Patent Grant
12017228
This is the U.S. National Stage of International Application No. PCT/EP2018/065581, filed Jun. 13, 2018, which was published in English under PCT Article 21(2), which in turn claims the benefit of European Application No. 17 290 123.3, filed Sep. 22, 2017. The prior applications are incorporated herein by reference in their entirety.
The technical field of the present application is the transfer of chemical, pharmaceutical, and/or biological material into or out of a container, such as a bioreactor. More specifically, aspects of the application relate to a disposable container, such as a disposable bioreactor, and a transfer interface connectable to a port of the disposable container.
Chemical, pharmaceutical, or biological material may be in the form of a fluid, such as a solution or a suspension. The (disposable) container may be a bioreactor (e.g., a fermenter), a mixer, a storage container or any other type of container used for fluid management in pharmaceutical and bioprocess industries. The container may be used for culturing cells or microorganisms. For example, the container may be used in culturing one or more of the following: bacteria, fungi, algae, plant cells, animal cells, protozoans, nematodes. Further, the container may accommodate cells and microorganisms that are aerobic, anaerobic, adherent or non-adherent. The system of the present application can also be used in the production of media, chemicals, food products, medicines, beverages, and other liquid products.
The disposable container may also be referred to as a single-use container or a single-use vessel (e.g., a single-use bioreactor). A majority of the components of the disposable container that contact the material inside the container may be disposed of after use. Use of disposable containers may substantially eliminate the burden of cleaning and sterilization required when using standard stainless steel equipment. Moreover, sterility can be easily and consistently maintained in the disposable container during repeated processing of multiple batches of chemical, pharmaceutical, or biological material.
The disposable container has at least one port for accessing the interior or inside of the container. The port may also be used for accessing the contents of the container. According to one example, the disposable container includes a chamber, and the at least one port includes an inlet port and an outlet port.
The at least one port may have a variety of uses. In particular, the port may deliver controlled volumes of fluid to the interior of the container. Further, ports may be used for extracting or sampling material, such as fluid, from the container or inserting probes, such as a temperature probe, to monitor conditions within the disposable container.
Periodic sampling of the contents of a container may be carried out in order to ensure that development of the contents is proceeding as desired. Further, it may be desirable to ensure that such sampling is carried out in a sterile manner, i.e., without having a negative effect on the contents of the container.
The disposable container may be manufactured from polymeric materials. In particular, the disposable container may be manufactured from fluoropolymers, or thermoplastics such as, polypropylene, polystyrene, polyethylene, Etlylene-Vynil Acetate, or polyurethane. The disposable container may also be made from layers of different materials, e.g., one layer of polyethylene and a second layer of polyamide. Other materials may also be used.
The disposable container may be sterilized before use with gamma radiation, steam, and/or aggressive chemicals such as ethylene oxide. Other sterilization methods may also be used. The disposable container may have various sizes, shapes, and configurations. For example, the disposable container may include a chamber having a capacity of at least 10 liters, 30 liters, 50 liters, 100 liters, 250 liters, 500 liters, 750 liters, 1000 liters, 1500 liters, or 3000 liters. Other volumes are also possible. According to one example, the disposable container may have a capacity of between 10 liters and 3000 liters, or between 50 liters and 2000 liters.
The disposable container may include a variety of components for processing chemical, pharmaceutical, or biological material. In particular, the disposable container may include one or more of the following: an impeller, a conductivity sensor, a thermowell. The disposable container may be at least partially filled with chemical, pharmaceutical, or biological material. The interior or chamber of the disposable container may be inflated. The disposable container may be made from a flexible, e.g. film, material. More specifically, the disposable container may have flexible walls. In particular, the disposable container may include a pre-sterilized, plastic bag. In some cases, the disposable container could be rigid, e.g. rigid thermoplastic, glass, or metal.
According to an aspect, a system for transferring chemical, pharmaceutical, and/or biological material into or out of a container is provided. The system comprises a disposable container having at least one port for accessing the interior of the container. The system further comprises a transfer interface connectable to the at least one port. The transfer interface comprises a plurality of extensible transfer elements for extracting one or more samples from the disposable container, preferably in a sterile manner.
The transfer elements may also be referred to as extracting elements, sampling elements, extractors, or probes. Each of the transfer elements has a corresponding biasing element for retracting the transfer element. The transfer interface further comprises a locking mechanism for locking one of the transfer elements such that the locked transfer element cannot be extended. Each of the transfer elements may have a corresponding locking mechanism. The biasing element may be implemented as a spring or as another device capable of applying a biasing force.
The transfer interface may be implemented as a fluid transfer interface. Unless otherwise indicated (e.g., via the term “multi-use”), the term “transfer interface” refers to a transfer interface for use with the disposable container. The transfer interface may be referred to as a sampling device.
The term “sterile manner” is used in the sense that transfer (e.g., fluid transfer) is performed aseptically. Accordingly, samples can be extracted or substances can be added to the disposable container in a process that is free from contaminants, such as microorganisms (e.g., bacteria, viruses or other exogenous microbes). Thus, during use of the transfer interface microorganisms (e.g., germs) or substances are prevented from getting from the outside into the interior of the container.
In some cases, extracting samples of material from the container in a sterile manner is carried out by ensuring one or more of the following:
Transfer elements may be repeatedly used as long as sterility is maintained. For example, testing has shown that some transfer elements remain sterile for up to 40 uses (e.g., 40 separate extractions of material from the container, 20 extractions and 20 insertions/additions, etc.).
At least one transfer element may include a sharp instrument, such as a needle. The needle may be hollow. More particularly, the transfer element may be implemented as a cannula, i.e., a flexible tube containing a sharp instrument (e.g. a trocar needle) at one end. The tube of the cannula may surround the inner or outer surface of the sharp instrument, thereby extending the effective length of the instrument by at least about 50% of its original length.
The transfer element may be used to extract or collect samples from the container, e.g. by extracting material, such as a fluid, contained within the container. Further, the transfer element can be used to introduce a material or substance into the container. The transfer elements of the transfer interface may collect samples from the container by connecting to a port of the container and extracting chemical, pharmaceutical, or biological material from the container via the port.
The locking mechanism may lock one of the transfer elements after the transfer element has collected a sample from the container.
The locking mechanism may be used to ensure that transfer elements that have already been used are not reused.
The transfer interface may further comprise a septum or membrane. The transfer elements may extend axially (i.e., substantially parallel to the long axis or lengthwise) along the interior of the transfer interface. In order to collect samples from the disposable container, the transfer elements may extend beyond the septum. In particular, the transfer elements may pierce or breach the septum in order to collect samples from the container. The transfer elements may retreat behind the septum when retracted. In particular, the transfer elements may extend and retract along the longitudinal axis of the transfer interface.
The septum may be used to ensure that the transfer elements remain sterile until use.
After one of the transfer elements retracts behind the septum, the septum may reseal, i.e., sterile extraction may again be possible using the same transfer element. A side of each transfer element may include a hole for fluid transfer. Accordingly, each one of the transfer elements may include a hole on its side, between the middle of the transfer element and a tip of the transfer element, where the tip extends into the container. For example, if a distance between the middle of the transfer element and the tip of the transfer element is X, the hole may be located about one fourth (or about one fifth) of X from the tip of the transfer element. The hole may be perpendicularly situated from the tip of the transfer element.
Locating the hole of the side of the transfer element and transferring fluid through the hole may have the effect of preventing the transfer element from coring the septum.
In addition, the transfer interface may include a guide for guiding transfer elements along the same path during each actuation and retraction. The transfer interface may include a guide for each transfer element.
The transfer interface may further comprise a plate covering the septum, the plate having holes or apertures corresponding to each of the transfer elements. In particular, a transfer element may pass through its corresponding hole as it extends and retreat within the hole when it retracts. Each of the holes may be covered by the septum, such that a part of the septum covering the hole is pierced or breached when the transfer element corresponding to the hole extends.
The plate may be located between the septum and the container when the transfer interface is connected to the at least one port. The plate may be made of metal, such as steel. According to one example, when an transfer element extracts or collects a sample from the disposable container, the transfer element passes through the septum and extends beyond the septum and the plate.
The at least one port may be a plurality of ports. The at least one part may include a sensor port for arranging a sensor on the container in order to sense at least one parameter of the content of the container. The sensor port may be or comprise a pH port for measuring a relative amount of hydrogen and/or hydroxide ions within the container. The sensor may be attached to a wall of the container. Additionally or alternatively, the sensor may access the content of the container via a tube protruding from the sensor port into the container.
The transfer interface may comprise a grip. The grip may have an ergonomic shape, such as a crescent shape. The grip may be arranged such that the tips of the crescent protrude from opposing sides of the transfer interface. The longitudinal axis of the grip may be substantially perpendicular to the longitudinal axis of the transfer interface. The grip may be detachable.
The transfer interface may further comprise a switch. Activation of the switch may cause one of the transfer elements to extend from the transfer interface (i.e. beyond the plate) to collect a sample from the container. Deactivation of the switch may cause the extended transfer element to retract into the transfer interface. The switch may be referred to as an actuator, and may be implemented as a button. In one example, activation of the switch may occur when a user presses a button on the transfer interface. Deactivation of the switch may occur when the user releases the button.
The locking mechanism may be triggered to lock the transfer element upon activation of the switch. For example, the user may activate the switch to cause the transfer element to extend from the transfer interface to collect material (e.g., a sample from the disposable container).
The user may toggle the switch to cause the activation of the switch, which in turn causes the extended transfer element to retract. The retracted transfer element is then locked. Accordingly, it will no longer be possible to cause the locked transfer element to extend, even upon a repeated activation of the switch. In particular, further (or repeated) activation of the switch may cause another one of the transfer elements to extend from the transfer interface to collect a sample from the container. In some cases, e.g. when all the transfer elements have already been used to collect samples from the container, further activation of the switch will not result in extension of an transfer element to collect samples from the container.
The transfer interface may be connectable to the at least one port via a fastening means, possibly designed to be non-removable. The fastening means may be implemented using a bayonet connection, a sanitary clamp, a screw system or a snapping system between the transfer interface and the port may be implemented via a fastening mechanism. The fastening mechanism may consist of a cylindrical male side with one or more radial pins, and a female receptor with matching L-shaped slots along with one or more biasing elements (e.g., springs) to keep to two parts locked together.
The transfer interface may comprise a body including the transfer elements. The transfer interface may further comprise a plurality of tubes extending away from the body and the transfer elements. In particular, there may be a tube corresponding to each one of the transfer elements. The tube may be attached to an end of its corresponding transfer element opposing the plate. In other words, the plate is on (or near) one end of the body of the transfer interface and the tube is attached to an transfer element at the other end. The ends are referred to with regard to the longitudinal axis of the transfer interface. Further, the tube may extend from the end of the transfer element away from the other components of the transfer interface.
The system may further comprise a housing. The container may be provided within the housing and the housing may support the container. The housing may be made from a rigid plastic (e.g., thermoplastic, rigid nylon or rigid PVC) or metal, such as stainless steel.
A mounting bracket may be attached to the housing. For example, components of the mounting bracket may be arranged in front of the at least one port so as to support the transfer interface when the transfer interface is connected to the port.
The housing may comprise an opening for accessing the container. In particular, the opening may be sized so that the ports of the container can be accessed and other parts of the container cannot be accessed. In other words, the housing may cover portions of the container other than the ports. The mounting bracket may be arranged in front of or over the opening.
According to another aspect, a method for configuring a system to transfer chemical, pharmaceutical, and/or biological material into or out of a container is provided. The method comprises providing a disposable container having at least one port. The at least one port is suitable for accessing the interior of the container. The method may further comprise connecting a transfer interface to the at least one port, the transfer interface comprising a plurality of transfer elements. The method further comprises extending one of the transfer elements from the transfer interface to the container to collect a sample from the container in a sterile manner. The method further comprises retracting the extended transfer element from the container by means of a biasing element corresponding to the extended transfer element. The method further comprises locking the transfer element such that the transfer element cannot be extended. In some cases, the locking step occurs after the retracting step. It is also possible that the locking and retracting steps are carried out at the same time or that the locking step is carried out while the retracting is ongoing.
According to yet another aspect, a use of a transfer interface for accessing the interior of a disposable container is provided. The transfer interface comprises a plurality of extendible transfer elements for collecting samples from the disposable container in a sterile manner. Each of the transfer elements has a corresponding biasing element for retracting the transfer element. The transfer interface further comprises a locking mechanism for locking one of the transfer elements such that the locked transfer element cannot be extended. In some cases, distinct locking mechanisms may be provided for locking each transfer element or one locking mechanism may be provided for locking all of the transfer elements. The transfer interface is to be connected to at least one port of the disposable container.
According to a further aspect, a system for transferring chemical, pharmaceutical, and/or biological material into or out of a container is provided. The system comprises a disposable container having at least one port for accessing the interior of the container. The port comprises at least one connecting protrusion extending parallel to the container, i.e., parallel to an exterior surface of the container. The system further comprises a transfer interface connectable to the port. The transfer interface comprises a plate. The transfer interface further comprises at least one connecting flange extending from the plate. The connecting flange may be arranged under the respective connecting protrusion to connect the transfer interface to the port such that when the transfer interface is connected to the port the plate is parallel to a surface of the container when the transfer interface is connected to the port.
The arrangement of the connecting flange and the connecting protrusion may have the effect of keeping (holding) the transfer interface in place when the transfer interface is connected to the port. In particular, the connecting flange and the connecting protrusion may hinder or prevent a deformation of the transfer interface, such that the plate remains parallel to a surface (i.e., an exterior surface) of the container.
The plate may be adapted to conform to the surface of the container. When the transfer interface is connected to the port, the plate may at least partly contact the surface of the container. In some cases, the plate may be substantially flush with the surface of the container when the transfer interface is connected to the port.
The arrangement of the connecting flange and the connecting protrusion (in addition to the shape of the plate) may also help ensure that the plate remains parallel to the surface of the container when the transfer interface is connected to the port.
Alternatively, the plate may be opposite an opening in the container, such that the plate does not contact the surface of the container. Accordingly, the arrangement of the connecting protrusion and the connecting flange may ensure a sterile connection between the transfer interface and the port by keeping the plate parallel to the surface of the container (e.g., the exterior surface extending away from the opening).
In some cases, the port further comprises at least one stopping protrusion extending away from the container. Accordingly, the connecting protrusion may extend inward (i.e., toward the center of the port) from the stopping protrusion. The system may further comprise at least one stopping flange extending from the transfer interface. The stopping flange may be located between the plate and an end of the transfer interface opposite the plate.
The stopping flange may abut the stopping protrusion when the transfer interface is connected to the port. The term “abut” may be understood in the sense of contact and/or support. In other words, the stopping flange may contact or support the stopping protrusion when the transfer interface is connected to the port.
The stopping flange may comprise an extending portion and a flat portion. The extending portion may extend radially outward from the flat portion. The stopping protrusion may comprise an extending part and a parallel part. The extending part may extend away from the container. The parallel part may extend in a direction parallel to the surface of the container. The parallel part may be parallel to the connecting protrusion. The parallel part may be spaced further away from the container than the connecting protrusion.
When the transfer interface is connected to the port, the extending portion may abut the parallel part of the stopping protrusion and the flat portion may abut the extending part of the stopping protrusion.
In the context of the present application, abut may be understood as contact or touch.
The arrangement of the stopping flange and the stopping protrusion may have the effect of keeping the plate parallel to the surface of the container, when the transfer interface is connected to the port, and hindering or preventing deformation of the transfer interface. In particular, the extending part may support the flat portion, even when pressure is exerted on the transfer interface, e.g., in view of the weight of the transfer interface (possibly combined with the weight of material to be transferred) and/or user handling of the transfer interface.
The combination of the arrangement of the stopping protrusion and the stopping flange with the arrangement of the connecting protrusion and the connecting flange may be particularly effective for keeping the plate parallel to the surface of the container and hindering deformation of the transfer interface.
The stopping protrusion may extend radially away from the container. In some cases, at least part of a circumference of the stopping protrusion is not covered by the connecting protrusion. The stopping protrusion may have the form of a hollow cylinder. The parallel part of the stopping protrusion may be further from the surface of the container than any other part of the stopping protrusion.
The stopping protrusion may be a right circular cylinder. Alternatively, the stopping protrusion may be an elliptic cylinder.
The stopping flange may extend radially outward from the transfer interface. The stopping flange may cover the entire circumference of the transfer interface. In other words, the stopping flange may form a complete ring extending from the transfer interface.
The connecting flange may extend radially outward from the plate. In some cases, at least part of a circumference of the transfer interface is not covered by the connecting flange. The connecting flange may be in contact with the surface of the container when the transfer interface is connected to the port.
In some cases, an O-ring may be located between the connecting flange and the stopping flange. Accordingly, the system may further comprise two internal flanges located between the connecting flange and the stopping flange. Each internal flange may extend radially outward from the transfer interface. Each internal flange may cover the entire circumference of the transfer interface. For example, when the transfer interface is shaped like a right circular cylinder, each internal flange may form a complete circle extending radially from the surface of the cylinder.
The O-ring may be located between the two internal flanges. The O-ring may be supported by the two internal flanges.
The port may comprise a port flange. The port flange may be attached to the disposable container. In particular, the port flange may be glued or welded to the disposable container.
The O-ring may be colored such that the O-ring is visible from outside the transfer interface. For example, the O-ring may be brightly colored so that a user can see that the O-ring is correctly positioned.
The connecting flange and the connecting protrusion may be parts of a bayonet connection to connect the transfer interface to the port.
The stopping protrusion may stop progress of the transfer interface toward the container. The stopping protrusion may also help prevent deformation of the transfer interface and keep the plate parallel to the surface of the container, as described above.
There may be two connecting flanges, a first gap, and a second gap. The two connecting flanges may extend around different parts of the circumference of the plate. The two connecting flanges may be diametrically opposed. The two gaps may be diametrically opposed.
The system may further comprise a holder for supporting the transfer interface when the transfer interface is connected to the port. The holder may be attachable to one or more of the following: the transfer interface, the port.
The holder may be made of metal, e.g. aluminum. Alternatively, the holder may be made from a plastic, e.g., a flexible plastic and/or a thermoplastic.
The holder may comprise an attachment for the transfer interface in the shape of a ring or a horseshoe.
The holder may comprise lateral extensions that contact the surface of the container when the transfer interface is connected to the port. The lateral extensions may support the transfer interface via the attachment for the transfer interface. In other words, the weight of the transfer interface may be transferred through the attachment and distributed to the container via the lateral extensions. The lateral extensions may be referred to as wings.
The holder may help keep the plate parallel to the surface of the container when the transfer interface is connected to the port. Moreover, the holder may hinder or prevent deformation of the transfer interface, e.g., resulting from the weight of the transfer interface or use of the transfer interface.
The combination of two arrangements and the holder may be very effective at keeping the plate parallel to the surface of the container and hindering deformation of the transfer interface. In particular, the combination of the arrangement of the connecting flange and the connecting protrusion, the arrangement of the stopping flange and the stopping protrusion, as well as the holder may work together to hinder or prevent deformation of the transfer interface and ensure that the plate remains parallel to the surface of the container when the transfer interface is connected to the port. The combination may keep the plate parallel to the surface of the container in spite of the weight of the transfer interface and/or continued use of the transfer interface.
According to an additional aspect, a system for transferring chemical, pharmaceutical, and/or biological material into or out of a container, such as a bioreactor is provided. The system comprises a disposable container having at least one port for accessing the interior of the container. The port comprises a supporting protrusion. The system further comprises a transfer interface connectable to the port.
The transfer interface comprises a plate. The supporting protrusion supports the transfer interface and extends from the surface of the container along at least 25% of the length of the transfer interface, such that the plate is parallel to (e.g., flush with) a surface of the container when the transfer interface is connected to the port.
The system may further comprise a triclamp for connecting the transfer interface to the port. The triclamp may be one of the following:
According to another aspect, a method for configuring a system to transfer chemical, pharmaceutical, and/or biological material into or out of a container, such as a bioreactor, is provided. The method may comprise providing a disposable container having at least one port. The at least one port is suitable for accessing the interior of the container. The port comprises at least one connecting protrusion extending parallel to the container. The method further comprises connecting a transfer interface to the port. The transfer interface comprises a plate. The plate may be adapted to conform to a surface of the container. At least one connecting flange extends from the plate. The connecting may comprise arranging the connecting flange under the connecting protrusion such that the plate is parallel to (e.g., flush with) the surface of the container. The connecting may result in a sterile connection between the transfer interface and the port.
When there are multiple connecting flanges and connecting protrusions, the connecting may comprise arranging the respective connecting flange under the respective connecting protrusion.
In the following text, a detailed description of examples will be given with reference to the drawings. It should be understood that various modifications to the examples may be made. In particular, one or more elements of one example may be combined and used in other examples to form new examples.
The port 106 may be connected to the container 102. In particular, the port 106 may be adhered or welded to the container 102.
A transfer interface 110 can be connected to the at least one port 106. The transfer interface 110 may be used to collect samples from the disposable container 102 in a sterile manner. In particular, components of the transfer interface 110 and the disposable container 102 may be pre-sterilized before use. The sterilization/pre-sterilization may be carried out via gamma irradiation, steam, electron beam processing (also referred to as electron irradiation) and/or aggressive chemicals.
Some sterilization methods may not be suitable depending on the composition of the container 102 or the transfer interface 110.
It may be desirable to collect the samples in such a way that they reflect the content of the container 102 as a whole. In other words, the content of the collected samples should be homogenous with the content of the container 102, and not heterogeneous with the content of the container 102.
The disposable container 102 may have at least one port 106 for accessing the material contained within the container 102. The container 102 may be a flexible, single-use bag, e.g., a plastic film. The container 102 could also be semi-rigid, or rigid. For example, the container 102 may be made from a rigid thermoplastic. Alternatively, the container 102 may be made from metal.
The disposable container 102 may be supported by the housing 104. The housing 104 may be made from metal, such as stainless steel. Other materials are also possible. The housing 104 may be reusable. The opening 108 in the housing 104 may be referred to as a window. The opening 108 may be large enough so that the port 106 can be accessed but small enough so as to minimize exposure of the container 102. Further, the size of the opening 108 may be minimized in order to maximize the support of the container 102 provided by the housing 104.
The transfer interface 110 may be connected to the port 106 in such a way that the transfer interface 110 cannot be disconnected, e.g., in order to preserve the sterility of the container 102. In other words, the transfer interface 110 may be permanently connected to the container 102.
Alternatively, the transfer interface 110 may be connected to the container 102 and disconnected from the container 102. Thus, the transfer interface 110 may be detachably connected to the container 102. The transfer interface 110 may be disposable or reusable after sterilization. Disposing of the transfer interface 110 after use, e.g., after each of the transfer elements have been used, may have the advantage of making use (e.g., sterilization) of the transfer interface 110 easier.
The samples or specimens collected via the transfer interface 110 may be fluid. The transfer interface 110 may also be used to insert or inject chemical, pharmaceutical, or biological material into the container 102.
Once the transfer interface 110 is detachably connected to the port 106, material may be removed from the container 102 without exposing the material to the atmosphere. In particular, a seal may be established between the transfer interface 110 and the disposable container 102. The seal may be established via a bayonet connection between the transfer interface 110 and the port 106. The seal may facilitate extraction of material from the container 102 in a sterile manner. The seal may be facilitated via an O-ring 207, as shown in
The bayonet connection may provide a particularly secure fit and help ensure sterility (e.g., ensure that undesired microorganisms do not enter the container 102) despite repeated use of the transfer interface 110.
The plate 201 may cover a septum. At least one connecting flange 204 may project out from the transfer interface 110 on the plane of the plate 201. For example, two connecting flanges 204 may project out from the transfer interface 110. The connecting flanges 204 may be diametrically opposed. In particular, the transfer interface 110 may have a substantially cylindrical shape. The plate 201 may be at one end of the transfer interface 110. Two internal flanges 205 may be located between the plate and the other end of the transfer interface 110.
There may be another O-ring (not shown) between the plate 201 and the connecting flange 204, to form a seal between the plate 201 and the connecting flange 204.
Distribution tubes 401 (see
The O-ring 207 may be referred to as a gasket or a sealing ring. The O-ring 207 may be colored. In particular, the O-ring 207 may be brightly colored and visible through the transfer interface 110. Coloring of the O-ring 207 may make it possible to ensure that the O-ring 207 is present and in a correct position. The O-ring 207 may be made from synthetic or natural rubber, thermoplastic, or another elastic or pliable material.
The connecting flange 204 may be rotated underneath a corresponding protrusion (e.g., a connecting protrusion 1201, see
In some cases, upon connection of the transfer interface 110 to the port 106, the plate 201 may be substantially flush the corresponding surface of the container 102. In other cases, the plate 201 may be arranged opposite an opening in the container 102.
A stopping flange 208 may press against or be substantially flush with the port 106 when the transfer interface 110 is connected to the container 102. In particular, the stopping flange 208 may extend to a part of the port 106 to keep the transfer interface 110 parallel to the surface of the container 102 and prevent potential deformation of the walls of the port 106 (for example, to maintain the port 106 in a cylindrical shape). Such deformation may lead to a leak. For example, the stopping flange 208 may contact a stopping protrusion 1205, as shown in
A containing tube 209 may contain one of the extendible transfer elements. The transfer element may be used for collecting samples from the disposable container 102. The transfer element may pass through the hole 203 in order to collect the sample and then retract behind the plate 201 once the sample has been retrieved. A biasing element may bring about retraction of the transfer element. In particular, the biasing element may apply a biasing force along the longitudinal axis of the transfer interface 110 to pull the transfer element away from the port 106.
The transfer element may comprise a sharp, hollow needle. In particular, the transfer element may be a cannula. The septum may be a soft, flexible membrane made from organic or inorganic material. For example, the septum may be made from an elastomer, such as a silicone elastomer, a fluoro elastomer, or a perfluoropolyether elastomer. In particular, the septum may be made from platinum-cured silicone.
The septum may have a cylindrical shape with a diameter of about 12.5-13.5 mm (e.g., 12.9 mm) and a height of about 2-3 mm (e.g., 2.5 mm).
An operating element or switch may cause the transfer element to extend from the transfer interface. The extended transfer element 351 may extend past (or beyond) the plate 201. During extension, the transfer element may pierce the septum behind the plate 201.
The switch may be activated when pressed by a user. In particular, the switch may be implemented as the button or a toggle switch. At S305, the extended transfer element 351 may retract, e.g., because the switch has been deactivated. When implemented as a button, the switch may be deactivated when the user releases the button. The extended transfer element 351 may retract into the containing tube 209. The transfer element may have a corresponding biasing element and retraction of the extended transfer element 351 may be effected via the biasing element.
The biasing element may be implemented as a spring or as another device capable of exerting a biasing force.
At S305 the locking mechanism 353 locks the transfer element such that the transfer element cannot be extended. Accordingly, even if the switch is activated, the transfer element will not be extended. However, activation of the switch may cause the extension of another transfer element of the transfer interface 110, different from the transfer element that was extended. Retraction of the transfer element may be caused by deactivation of the switch. In particular, deactivation of the switch may cause the extended transfer element 351 to retreat into the body of the transfer interface 110, as shown at S305.
The locking mechanism 353 may be triggered to lock the transfer element upon deactivation of the switch. Deactivation of the switch may be effected by the user releasing the button or when the user engages the switch a second time (e.g., press the button once for activation and a second time for deactivation). Alternatively, the switch may be manually toggled (e.g., similar to a light switch being switched off) in order to effect deactivation of the switch.
The locking mechanism 353 may also be triggered automatically. For example, the extended transfer element 351 may retract after a certain amount of time rather than upon user-triggered deactivation of the switch. The locking mechanism 353 may then be triggered by the retraction of the extended transfer element 351.
The locking mechanism 353 may help ensure that samples can be extracted or collected from the container 102 in a sterile manner, particularly by preventing an transfer element from being used multiple times.
The distribution tubes 401 extend from the body of the transfer interface 110. The distribution tubes 401 extend in an axial direction. The distribution tubes 401 may carry samples collected from the container 102 via the transfer elements away from the container 102. The samples may be fluid.
The mounting bracket 501 may be attachable to the transfer interface 110. The mounting bracket 501 may fit around a body of the transfer interface 110.
The mounting bracket 501 may be attached to the housing around the opening 108. Further, the mounting bracket 501 may center the transfer interface at the port 106.
Use of the mounting bracket 501 may prevent the transfer interface 110 from being prematurely detached from or misaligned with the port 106 (as shown in
The multi-use transfer interface 710 may be used to collect samples from or insert substances into the container, as discussed in connection with the transfer interface 110 and the container 102.
The triclamp 712 may include two clamp prongs or members pivotably connected to one another at a hinge 713. The triclamp 712 may include a lock and a fastening element 714. The lock may be referred to as a triclover and can be removable or permanently locked.
Twisting of the fastening element 714 may cause the prongs of the triclamp 712 to close around the transfer interface 710, thereby securing it to the port 716. The triclamp 712 may create a compressing clamping force to join the transfer interface 710 to the port 716. The triclamp 712 may include an elastomeric seal compressed or sandwiched between the two prongs, thereby creating a connection that is air tight and that can withstand elevated pressure conditions. The triclamp 712 may hold the transfer interface 710 in sealed engagement with the port 716.
Advantages of the triclamp 712 (or a similar element) connection as shown in
The triclamp 712 could also be used in the context of a single-use container, e.g. the container 102. However, the triclamp 712 requires multiple parts. Accordingly, manufacturing and/or assembling the clamp may be complicated. Further, the fastening element 714 may present problems with regard to the sterility of the container 102. In particular, it might be preferable to use a permanent clamp that cannot be unfastened in order to ensure that the container 102 is kept sterile. Also, the triclamp 712 may be bulky and/or heavy and difficult to assemble for a single user or operator
The multi-use transfer interface 710 may be used to collect samples from the container. It may be desirable to collect the samples in such a way that they reflect the content of the container as a whole. In other words, the content of the collected samples should be homogenous with the content of the container. For a 1½ (3.81 cm) triclamp size, the classical distance between triclamp connection interface and the container wall (or surface) is greater than 20 mm, which may create dead volume in the port 716. In particular, it may be desirable to reduce the distance between a transfer interface (e.g., the transfer interface 710) and a surface (or wall) of the container (e.g., the container 102) to less than 20 mm, more specifically, less than 10 mm or less than 5 mm.
Accordingly, it may be difficult to connect the transfer interface 110 to the disposable container 102 such that the transfer interface 110 is parallel to a wall or surface of the disposable container 102.
Moreover, it may be difficult to connect the transfer interface 110 to the disposable container 102 such that the plate 201 at least partly contacts the surface of the container and there is less than a specified distance between the plate 201 and the surface of the container. In particular, the specified distance between the surface (i.e. exterior surface, outer surface or wall) of the disposable container 102 and the transfer interface 110 connected to the port 106 may be one to five millimeters. Accordingly, it may be desirable that the plate 201 is substantially flush with the surface of the container 102, such that that no part of the plate 201 is more than five millimeters from surface of the container 102 when the transfer interface 110 is connected to the port 106.
As noted above, it may be desirable that all samples extracted from the container 102 be representative of the entire contents of the container 102, i.e., all samples are homogeneous. Maintaining a minimum distance (i.e., the specified distance) between the transfer interface 110 and the container 102 may help ensure that a sample extracted from the container 102 is homogenous with the contents of the container 102. If the transfer interface 110 is not substantially flush with the surface (e.g., a wall) of the container 102, e.g., the distance between an end of the transfer interface 110 and the wall of the container 102 is greater than the specified distance, this may result in extraction of a sample that differs from the contents of the container 102 as a whole. In particular, more than the specified distance between the transfer interface and the wall of the container 102 may result in extraction of heterogeneous samples. Such heterogeneous samples may not have the same properties as the contents of the container 102 as a whole, which may limit their usefulness.
The compromised connection may result in deformation of the port 106 and/or the transfer interface 110. In the case of the compromised connection, at least part of the stopping flange 208 might no longer contact the port 106. Such a compromised connection may result in leakage from the container 102 and/or loss of sterility.
The problem shown in
In particular, the port 106 may be made of flexible or bendable material. For example, the port 106 may be made from thermoplastics welded onto the container 102 (e.g., polyethylene) rather than a more rigid substance, such as rigid plastic (e.g., rigid PVC) or metal.
Further, the length and/or the weight of the transfer interface 110 may be substantially greater than the length of the port 106 which extends from the container 102. Moreover, extraction of samples from the container 102 may put stress on the connection between the port 106 and the transfer interface 110. Accordingly, the port 106 may be deformed, such that there is a gap 901 between the stopping flange 208 and the port 106, as shown. The gap 901 between the stopping flange 208 and the port 106 may be created due to the weight of the transfer interface 110 and/or use of the transfer interface 110. The gap 901 between the stopping flange 208 and the port 106 may form even after the transfer interface 110 has been permanently connected to the port 106, e.g., via the bayonet connection, triclamp connection with non-removable triclover, another kind of permanent mechanical connection and/or an adhesive such as glue. However, even the permanent connection may not be sufficient to prevent the gap 901 from forming.
When the gap 901 is present, the plate 201 is not parallel to the surface of the container 102.
When connected to the port 106, the plate 201 may be aligned with a flange of the port 106 (e.g., the plate 201 may be aligned with the port flange 1203). The plate may be parallel to an interior part of the port 106. Accordingly, the plate 201 may be substantially flush with the surface (i.e., wall) of the container 102. Alternatively, the plate 201 may be opposite an opening in the surface of the container 102 and substantially parallel to a portion of the surface surrounding the opening.
In order to effect connection of the transfer interface 110 to the port 106, the bayonet connection may be used. In particular, the transfer interface 110 may be pushed into the port 106 such that at least a portion of the transfer interface 110 is contained within the port. The transfer interface 110 is then arranged so that the connecting flange 204 is under the respective connecting protrusion 1201. The arranging may be effected by twisting the transfer interface 110 in order to lock the transfer interface 110 in place.
The plate 201 may contact (e.g., the plate 201 may be substantially flush with) the surface of the container 102. Accordingly, when connected, the plate 201 may be substantially flush with the surface of the flexible wall of the container 102. In particular, there may be no more than the specified distance between the wall of the container 102 and the plate 201. Further, it is possible that the plate 201 is slightly convex, so as to effect a tighter connection between the transfer interface 110 and the container 102. Thus, when pushed together there may be a plurality of points of contact (e.g., many) between the plate 201 and the surface of the container 102, such that no more than the specified distance exists between any point on the plate 201 and the surface of the container 102. It is also possible that the surface of the container 201 is elastic, e.g. compressible silicone, such that it resists a distorting influence or deforming force and returns to its original shape when the force is removed.
Further, a surface of the container 102 accessible through the port 106 (i.e., opposite the port 106) may differ from the rest of the surface of the container 102. For example, the surface accessible through the port 106 may be more flexible or compressible than the rest of the container 102.
Rather than being in contact with the surface of the container 102, the plate 201 may be opposite an opening in the container 102. In this case, if the surface of the container 201 were contiguous (i.e., the opening did not exist), the plate 201 would contact the surface of the container 201 when the transfer interface 110 is connected to the port 106. Thus, when the transfer interface 110 is connected, the plate 201 may be substantially level with the surface of the container surrounding the opening.
In either case (i.e., with or without an opening in the container 201), the plate 201 may be parallel to the surface of the container 201.
The O-ring 207 may be colored such that it is visible when the transfer interface 110 is connected to the port 106, as shown in
The cut-out visible in
The supporting protrusion 1105 may provide additional support or guidance for the transfer interface 1100, particularly in view of its additional length (i.e., the additional distance that the supporting protrusion 1105 extends from the container 102 in comparison to the distance that the port 716 extends from the container described in the context of
In particular, the design shown in
Accordingly, the configuration shown in
The configuration shown in
In
In addition, the port 106 includes a port flange 1203. The configuration of
The plate 201 may be a relatively inflexible material (e.g. metal, such as aluminum) and the surface of the container 102 may be a flexible material (e.g., a flexible plastic such as flexible PVC). In particular, when the connecting flange 204 is underneath the connecting protrusion 1201 the surface of the container 102 may exert a biasing force on the plate 201. In other words, the surface of the container 102 pushes against the plate 201.
Similar to the transfer interface 110, the transfer interface 1210 includes a connecting flange 204 extending from the plate 201. There may be two diametrically opposed connecting flanges 204, e.g., as shown in
Accordingly, to effect connection of the transfer interface 1210 to the port 106, the transfer interface 1210 may be pushed into the port 106. For example, the transfer interface 1210 may be pushed against the surface of the container 102 such that the plate 201 is substantially flush with the surface of the container. The transfer interface 1210 may then be twisted so that the connecting flange 204 is arranged under the connecting protrusion 1201. This arrangement may cause the plate 201 to contact the surface of the container 102, or may cause the plate 201 to cover the opening in the surface of the container 102 accessible through the port 106. In particular, the plate 201 may be kept parallel to the surface of the container via the arrangement of the connecting flange 204 under the connecting protrusion 1201.
Arranging the connecting flange 204 under the connecting protrusion 1201 may involve pushing the transfer interface 1210 against the surface of the container 102.
The arrangement of the connecting flange 204 under the connecting protrusion 1201 may ensure that a pressing force is applied against the surface of the container 102 by the plate 201 so as to keep the plate 201 substantially flush with the surface of the container 102.
Further, the plate 201 may be adapted to conform to the surface of the container 102. For example, the plate may be slightly convex so as to exert a greater pressing force on the surface of the container 102. The surface of the container accessible through the port 106 may be different from the rest of the surface of the container 102. In particular, the surface of the container 102 accessible through the port 106 may be silicone whereas the surface of the rest of the container 102 may be nylon or polyethylene. Alternatively, the entire surface of the container 102 may be made of silicone or a flexible plastic material.
It may be sufficient that the plate at least partly contacts the surface of the container 102. In particular, it may be sufficient if there is no more than the specified distance separating portions of the plate 201 from the surface of the container 102. Alternatively, the entire plate may be in contact with the surface of the container 102. In some cases, it may also be desirable to reduce the distance between any portion of the plate 201 and the surface of the container 102 to a distance of less than the specified distance, i.e., such that the plate 201 is substantially flush with the port 106.
As noted above, the specified distance may be one to five millimeters. In particular, the specified distance may be three millimeters.
The O-ring 207 and the internal flanges 205 may help ensure that there is a seal between the transfer interface and the container 102 and that any extracted sample from the container is homogeneous with the entire content of the container 102.
The configuration of
As shown in more detail in
When the transfer interface 1210 is connected to the port 106, the stopping protrusion 1205 may contact the stopping flange 1208. More specifically, the stopping protrusion 1205 may include an extending part 1207 that contacts the flat portion 1209 of the stopping flange 1208.
The extending portion 1211 of the stopping flange 1208 may contact a parallel part 1213 of the stopping protrusion 1205. Accordingly, the extending part 1207 of the stopping protrusion 1205 may extend away from the container 102. The parallel part 1213 of the stopping protrusion 1205 may extend in a direction substantially parallel to the surface of the container 102. The parallel part 1213 may be substantially parallel to the connecting protrusion 1201 and the extending portion 1211.
Accordingly, when the transfer interface 1210 is connected to the port 106, the contact between the stopping flange 1208 and the stopping protrusion 1205 may prevent the connection between the transfer interface 1210 and the port 106 from being compromised, especially because of the weight of the transfer interface 1210 and/or use of the transfer interface 1210. In particular, the step-configuration of the stopping flange 1208, shown in
More particularly, when the transfer interface 1210 is connected to the port 106, the extending portion 1211 may contact the parallel part 1213, as shown in
When the transfer interface 1210 is connected to the port 106, the extending portion 1211 abuts the parallel part 1213 of the stopping protrusion 1205. Further, the flat portion 1209 abuts the extending part 1207 of the stopping protrusion 1205. The abutment or contact makes it possible for the stopping protrusion 1205 to provide further support for the transfer interface 1210.
The stopping protrusion 1205 may be substantially cylindrical. In particular, the stopping protrusion 1205 may form a hollow elliptic or circular cylinder. The connecting protrusion 1201 may extend radially inward from the stopping protrusion 1205.
The connecting protrusion 1201 may cover only a part of the inner circumference of the stopping protrusion 1205. For example, a quarter of the inner circumference of the stopping protrusion 1205 may be covered by the connecting protrusion 1201. A second quarter of the stopping protrusion 1205 may be covered by a gap, followed by another portion of the stopping protrusion 1201 followed by another gap. Accordingly, about half of the circumference of the stopping protrusion 1205 may be covered by the connecting protrusion 1201.
In the context of the present application, the term “circumference” does not necessarily imply a circular shape. For example, the shape could be elliptical or substantially circular.
Similar to the stopping flange 1208 with respect to the transfer interface 110, the stopping flange 1208 may extend radially outward from the transfer interface 1210. The stopping flange 1208 may cover the entire circumference of the transfer interface 1210. In other words, the stopping flange 1208 may extend radially outward along the entire circumference of the transfer interface 1210.
The at least one connecting flange 204 may extend radially outward from the plate 201. At least part of a circumference of the plate might not be covered by the connecting flange 204. In other words, the connecting flange 204 might not extend outward from portions of the plate 201. The pattern of portions of the connecting protrusion 1201 and gaps along the stopping protrusion 1205 may mirror the connecting flange 204 and gaps between the connecting flange 204 along the circumference of the plate 201. In particular, the may be two diametrically opposed connecting flanges 204 mirrored by two connecting protrusions 1201.
Accordingly, substantially half of the circumference of the transfer interface may be covered by the at least one connecting flange 204. In other words, the connecting flange 204 may extend radially outward from about half of the circumference of the transfer interface 1210. Along the other half of the circumference of the transfer interface 1210 there may be gaps between the at least one connecting flange 204.
The connecting flange 204 may extend radially outward from the transfer interface at the location of the plate 201. The connecting flange 204 may be in contact with the surface of the container 102 when the transfer interface 1210 is connected to the port 106. Alternatively, the connecting flange 205 may hold the plate 201 over an opening in the surface of the container 102, such that the plate 201 is substantially level with a portion of the surface surrounding the opening. The transfer interface 1210 may be permanently connected to the port 106, e.g., through use of an adhesive. The permanent connection between the transfer interface 1210 and the port 106 may help ensure stability.
The O-ring 207 may be located between the connecting flange 204 and the stopping flange 1208. More particularly, the O-ring 207 may be located between two internal flanges 205. The two internal flanges 205 may be located between the stopping flange 1208 and the connecting flange 204. Each internal flange 205 may extend radially outward from the transfer interface 1210. Each internal flange 205 may cover the entire circumference of the transfer interface 1210 or approximately the entire circumference of the transfer interface 1210. For example, each internal flange 205 may cover enough of the circumference of the transfer interface 1210 in order to support the O-ring 207. The O-ring 207 may be located between the two internal flanges 205.
The port flange 1203 may extend radially outward from the port 106. The port flange 1203 may help provide stability and help ensure that the plate 201 remains parallel to the surface of the container 102. In addition, along with the step configuration discussed above, the port flange 1203 may help ensure that the connection between the transfer interface 1210 and the port 106 is not compromised, and that the transfer interface 1210 is not deformed through use or via its own weight or via the weight of samples extracted from the container 102.
The O-ring 207 may be colored such that the O-ring 207 is visible from outside the transfer interface 1210. Coloring of the O-ring may facilitate correct insertion of the transfer interface 1210 into the port 106. In particular, if the colored O-ring 207 appears to be straight and symmetrical when the transfer interface 1210 is inserted into the port 106, then it may be assumed that the transfer interface 1210 has been inserted correctly. If the O-ring 207 is visibly crooked or not symmetrical, then it may be assumed that the transfer interface 1210 has not been correctly inserted into the port 106.
The connecting flange 204 and the connecting protrusion 1201 may be parts of the bayonet connection used to connect the transfer interface 1210 to the port 106.
The stopping protrusion 1205 may stop further progress of the transfer interface 1210 toward the container 102. In addition, the stopping protrusion 1205 may impart stability to the transfer interface 1210 and may help prevent the deformation of the transfer interface 1210 shown in
There may be a plurality of connecting flanges 204. In particular, there may be two connecting flanges 204. The two connecting flanges 204 may be separated by a first gap and a second gap. Each of the two connecting flanges 204 may extend around approximately a quarter of the circumference of the plate 201. The two portions may be diametrically opposed. Each of the two gaps may also extend around approximately a quarter of the circumference of the plate. The two gaps may be diametrically opposed.
The transfer interface 1210 and the configuration of
Thus, via the stopping protrusion 1205 and the stopping flange 1280, it may be possible to provide a way to prevent deformation of the transfer interface (e.g., the transfer interface 1100 or the transfer interface 110) without including a port on the container 102 that extends any further from the container 102 than the port 106 (e.g., a standard bioreactor port). In particular, it may be desirable to provide the port 106 such that the distance which the port 106 extends from the container 102 is minimized.
The transfer interface 1210 might also be advantageous because of its relatively low weight and simplicity. In particular, the triclamp 1103 may have at least four parts including the gasket 1107, a fastening element similar to the fastening element 714, and two prongs to encompass the transfer element 1100 and the supporting protrusion 1105. Accordingly, while the triclamp 1103 may limit potential deformation of the transfer interface 1100 and keep the transfer interface 1100 substantially flush with the surface of the container, particularly in view of the extended port 1101, the transfer interface 1210 in combination with the port 106 may be even more advantageous because the transfer interface 1210 is a single piece and potential deformation (e.g., resulting from repeated use) can be hindered without a non-standard port extending further than usual from the container 102 (as discussed in the context of
When connected, the transfer interface 110 is parallel to (e.g., substantially flush with) the surface of the container 102. Port flanges 1203 are shown inside the housing 104. As discussed above, the port flanges 1203 may stabilize the port and the transfer interface 1210. There may be multiple port flanges 1203 or just one port flange 1203. The transfer interface 110 may contact the port 106 at a junction 1301.
The weight of the transfer interface 110 may exert pressure on the port 106, particularly at the junction 1301.
In some cases the weight of the transfer interface 110 may be sufficient to compromise the connection between the transfer interface 110 and the port 106, particularly as shown in
In addition or alternatively, another approach may be used to prevent deformation of the transfer interface 110 as discussed above and as shown in
The holder 1401 may support the transfer interface 110 when the transfer interface 110 is connected to the port 106. Accordingly, the holder 1401 may prevent deformation of the transfer interface 110. In addition, the holder 1401 may prevent damage to the container 102. In particular, when the connection between the transfer interface 110 and the port 106 is compromised or the transfer interface 110 is deformed, compression or pressure may be brought to bear on the surface of the container 102, thereby damaging the surface of the container 102.
The holder 1401 may be attachable to the transfer interface 110 and/or the port 106.
For example, the holder 1401 may include an attachment 1403 for the transfer interface 110. The attachment 1403 may have the shape of a ring, as shown in
The holder 1401 may also include lateral extensions 1405. The lateral extensions 1405 may contact the housing 104 or the surface of the container 102 when the transfer interface 110 is connected to the port 106. The lateral extensions 1405 may be referred to as wings or supporting elements. The lateral extensions 1405 may support the transfer interface via the attachment 1403. In particular, the lateral extensions 1405 may help distribute the weight of the transfer interface 110 across the surface of the container 102.
The arrows shown in
The holder 1401 may be plastic or metal. The holder 1401 can be designed with or without the lateral protrusions 1405. The design of the lateral protrusions 1405 may be adapted to the container 102. For example, different lateral protrusions 1405 may be used depending on whether the container 102 is within the housing 104 and the lateral protrusions 1405 will rest against the housing 104 or the container 102 is without the housing 104.
In addition, if the housing 104 is not present, the shape of the lateral protrusions 1405 may differ depending on the flexibility or rigidity of the surface of the container 102.
The installation of the holder 1401 onto the transfer interface 110 may be quick and easy. In particular, the holder 1401 may be attached or clipped to the transfer interface 110 and the port 106 after the transfer interface 110 has been connected to the port 106. Accordingly, the holder 1401 may be attached at virtually any point of the transfer interface rotated until an opening 1407 is vertically aligned with a vertical plane of the container 102 (i.e., the vertical plane of the contents of the container 102) and then slid along the longitudinal axis of the transfer interface 110 toward the surface of the container 102 until being fitted into place, as discussed in the context of
The holder 1401 may be used in combination with the transfer interface 110 or with the transfer interface 1210 discussed in connection with
It should be noted that the lateral extensions 1405 are optional. In other words, the holder 1401 may be used without the lateral extensions 1405. In particular, while the lateral extensions 1405 may help distribute the weight of the transfer interface 110 across the housing 104, the holder 1401 may be sufficient to support the transfer interface 110 without the lateral extensions 1405.
The lateral extensions may be positioned against the housing 104, as shown in
The holder 1801 includes lateral extensions 1805. The lateral extensions 1805 may be similar or identical to the lateral extensions 1405. In addition, the holder 1801 includes an attachment 1803. Rather than the ring shape of the attachment 1403, the attachment 1803 has a horseshoe shape. Accordingly, it may be possible to attach the holder 1801 to the transfer interface 110 more easily via the attachment 1803 in comparison to the attachment 1403. In particular, it might not be necessary to detach the distribution tubes 401 or other components of the transfer interface 110 in order to attach the holder 1801.
| Number | Date | Country | Kind |
|---|---|---|---|
| 17290123 | Sep 2017 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2018/065581 | 6/13/2018 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2019/057354 | 3/28/2019 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 6032543 | Arthun | Mar 2000 | A |
| 7282176 | Glachet | Oct 2007 | B2 |
| 8539988 | Guedon | Sep 2013 | B2 |
| 9120585 | Olivier | Sep 2015 | B2 |
| 9920841 | Saragosa | Mar 2018 | B2 |
| 20040005259 | Sacca | Jan 2004 | A1 |
| 20140103077 | Zumbrum | Apr 2014 | A1 |
| 20150345689 | Selker et al. | Dec 2015 | A1 |
| 20160298068 | Schumacher et al. | Oct 2016 | A1 |
| Number | Date | Country |
|---|---|---|
| 199 06 514 | Aug 1999 | DE |
| 10 2006 005533 | Aug 2007 | DE |
| 2 738 399 | Jun 2014 | EP |
| 2 829 598 | Jan 2015 | EP |
| WO 0066706 | Nov 2000 | WO |
| WO 2011071897 | Jun 2011 | WO |
| Entry |
|---|
| English translation of DE 19906514 , generated 2022. |
| International Search Report and Written Opinion, dated Nov. 26, 2018, from PCT Application No. PCT/EP2018/065581, 22 pages. |
| Extended European Search Report, dated Jul. 9, 2018, from EP Patent Application No. 17290123.3, 15 pages. |
| Number | Date | Country | |
|---|---|---|---|
| 20200206744 A1 | Jul 2020 | US |
