones, polyethersulphones, polyphenyleneoxide, polyphenylenesulphide and blends thereof. Alteratively, one can make the face portion from ceramic or metal inserts alone or that are overmolded with a plastic cover One can also form a polymeric face with a metal outer layer using plasma coating processes.  
         [0080]     The seals of the present invention can be made of a variety of materials typically used for making resilient seals. These materials include but are not limited to natural rubber, synthetic rubbers, such as silicone rubbers, including room temperature vulcanizable silicone rubbers, catalyzed (such as by platinum catalysts) silicone rubbers and the like, thermoplastic elastomers such as SANTOPRENE® elastomers, polyolefins such as polyethylene or polypropylene, especially those containing gas bubbles introduced either by a blowing agent or entrained gas such as carbon dioxide, PTFE resin, thermoplastic perfluoropolymer resins such as PFA and MFA resins available from Ausimont, USA of Thorofare, N.J. and E.I. DuPont de Nemours of Wilmington, Del., urethanes, especially closed cell foam urethanes, KYNAR® PVDF resin, VITON® elastomer, EPDM rubber, KALREZ resin and blends of the above.  
         [0081]     Suitable materials for molded in place seals can be curable rubbers, such as room temperature vulcanizable silicone rubbers, thermoplastic elastomers such as SANTOPRENE® elastomers, polyolefins such as polyethylene or polypropylene, especially those containing gas bubbles introduced either by a blowing agent or entrained gas such as carbon dioxide and elastomeric fluoropolymers  
         [0082]     Other materials used in the devices should also be FDA grade components such as FDA grade silicones, PTFE resins and the like.  
         [0083]     The present invention provides a sterile and steam sterilizable connecting device for fluid transfer. It may be single actuation (one open one close) or it may be multiple actuations with a single sterile connection (multiple openings and closings so long as the sterile connection upstream and downstream is maintained). Additionally, with the use of multiple seals or seals of long length, one is able to ensure that the sterility of the device is maintained even with multiple actuations.