Apparatus and method for aseptically transferring fluid from a fluid container

Abstract

A sterile closure assembly for a fluid container includes a cap connectable to an opening of the fluid container and a fluid dispenser connectable to an outer surface of the housing of the cap. The fluid dispenser includes a body and a fluid line disposed within the body, a housing disposed about the body, and an insert connectable to a second end of the body. The body includes an aperture closer to the second end, the aperture connected to the fluid line and configured to be in fluid communication with the fluid container when the fluid dispenser is connected to the cap. The fluid dispenser is configured such that a downwardly directed force toward the fluid container fits the insert into a support of a cavity and disconnects the insert from the body of the fluid dispenser to seal the fluid container.

Description

[0001] priority

[0002] This application claims priority to U.S. Provisional Application No. 63 / 303,016, filed January 25, 2022, the disclosure of which is incorporated herein by reference. Technical Field

[0003] This disclosure generally relates to a system for aseptically delivering fluid from a fluid container. More specifically, this disclosure relates to an aseptic sealing assembly comprising a cap for aseptically delivering fluid from a fluid container and a fluid dispensing assembly, method, and components. Background Technology

[0004] Chemical and / or biological processes may utilize or produce process materials stored in storage containers, such as bioprocess bags, bottles, and the like with rigid connection systems, containing pharmaceuticals or biological fluids, acids, solvents, bases, photoresists, dopants, inorganic solutions, organic solutions, or the like. Process materials may require freezing or otherwise maintaining cryogenic temperatures within the storage container. When using such fluids, the storage container must appropriately contain the chemicals during storage, transportation, and ultimately during its manufacturing process. Currently, methods and fluid transfer assemblies are used to transfer fluids to or from storage containers with rigid connection systems; however, the sterility of these systems cannot be guaranteed. Summary of the Invention

[0005] This disclosure generally relates to a system for aseptically delivering fluid from a fluid container. More specifically, this disclosure relates to an aseptic sealing assembly comprising a cap for aseptically delivering the fluid from the fluid container, and fluid dispensing assemblies, methods, and components.

[0006] In one embodiment, a sterile sealing assembly for a fluid container is provided. The sterile sealing assembly includes: a cap connectable to an opening of the fluid container, the cap having a housing, a cavity within the housing having a support, and a first set of seals; and a fluid applicator connectable to an outer surface of the housing of the cap. The fluid applicator includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and an insert connectable to the second end of the body. The body includes an orifice closer to the second end, the orifice being connected to the fluid line and configured to be in fluid communication with the fluid container when the fluid applicator is connected to the cap. Furthermore, the fluid applicator is configured such that a downwardly oriented force toward the fluid container engages the insert into the support of the cavity and disconnects the insert from the body of the fluid applicator to seal the fluid container.

[0007] In another embodiment of the invention, a sterile sealing assembly is provided, the assembly including a cap connectable to an opening of a fluid container, the cap including a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals. The port includes a port housing and an insert connected to one end of the port housing, wherein the insert is configured to open and close a fluid communication channel between the fluid container and the port; and a fluid applicator connectable to an outer surface of the port housing. The fluid applicator includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and a coupling member engageable with the insert. The coupling member of the fluid applicator can be rotatably engaged with the insert of the port, such that the fluid line, together with the insert, can be guided downward toward the fluid container to open the fluid communication channel with the fluid container.

[0008] In one embodiment, a method is provided for aseptically transferring fluid to and from a fluid container. The method includes the step of attaching a cap to an opening of the fluid container, the cap including a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals. The port includes a port housing and an insert connected to one end of the port housing, wherein the insert is configured to open and close a fluid communication channel between the fluid container and the port. The method further includes transferring fluid into the fluid container by aseptically attaching and disconnecting a fluid applicator to an outer surface of the port housing, wherein the fluid applicator includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and a coupling that engages with the insert. When the coupling of the fluid applicator engages with the insert of the port by rotational engagement, the fluid line, together with the insert, is guided downward toward the fluid container to open the fluid communication channel with the fluid container.

[0009] In another embodiment, a fluid applicator is provided that can be attached to the outer surface of a fluid container cap. The fluid applicator includes a body having a first end and a second end, wherein the body includes a fluid line disposed between the first end and the second end; and a housing disposed around the body. The fluid line at the second end of the body is configured to connect with an insert disposed in the cap by rotation of the body, wherein the housing includes a compressible bellows to allow aseptic insertion of the fluid line into the fluid container. Attached Figure Description

[0010] Figure 1 This is a schematic diagram of a sterile sealing assembly according to an embodiment.

[0011] Figures 2A to 2B It is based on Figure 1 Exploded perspective view of the cover and fluid applicator.

[0012] Figure 3A , 3B 3C is according to the embodiments Figure 1 A cross-sectional view of the sterile closed assembly, showing the connection of the fluid applicator and cap and the fluid transfer therein.

[0013] Figures 3D to 3E According to the embodiments Figure 1 A cross-sectional view of the sterile closed assembly, showing the disconnected connection of the fluid applicator and cap.

[0014] Figures 4A to 4BThis is a cross-sectional view of the aseptic closed assembly according to an embodiment, showing the connection of the fluid applicator and insert.

[0015] Figures 5A to 5B This is a perspective view and a cross-sectional view of a sterile closure assembly according to another embodiment.

[0016] Figure 6A , 6B 6C is according to the embodiment Figures 5A to 5B Perspective view, exploded view and cross-sectional view of the lid of the aseptic sealing assembly.

[0017] Figure 7A , 7B 7C is according to another embodiment Figures 5A to 5B Perspective view, exploded view and cross-sectional view of the lid of the aseptic sealing assembly.

[0018] Figure 8A , 8B According to the embodiments Figures 5A to 5B Perspective and cross-sectional views of the sterile closure assembly, showing the connection between the fluid applicator and the cap.

[0019] Figure 8C , 8D It is a fluid container according to an embodiment. Figures 5A to 5B A perspective view of the sterile, closed assembly.

[0020] Figure 9A , 9B This is a cross-sectional view of the secondary body and the second port of the aseptic sealing assembly according to an embodiment.

[0021] Figure 10A , 10B This is a cross-sectional view of the secondary body and second port of a sterile sealing assembly according to another embodiment.

[0022] Figure 11A , 11B It is based on Figures 10A to 10B A perspective view of the secondary body and second port of the aseptic sealing assembly of the embodiment.

[0023] The same symbol indicates the same feature. Detailed Implementation

[0024] This disclosure generally relates to a sterile closure assembly for the aseptic delivery of fluid from a fluid container. More specifically, this disclosure relates to a sterile closure assembly comprising a cap and a fluid dispensing assembly for aseptically coupling and delivering (e.g., filling and removing) fluid in a storage container to prevent contamination. The term sterile, as used herein, relates at least to the formation of a barrier or fluid path between the fluid dispensing assembly and the fluid container to maintain the fluid substantially free from contamination by the external environment to maintain the sterility of the internal contents and / or components. While fluids related to chemical and / or biological processes are discussed below, it should be understood that this discussion is not intended to limit the scope of the invention, but rather to provide examples thereof. Fluids include, but are not limited to, substances that flow or deform when shear stress is applied. Fluids may include, for example, liquids.

[0025] For example, in the bioprocessing market, customers freeze, transport, and thaw their pharmaceuticals in various liquid storage containers (e.g., bottles, bags, barrels, cylinders, or the like). While customers can use various aseptic connectors to aseptically transfer fluids to bag assemblies, the use of bottles, barrels, cylinders, or larger bag assemblies is not widespread because fluid transfer or formation in these assemblies cannot be achieved using simple aseptic connection assemblies. For example, fluid transfer is not in a closed system and requires additional equipment or features to maintain the aseptic nature of the fluid, as the fluid transfer assembly is attached to the top of the bottle, barrel, cylinder, or larger bag assembly. For example, customers may use bottles with caps on top openings, which have tubing connection ports or polymer stoppers covering the top opening of the bottle. While caps can be used for aseptic filling bottles and polymer stoppers for closing bottles, in both cases, customers need to remove the cap and replace it with a solid cap for freezing, transport, and thawing process steps, or remove the polymer stopper for filling and / or removing liquids, such as pharmaceuticals. However, changing the cap and / or polymer stopper opens the system and exposes the fluid in the bottle to the external environment, which can lead to contamination. To limit and / or reduce the amount of contaminants that can enter the bottle during cap and / or polymer stopper changes, a hood can be used to attempt to maintain the sterility of the system. To simplify the filling and removal of fluid from the bottle, for example, without requiring a hood or additional equipment to maintain the sterility of the system, and to reduce the chance of contaminating the fluid in the bottle, a system is needed for the aseptic transfer of fluid from a fluid storage container (e.g., a bottle, barrel, tank, or the like).

[0026] Embodiments of this disclosure relate to a sterile closure assembly comprising a cap and a fluid applicator that allow aseptic delivery of fluid from a fluid container, such as a bottle or other fluid container (e.g., a bucket, tub, or larger bag assembly) having a rigid opening capable of engaging the cap. It should be understood that, as used herein, a rigid opening refers at least to an opening formed on a fluid container made of a relatively rigid material (e.g., one or more polymers). For example, fluid containers may be made of polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate resin (PETG), polycyclohexyldimethyl terephthalate (PCTA), polycyclohexyldimethyl glycol (PCTG), polycarbonate (PC), polypropylene (PP), polyamide (PA), polyethersulfone (PES), polyphenylene sulfone (PPSU), polymethyl methacrylate (PMMA), high-impact polystyrene (HIPS), polyvinyl naphthalene (PEN), polyether ether ketone (PEEK), cyclic olefin polymers, cyclic olefin copolymers, fluoropolymers or the like, and copolymers comprising said materials.

[0027] The aseptic cap and fluid dispenser may include a reusable aseptic cap that allows the user to aseptically connect and disconnect a fluid storage container with a rigid opening, such as a rigid opening on a bottle or bag assembly, before and after the freezing / thawing process steps. The aseptic closure assembly allows the user to fill the bottle before freezing and empty it after thawing without needing to replace the cap and / or polymer stopper during the filling and emptying process, and avoids disruption of the aseptic barrier and / or fluid path between the fluid dispenser and the fluid storage container. The aseptic cap and fluid dispenser allow the bottle to be used as a closed system, for example, by opening it to the external environment to prevent fluid contamination, thus maintaining the sterility of the fluid in the fluid handling system, particularly for bioprocess fluid handling. It should be understood that, at least due to the design and construction of the aseptic closure assembly, the fluid storage container and aseptic closure assembly can be used in freezing / thawing process steps down to -85°C, where no existing aseptic cap design is currently available for use under such conditions, and especially in this top-feed and remove device. It should be understood that although the description of the fluid storage container and the aseptic closure assembly is discussed in relation to temperatures down to -85°C, the fluid storage container and the aseptic closure assembly can also be used at low temperatures, such as below -190°C, and even more preferably below -196°C.

[0028] Figure 1This is a schematic diagram of a sterile closure assembly 10 for a fluid container 1 according to an embodiment. The sterile closure assembly 10 may include a cap 12 and a fluid applicator 14 connectable to a top opening of the fluid container 1, wherein the cap 12 and the fluid applicator 14 are configured to couple together to form a sealed fluid connection. The fluid applicator 14 includes a fluid passage extending from the opening through the fluid applicator 14. The cap 12 is configured to sterilely connect the fluid passage of the fluid applicator 14 to the fluid container 1 to provide sterile fluid communication when the fluid applicator 14 is connected to the cap 12, as discussed further below.

[0029] Therefore, the aseptic closure assembly 10 is configured to aseptically connect and disconnect from a fluid container to aseptically transfer fluid to or from the fluid container, which can be used at temperatures as low as -85°C. It should be understood that the aseptic closure assembly 10 can also be used at other temperatures, such as 0°C, room temperature, or the like, while maintaining the advantages of this disclosure. Therefore, as discussed above, the fluid container 1 having the aseptic closure assembly 10 is configured for storage at freezing temperatures (e.g., below 0°C or lower). In embodiments, the fluid container 1 having the aseptic closure assembly 10 can also be heated back to ambient temperature without any substantial deformation. Substantial deformation includes, for example, visible cracks in the material, shrinkage or expansion relative to its original shape at ambient temperature, which can interfere with or adversely affect the sealing of the connections. Temperature rebound testing can be performed according to ASTM D1329, ISO 2921, or any other suitable test method to determine the appropriate resilience properties of the material at usable temperatures. Brittleness testing can be performed according to ASTM D2137, ISO 28702 or any other suitable test method to determine crack resistance at usable temperatures.

[0030] Fluid container 1 is typically used to contain fluids, such as liquids suitable for manufacturing and / or bioprocessing, including but not limited to semiconductor manufacturing, pharmaceutical manufacturing, or bioprocessing or the like. Therefore, it should be understood that fluid container 1 can store liquids containing liquid chemicals, such as but not limited to photoresists, acids, solvents, bases, dopants, inorganic solutions, organic solutions, pharmaceuticals, biofluids, or the like.

[0031] In embodiments, the fluid container 1 may be a plastic bottle and / or a bag-in-bottle or bag-in-can container. In other embodiments, the fluid container 1 may be a bag assembly with a rigid connection structure, such as a boat fitting, fitting, plastic port, or the like, or a combination thereof. It should be understood that the container may be any type of container with a rigid opening 2 for attaching the aseptic closure assembly 10, as discussed below. This fluid container 1 (or rigid connection structure) may be made of a relatively rigid material, such as one or more polymers. For example, the fluid container 1 may be made of polyethylene (PE), polyethylene terephthalate (PET), polyethylene terephthalate resin (PETG), polycyclohexyldimethyl terephthalate (PCTA), polycyclohexyldimethyl glycol (PCTG), polycarbonate (PC), polypropylene (PP), polyamide (PA), polyethersulfone (PES), polyphenylene sulfone (PPSU), polymethyl methacrylate (PMMA), high-impact polystyrene (HIPS), polyvinyl naphthalene (PEN), polyether ether ketone (PEEK), cyclic olefin polymers, cyclic olefin copolymers, fluoropolymers or the like, and copolymers comprising said materials.

[0032] The cover 12 can be connected to a rigid opening 2 of the fluid container 1 to secure the cover 12 to the fluid container 1. The cover 12 can be connected to the fluid container 1 by pressing the cover 12 into the rigid opening, or the cover 12 and the rigid opening 2 can contain interlocking threads. It should be understood that the cover 12 can also be connected to the fluid container 1 in other ways, such as using mechanical fasteners, such as clamps, corresponding engagement features or the like, or welding or joining techniques, such as thermal joining, pulse welding, laser welding, ultrasonic welding or similar fusion / fusion welding techniques. In embodiments, the cover 12 can be connected to the fluid container using a tamper-proof connection system. For example, the cover 12 with a tamper-proof connection system can include an inwardly biased retaining arm that, once pressed into a predetermined position on the rigid opening 2, engages with a corresponding protrusion around the rigid opening 2 of the fluid container 1, so that the cover 12 cannot be easily removed from the fluid container 1 without leaving visible signs of damage to the cover 12 and / or the fluid container 1. In another embodiment, the cover 12 with the tamper-proof connection system may include a protrusion at the lower part of the thread, such that once the cover 12 is threaded into a predetermined position, for example, by reversing the rotation of the cover 12 at the rigid opening 2, the cover 12 cannot be removed from the fluid container 12. In yet another embodiment, if the cover 512 is removed from the fluid container, the tamper-proof connection system may include a ring on the cover 512 that disengages from the cover 512. Therefore, if the fluid container 1 has been opened or attempted to be opened, and may be contaminated and / or damaged, the tamper-proof connection system can warn the customer or user of the fluid container 1 with the cover 12.

[0033] Figures 2A to 2BAn embodiment of the aseptic closed assembly 10 discussed above is shown. Figure 2A As shown, the aseptic closure assembly 10 includes a cap 12 and a fluid applicator 14. The fluid applicator 14 includes a body 205 having a first end and a second end, a fluid line 210 disposed within the body between the first and second ends, a housing 215 disposed around the body 205, a set of seals 220, and an insert 225 connectable to and / or releasable from the second end of the body 205. The insert 225 can be connected to and / or releasable from the other end of the body 205 by pressing it into the second end of the body (e.g., around the seal 220 of the second end of the body 205). It should be understood that the insert 225 can also be connected to the body 205 using various structures that allow for the connection and release of the insert 225. For example, in an embodiment, the second end of the body 205 may include an engagement portion or protrusion extending from the second end of the body 205, which engages with a corresponding groove in the insert 225. Therefore, the engaging portion or protrusion at the second end of the body 205 can be inserted into and rotated within the groove of the insert 225 for connecting and releasing the insert 225 from the body 205.

[0034] The fluid line 210 near the first end of the body 205 may include a pipe connector for connection to a fluid delivery system to deliver (e.g., fill or remove) fluid relative to the fluid container 1. The pipe connector may be selected from the group consisting of hose barbs, overmolded connections, screw connections, press-fit connections, snap-fit ​​connections, or combinations thereof. It is also understood that the pipe connector may be integrally formed with the fluid delivery system, for example, by molding or overmolding the fluid applicator 14 with the fluid delivery system.

[0035] The body 205 may also include an aperture 206 located near the second end, which is fluidly connected to a fluid line 210 and configured to be in fluid communication with the fluid container 1 when the fluid applicator 14 is connected to the cap 12. The fluid applicator 14 may also include an expansion portion 230 that is in fluid communication with the aperture 206 provided through the body 205, such that when fluid is supplied or removed through the fluid line 210 of the fluid applicator 14, fluid flows from the aperture 206 through the expansion portion 230 and around the insert 225 into the fluid container 1, or from the fluid container 1 around the insert 225 through the expansion portion 230 and then through the aperture 206. In an embodiment, the fluid applicator 14 includes a first retaining feature 235 for engaging the outer surface of the housing 240 of the cap 12, as discussed below.

[0036] like Figure 2BAs seen, the cover 12 includes a housing 240, a cavity 245 within the housing 240, a support 250 provided within the cavity 245, and a set of seals 255. The housing 240 of the cover 12 includes a second retaining feature 260 having a shape complementary to the first retaining feature 235, such that the first retaining feature 235 can engage the second retaining feature 260 for securely attaching the fluid applicator 14 to the cover 12, and disengage from the second retaining feature 260 for releasing the fluid applicator 14 from the cover 12. It should be understood that the first retaining feature 235 may include multiple arms connected to the corresponding second retaining feature 260, for example, having hooks that snap, slide, or engage on or within the second retaining feature 260. It is also understood that the first retaining feature 235 and the second retaining feature 260 may include other structures for engaging and disengaging the fluid applicator. For example, the second retaining feature 260 may include multiple slots or threads that allow engagement and rotation of the first retaining feature 235 to secure the attachment of the fluid applicator 14 to the cover 12, or may include slots, tabs, flanges, latches, hooks, or any other suitable structures for retaining the fluid applicator 14. The set of seals 255 may include a first seal 255 surrounding the outer surface of the housing 240 of the cover 12, the first seal 255 being configured to seal against the inner surface of the housing 215, and a second seal 255 surrounding the cavity 245 for sealing the insert 255 when it is inserted into the cavity 245 and the support 250.

[0037] Cavity 245 and support 250 are used to receive insert 225 for aseptically delivering fluid to or from fluid container 1. For example, in an embodiment, after cap 12 is attached to fluid container 1 and fluid is delivered to fluid container 1, fluid applicator 14 is configured such that a downward force at least toward fluid container 1 inserts insert 225 into support 250 of cavity 245, and allows insert 225 to be disengaged from body 205 of fluid applicator 14 to seal fluid container, for example, insert 225 is press-fitted into cap 12 without requiring additional fitting or alteration of cap 12. It should be understood that insert 225 may also be used to seal cap 12 using other structures for engaging / disengaging insert 225, such as threaded connection systems, engagement portions and grooves, bumps or protrusions or the like.

[0038] The aseptic closure assembly 10, comprising a fluid applicator 14 and a cap 12, may be made of the same or similar materials as the fluid container 1, and / or each other or combinations thereof. In embodiments, the fluid applicator 14 and cap 12, comprising a body 205, a housing 215, and an insert 225, may be made of, for example, polyolefins, such as, but not limited to, polypropylene, high-density polyethylene, linear low-density polyethylene, or the like. Other non-limiting examples of polymers suitable for manufacturing various embodiments of the aseptic closure assembly 10 (including cap 12 and fluid applicator 14) include fluoropolymers, polyesters, polycarbonates, and polyamides. It should be understood that the materials described are examples, and the actual materials used for cap 12 and fluid applicator 14 may vary beyond the list within the principles of this common practice, or may be mixtures of any of the above materials. In one embodiment, the material of cap 12 is the same as the material of fluid applicator 14. In another embodiment, the material of cap 12 may be different from the material of fluid applicator 14. In another embodiment, the materials of the different components of the fluid applicator 14, such as the body 205, housing 215 and insert 225, may be made of the same material or different materials or combinations thereof.

[0039] Seals 220 and 255 may be O-rings or gaskets formed from, but not limited to, at least one of silicone, fluoropolymers, ethylene vinyl acetate (EVA), thermoplastics, or other biocompatible flexible and / or compressible materials for sealing purposes, which are relatively inert, for example, do not leach or significantly absorb pharmaceutical, chemical, or biological fluids, and are non-reactive, or combinations thereof. Seals may also include star-shaped rings, or thermoplastic materials or other flexible and / or compressible materials for sealing, which are melt-treated, for example, overmolded or embedded, to fill grooves in the corresponding components with thermoplastic or flexible materials, and / or formed from any of the above materials.

[0040] Please refer to the following text. Figures 3A to 3E The operation and connection / disconnection of the aseptic closure assembly 10 with the cap 12, including the fluid applicator 14, are discussed. It should be understood that the aseptic closure assembly 10 can be used to transfer fluid to or from a fluid container, which may be used for filling or removing fluid. For example, when the aseptic closure assembly 10 is used to fill a fluid container, one of the fluid lines is used to vent any gas in the fluid container that is expelled when the fluid is filling the fluid container. Alternatively, when the aseptic closure assembly 10 is used to remove fluid from a fluid container, one of the fluid lines may be used to supply an inert gas, such as nitrogen or air, to induce fluid through another fluid line 210, or a negative pressure system, such as a vacuum, may be used to remove fluid from the fluid container. In a non-limiting example, the transfer of fluid to fill a fluid container is discussed below.

[0041] Figures 3A to 3CThe fluid dispenser 14, connected to the cap 12, is used to deliver fluid (e.g., filling) into the fluid container 1, wherein the cap 12 is connected and secured to a rigid opening 2 of the fluid container 1. The fluid dispenser 14 is secured to the cap 12 via retaining features (not shown) of the fluid dispenser 14 and the cap 12. As discussed above, initially, the orifice 206 of the body 205 is sealed relative to the housing 215 between seals 220 (e.g., a first seal and a second seal), preventing fluid from being dispensed from the fluid dispenser 14. After the fluid dispenser 14 is connected to the cap 12 and fluid is ready for delivery, the body 205 is pushed downward toward the fluid container 1, such that the orifice 206 of the body 205 is configured to communicate fluidly with the expansion portion 230 of the housing 215. Thus, as Figure 3B and 3C As seen, the second seal 220 is disposed within the expansion portion, allowing fluid to pass through the fluid line 210 of the fluid applicator 14, through the orifice 206, through the expansion portion 230, and around the second end of the body 205 and the insert 225 into the cavity 245 and the support 250, and into the fluid container 1, as shown by arrow F. It should be understood that the fluid applicator 14 may include the second fluid line 210, which can be used to deliver fluid and / or serve as a vent to allow venting of the fluid container 1 when fluid is discharged from the fluid container 1, the gas flowing along the opposite path of fluid filling.

[0042] like Figures 3D to 3E As seen, after completing the transfer of fluid into the fluid container 1, the fluid applicator 14 can be further downward toward the fluid container 1, such that the insert 225 is fitted into the support 250 of the cavity 245. The insert 225 is inserted into the cavity 245 and sealed by the seal 255, which engages the insert 225 at the opening of the cavity 245. Figure 3EAs explained, the engagement force of the insert 225 into the cavity 245 is greater than the engagement force of the insert 225 at the second end of the body 205. For example, through the compressibility and / or elastic modulus of the seal, the insert 225 is disconnected from the second end of the body 205 when the fluid applicator 14 is disengaged from the cap 12, and remains in the cavity 245 to seal the fluid container 1 when the fluid applicator 14 is disconnected from the cap 12. It should be understood that the fluid applicator 14 can be configured such that when pressed in the downward direction, the seal 220 can seal the hole 206 by sealing the second end of the body with the housing 215, or allow the body 205 to move in the upward direction such that the hole 206 is not in the expansion portion 230, but is sealed between the first and second seals 220 and the housing 215. It is also understood that the insert 225 can engage with the cavity 245 and / or the support 250 to seal the fluid container 1 using other removable or non-removable structures. For example, in one embodiment, the insert 225 may include retaining features, such as hooks, protrusions, or threaded connections, which engage complementary retaining features in the cavity 245 and / or support 250 to engage the insert 225 and disengage the insert 225 from the body 205. In another embodiment, the insert 225 may include permanent retaining features, such as outwardly biased hook structures that, when inserted into the cavity, are outwardly biased to engage complementary structures in the cavity 245 and / or support 250. In this case, the aseptic closure assembly cannot be used for reusable applications because the insert is permanently attached to the cap 12.

[0043] In another embodiment, such as Figure 4A and 4B As seen, the aseptic closure assembly 10 includes an insert 425 that is removable from the cavity 245 of the cover 12 and / or the support 250. Figure 4A and 4B The aseptic closed assembly 10 has the same characteristics as described above. Figure 2A and 2B The aseptic closed assembly 10 discussed has the same or similar characteristics, and components with the same or similar characteristics will not be discussed in detail below. For example, such as Figure 4A As seen, the second end of the body 205 includes an engagement 407, such as a hook, for engaging the complementary engagement or component 426 of the insert 425. In an embodiment, the complementary engagement or component 426 of the insert 425 may include an opening that allows the engagement 407 of the body 205 to be inserted beneath the engagement or component 426, such that rotation of the body 205 of the fluid applicator 14 engages the engagement 407 of the body 205 with the complementary engagement or component 426 of the insert 425. Thus, when the insert 425 is inserted into the cap 12 of the fluid container 1 to seal the fluid container 1, as... Figure 4BAs explained, when an upward force is applied to the body 205 of the fluid applicator 14, the engagement 407 of the body 205 engages the complementary engagement or component 426 of the insert 425, allowing the insert 425 to be removed from the cavity 245 and / or the support 250, enabling fluid to be transferred from the fluid container 1, for example, filling or removing it. After the fluid transfer to the fluid container 1 is complete, the insert 425 can be removed, or as... Figure 4A As explained, by guiding the body 205 of the fluid applicator 14 downward toward the fluid container 1 (as described above regarding...) Figure 2A , 2B (As discussed) and rotating the body 205, such that the insert 425 is disengaged from the body 205 by removing the engagement 407 of the body 205 through the opening of the insert 425, allowing the insert 425 to be fitted into the support 250 of the cavity 245. The insert 425 is inserted into the cavity 245 to seal the fluid container 1 by sealing the opening of the cavity 245 with the insert 425 and the seal 255. It should be understood that, in embodiments, the seal 220 on the second end of the body 205 prevents contamination of any container on the top surface of the insert 425 by sealing the body 205 with the insert 425 during fluid transfer. It is also understood that, in embodiments, a membrane, cap, valve or similar sealing device that maintains an airtight seal may be attached and / or coupled to the cap 12 and / or fluid applicator 14 of the fluid container for aseptic connection / disconnection of the fluid container. Next, when the fluid container is coupled to the fluid dispenser 14, a membrane, cap, valve or similar sealing device can be punctured, removed and / or rotated to allow the delivery of sterile fluid.

[0044] Figure 5A and 5B This is a schematic and cross-sectional view of a sterile closure assembly 502 for a fluid container (e.g., fluid container 1 as discussed above) according to another embodiment. The sterile closure assembly 502 includes a cap 512 connectable to the fluid container and a fluid applicator 514, wherein the cap 512 and the fluid applicator 514 are configured to couple together to form a sealed sterile fluid connection. The fluid applicator 514 includes a fluid passage through a body 505 and a fluid passage through a secondary body 508 extending from an opening. The cap 512 is configured to sterilely connect several fluid passages of the fluid applicator 514 to the fluid container to provide fluid communication when the fluid applicator 514 is connected to the cap 512, as discussed further below.

[0045] Therefore, the aseptic closure assembly 502 is configured to connect and disconnect fluid containers for aseptic delivery of fluids in fluid containers at temperatures as low as -85°C. It should be understood that the aseptic closure assembly 502 can also be used at other temperatures, such as 0°C, room temperature, or the like, while maintaining the advantages of this disclosure. Therefore, as discussed above, fluid containers having the aseptic closure assembly 502 are configured for storage at freezing temperatures (e.g., below 0°C or lower). In embodiments, fluid containers having the aseptic closure assembly 502 can also be heated back to ambient temperature without any substantial deformation. Substantial deformation includes, for example, visible cracks in the material, shrinkage or expansion relative to its original shape at ambient temperature, which can interfere with (some) the connections or adversely affect the seal of said connections. Temperature rebound testing can be performed according to ASTM D1329, ISO 2921, or any other suitable test method to determine the appropriate rebound characteristics of the material at the temperatures where it may be used. Brittleness testing can be performed according to ASTM D2137, ISO 28702 or any other suitable test method to determine crack resistance at usable temperatures.

[0046] The cap 512 can be attached to a rigid opening of the fluid container to secure the cap 512 to the fluid container. The cap 512 can be attached to the fluid container by pressing the cap 512 into the rigid opening, or the cap 512 and the rigid opening can contain interlocking threads. It should be understood that the cap 512 can also be attached to the fluid container 1 in other ways, for example, using mechanical fasteners, such as clamps, corresponding engagement features or the like, or welding or joining techniques, such as thermal joining, pulse welding, laser welding, ultrasonic welding or similar fusion / fusion welding techniques. In embodiments, the cap 512 can be attached to the fluid container using a tamper-proof connection system. For example, a cap 512 with a tamper-proof connection system may include an inwardly biased retaining arm that engages a corresponding protrusion around the rigid opening of the fluid container, so that once pressed into a predetermined position on the rigid opening, the cap 512 cannot be easily removed from the fluid container without leaving visible signs of damage to the cap 512 and / or the fluid container. In another embodiment, the cover 512 with the tamper-proof connection system may include a protrusion at the lower part of the thread, such that once the cover 512 is threaded into a predetermined position, for example by reversing the rotation of the cover 512 over a rigid opening, the cover 512 cannot be removed from the fluid container 501. In yet another embodiment, if the cover 512 is removed from the fluid container, the tamper-proof connection system may include a ring on the cover 512 that disengages from the cover 512. Therefore, if the fluid container has been opened or attempted to be opened, and may be contaminated and / or damaged, the tamper-proof connection system can warn the customer or user of the fluid container with the cover 512.

[0047] The cover 512 includes a housing 540, a cavity 545 within the housing 540, a port 570, and a set of seals 255. The housing 540 of the cover 512 includes a second retaining feature 560 having a shape complementary to a first retaining feature 535 on the body 505 and secondary body 508 of the fluid applicator 514 for engaging the outer surface of the housing 540 of the cover 512. The first retaining feature 535 is capable of engaging the second retaining feature 560 for securely attaching the fluid applicator 514 to the cover 512 and for disengaging it for release of the fluid applicator 514 from the cover 512. For example, in an embodiment, the second retaining feature 560 may include a pin or protrusion that engages a corresponding groove formed by the first retaining feature 535 on the body 505 and secondary body 508 of the fluid applicator 514. The insert 525 is configured to engage and disengage with the port 570, allowing a fluid communication channel to be opened and closed between the fluid container and the port 570, as discussed further below. For example, in one embodiment, after the cap 512 is attached to the fluid container, the fluid applicator 514 is configured to engage the insert 525 such that a downward force toward the fluid container and its rotation engage the insert 525 with the fluid applicator 514 and allow the insert 525 to be disconnected from the port 570, allowing the body 505 (and / or secondary body 508) of the fluid applicator 514 to be inserted into the fluid container for aseptic delivery of fluid to / from the fluid container. After the fluid has been delivered with the fluid container, it should be understood that the insert 525 can be re-engaged with the port 570 such that the insert 525 and the seal 555 seal the port 570, maintaining fluid communication with the fluid container.

[0048] For example, in an embodiment, such as Figure 6A , 6BAs seen in 6C, the cover 512 includes a housing 540, a cavity 545 within the housing 540, a port 570 connected to the cavity, and a set of seals 555. Each port 570 includes a port housing 571 and an insert 525 connected to one end of the port housing 571. The insert 525 is configured to engage and disengage from the port housing 571, allowing a fluid communication passage to be opened and closed between the fluid container and the port 570, as discussed further below. For example, in an embodiment, the insert 525 includes external engagement members or components 527 spaced around the circumference or outer periphery of the insert 525, which can engage with external complementary engagement members or components 572 disposed on the outer surface of the port housing 571. In an embodiment, space is provided between the external engagement members or components 527 and the complementary engagement members or components 572, allowing the insert 525 to engage and disengage from the port housing 571 by being positioned in the corresponding space through rotation of the insert 525. It should be understood that when the insert 525 engages with the port housing 571, a seal 555 disposed along the inner circumference of the outer engagement member or component 527 seals the port 570, preventing it from fluid communication with the fluid container. It should be understood that the port 570 may have the same or similar structure, or may have different structures, as discussed below.

[0049] In another embodiment of cover 512, such as Figure 7A , 7B As seen in 7C, the cover 512 includes a housing 740, a cavity 745 within the housing 740, a port 770 connected to the cavity, and a set of seals 720. Each port 770 includes a port housing 771 and an insert 725 connected to one end of the port housing 771. The insert 725 is configured to engage and disengage from the port housing 771, allowing a fluid communication passage to be opened and closed between the fluid container and the port 770, as discussed further below. For example, in one embodiment, the insert 725 includes external engagement members or components 727 spaced around the outer surface of the insert 725, which can engage with external complementary engagement members or components 772 disposed along the inner periphery of the port housing 771. In another embodiment, space is provided between the external engagement member or component 727 and the complementary engagement member or component 772, allowing the insert 725 to engage and disengage from the port housing 771 by rotation of the insert 725 into the corresponding space. It should be understood that when the insert 725 engages with the port housing 771, a seal 720 disposed along the outer periphery of the insert 725 seals the port 770, preventing it from fluid communication with the fluid container. It should be understood that although the inserts 525, 725 and the port housings 571, 771 have been discussed above as having external and complementary engagements or components, this disclosure is intended to be non-limiting, and other mechanical structures that allow the insert to engage and disengage from the port are included herein. For example, threaded connections or snap-fit ​​couplings may also be used to engage and disengage the insert from the port.

[0050] It should be understood that although cover 512 is described and shown as a separate workpiece, this public is not intended to be limiting. For example, cover 512 may be constructed from a port connected to a housing, or cover 512 may be constructed as a single molded part or assembly. Different inserts may then be used to supplement the fluid applicator's engagement. It should also be understood that port 570 may be a single port provided by cover 512, wherein port 570 is configured to allow connection to two separate fluid lines in a fluid applicator associated with it.

[0051] Return to reference Figure 5A and 5B The fluid applicator 514 includes a body 505 having a first end and a second end, a secondary body 508 having a first end and a second end, a fluid line 510 connected to the body 505 and the secondary body 508, a housing 515 disposed around the body 505, a secondary outer shell 509 disposed around the secondary body 508, and a set of seals 520. The body 505 and the secondary body 508 each include an aperture 506 near the second end, the aperture 506 being in fluid communication with the fluid line 510 and configured to be in fluid communication with a fluid container when the fluid applicator 514 is connected to a cap 512. In an embodiment, the housing 515 and the secondary outer shell 509 of the fluid applicator 514 each include a first retaining feature 535 for engaging the outer surface of the outer shell 540 of the cap 512, as discussed above. The housing 515 includes a foldable structure that allows the fluid line 510 to be inserted into the fluid container while maintaining the sterility of the fluid line 510. For example, in one embodiment, housing 515 includes an accordion-like structure with bellows that contracts and expands as fluid line 510 moves into and out of housing 515 (e.g., when fluid line 510 is used as a suction tube for insertion into a fluid container) to allow for compression and expansion of housing 515. It should be understood that other foldable structures may be used, such as a sliding housing with seals within the housing, or similar structures that allow for sterile fluid communication with the fluid container. Secondary body 508 may have the same or similar structure as body 505, and in one embodiment, secondary body 508 includes a secondary housing 509 surrounding secondary body 508 that allows only partial movement of fluid line 510 into the fluid container by rotation of secondary body 508; for example, a structure without a suction tube, but allowing only partial insertion into the fluid container.

[0052] The fluid line 510, located closer to the first end of the main body 505 and the secondary body 508, may include a pipe connector for connection to a fluid delivery system for delivering (e.g., filling or removing) fluid relative to a fluid container. The pipe connector may be selected from the group consisting of hose barbs, overmolded connections, screw connections, press-fit connections, snap-fit ​​connections, or combinations thereof. It should also be understood that the pipe connector may be integrally formed with the fluid delivery system, for example, by molding or overmolding the fluid applicator with the fluid delivery system.

[0053] In an embodiment, the fluid applicator 514, comprising a main body 505 and a secondary body 508, includes a coupling 507, for example, having complementary coupling parts 526, 726 (e.g., inserts 525, 725 on the second ends of the main body 505 and the secondary body 508) that engage with the second ends of the main body 505 and the secondary body 508. Figure 6B , 7B (As illustrated) Protrusions of matching shape. For example, engaging members 526, 726 include openings capable of receiving engaging members 507 of the main body 505 and / or secondary body 508, such that rotation of the main body 505 and / or secondary body 508 of the fluid applicator 514 engages the engaging members 507 of the main body 505 and / or secondary body 508 with complementary engaging members or members 526, 726 of the inserts 525, 725. Thus, when a downward rotational force is applied to the main body 505 and / or secondary body 508 of the fluid applicator 514, the engaging members 507 of the main body 505 and / or secondary body 508 engage the complementary engaging members 526, 726 of the inserts 525, 725, such that further rotation of the main body 505 and / or secondary body 508 causes the inserts 525, 725 to rotate, thereby disengaging the inserts 525, 725 from the port 570. Next, inserts 525 and 725 can be inserted into the fluid container to allow fluid to be transferred from the fluid container, for example, by filling or removing it. After the transfer of fluid to the fluid container is complete, inserts 525 and 725 can be oriented upward toward port 570, allowing them to rotate to engage and seal port 570. Inserts 525 and 725 into cavity 545 and port 570 to seal the fluid container by sealing port 570 with inserts 525 and 725 and seal 555. It should be understood that, in embodiments, a membrane, cap, valve, or similar sealing device that maintains an airtight seal can be attached and / or coupled to the cap 512 and / or port 570 of the fluid container and / or fluid applicator 514 for aseptic connection / disconnection of the fluid container. Then, when the fluid applicator 514 is coupled to the fluid container, the membrane, cap, valve, or similar sealing device can be punctured, removed, and / or rotated to further allow the transfer of sterile fluid.

[0054] The aseptic closure assembly 502, comprising a fluid applicator 514 and a cap 512, may be made of the same or similar materials as the container material, and / or each other or combinations thereof. In embodiments, the fluid applicator 514 (comprising a body 505, a secondary body 508, a housing 515, a second housing 509, and an insert 525) and the cap 512 may be made of, for example, polyolefins, such as (e.g.) but not limited to, polypropylene, high-density polyethylene, linear low-density polyethylene, or the like. Other non-limiting examples of polymers suitable for manufacturing various embodiments of the aseptic closure assembly 502 (including the cap 512 and the fluid applicator 514) include fluoropolymers, polyesters, polycarbonates, and polyamides. It should be understood that the materials are examples, and the actual materials used for the cap 512 and the fluid applicator 514 may vary beyond the list of described materials within the principles of this disclosure, or may be mixtures of any of the above materials. In embodiments, the material of the cap 512 is the same as the material of the fluid applicator 514. In another embodiment, the material of the cover 512 may be different from the material of the fluid applicator 514. In another embodiment, the materials of the different components of the fluid applicator 514, such as the main body 505, the secondary body 508, the housing 515, the secondary housing 509, and the insert 525, may be made of the same material or different materials or combinations thereof. In an embodiment, the housing 515 may be made of silicon or a flexible polymer to allow for compression and expansion of the housing.

[0055] Seals 520 and 555 may be O-rings or gaskets formed from, but not limited to, at least one of silicone, fluoropolymers, ethylene vinyl acetate (EVA), thermoplastics, or other biocompatible flexible and / or compressible materials for sealing purposes, which are relatively inert, for example, do not leach or significantly absorb drugs or biofluids, and are non-reactive, or combinations thereof. Seals may also include star-shaped rings, or thermoplastic materials or other flexible and / or compressible materials for sealing, which are melt-treated, for example, overmolded or embedded, to fill grooves in the corresponding components with thermoplastic or flexible materials, and / or formed from any of the above materials.

[0056] Please refer to the following text. Figures 8A to 9B The operation and connection / disconnection of fluid applicator 514 and cap 512 are discussed. It should be understood that any insert or port and related structure discussed above can be used, but insert 525 will be discussed below as a non-limiting example.

[0057] Figure 8A and 8BThe body 505 of a fluid dispenser 514, connected to a cap 512, is described for dispensing fluid (e.g., filling) into a fluid container, wherein the cap 512 is attached and secured to a rigid opening in the fluid container. The body 505 of the fluid dispenser 514 is secured to the cap 512 via a second retaining feature 560 on a port 570 of the cap 512, rotating a first retaining feature 535 of the fluid dispenser 514 onto the cap 512. Initially, the orifice 506 of the body 505 is sealed relative to the housing 515 between seals 520 (e.g., a first seal and a second seal), preventing fluid from being dispensed from the body 505 of the fluid dispenser 514. After the body 505 of the fluid dispenser 514 is attached to the cap 512 and fluid is ready for dispensing, the body 505 is pushed downward toward the fluid container and rotated such that a coupling 507 on the body 505 engages a complementary coupling 526 of the insert 525. After the body 505 and insert 525 are engaged, the body 505 is further rotated so that the external connector 527 disengages from the complementary connector or component 572 of the port 570, allowing the fluid line 510 and insert 525 to be inserted into the fluid container to form a sterile fluid communication channel between the fluid applicator 514 and the fluid container.

[0058] For example, such as Figure 8C and 8D As seen, the fluid line 510 and insert 525 can be oriented downward toward the fluid container 501, such that the orifice 506 is not located between the seal 520 and the housing (not shown). The orifice 506 and insert 525 can then be displaced at different heights within the fluid container 501 for conveying fluid to or from the fluid container 501; for example, as an immersion tube, the immersion tube can be lowered (or raised) to near the fluid level to prevent foaming or allow fluid to drain. In an embodiment, when the orifice 506 and insert 525 are displaced into the fluid container 501, the housing (e.g., a housing 515 with an accordion-like structure having a bellows) can contract and expand to allow for compression and expansion of the housing and insertion of the fluid line 510 into the fluid container. Thus, since the outer surface of the fluid line 510 only contacts the inner surface of the housing and the fluid in the fluid container 501, the outer surface of the fluid line 510 can remain sterile. It is also understood that, because the fluid line 510 can be lowered (or raised) at different heights, this structure allows for the automatic filling or removal of fluid from the fluid container 501. For example, when the housing is transparent, the housing and / or fluid line may include index markers or measurements to indicate the depth to which the fluid line enters the fluid container 501. Therefore, the insertion depth of the fluid line 510 can be controlled for filling and / or removing fluid from the fluid container 501.

[0059] After the fluid transfer process is completed, the orifice 506 and insert 525 can be lifted upwards, such that the orifice 506 is positioned between the seal 520 and the housing 515, and the insert 525 engages with the port 570 by rotation of the insert 525. It should be understood that when the insert 525 engages with the port 570, the seal 555 and insert 525, disposed along the inner circumference of the outer engagement member or component 527, seal the port 570, preventing it from fluid communication with the fluid container 501. As the body 505 rotates further, the engagement member 507 on the body 505 disengages from the complementary engagement member 526 of the insert 525. Therefore, when the fluid applicator 514 rotates such that the first retaining feature 535 of the fluid applicator body 505 disengages from the second retaining feature 560 on the port 570 of the cover 512, the fluid applicator 514 can be removed from the cover 512 and the fluid container 501. It should be understood that since the insert 525 only contacts the fluid applicator 514 for transferring fluid to the fluid container 501, the fluid handling system remains closed because no second step is required to seal the fluid container 501, such as replacing the sterile sealing assembly with a plug or the like. This makes the fluid handling system susceptible to contamination.

[0060] Similarly, such as Figure 8D As seen, the secondary body 508 of the fluid applicator 514 can be attached to the cover 512 via a second retaining feature 560 that rotates the first retaining feature 535 onto the port 570 of the cover 512. For example, as Figures 9A to 9B As seen, initially, the orifice 506 of the secondary body 508 is sealed relative to the secondary housing 509 between seals 520 (e.g., a first seal and a second seal), preventing fluid from being delivered through the secondary body 508 of the fluid dispenser 514. After the fluid dispenser 514 is connected to the cap 512 and fluid is ready for delivery, the secondary body 508 can be pushed and rotated in a downward direction toward the fluid container 501, causing the engagement 507 on the secondary body 508 to engage the complementary engagement 526 of the insert 525. After the secondary body 508 and the insert 525 are engaged, the secondary body 508 is further rotated, causing the outer engagement 527 to disengage from the complementary engagement or component 572 of the port 570, allowing the fluid line 510 and the insert 525 to be inserted into the fluid container to form a fluid communication channel between the secondary body 508 of the fluid dispenser 514 and the fluid container.

[0061] For example, such as Figure 9BAs seen, the fluid line 510 and insert 525 can be oriented downward toward the fluid container 501, such that the orifice 506 is not located between the seal 520 and the secondary housing 509. The orifice 506 and insert 525 can then be displaced within the fluid container 501 below the cover 512 for conveying fluid to or from the fluid container 501. In an embodiment, when the orifice 506 and insert 525 are displaced into the fluid container 501, the secondary housing 509 allows the fluid line 510 to move at least partially into the fluid container 510, such that a portion of the outer surface of the fluid line 510 is not exposed to the environment to maintain the sterility of the fluid.

[0062] After the fluid transfer process is completed, the orifice 506 and insert 525 can be lifted upwards, such that the orifice 506 is positioned between the seal 520 and the secondary housing 509, and the insert 525 engages with the port 570 by rotation of the insert 525. It should be understood that when the insert 525 engages with the port 570, the seal 555 and insert 525, disposed along the inner circumference of the outer engagement member or component 527, seal the port 570, preventing it from fluid communication with the fluid container 501. As the secondary body 508 rotates further, the engagement member 507 on the secondary body 508 disengages from the complementary engagement member 526 of the insert 525. Therefore, as the secondary body 508 of the fluid dispenser 514 rotates, the first retaining feature 535 of the secondary housing 509 disengages from the second retaining feature 560 on the cover 512, and the fluid dispenser 514 can be removed from the cover 512 and the fluid container 501. It should be understood that since the insert 525 only contacts the fluid applicator 514 for transferring fluid to the fluid container 501, the fluid handling system remains closed because no second step is required to close the fluid container 501, such as replacing the sterile closure assembly with a plug or the like. This makes the fluid handling system susceptible to contamination.

[0063] Figures 10A to 10B Another embodiment of the secondary body and the second port is shown. In this embodiment, the second port 1070 has a different structure from the first port (e.g., port 570 as discussed above), and the secondary body 1008 has a different structure from the secondary body 508. For example, in this embodiment, the cover 1012 includes a first cavity and a first port (e.g., cavity 545 and port 570, as discussed above). Figures 5A to 9B(As shown) and connected to the second cavity 1045 and the second port 1070. The second port 1070 includes a second housing 1071, a second insert 1025 configured to seal one end of the second port 1070, and a first spring 1080 biasing the second insert 1025 in a closed position (e.g., an upward position away from the fluid container). The fluid applicator includes a secondary body 1008 having a second housing 1009, a sealing end 1013 disposed within the second housing 1009, a second spring 1011 biasing the sealing end 1013 toward a hole 1006 in the secondary body 1008 in the second housing 1009, and a third set of seals 1020. The second housing 1009 is configured to engage the outer surface of the second port 1070 such that the connection between the second housing 1009 and the second port 1070 causes the secondary body 1008 to be oriented toward the fluid container bias insert 1025 to provide a second fluid communication channel between the secondary body 1008 and the fluid container.

[0064] like Figure 10A As seen, initially, the orifice 1006 of the secondary body 1008 seals relative to the second housing 1009 between the seal 1020 (e.g., the first seal) and the sealing end 1013, preventing fluid from being delivered through the secondary body 1008 of the fluid dispenser. After the secondary body 1008 of the fluid dispenser is connected to the cap 1012 and fluid is ready for delivery, the sealing end 1013 is biased away from the second end of the secondary body 1008 to open a fluid communication channel for the orifice 1006. The secondary body 1008 can also be pushed and rotated in a downward direction toward the fluid container, such that the insert 1025 can be biased toward the fluid container to form a fluid communication channel between the orifice 1006 of the secondary body 1008 of the fluid dispenser and the fluid container. For example, in one embodiment, a downward force toward the fluid container biases the sealing end 1013 relative to the second housing 1009, allowing the orifice 1006 to fluidly communicate with the port 1070. The second end of the secondary body 1008 engages with the insert 1025, such that a downward directional force displaces the insert 1025 relative to the port 1070, allowing fluid to flow around the insert 1025 into the fluid container.

[0065] After the fluid transfer process is complete, the orifice 1006 and insert 1025 are rotatable, causing the spring 1080 to bias the insert 1025 in the closed position. The insert 1025 engages with the second port 1070, causing the seal 1055 and insert 1025 to seal the port 1070, making it fluidly connected to the fluid container. As the secondary body 1008 rotates further, the second housing 1009 disengages from the second port 1070, and the spring 1011 biases the sealing end 1013 toward the second end of the secondary body 1008, positioning the orifice 1006 between the seal 1020 and the sealing end 1013 of the secondary body 1008. It should be understood that because the insert 1025 only contacts the secondary body 1008 of the fluid dispenser for fluid transfer to the fluid container, the fluid handling system remains closed because a second step to close the fluid container, such as replacing the sterile closure assembly with a stopper or the like, is not required, which makes the fluid handling system susceptible to contamination.

[0066] It should be understood that, in one embodiment, when the insert is pushed downward, the second port 1070 forms a fluid connection with the fluid container, such that a fluid communication channel is directly formed with the fluid container. In another embodiment, as... Figure 11A , 11B As seen, the second port 1070 includes a conduit with an angled design, such as a J-tube design, which directs fluid to one side of the fluid container. The J-tube can be press-fitted to the port or mechanically attached, such as a screw, bolt, or the like. The angled conduit design prevents foaming of the fluid during filling by directing fluid to the side of the fluid container, allowing the fluid to cascade down the side of the fluid container. Figure 11A , Figure 11B Further demonstrating that ports 570 and 1070 can have different designs, such that the body 505 of the fluid applicator 514 can include a baffle design connected to the first port 570, and the secondary body 1008 of the fluid applicator 514 is connected to the second port 1070 for delivering fluid to the fluid container 501. It should be understood that the ports of the cap can have the same or different designs depending on the application, and are not limited to the designs discussed above.

[0067] In another embodiment, a method for aseptically transferring fluid into and from a fluid container is provided for freezing / thawing applications. (See reference) Figure 5A and 5BThe method includes the step of attaching a cap 512 to an opening of a fluid container. The cap 512 includes a housing 540, a cavity 545 within the housing 540, a port 570 connected to the cavity 545, and a set of seals 555. Each port 570 includes a port housing 571 and an insert 525 connected to one end of the port housing 571, wherein the insert 525 is configured to open and close a fluid communication passage between the fluid container and the port 570. The method further includes delivering fluid into the fluid container by aseptically attaching a fluid applicator 514 to and disconnecting it from the outer surface of the port housing 571. The fluid applicator 514 may include a main body 505 having a first end and a second end, a secondary body 508 having a first end and a second end, a fluid line 510 connected to the main body 505, a housing 515 disposed around the main body 505, a second set of seals, a secondary housing 509 disposed around the secondary body 508, and a coupling member 507 on the main body 505 and the secondary body 508 that can engage with an insert 525. When the coupling member 507 engages with the insert 525 at the port 570 by rotational engagement, the fluid line 510, together with the insert 525, can be guided downward toward the fluid container to open a fluid communication channel with the fluid container, allowing fluid to be transferred from the fluid container, for example, filling or removing it. After the fluid transfer to the fluid container is completed, the insert 525 can be oriented upward toward the port 570, allowing the insert 525 to be rotated to engage and seal the port 570. The fluid container is sealed by inserting the insert 525 into the cavity 545 and the port 570, and by sealing the port 570 with the insert 525 and the seal 555.

[0068] The fluid container can then be stored, transported, and used during the manufacturing process. For example, in one embodiment, the fluid container can be frozen, such that the fluid delivered in the fluid container is frozen to approximately -85°C. The fluid container can then be transported, and the delivered fluid can be thawed at a temperature between approximately 1°C and 10°C to allow fluid flow. The fluid applicator 514 can then be used for aseptic connection and disconnection of the fluid container. For example, in one embodiment, the body 505 of the fluid applicator 14 can be rotated within a housing, and the housing 515 can be compressed, allowing the fluid line 510 to be aseptically inserted into the fluid container. When the secondary body 508 is attached to the cap 512, a vacuum system (or positive pressure) can be used to remove fluid from the fluid container through the fluid line of the body 505.

[0069] aspect:

[0070] Any aspect of aspect 1 to 11 can be combined with any aspect of aspect 12 to 17 and / or 18 to 19 and / or 20, and vice versa.

[0071] Aspect 1. A sterile sealing assembly for a fluid container, comprising: a cap connectable to an opening of the fluid container, the cap including a housing, a cavity having a support within the housing, and a first set of seals; and a fluid applicator connectable to an outer surface of the housing of the cap, wherein the fluid applicator includes a body having a first end and a second end and a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and an insert connectable to the second end of the body, wherein the body includes an orifice closer to the second end, the orifice being connected to the fluid line and configured to be in fluid communication with the fluid container when the fluid applicator is connected to the cap, and wherein the fluid applicator is configured such that a downwardly oriented force toward the fluid container engages the insert into the support of the cavity and disconnects the insert from the body of the fluid applicator to seal the fluid container.

[0072] Aspect 2. The aseptic closure assembly of Aspect 1, wherein the fluid container is a bottle.

[0073] Aspect 3. A sterile closure assembly of any of Aspects 1 to 2, wherein the housing includes an expansion portion in fluid communication with the orifice, such that when fluid is supplied or removed through the fluid line of the fluid applicator, the fluid flows from the orifice through the expansion portion and around the insert into the fluid container, or flows from the fluid container around the insert through the expansion portion and then through the orifice.

[0074] Aspect 4. A sterile closure assembly of any of Aspects 1 to 3, wherein the insert is engaged in the cavity and the support by press-fitting and disconnected from the body, and / or engaged by rotation of the fluid applicator, while the insert engages in the support of the cavity.

[0075] Aspect 5. The aseptic sealing assembly of Aspect 4, wherein the first set of seals includes a first seal surrounding the outer surface of the cover and a second seal surrounding the cavity, the first seal being connectable to the inner surface of the housing.

[0076] Aspect 6. A sterile sealing assembly of any of aspects 1 to 5, wherein the second set of seals includes a third seal disposed on the body above the hole along the length direction of the body and a fourth seal disposed below the hole, wherein the third seal and the fourth seal engage the housing when the hole is located above the expansion portion.

[0077] Aspect 7. A sterile closure assembly of any of Aspects 1 to 6, wherein the housing includes a plurality of first retaining features extending from one end of the housing, the plurality of first retaining features being configured to engage a second retaining feature disposed on the outer surface of the housing of the cover, wherein the first retaining features and the second retaining features have complementary shapes.

[0078] Aspect 8. A sterile sealing assembly of any of aspects 1 to 7, wherein the first set of seals and the second set of seals comprise one or more of silicone and ethylene vinyl acetate (EVA).

[0079] Aspect 9. A sterile closure assembly of any of aspects 1 to 8, wherein at least one of the cap or the insert comprises a fluoropolymer.

[0080] Aspect 10. A sterile closure assembly of any of Aspects 1 to 8, wherein the cap is connected to the fluid container using a tamper-proof connector.

[0081] Aspect 11. A sterile closure assembly of Aspect 4, wherein the fluid applicator includes an engagement member for engaging the insert or engagement component, such that the fluid applicator can engage the insert by rotation of the fluid applicator to remove the insert from the support of the cavity.

[0082] Aspect 12. A sterile closure assembly according to any of aspects 1 to 11, wherein the housing includes a plurality of arms extending from one end of the housing, the plurality of arms being configured to engage with a plurality of grooves corresponding to the outer surface of the housing of the cover, wherein the plurality of arms and the plurality of grooves have complementary shapes for engaging and disengaging from each other.

[0083] Aspect 13. The aseptic closure assembly according to any one of aspects 1 to 11 further includes a member for engaging the fluid applicator to and disengaging from the cap.

[0084] Aspect 14. A sterile closure assembly for a fluid container, comprising: a cap connectable to an opening of the fluid container, the cap including a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals, wherein the port includes a port housing and an insert connected to one end of the port housing, wherein the insert is configured to open and close a fluid communication passage between the fluid container and the port; and a fluid applicator connectable to an outer surface of the port housing, wherein the fluid applicator includes a body having a first end and a second end and a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and a coupling member engageable with the insert, wherein the coupling member of the fluid applicator is rotatably engaged with the insert of the port such that the fluid line, together with the insert, is guided downward toward the fluid container to open the fluid communication passage with the fluid container.

[0085] Aspect 15. A sterile closure assembly for a fluid container of aspect 14, wherein the cover includes a second cavity and a second port connected to the second cavity, wherein the second port includes a second housing, a second insert configured to seal one end of the second port, and a first spring biasing the second insert in a closed position.

[0086] Aspect 16. A sterile closure assembly for a fluid container according to aspect 15, further comprising a secondary body of the fluid applicator, the secondary body having a second housing, a second spring biasing the secondary body within the second housing, and a third set of seals, wherein the second housing is configured to engage the outer surface of the second port such that the connection between the second housing and the second port causes the secondary body to bias the insert toward the fluid container to provide a second fluid communication channel between the secondary body and the fluid container.

[0087] Aspect 17. A sterile closure assembly for a fluid container of aspect 16, wherein the second port further includes a conduit connected to the second port, the conduit being configured to direct fluid to one side of the fluid container.

[0088] Aspect 18. A sterile closure assembly for a fluid container of aspect 17, wherein the secondary body comprises a tube connector selected from the group consisting of hose barbs, overmolded connections, screw connections, press-fit connections, snap-fit ​​connections, or combinations thereof.

[0089] Aspect 19. A sterile closure assembly for a fluid container from any of Aspects 14 to 18, wherein the housing includes a compressible bellows to allow the fluid line to be sterilely inserted into the fluid container.

[0090] Aspect 20. A method for aseptically transferring fluid into and from a fluid container, the method comprising the steps of: attaching a cap to an opening of the fluid container, the cap including a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals, wherein the port includes a port housing and an insert connected to one end of the port housing, wherein the insert is configured to open and close a fluid communication channel between the fluid container and the port; transferring fluid into the fluid container by aseptically attaching a fluid applicator to an outer surface of the port housing and disconnecting it from the outer surface, wherein the fluid applicator includes a body having a first end and a second end and a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and a coupling member engageable with the insert member, wherein when the coupling member of the fluid applicator engages with the insert member of the port by rotational engagement, the fluid line is guided downward toward the fluid container along with the insert member to open the fluid communication channel with the fluid container.

[0091] Aspect 21. The method of Aspect 20 further comprises the steps of: freezing the delivery fluid in the fluid container to about -85°C; thawing the delivery fluid at a temperature between about 1°C and 10°C to allow the fluid to flow; aseptically connecting the fluid applicator to the fluid container and disconnecting it from the fluid container; rotating the fluid line in the housing of the fluid applicator and compressing the fluid applicator such that the fluid line is aseptically inserted into the fluid container; and removing the fluid from the fluid container through the fluid line.

[0092] Aspect 22. A fluid applicator connectable to the outer surface of a lid of a fluid container, comprising: a body having a first end and a second end, wherein the body includes a fluid line disposed between the first end and the second end; and a housing disposed around the body, wherein the fluid line at the second end of the body is configured to be rotatable via the body to engage with an insert disposed in the lid, and wherein the housing includes a compressible bellows to allow aseptic insertion of the fluid line into the fluid container.

[0093] The examples disclosed in this application should be considered illustrative rather than restrictive in all respects. The scope of the invention is indicated by the appended claims rather than by the foregoing description; and all variations within the meaning and scope of the equivalence of the claims are to be included therein.

Claims

1. A sterile closure assembly for a fluid container, comprising: A cover, the cover being connectable to the opening of the fluid container, the cover comprising a housing, a cavity within the housing having a support member, and a first set of seals; and A fluid applicator capable of connecting to the outer surface of the housing of the cover, wherein the fluid applicator includes a body having a first end and a second end, a fluid conduit disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and an insert capable of connecting to the second end of the body. The body includes an opening closer to the second end, the opening being connected to the fluid line and configured to be in fluid communication with the fluid container when the fluid applicator is connected to the cap. The fluid applicator is configured such that a downward force directed toward the fluid container engages the insert into the support of the cavity and disconnects the insert from the body of the fluid applicator to seal the fluid container.

2. The aseptic sealing assembly according to claim 1, wherein the fluid container is a bottle.

3. The aseptic closure assembly of claim 1, wherein the housing includes an expansion portion in fluid communication with the orifice, such that when fluid is supplied or removed through the fluid line of the fluid applicator, the fluid flows from the orifice through the expansion portion and around the insert into the fluid container, or flows from the fluid container around the insert through the expansion portion and then through the orifice.

4. The aseptic closure assembly according to claim 1, wherein the insert is engaged in the cavity and the support by pressing and disconnected from the body, and / or engaged by rotation of the fluid applicator, while the insert is engaged in the support of the cavity.

5. The aseptic sealing assembly of claim 4, wherein the first set of seals includes a first seal surrounding the outer surface of the cover and a second seal surrounding the cavity, the first seal being connectable to the inner surface of the housing.

6. The aseptic sealing assembly according to claim 3, wherein the second set of seals includes a third seal disposed on the body above the hole along the length direction of the body and a fourth seal disposed below the hole, wherein when the hole is located above the expansion portion, the third seal and the fourth seal engage the housing.

7. The aseptic closure assembly of claim 1, wherein the housing includes a plurality of first retaining features extending from one end of the housing, the plurality of first retaining features being configured to engage a second retaining feature disposed on the outer surface of the housing of the cover, wherein the first retaining features and the second retaining features have complementary shapes.

8. The aseptic closure assembly of claim 4, wherein the fluid applicator includes an engagement member for engaging the insert or engagement member, such that the fluid applicator can engage the insert by rotation of the fluid applicator to remove the insert from the support of the cavity.

9. The aseptic closure assembly of claim 1, wherein the housing includes a plurality of arms extending from one end of the housing, the plurality of arms being configured to engage corresponding plurality of slots disposed on the outer surface of the housing of the cover, wherein the plurality of arms and the plurality of slots have complementary shapes for engaging and disengaging from each other.

10. A sterile closure assembly for a fluid container, comprising: A cap, connectable to an opening of the fluid container, the cap comprising a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals. The port includes a port housing and an insert connected to one end of the port housing, wherein the insert is configured to open and close a fluid communication channel between the fluid container and the port; and A fluid applicator capable of being connected to the outer surface of the port housing, wherein the fluid applicator includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and a coupling capable of engaging with the insert. The coupling of the fluid applicator is capable of engaging with the insert of the port by rotational engagement, such that the fluid line, together with the insert, is guided downward toward the fluid container to open the fluid communication channel with the fluid container.

11. The aseptic closure assembly for a fluid container of claim 10, wherein the cap comprises a second cavity and a second port connected to the second cavity, wherein, The second port includes a second housing, a second insert configured to seal one end of the second port, and a first spring biasing the second insert into a closed position.

12. The aseptic closure assembly for a fluid container according to claim 11, further comprising a secondary body of the fluid applicator, the secondary body having a second housing, a second spring biasing the secondary body within the second housing, and a third set of seals, wherein the second housing is configured to engage the outer surface of the second port such that connection between the second housing and the second port causes the secondary body to bias the insert toward the fluid container to provide a second fluid communication channel between the secondary body and the fluid container.

13. The aseptic closure assembly for a fluid container according to claim 12, wherein the second port further includes a conduit connected to the second port, the conduit being configured to direct fluid to one side of the fluid container.

14. The aseptic closure assembly for a fluid container according to claim 13, wherein the secondary body comprises a tube connector selected from the group consisting of hose barbs, overmolded connections, screw connections, press-fit connections, snap-fit ​​connections, or combinations thereof.

15. The aseptic closure assembly for a fluid container according to claim 10, wherein the housing includes a compressible bellows to allow the fluid line to be aseptically inserted into the fluid container.

16. A method for aseptically transferring fluid into and from a fluid container, the method comprising the steps of: A cap is attached to the opening of the fluid container, the cap including a housing, a cavity within the housing, a port connected to the cavity, and a first set of seals, wherein the port includes a port housing and an insert connected to one end of the port housing, wherein the insert is configured to open and close a fluid communication channel between the fluid container and the port; Fluid is delivered to the fluid container by aseptically connecting a fluid applicator to the outer surface of the port housing and disconnecting it from the outer surface. The fluid applicator includes a body having a first end and a second end, a fluid line disposed within the body between the first end and the second end, a housing surrounding the body, a second set of seals, and a coupling capable of engaging with the insert. When the coupling of the fluid applicator engages with the insert of the port by rotational engagement, the fluid line is guided downward toward the fluid container along with the insert to open the fluid communication channel with the fluid container.

17. The method of claim 16, further comprising the following steps: The transfer fluid in the fluid container is frozen to approximately -85°C; The delivered fluid is thawed at a temperature between 1°C and 10°C to allow the fluid to flow; Aseptically connect the fluid applicator to the fluid container and disconnect it from the fluid container; Rotate the fluid line in the housing of the fluid applicator and compress the fluid applicator so that the fluid line is aseptically inserted into the fluid container; and The fluid is removed from the fluid container through the fluid pipeline.

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