Fluid dispensing system with disposable manifold assembly for extended filling

Abstract

The fluid distribution system includes disposable distributor manifolds, each having a distributor manifold inlet and a plurality of distributor manifold outlets in fluid communication with the distributor manifold inlet. A set of disposable fill manifolds can be connected in sequence to a respective one of the outlets of a disposable distributor manifold immediately upstream of the connection of the set of disposable fill manifolds. In embodiments, the upstream distributor manifold can be used to deliver fluid to a set of intermediate distributor manifolds, where the number of the set of intermediate distributor manifolds corresponds to the number of outlets of the upstream distributor manifold.

Description

[0001] Cross-reference to related applications

[0002] This patent application claims priority to U.S. non-provisional patent application No. 17 / 934,962, filed September 23, 2022, entitled "Fluid Dispensing System with Disposable Manifold Assembly for Extended Dispensing," and U.S. provisional patent application No. 63 / 295,483, filed December 30, 2021, entitled "Fluid Dispensing System with Disposable Manifold Assembly for Extended Dispensing," the entire contents of which are incorporated herein by reference. Background Technology

[0003] Single-use systems (SUS) (such as biocontainer bags) are increasingly used in biopharmaceutical applications. SUS can be used in systems such as bioreactors and mixing systems. Exemplary upstream SUS applications include media preparation processes such as mixing and filtration, including, for example, tangential flow filtration (TFF). Examples of downstream SUS applications include, for example, chromatographic concentration and double filtration, as well as buffer preparation.

[0004] Compared to traditional reusable stainless steel systems, disposable systems offer several advantages. Disposable technology increases process flexibility, reduces the risk of cross-contamination, reduces or even eliminates the need for cleaning, reduces the requirement for internal sterilization (such as autoclaving) and cleaning chemical inventory, and minimizes process downtime.

[0005] One aspect of biopharmaceutical processing involves managing the movement of liquids through various elements, including pipes, valves, and sensors. Particularly in batch dispensing processes, it is necessary to divide the liquid equally from a large container into multiple individual containers while maintaining sterility.

[0006] Commercially available conventional systems consist of manifolds with a fixed number of outlets, which cannot be expanded. For example, if the requirement is to fill twenty containers from a large tank, a conventional system would include a manifold with a single inlet and twenty outlets. This arrangement allows for aseptic filling, but each manifold can only fill a maximum of 20 containers.

[0007] In this field, there remains a need for disposable applications involving the dispensing of fluid from a supply device into several smaller containers. For example, there is a continued need in the field for additional solutions to aseptically dispense liquid into large quantities of outlets and into containers (such as bags and bottles).

[0008] It is understood that this background description is intended to aid the reader's understanding and should not be construed as indicating that any of the problems described are themselves of importance in the art. While the principles described may mitigate problems inherent in other systems in some respects and embodiments, it should be understood that the scope of the protected innovation is defined by the appended claims, and not by the ability of any disclosed feature to solve any specific problem identified herein. Summary of the Invention

[0009] This disclosure relates in one aspect to embodiments of a fluid distribution system. In one embodiment, the fluid distribution system includes a first disposable distributor manifold, a slide plate, a first distributor valve assembly, and a set of disposable filling manifolds. The first disposable distributor manifold has a first distributor manifold inlet and a plurality of first distributor manifold outlets in fluid communication with the first distributor manifold inlet. The slide plate includes a pump. The first disposable distributor manifold is detachably mounted to the slide plate and fluidly arranged with the pump to provide supply fluid to the first distributor manifold inlet. The first distributor valve assembly includes a plurality of valves mounted to the slide plate and arranged with the first disposable distributor manifold such that each of the first distributor manifold outlets can be independently shut off by a corresponding valve in the first distributor valve assembly.

[0010] The set of disposable refill manifolds corresponds to the number of first dispenser manifold outlets. Each disposable refill manifold has a refill manifold inlet, a plurality of refill manifold outlets in fluid communication with the refill manifold inlet, and a sterile fluid connector configured to connect the refill manifold inlet to one of the plurality of first dispenser manifold outlets.

[0011] In another aspect, this disclosure relates to embodiments of a technique for aseptically dispensing fluids. In one embodiment, the method of aseptically dispensing fluid includes: delivering fluid into a dispenser manifold inlet of a disposable dispenser manifold; discharging a first supply fluid from a first dispenser manifold outlet of a plurality of dispenser manifold outlets of the disposable dispenser manifold through a first sterile fluid passage to a dispensing manifold inlet of a first disposable dispensing manifold; discharging portions of the first supply fluid from the plurality of dispensing manifold outlets of the first disposable dispensing manifold to a corresponding one of a first set of disposable containers, the first set of disposable containers being aseptically fluid connected to the plurality of dispensing manifold outlets of the first disposable dispensing manifold; and disconnecting the first disposable dispensing manifold from the disposable dispenser manifold after discharging the portions of the first supply fluid.

[0012] A second supply fluid is discharged from a second distributor manifold outlet of the plurality of distributor manifold outlets of the disposable dispenser manifold through a second sterile fluid passage to a dispensing manifold inlet of the second disposable dispensing manifold. Individual portions of the second supply fluid are discharged from the plurality of dispensing manifold outlets of the second disposable dispensing manifold to a corresponding one of a second set of disposable containers, the second set of disposable containers being sterilely fluidly connected to the plurality of dispensing manifold outlets of the second disposable dispensing manifold.

[0013] In another embodiment, a method of aseptically dispensing fluid includes delivering a first supply fluid into a dispenser manifold inlet of a first disposable dispenser manifold. The first supply fluid is discharged from a first dispenser manifold outlet of a plurality of dispenser manifold outlets of the first disposable dispenser manifold through a first sterile fluid passage to a dispenser manifold inlet of a second disposable dispenser manifold. The first supply fluid is discharged from a first dispenser manifold outlet of a plurality of dispenser manifold outlets of the second disposable dispenser manifold through a second sterile fluid passage to a dispensing manifold inlet of a first disposable filling manifold. Portions of the first supply fluid are discharged from the plurality of dispensing manifold outlets of the first disposable filling manifold to a corresponding one of a first set of disposable containers, the first set of disposable containers being aseptically fluid connected to the plurality of dispensing manifold outlets of the first disposable filling manifold. After dispensing the portions of the first supply fluid, the first disposable filling manifold is disconnected from the second disposable dispenser manifold.

[0014] A second disposable dispensing manifold is connected to a second dispensing manifold outlet among the plurality of dispensing manifold outlets of a second disposable dispenser manifold via a third sterile fluid channel. A second supply fluid is introduced into the dispensing manifold inlet of the first disposable dispenser manifold. The second supply fluid is discharged from a first dispensing manifold outlet among the plurality of dispensing manifold outlets of the first disposable dispenser manifold to the dispensing manifold inlet of the second disposable dispenser manifold via a first sterile fluid channel. The second supply fluid is discharged from a second dispensing manifold outlet among the plurality of dispensing manifold outlets of the second disposable dispenser manifold to the dispensing manifold inlet of the second disposable dispensing manifold via a third sterile fluid channel. A portion of the second supply fluid is discharged from the plurality of dispensing manifold outlets of the second disposable dispensing manifold to a corresponding one of a second set of disposable containers, the second set of disposable containers being sterilely fluidly connected to the plurality of dispensing manifold outlets of the second disposable dispensing manifold.

[0015] Further and alternative aspects and features of the disclosed principles will become apparent from the following detailed description and accompanying drawings. As will be understood, the fluid dispensing system and method of aseptic fluid dispensing disclosed herein can be implemented in other and different embodiments and can be modified in various respects. Therefore, it should be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and do not limit the scope of the appended claims. Attached Figure Description

[0016] Figure 1 This is a perspective view of an embodiment of a fluid distribution system constructed in accordance with the principles of this disclosure, which takes the form of an embodiment of a dispenser slide constructed in accordance with the principles of this disclosure.

[0017] Figure 2 yes Figure 1 A front view of the dispenser slide.

[0018] Figure 3 yes Figure 1 Another perspective view of the dispenser slide and a perspective view of an embodiment of the workstation configured to hold multiple disposable containers for receiving equal portions of fluid from the fluid dispensing system.

[0019] Figure 4 yes Figure 3 Front view of the dispenser slide and workstation.

[0020] Figure 5 yes Figure 1 Another perspective front view of the dispenser slide, including another embodiment of the fluid dispensing system constructed in accordance with the principles of this disclosure, and a perspective view of another embodiment of a workstation configured to hold a plurality of disposable containers for receiving equally divided portions of fluid from the fluid dispensing system.

[0021] Figure 6 yes Figure 5 Front view of the dispenser slide and workstation.

[0022] Figure 7 The present invention relates to a perspective view of another embodiment of a fluid distribution system constructed in accordance with the principles of this disclosure, and a perspective view of another embodiment of a workstation, the fluid distribution system including embodiments of a distributor slide and a distribution tower having a disposable filling manifold of the fluid distribution system mounted thereon, and the workstation being configured to hold a plurality of disposable containers for receiving equal portions of fluid from the fluid distribution system.

[0023] Figure 8 yes Figure 7 Front view of the distributor slide, distribution tower, and workstation.

[0024] Figure 9 yes Figure 7 Another front view of the distribution tower.

[0025] Figure 10 yes Figure 7 A perspective view of the distribution tower; for illustration purposes, cabinets are represented by broken lines.

[0026] Figure 11 This is a perspective view of another embodiment of a fluid distribution system constructed according to the principles of this disclosure, and a perspective view of a workstation of another embodiment, the fluid distribution system including a distributor slide, Figure 7 The distribution tower of one embodiment and another embodiment of the distribution tower, the other embodiment of the distribution tower having a disposable filling manifold of a fluid distribution system mounted thereon, the workstation being configured to hold a plurality of disposable containers for receiving equal portions of fluid from the fluid distribution system.

[0027] Figure 12 yes Figure 11 A top view of the distributor slide, distribution tower, and workstation.

[0028] Figure 13-33 This is a schematic diagram of a series of dispensing steps in an embodiment of a method for aseptically dispensing fluid in accordance with the principles of this disclosure.

[0029] It should be understood that the accompanying drawings are not necessarily drawn to scale, and the disclosed embodiments are illustrated by way of diagrams and partial views. In some cases, details that are not necessary for understanding this disclosure or that make other details difficult to perceive may have been omitted. It should be understood that the content of this disclosure is not limited to the specific embodiments described herein. Detailed Implementation

[0030] Embodiments of the fluid dispensing system constructed according to the principles of this disclosure are suitable for use with embodiments of aseptic fluid dispensing methods following the principles of this disclosure. Embodiments of the fluid dispensing system constructed according to the principles of this disclosure can be used in biopharmaceutical environments as well as other industrial applications (where different fluids, solutions, reagents, and / or chemicals are stored for metering to a processing station).

[0031] For example, embodiments of the fluid dispensing system constructed according to the principles of this disclosure are suitable for use in biological processing systems, wherein the supply of fluid is distributed into multiple containers for use in bioprocessing applications. Embodiments of the fluid dispensing system constructed according to the principles of this disclosure can be used in applications related to batch dispensing in pharmaceutical manufacturing. Embodiments of the fluid dispensing system constructed according to the principles of this disclosure can be used in applications related to formulation and dispensing, as well as other applications related to the aseptic dispensing of liquids.

[0032] In one embodiment, the fluid dispensing system includes a scalable series of disposable manifolds that are fluidly connected in series within a closed, sterile system. In another embodiment, the fluid dispensing system includes two, three, or more disposable manifolds connected in series to effectively increase the number of containers that can be aseptically dispensed through the upstream disposable manifold to a number greater than the number of outlets present. Therefore, the number of containers that can be dispensed using a fluid dispensing system constructed according to the principles of this disclosure is scalable to meet the specific parameters of a given application.

[0033] In one embodiment, the fluid dispensing system includes a disposable dispenser manifold adapted for sequential aseptic fluid connection to a set of disposable filling manifolds corresponding to the number of dispenser manifold outlets. In another embodiment, each manifold includes a replaceable component, which is installed into the fluid dispensing system for single-use in bioprocessing applications and unloaded after its intended single-use for disposal. In yet another embodiment, the fluid dispensing system includes an upstream disposable dispenser manifold adapted for sequential aseptic fluid connection to a set of intermediate disposable dispenser manifolds corresponding to the number of dispenser manifold outlets of the upstream disposable dispenser manifold. The system also includes multiple sets of disposable filling manifolds, wherein each set of disposable filling manifolds corresponds to the number of dispenser manifold outlets of a corresponding intermediate dispenser manifold in that set.

[0034] In one embodiment, the fluid distribution system is incorporated into a distributor slide, the distributor slide including at least one disposable distributor manifold and a set of disposable filling manifolds, the disposable filling manifolds being adapted to be in fluid communication with one of a plurality of distributor manifold outlets. In other embodiments, the fluid distribution system is incorporated into a distributor slide and one or more distribution towers, wherein the distribution towers are adapted to receive one of a set of disposable filling manifolds.

[0035] Embodiments of the fluid distribution system constructed according to the principles of this disclosure are configured as relatively compact solutions to achieve scalable variations of fluid distribution schemes for intended use in bioprocessing applications. Embodiments of the fluid distribution system constructed according to the principles of this disclosure may include a fluid supply, at least one disposable distributor manifold, a set of disposable filling manifolds, and multiple containers, each disposable filling manifold having a filling manifold inlet and multiple filling manifold outlets, the filling manifold inlet being adapted to be in fluid communication with one of the multiple distributor manifold outlets, the multiple containers corresponding to the product of the number of filling manifold outlets and the number of disposable filling manifolds in the set. Multiple sets of containers can be individually filled with each of the sets of disposable filling manifolds within a relatively small footprint (particularly compared to conventional distribution towers configured for similar bioprocessing applications) to store fluids for the intended bioprocessing application. Containers can be delivered to a storage area (e.g., a workstation supporting multiple biocontainer bags for bioprocess applications, such as chromatography / tangential flow filtration (TFF) applications) as required. Embodiments of the fluid dispensing system constructed according to the principles of this disclosure can be used as an alternative to conventional systems for similar bioprocess applications, which use a single-use manifold for dispensing containers no more than the number of outlets of the single-use manifold.

[0036] Now turn to the attached image. Figure 1 and Figure 2 An embodiment of a fluid distribution system 50 constructed according to the principles of this disclosure is shown, the fluid distribution system being integrated into a distributor chute 52 constructed according to the principles of this disclosure, the fluid distribution system including an upstream disposable distributor manifold 53, an intermediate disposable distributor manifold 54, and a disposable filling manifold 55 connected in series. The distributor chute 52 includes a pump 57 (see...). Figure 3 The pump is configured to draw fluid from a fluid supply device (not shown) and deliver the fluid to manifolds 53-55 connected in series.

[0037] In the illustrated embodiment, each manifold 53-55 includes a replaceable portion that is initially installed in the dispenser slide 52 for use in bioprocessing applications and then removed for disposal. After its intended use in the bioprocessing application is complete, the respective manifold 53-55 can be disconnected from the dispenser slide 52 according to a predetermined hierarchy and replaced with another disposable manifold having a similar construction.

[0038] In embodiments, the fluid distribution system 50 can be used with any suitable fluid that can be stored in a suitable container (such as a tank) in fluid communication with, for example, a pump 57. In embodiments, the fluid distribution system 50 constructed according to the principles of this disclosure may include at least two disposable manifolds 54, 55 connected in series in fluid connection.

[0039] Intermediate disposable dispenser manifold 54 is one of a group of intermediate disposable dispenser manifolds 54 having substantially the same construction and configured to be sequentially mounted onto dispenser slide 52. Similarly, disposable filling manifold 55 is one of a group of disposable filling manifolds 55 having substantially the same construction and configured to be sequentially mounted onto dispenser slide 52. The fluid distribution system 50 shown is configured to receive fluid (such as a buffer solution for a intended bioprocessing application, such as chromatography, TFF, etc.) from the supply device before replacing the upstream disposable dispenser manifold 53 and opening the closed system (six outlets for each of the group of twenty disposable filling manifolds 55 × five outlets for each of the group of four intermediate disposable dispenser manifolds 54 × four outlets for the upstream disposable dispenser manifold 53), and to sequentially distribute the fluid into up to one hundred and twenty containers by using the group of disposable filling manifolds 55 and disposable dispenser manifolds 54 in sequence.

[0040] In other embodiments, the fluid distribution system 50 may be configured to fill different maximum numbers of containers in a closed system before needing to be opened to continue distributing fluid to more containers. In one embodiment, the intermediate disposable dispenser manifold 54 may include at least one manifold with a different configuration than at least one other manifold in the group (e.g., a different number of outlets), and in another embodiment, the disposable filling manifold 55 may include at least one manifold with a different configuration than at least one other manifold in the group (e.g., a different number of outlets).

[0041] Reference Figure 2 Each of the upstream disposable distributor manifold 53, the intermediate disposable distributor manifold 54, and the disposable filling manifold 55 can have a similar structure. In the illustrated embodiment, each manifold 53-55 includes a piping assembly that interconnects the various ports of the manifold and is associated with a control valve to control the flow of fluid through the manifold. In this embodiment, the piping assembly includes multiple flexible lines adapted to be selectively closed by pinch valves mounted externally thereon. In this embodiment, the flexible piping can be made of any suitable material, such as silicone, thermoplastic elastomer (TPE), etc.

[0042] In embodiments, manifolds 53-55 may be made of any suitable material and may include suitable conduits defining fluid conduits passing through them. In embodiments, manifolds 53-55 may include any of a range of suitable materials and components readily known to those skilled in the art, such as silicone tubing, plastic injection-molded adapters, and commercially available connectors and disconnectors (e.g., from Pall Corporation, New York). Presto sterile connectors and (Aseptic disconnector). The manifolds 53-55 in the figure are made of tubing that can be selectively shut off by a pinch valve.

[0043] An upstream disposable distributor manifold 53 is detachably mounted to a distributor slide plate 52. The upstream disposable distributor manifold 53 has an upstream distributor manifold inlet 60 and multiple upstream distributor manifold outlets 61, 62, 63, and 64, the outlets being in fluid communication with the inlet through the hollow body of the manifold 53. The illustrated upstream disposable distributor manifold 53 includes four upstream distributor manifold outlets 61-64. In other embodiments, the number of upstream distributor manifold outlets 61-64 may vary. The upstream distributor manifold inlet 60 is fluidly arranged with a pump 57 mounted on the distributor slide plate 52 via suitable piping and connectors to supply fluid to a series of manifolds 53-55.

[0044] An intermediate disposable distributor manifold 54 is detachably mounted to a distributor slide plate 52. The intermediate disposable distributor manifold 54 has an intermediate distributor manifold inlet 70 and a plurality of intermediate distributor manifold outlets 71, 72, 73, 74, and 75, the intermediate distributor manifold outlets being in fluid communication with the intermediate distributor manifold inlet 70 through the hollow body of the manifold 54. The intermediate distributor manifold inlet 70 is in fluid communication with one of the upstream distributor manifold outlets (in this case, the fourth distributor manifold outlet 64). The illustrated intermediate disposable distributor manifold 54 includes five intermediate distributor manifold outlets 71-75. In other embodiments, the number of intermediate distributor manifold outlets 71-75 may be different.

[0045] Intermediate disposable dispenser manifold 54 is one of a group of intermediate disposable dispenser manifolds 54. This group of intermediate disposable dispenser manifolds 54 corresponds to the number (in this case, four) of upstream dispenser manifold outlets 61-64. Each intermediate disposable dispenser manifold 54 has a sterile fluid connector 77 configured to fluidly connect the intermediate dispenser manifold inlet 70 to one of the upstream dispenser manifold outlets. In an embodiment, each intermediate disposable dispenser manifold in the group of intermediate disposable dispenser manifolds 54 has a similar structure. In an embodiment, at least one intermediate disposable dispenser manifold 54 in the group of intermediate disposable dispenser manifolds 54 may have a different structure than at least one other intermediate disposable dispenser manifold in the group, for example, having a different number of intermediate dispenser manifold outlets.

[0046] In this embodiment, the distribution manifolds 53 and 54 are curved, which makes all the connecting pipes substantially the same length. This structure allows for a relatively compact manifold length and footprint, while also simplifying the manifold manufacturing process.

[0047] A disposable refill manifold 55 is detachably mounted to a dispenser slide plate 52. The disposable refill manifold 55 has a refill manifold inlet 80 and a plurality of refill manifold outlets 81, 82, 83, 84, 85, and 86, the outlets being in fluid communication with the refill manifold inlet 80 through a hollow body of the manifold 55. The refill manifold inlet 80 is in fluid communication with one of the intermediate dispenser manifold outlets 71-75 (in this case, the first intermediate dispenser manifold outlet 71). The illustrated disposable refill manifold 55 includes six refill manifold outlets 81-86. In other embodiments, the number of refill manifold outlets 81-86 may be different.

[0048] A disposable dispensing manifold 55 is one of a group of disposable dispensing manifolds 55. In an embodiment, the group of disposable dispensing manifolds 55 corresponds to the product of the number of outlets of each of two or more distributor manifolds connected in series upstream of the dispensing manifold inlet. In an embodiment where only one disposable distributor manifold is connected in series with the dispensing manifold inlet, the group of disposable dispensing manifolds 55 may correspond to the number of distributor manifold outlets of a single distributor manifold. In the illustrated embodiment, the group of disposable dispensing manifolds 55 comprises twenty disposable dispensing manifolds 55, which corresponds to the product of the number of intermediate distributor manifold outlets (five) and the number of upstream distributor manifold outlets (four). In an embodiment, the group of disposable dispensing manifolds 55 corresponds at least to the number of intermediate distributor manifold outlets. Each disposable dispensing manifold has a sterile fluid connector 87 configured to fluidly connect the dispensing manifold inlet 80 to one of the plurality of intermediate distributor manifold outlets 71-75.

[0049] In one embodiment, each of the disposable refueling manifolds 55 in the group has a similar structure. In another embodiment, at least one disposable refueling manifold 55 in the group may have a different structure from at least one other disposable refueling manifold in the group, for example, a different number of refueling manifold outlets than at least one other disposable refueling manifold in the group.

[0050] Reference Figure 2 The fluid distribution system 50 shown in the figure includes manifolds 53-55 ( Figure 2 Only the first one is shown in the diagram. Each outlet of the upstream distributor valve assembly 91 is associated with a plurality of valves 90 mounted on the slide plate 52 and arranged with the upstream disposable distributor manifold 53, such that each of the upstream distributor manifold outlets 61-64 can be independently closed by a corresponding valve 90 of the upstream distributor valve assembly 91. The intermediate distributor valve assembly 92 includes a plurality of valves 90 mounted on the slide plate 52 and arranged with the intermediate disposable distributor manifold 54, such that each of the intermediate distributor manifold outlets 71-75 can be independently closed by a corresponding valve 90 of the intermediate distributor valve assembly 92. The filling valve assembly 93 includes a plurality of valves 90 mounted on the slide plate 52 and arranged with the disposable filling manifold 55, such that each of the filling valve outlets 81-86 can be independently closed by a corresponding valve 90 of the filling valve assembly 93.

[0051] In embodiments, valve devices 91-93 may include any suitable valve adapted to selectively shut off their associated outlets. In the illustrated embodiment, valve devices 91-93 include pinch valves adapted to effectively shut off associated manifold outlets by means of a pinch manifold to control fluid flow within the system. Valve 90 is secured to slide plate 52 and provides means for removably mounting manifolds 53-55 to slide plate 52. In other embodiments, as readily apparent to those skilled in the art, different types of valves, such as solenoid valves, may be used. In embodiments, valve 90 may be operated by a suitable source, such as a pneumatic or electrical source. In embodiments, a control unit may be used to coordinate the operation of valve 90 of valve devices 91-93, the control unit being appropriately programmed to operate or one or more desired fluid dispensing sequences.

[0052] Reference Figure 1 The distributor slide plate 52 in the figure includes a first filling valve device 93 and a second filling valve device 94. The first filling valve device 93 is located on one side of the distributor slide plate 52, which includes the upstream and intermediate distributor manifolds 53 and 54. The second filling valve device 94 is located on the other side of the distributor slide plate 52.

[0053] The valves of the first refill valve assembly 93 are spaced apart from each other along a vertical axis. A single-use refill manifold 55 is mounted on the distributor slide plate 52, so that the valves of the first refill valve assembly 93 are associated with each refill manifold outlet. This arrangement is suitable for refilling storage containers such as… Figure 3 The container in the workstation 100 configured as shown is particularly useful.

[0054] The valves of the second filling valve device 94 are arranged at intervals along the horizontal axis. For example... Figure 5 As shown, a single-use filling manifold 55' can be mounted onto the distributor slide plate 52, so that the valves of the second filling valve assembly 94 are associated with each filling manifold outlet. This arrangement is suitable for filling storage containers such as... Figure 5 This is particularly useful when the container is in the workstation 100' configured as shown.

[0055] Reference Figure 1 The dispenser slide 52 includes a trolley 105, a cabinet 110, disposable manifolds 53-55, and valve devices 91-94. The cabinet 110 is mounted on top of the trolley 105 and is configured to house the hydraulic and automated equipment of the liquid dispensing system 50. The manifolds 53-55 include disposable manifolds detachably mounted to the cabinet 110, such that the manifolds 53-55 are operably arranged together with the valves of the valve devices 91-93 mounted on the cabinet 110.

[0056] The trolley 105 includes a base 112 and a plurality of wheels 114 rotatably connected to the base 112. In the illustrated embodiment, the base 112 is rectangular, and a wheel 114 is rotatably connected to each corner of the base 112. In other embodiments, the base 112 may be generally square.

[0057] Cabinet 110 is mounted on base 112 of trolley 105. In an embodiment, cabinet 110 includes storage units for automation and hydraulic equipment and is made of a suitable metal (e.g., stainless steel). Cabinet 110 defines an internal cavity that can be suitably configured to store and support components of a fluid distribution system. Valves of valve devices 91-94 can be supported by cabinet 110. In the illustrated embodiment, a clamping portion of each valve extends from the outer surface of cabinet 110 and is associated with a manifold outlet, respectively.

[0058] Reference Figure 3 In one embodiment, cabinet 110 houses a control unit 120 and at least one pump body 57. Pump 57 is operatively coupled to control unit 120, allowing control unit 120 to selectively operate pump 57. Pump 57 is adapted to selectively generate a fluid flow to supply fluid to manifolds 53-55. In one embodiment, pump 57 can be any suitable pump capable of generating a fluid flow through the manifold to deliver to a disposable container 125 connected to the filling manifold 55 and meeting the specifications for the intended application. In one embodiment, pump 57 includes a variable displacement pump. In another embodiment, fluid distribution system 50 includes multiple pumps capable of supplying one or more types of fluid to manifolds 53-55.

[0059] In an embodiment, the control unit 120 may include any suitable device configured to control the operation of at least one component of the liquid dispensing system 50 during a dispensing operation. In an embodiment, the control unit 120 includes a processor 121, a non-transitory computer-readable medium 122 carrying a liquid dispensing program, a data storage device 123, and a display device 125. The processor 121 is arranged with the computer-readable medium 122 to execute the fluid dispensing program. The processor 121 is operatively arranged with the display device 125 to selectively display output information from the fluid dispensing program and / or receive input information from a graphical user interface displayed on the display device 125.

[0060] The processor 121 can be configured as a controller to selectively operate at least one component of the fluid distribution system 50, such as the pump 57 and valve devices. In an embodiment, the processor 121 communicates electrically with the pump and valve devices to selectively operate the valves based on instructions from the fluid distribution program.

[0061] In embodiments, the controller and processor 121 may comprise separate devices, and the controller may be arranged to operatively communicate with the processor 121. In embodiments, the controller may include user input and / or interface devices having one or more user-actuated mechanisms (e.g., one or more buttons, sliders, rotary knobs, keyboards, and mice) adapted to generate one or more user-actuated input control signals. In embodiments, the controller may be configured to include one or more other user-actuated mechanisms to provide various other control functions of the fluid distribution system, as understood by those skilled in the art. The controller may be associated with a display device 125 adapted to display a graphical user interface. The graphical user interface may be configured in embodiments to function as both a user input device and a display device. In embodiments, the display device 125 may include a touchscreen device adapted to receive input signals from a user touching different portions of a display screen. In embodiments, the controller may be in the form of a smartphone, tablet, personal digital assistant (e.g., a wireless mobile device), laptop, desktop computer, or other type of device.

[0062] In an embodiment, the fluid dispensing procedure has a scaling module configured to sequentially execute a dispensing sequence according to the principles of this disclosure by passing through a series of valve opening and closing conditions. For example, the scaling module may be configured to open a corresponding one of an upstream distributor manifold outlet and an intermediate distributor manifold outlet, and close the other of the upstream distributor manifold outlet and an intermediate distributor manifold outlet, to perform a corresponding sequential series of dispensing operations using a corresponding one of the set of one-time dispensing manifolds. The scaling module may, with one of the upstream distributor manifold outlets open, sort the open states of each intermediate distributor manifold outlet, then close the one of the upstream distributor manifold outlets, and open the second of the upstream distributor manifold outlets while the others are closed. The scaling module may coordinate the sequential dispensing operations of the remaining valves in a similar manner. In an embodiment, the scaling module includes logic for scaling the dispensing operations to the number of containers required for a given closed system dispensing sequence.

[0063] In one embodiment, the control unit 120 is in electrical communication with each pump 57 for delivering fluid to manifolds 53-55 and each valve of valve devices 91-94. The control unit 120 is configured to selectively operate the pumps 57 and valve devices 91-94 according to logic and operating parameters included in the fluid dispensing procedure. In another embodiment, the control unit 120 is configured to control at least one of the pump speed and volumetric displacement of the pump 57 to control the amount of fluid dispensed into disposable containers 125 connected to the dispensing manifold 55. In the illustrated embodiment, the control unit 120 is configured to independently operate each valve of the different valve devices 91-93 to place each valve device in a series of sequential valve conditions so that the number of disposable containers 125 dispensed is greater than the number of dispensing manifold outlets of any one of the disposable dispensing manifolds 55 in that group of disposable dispensing manifolds 55.

[0064] In one embodiment, the control unit 120 is configured to selectively operate the pump 57 based on at least one input signal received from each workstation 100 of the holding container 125. In another embodiment, the control unit 120 is configured to operate the dispenser slide 52 to perform at least one dispensing sequence.

[0065] In one embodiment, processor 121 includes a specially programmed processor capable of dispensing a series of disposable containers 125 using at least one dispenser manifold 53, 54 and a set of disposable dispensing manifolds 55. In the illustrated embodiment, processor 121 is configured to facilitate control and operation of the fluid dispensing system 50. In another embodiment, processor 121 may be configured to receive input signals from a controller, send input control signals to the controller, and / or send output information to the controller. In the illustrated embodiment, the controller and processor 121 include the same means.

[0066] In one embodiment, the processor 121 is configured to display fluid data received from at least one sensor electrically communicating with the control unit 121 on a display device 125. The fluid data may also be stored in a data storage device 123 operatively arranged with the processor 121.

[0067] In embodiments, processor 121 may include any suitable computing device, such as a microprocessor, computer host, digital signal processor, portable computing device, electronic notebook, device controller, logic device (e.g., a programmable logic device configured to perform processing functions), digital signal processing (DSP) device, or computing engine within an appliance. In embodiments, processor 121 may also include one or more additional input devices (e.g., a keyboard and a mouse).

[0068] Processor 121 may have one or more associated memory devices for storing data and information. These memory devices may include any suitable type, including volatile and non-volatile memory devices such as RAM (Random Access Memory), ROM (Read-Only Memory), EEPROM (Electrically Erasable Programmable Read-Only Memory), flash memory, etc. In embodiments, processor 121 is adapted to execute programming stored on non-transitory computer-readable medium 122 to perform various methods, processes, and modes of operation in accordance with the principles of this disclosure.

[0069] In an embodiment, the non-transitory computer-readable medium 122 may contain a fluid dispensing program configured to implement embodiments of a method for dispensing fluid according to the principles of this disclosure. In an embodiment, the fluid dispensing program includes a graphical user interface (GUI) that can be displayed by a display device 125. The GUI can be used to facilitate a user inputting commands and data into the fluid dispensing program and to display the output generated by the fluid dispensing program.

[0070] The fluid dispensing program can be stored on any suitable computer-readable storage medium. For example, in embodiments, a fluid dispensing program following the principles of this disclosure can be stored on a hard disk, floppy disk, CD-ROM drive, magnetic tape drive, compression drive, flash memory drive, optical storage device, magnetic storage device, etc.

[0071] In one embodiment, processor 121 is operatively in communication with data storage device 123, which includes at least one database containing fluid allocation data. In another embodiment, a fluid allocation procedure can be configured to store fluid allocation data generated during system operation in data storage device 123. In yet another embodiment, the fluid allocation data can be logically associated with time data in the data storage device, thereby enabling the retrieval of various data for a given time.

[0072] Reference Figure 4 The workstation 100 is configured to hold a plurality of disposable containers 125. Each disposable container 125 has an access port 130, which is fluidly connected to a corresponding one of the filling manifold outlets 81-86 via a sterile fluid disconnector 131 and a sterile fluid connector 132.

[0073] Workstation 100 includes a workstation configured to hold fluid in disposable container 125, wherein a fluid distribution system equally distributes the fluid in disposable container 125 from a larger supply. Workstation 100 includes a cart 140, a frame structure 143, and a weighing scale 145.

[0074] A frame structure 143 is mounted on a cart 140 and configured to support disposable containers 125 in a stacked arrangement. The frame structure 143 includes four uprights 147 and four intersecting members 148. The four uprights are connected to and spaced apart from corresponding corners of the cart 140, and each intersecting member extends between two uprights 147, thus giving the frame structure 143 a rectangular configuration. In the illustrated embodiment, the workstation includes six shelves 149, each configured to support at least one disposable container 125, so that the frame structure 143 can support disposable containers 125 in a vertically stacked arrangement. In other embodiments, the workstation 100 may be configured to support different numbers of disposable containers 125, including configuring each shelf 149 to support multiple disposable containers 125.

[0075] The trolley 140 includes a base and a plurality of wheels rotatably attached to the base. In the illustrated embodiment, the base is rectangular, with wheels rotatably attached to each corner of the base. In other embodiments, the base may be substantially square. The base of the trolley 140 is mounted to the bottom of the frame structure 143. The trolley 140 can be positioned on a weighing scale 145, such that the weighing scale 145 supports the weight of the trolley 140 (and thus also supports the frame structure 143 and the container 125 stored therein).

[0076] In this embodiment, the weighing scale 145 can be any suitable scale adapted to weigh loads within a range corresponding to the intended fluid application. In this embodiment, the weighing scale 145 includes a suitable load cell that generates an electrical signal indicating the measured weight. The weighing scale 145 can be configured to generate the weight signal and can be positioned to electrically communicate with the control unit 120 to transmit the weight signal to the control unit 120. The control unit 120 can use the weight signal to provide a feedback loop to verify that the expected fluid volume is allocated to the container 125 stored in the workstation 100. In this embodiment, the control unit 120 can be configured to convert the measured fluid weight into a volumetric measurement of the fluid.

[0077] In other embodiments, workstations suitable for use with fluid distribution systems constructed according to the principles of this disclosure may have different configurations. For example, in other embodiments, the volume / weight of container 125 may be monitored using other techniques, as those skilled in the art will understand, such as fill level sensors. In embodiments, fill level sensors are configured to generate fill level signals indicating the amount of material within the storage volume of a disposable container as detected by the fill level sensors. Each fill level sensor may be electrically communicating with a control unit, allowing the control unit to use the level signal as a feedback loop. In embodiments, capacitive fill level sensors may be used to measure the fill level of a fluid medium or solid material disposed within the container storage volume. In embodiments, capacitive fill level sensors may be suitable commercially available strip sensors, such as those available from Balluff Ltd., which can detect the fill level along a strip over a predetermined length (e.g., 850 mm). In an embodiment, a capacitive filling level sensor for measuring the filling level can be configured to generate a measuring impedance in response to the detection range of material stored in a disposable container. The ohmic component of the measuring impedance (particularly the capacitive component therein) reflects the measured value of the filling level of the material in the container and can be used to generate a filling level signal.

[0078] Each disposable container 125 is fluidly connected to a corresponding dispensing manifold outlet of the dispenser slide 52 via a flexible conduit extending between each container 125 and its associated dispensing manifold outlets 81-86, and fluid communication is selectively maintained via a corresponding sterile connector 132. In embodiments, the sterile connector 132 can be any suitable connector, such as commercially available sterile connectors familiar to those skilled in the art. In embodiments, the conduit fluidly communicating the container 125 with the associated dispensing manifold outlets 81-86 is adapted to be selectively closed by a pinch valve mounted externally thereto, and in embodiments includes flexible conduit made of any suitable material, such as silicone, thermoplastic elastomer (TPE), etc.

[0079] In embodiments, the disposable container 125 includes any suitable container configured to store a desired volume of material for the intended application. In embodiments, the disposable container 125 includes a "2D" (or "two-dimensional") bio-container bag, as is well known to those skilled in the art.

[0080] In the illustrated embodiment, the disposable container 125 comprises a 2D biocontainer bag made of a flexible film material. The biocontainer bag 125 may include two or more ports and tubing with connecting ends, the ports and tubing being configured to receive material within and / or discharge material from the bag's internal storage volume. In other embodiments, the biocontainer bag 125 includes at least one additional port configured for use as a sampling port. In embodiments, the biocontainer bag 125 may define a storage volume of a predetermined size, for example, a volume ranging from one liter to twenty liters. In other embodiments, the storage volume may be of different sizes, such as one hundred liters. In embodiments, the biocontainer bag 125 comprises a suitable commercially available disposable biocontainer bag, such as Allegro, available from Pall Corporation in Port Washington, New York. TM 2D bio-container bag.

[0081] In an embodiment, the biocontainer bag 125 may include at least a pair of flexible panels joined together. The flexible panels cooperate to define an internal storage volume configured to hold a predetermined volume of material (e.g., one hundred liters). In an embodiment, each panel is made of a suitable plastic material. For example, in an embodiment, each panel is made of a low-density polyethylene (LDPE) fluid contact portion and an outer film having an ethylene-polyvinyl alcohol copolymer (EvOH) gas-barrier inner film. In an embodiment, the biocontainer bag may be made of a material that meets at least one of the following requirements: in vivo USP for VI-50°C grade plastics. <88> Bioreactivity testing, which aims to monitor the systemic toxicity, tissue irritation, and implantation biocompatibility of biocontainer extracts; USP for plastics. <87> Bioreactivity tests (in vitro) (cytotoxicity); and Sections 4 (hemolysis), 5 (cytotoxicity), 6 (implantation tests), 10 (stimulation and sensitization tests), and 11 (acute systemic toxicity) of ISO 10993 "Bio-evaluation of medical devices" (Section 8.2.2: ISO 10993 "Bio-evaluation of medical devices").

[0082] Reference Figure 5 In one embodiment, the fluid distribution system 50' includes a disposable filling manifold 55' mounted on a distributor slide plate 52, such that the valves of the second filling valve assembly 94 are associated with each of the filling manifold outlets 81', 82', 83', 84', 85', and 86', respectively. The valves of the second filling valve assembly 94 are arranged at intervals along a horizontal axis. With this arrangement, the filling manifold outlets 81'-86' can be positioned as follows: Figure 5 and 6 Above the workstation 100' shown in the configuration.

[0083] Figure 5 and Figure 6 The workstation 100' shown includes a cart 140, a frame structure 143', and a weighing scale 145. The frame structure 143' is mounted on the cart 140 and configured to support one or more biocontainer boxes. The frame structure 143' includes an upright structure configured to hold the boxes in place and forms a pair of handle portions 152 adapted for gripping as the workstation 100' moves on the surface where the wheels of the cart 140 are located. The workstation 100' includes a workstation configured to hold fluid in at least one disposable box, and a liquid dispensing system 50' equally distributing the fluid in the at least one disposable box from a larger supply. Figure 5 The workstation 100' can be compared with other workstations in other aspects. Figure 3 The workstations are 100 similar.

[0084] Reference Figure 7-10 In an embodiment, the fluid distribution system 250 constructed according to the principles of this disclosure includes at least one disposable filling manifold 255 and at least one filling valve assembly 293 mounted on a distribution tower 295 separate from the distributor slide plate 252. The illustrated distribution tower 295 includes a trolley 305 and a filling tower 310. The filling tower 310 extends from the trolley 305. Figure 7 and Figure 8 In the illustrated embodiment, two of the disposable dispensing manifolds, 255 and 255', are mounted on the dispensing tower of the distribution tower. In this embodiment, a dispensing valve device 293 is mounted on tower 310 and can be associated with one of the disposable dispensing manifolds 255 mounted on dispensing tower 310, such that the valve of the dispensing valve device 293 is associated with the outlet of each dispensing manifold. The outlet of the disposable dispensing manifold 255 can be positioned to be in fluid communication with corresponding plurality of disposable containers that can be supported by workstations 300 and 301.

[0085] In one embodiment, after the first 255 of the disposable dispensing manifold installed on the dispensing tower 310 has been used for a dispensing operation, another 255' of the disposable dispensing manifold installed on the dispensing tower 310 can be associated with another intermediate distributor manifold outlet of the dispensing valve device 293 and the intermediate disposable distributor manifold 254 installed on the dispensing tower 310. Then, the remaining disposable dispensing manifold 255' installed on the dispensing tower 310 can be used with another set of disposable containers in a second dispensing operation.

[0086] Reference Figure 9 and Figure 10The dispensing tower 310 of the distribution tower 295 is illustrated, having a dispensing valve assembly 293 and a disposable dispensing manifold 255 mounted thereon. The dispensing tower 310 includes a housing 315 that can support a plurality of valves, including the dispensing valve assembly 293, such that clamping portions of the valves extend from the outer surface of the housing 315. Figure 9 As shown, the clamping portion 297 can be associated with one of the corresponding outlets 281 of the filling manifold (only one is shown).

[0087] Reference Figure 11 and 12 In an embodiment, the fluid distribution system 450 constructed according to the principles of this disclosure includes at least one disposable filling manifold 455 and at least one filling valve device 493 mounted on a distribution tower 497 separate from the distributor slide plate 452. Figure 11 and Figure 12 In the illustrated embodiment, a pair of distribution towers 495 and 497 are provided. In another embodiment, the fluid distribution system 450 includes a plurality of distribution towers configured to support a plurality of different disposable containers dispensed via the fluid distribution system.

[0088] In the illustrated embodiment, a distribution tower 495 is structurally similar to... Figure 7-10 The distribution tower 295 is similar. Other distribution towers 497 include a gantry 505 comprising first and second columns 507, 508, and a beam 509 extending between the upper ends of the first and second columns 507, 508. Each column 507, 508 includes a trolley at its base, the trolley being configured to assist in the movement of the gantry 505. One of the set of single-use filling manifolds 455 and filling valve devices 493 is mounted to the beam.

[0089] Reference Figure 11 In this embodiment, the inlet of the disposable dispensing manifold can be in fluid communication with one of the outlets of the intermediate dispensing manifold 454 of the disposable intermediate dispensing manifold mounted on the dispensing slide plate 452. The outlet of the disposable dispensing manifold 455 can be in fluid communication with a plurality of corresponding disposable containers supported by workstations 500 and 501.

[0090] In one embodiment, the dispensing manifold inlet of the disposable dispensing manifold 456 mounted to the dispensing tower 510 can be positioned in fluid communication with the outlet of another intermediate distributor manifold of the disposable intermediate distributor manifold 454 mounted to the distributor slide plate 452. The dispensing manifold outlet of the disposable dispensing manifold 456 can be positioned to communicate with a workstation (e.g., workstation 500, 501, or other workstations with different configurations) Figure 7 The workstation shown is supported by another set of disposable containers that are fluidly connected.

[0091] In other embodiments, the fluid distribution system constructed according to the principles of this disclosure may include different devices configured to maintain a fluid supply for delivery to a manifold for distributed, proportional distribution in multiple disposable containers. For example, in other embodiments, the fluid distribution system constructed according to the principles of this disclosure may include at least one tower configured to hold one or more tanks filled with fluid for the fluid distribution system. In other embodiments, the fluid distribution system constructed according to the principles of this disclosure may include one or more tanks filled with fluid for the system.

[0092] In other embodiments of the fluid distribution system constructed according to the principles of this disclosure, the structure of the fluid distribution system may take alternative forms. For example, in one embodiment, a distribution tower may be replaced by a tank. In other embodiments, the fluid distribution system may be scaled up to meet greater capacity or scaled down for laboratory use. In one embodiment, the fluid distribution system may include a disposable manifold made of a rigid plastic structure. In one embodiment, the fluid distribution system constructed according to the principles of this disclosure can be used to process a variety of liquids to meet the requirements of desired applications.

[0093] In embodiments of the method of using a fluid distribution system following the principles of this disclosure, the fluid distribution system constructed according to the principles of this disclosure is used to deliver a portion of fluid to a series of disposable containers discussed herein. In embodiments, the method of using the fluid distribution system following the principles of this disclosure can be used with any embodiment of a fluid distribution system according to the principles discussed herein, which may include embodiments of a dispenser slide having at least one disposable dispenser manifold according to the principles of this disclosure.

[0094] In one embodiment, a method for aseptically dispensing fluid includes delivering fluid into a dispenser manifold inlet of a disposable dispenser manifold. A first supply fluid is discharged from a first dispenser manifold outlet of a plurality of dispenser manifold outlets of the disposable dispenser manifold through a first sterile fluid passage to a dispensing manifold inlet of a first disposable dispensing manifold. Portions of the first supply fluid are discharged from the plurality of dispensing manifold outlets of the first disposable dispensing manifold to a corresponding one of a first set of disposable containers, each sterilely fluid-connected to one of the plurality of dispensing manifold outlets of the first disposable dispensing manifold. After dispensing the portions of the first supply fluid, the first disposable dispensing manifold is disconnected from the disposable dispenser manifold.

[0095] The second supply fluid is discharged from the second distributor manifold outlet of the multiple distributor manifold outlets of the disposable distributor manifold through the second sterile liquid channel to the filling manifold inlet of the second disposable filling manifold. Each portion of the second supply fluid is discharged from the multiple filling manifold outlets of the second disposable filling manifold to a corresponding one of the second set of disposable containers, which are respectively sterilely fluid connected to the multiple filling manifold outlets of the second disposable filling manifold.

[0096] In an embodiment, the method further includes sequentially discharging additional supplied fluid from each of the other dispenser manifold outlet ports of the disposable dispenser manifold through a separate sterile fluid passage to the inlet of the respective other disposable dispensing manifold. Portions of the additional supplied fluid are discharged from the plurality of dispensing manifold outlets of each respective other disposable dispensing manifold to a corresponding one of an additional set of disposable containers, each sterilely fluid-connected to the plurality of dispensing manifold outlets of each respective other disposable dispensing manifold. After discharging the respective portions of the additional supplied fluid, each respective other disposable dispensing manifold is disconnected from the disposable dispenser manifold.

[0097] In one embodiment, the method further includes mounting the disposable distributor manifold to the filling plate before supplying fluid to the distributor manifold inlet of the disposable distributor manifold. After the additional supply of fluid has been sequentially discharged from each of the other distributor manifold outlet ports of the disposable distributor manifold, the disposable distributor manifold is removed from the filling plate.

[0098] In one embodiment, the disposable dispenser manifold includes a first disposable dispenser manifold. In another embodiment, the first supply fluid is introduced into the dispenser manifold inlet of the second disposable dispenser manifold, and then discharged from the first dispenser manifold outlet among a plurality of dispenser manifold outlets of the disposable dispenser manifold. The second disposable dispenser manifold in a first sterile fluid channel is inserted between the first dispenser manifold outlet among a plurality of dispenser manifold outlets of the first disposable dispenser manifold and the filling manifold inlet of the first disposable dispensing manifold, and the first supply fluid is discharged from the first dispenser manifold outlet among a plurality of dispenser manifold outlets of the second disposable dispenser manifold through the first sterile fluid channel to the filling manifold inlet of the first disposable dispensing manifold.

[0099] In another embodiment, a method of aseptically dispensing fluid includes delivering a first supply fluid into a dispenser manifold inlet of a first disposable dispenser manifold. The first supply fluid is discharged from a first dispenser manifold outlet of a plurality of dispenser manifold outlets of the first disposable dispenser manifold through a first sterile fluid passage to a dispenser manifold inlet of a second disposable dispenser manifold. The first supply fluid is discharged from a first dispenser manifold outlet of a plurality of dispenser manifold outlets of the second disposable dispenser manifold through a second sterile fluid passage to a filling manifold inlet of a first disposable filling manifold. Each portion of the first supply fluid is discharged from a plurality of filling manifold outlets of the first disposable filling manifold to a corresponding one of a first set of disposable containers, each sterilely fluid-connected to a plurality of filling manifold outlets of the first disposable filling manifold.

[0100] After discharging portions of the first supply fluid, the first disposable dispensing manifold is disconnected from the second disposable dispenser manifold, and the second disposable dispensing manifold is connected to the second dispenser manifold outlet among the plurality of dispenser manifold outlets of the second disposable dispenser manifold via a third sterile fluid channel. The second supply fluid is introduced into the dispenser manifold inlet of the first disposable dispenser manifold. The second supply fluid is discharged from the first dispenser manifold outlet among the plurality of dispenser manifold outlets of the first disposable dispenser manifold through the first sterile fluid channel to the dispenser manifold inlet of the second disposable dispenser manifold. The second supply fluid is discharged from the second dispenser manifold outlet among the plurality of dispenser manifold outlets of the second disposable dispenser manifold through the third sterile fluid channel to the dispensing manifold inlet of the second disposable dispensing manifold. Each portion of the second supply fluid is discharged from the plurality of dispensing manifold outlets of the second disposable dispensing manifold to a corresponding one of the second set of disposable containers, each sterilely fluid-connected to one of the plurality of dispensing manifold outlets of the second disposable dispensing manifold.

[0101] In an embodiment, the method further includes sequentially discharging additional supplied fluid from each of the other dispenser manifold outlet ports of the second disposable dispenser manifold through a separate sterile fluid passage to the manifold inlet of a corresponding other disposable dispensing manifold. Portions of the additional supplied fluid are discharged from multiple manifold outlets of each corresponding other disposable dispensing manifold to a corresponding one of an additional set of disposable containers, each sterilely fluid-connected to multiple manifold outlets of each corresponding other disposable dispensing manifold.

[0102] In one embodiment, the method further includes disconnecting each corresponding additional disposable dispensing manifold from the second disposable dispenser manifold after discharging portions of the additional supplied fluid. In another embodiment, the method further includes disconnecting the second disposable dispenser manifold after sequentially discharging the additional supplied fluid from each of the other dispenser manifold outlet ports of the second disposable dispenser manifold, and connecting a second dispenser manifold outlet of the plurality of dispenser manifold outlets of the first disposable dispenser manifold to the dispenser manifold inlet of the third disposable dispenser manifold via a fourth sterile fluid passage.

[0103] In an embodiment, the method further includes supplying a third supply fluid into the distributor manifold inlet of the first disposable distributor manifold. The third supply fluid is discharged from a second distributor manifold outlet of a plurality of distributor manifold outlets of the first disposable distributor manifold through a fourth sterile fluid passage to the distributor manifold inlet of the third disposable distributor manifold. The third supply fluid is discharged from a first distributor manifold outlet of a plurality of distributor manifold outlets of the third disposable distributor manifold through a fifth sterile liquid passage to the filling manifold inlet of the third disposable filling manifold. Each portion of the third supplied liquid is discharged from a plurality of filling manifold outlets of the third disposable filling manifold to a corresponding one of a third set of disposable containers, each sterilely fluid-connected to a plurality of filling manifold outlets of the third disposable filling manifold.

[0104] In an embodiment, the method further includes sequentially discharging additional supplied fluid from each of the other dispenser manifold outlet ports of the third disposable dispenser manifold through a separate sterile fluid passage to the manifold inlet of a corresponding other disposable dispensing manifold. Portions of the additional supplied fluid are discharged from multiple manifold outlets of each corresponding other disposable dispensing manifold to a corresponding one of an additional set of disposable containers, each sterilely fluid-connected to multiple manifold outlets of each corresponding other disposable dispensing manifold.

[0105] In an embodiment, the method further includes sequentially discharging one of an additional set of supplied fluids from the outlet port of each of the other distributor manifolds of the first disposable distributor manifold into a set of intermediate disposable distributor manifolds.

[0106] In another embodiment of the method for aseptically dispensing fluid following the principles of this disclosure, the method includes sequentially dispensing supplied fluid from different of a plurality of dispenser manifold outlets of a disposable dispenser manifold, each dispenser manifold outlet being in fluid communication via a corresponding sterile fluid conduit to a corresponding inlet of a plurality of disposable inlet manifolds, wherein the sequential dispensing of fluid is performed by operating a valve device to sequentially pass through a series of different conditions (including, for each dispenser manifold outlet port, the dispenser manifold outlet port being open while other dispenser manifold outlets are closed).

[0107] In an embodiment, for each disposable dispensing manifold, a portion of the fluid supply received from one of the dispenser manifold outlets in fluid communication with it is discharged from each of the plurality of dispensing manifold outlets into one of a corresponding set of disposable containers, which are respectively sterilely fluidly connected thereto. In an embodiment, the fluid supply is sequentially discharged by operating a valve device to sequentially open each sterile fluid conduit while the other sterile fluid conduits are closed.

[0108] Reference Figure 13-32 This shows a series of betting sequences. Figure 13-16 The first betting order 700 is described. (See reference...) Figure 13 The inlet 701 of the first dispensing manifold 702 in a set of dispensing manifolds is connected to the outlet 703 of the first intermediate distributor manifold 704. The first set of disposable containers 705 can be aseptically connected to the outlet 707 of the first dispensing manifold 702. (Refer to...) Figure 14 The first set of disposable containers 705 can be dispensed with fluid via a first upstream distributor manifold 708 and a first intermediate distributor manifold 704, the first intermediate distributor manifold 704 being fluidly connected to the first upstream distributor manifold outlet 709 of the first upstream distributor manifold 708. (Refer to...) Figure 15 The first set of disposable containers can be disconnected from the first dispensing manifold 702. (See reference...) Figure 16 After the fluid dispensing system has been used to distribute fluid to a first set of containers that are sterilely connected to the outlet of the first disposable dispensing manifold 702, the first disposable dispensing manifold 702 can be disconnected from the first outlet 703 of the intermediate disposable dispenser manifold 704.

[0109] Figure 17-21 The second betting order 720 is described. (See reference...) Figure 17 Another 721 in this set of disposable dispensing manifolds can be aseptically connected to the second outlet 722 of the first intermediate disposable dispenser manifold 704. (Refer to...) Figure 18 The second set of disposable containers 725 can be aseptically connected to the outlet 727 of the second disposable dispensing manifold 721. (Refer to...) Figure 19The fluid dispensing system can be used to distribute fluid to a second set of containers 725 that are aseptically connected to an outlet 727 of a second disposable dispensing manifold 721. The second set of disposable containers 721 can be dispensed using fluid passing through a first upstream dispensing manifold 708 and a first intermediate dispensing manifold 704, the first intermediate dispensing manifold 704 being fluidly connected to the first upstream dispensing manifold outlet 709 of the first upstream dispensing manifold 708. (Refer to...) Figure 20 The second set of disposable containers 725 can be disconnected from the second filling manifold 721. (See reference...) Figure 21 After the fluid dispensing system has been used to dispense fluid to a second set of containers that are sterilely connected to the outlet 727 of the second disposable dispensing manifold 721, the second disposable dispensing manifold 721 can be disconnected from the second outlet 722 of the first intermediate disposable dispenser manifold 704.

[0110] Reference Figure 22-26 , Figure 17-21 The filling sequence described herein can be repeated for each of the remaining outlets 733, 734, 735, and 736 of the first intermediate disposable distributor manifold 704.

[0111] Reference Figure 27 After each outlet 703, 722, 733-736 of the first intermediate distributor manifold 704 has been used to execute the dispensing sequence, the first intermediate distributor manifold 704 can be disconnected from the first outlet 709 of the upstream distributor manifold 708. (Refer to...) Figure 28 The second outlet 740 in this intermediate distributor manifold can be aseptically connected to the second outlet 742 of the upstream distributor manifold 708. (See reference...) Figure 29 The second intermediate distributor manifold 740 can be used in a similar manner to the first intermediate distributor manifold described above. (Refer to...) Figure 30 , Figure 17-21 The filling sequence described herein can be repeated for each outlet 751-756 of the second intermediate disposable distributor manifold 740. (See reference...) Figure 31 After each outlet 751-756 of the second intermediate distributor manifold 740 is used to perform the dispensing sequence, the second intermediate distributor manifold 740 can be disconnected from the second outlet 742 of the upstream distributor manifold 708.

[0112] Reference Figure 32 , Figure 17-31 The filling sequence described herein can be repeated for each of the remaining outlets 773, 774 of the upstream distributor manifold 708. (See reference...) Figure 33After the fourth intermediate distributor manifold 777 performs the dispensing sequence via the fourth upstream distributor manifold outlet 774 of the first upstream distributor manifold 708, the first upstream distributor manifold 708 can be removed from the distributor slide, and the closed system is opened. After use in a predetermined bioprocessing application, the first upstream distributor manifold 708 can be disconnected from the distributor slide and replaced with another disposable upstream distributor manifold of similar structure, placed in series with one of another set of intermediate distributor manifolds and one of another set of dispensing manifolds to provide a second closed system.

[0113] In one embodiment, the fluid distribution system is configured to provide a closed system for use with a "X" group dispensing sequence, wherein the "X" group dispensing sequence is equal to the number of outlets in the first distributor manifold. In another embodiment, the fluid distribution system is configured to provide a closed system for use with a "X" and "Y" product group dispensing sequence, wherein the "X" group dispensing sequence is equal to the number of outlets in the first distributor manifold, and the "Y" group sequence is equal to the number of outlets in a second distributor manifold connected in series with the first distributor manifold.

[0114] All references cited in this article, including publications, patent applications and patents, are incorporated herein by reference to the same extent that each reference is individually and explicitly stated to be incorporated herein by reference and is listed in its entirety.

[0115] The terms "an," "a," and "described," and their use in the context of describing the invention (particularly in the context of the following claims), should be interpreted as encompassing both the singular and the plural, unless otherwise stated herein or clearly contradicted by the context. The terms "comprising," "having," "including," and "comprise" should be understood as open-ended terms (i.e., meaning "including but not limited to"), unless otherwise stated. The terms "first," "second," etc., are used for convenience of reference only and are not intended to be restrictive, for example, regarding time or sequence requirements, unless otherwise stated herein or clearly contradicted by the context. Unless otherwise stated herein, the description of numerical ranges herein is merely a shorthand method, individually referring to each individual value falling within the range, each individual value incorporated into the specification as if individually described herein. Unless otherwise stated herein or clearly contradicted by the context, all methods described herein can be performed in any suitable order. The use of any and all examples, or exemplary language provided herein (e.g., "as"), is merely for better illustrative purposes and does not constitute a limitation on the scope of the invention, unless otherwise required. No language in the specification should be construed as indicating that any element not claimed is essential to the implementation of the invention.

[0116] Preferred embodiments of the invention are described herein, including the best modes of carrying out the invention known to the inventors. Variations of these preferred embodiments may become apparent to those skilled in the art upon reading the foregoing description. The inventors intend that skilled craftsmen will be able to employ these variations as appropriate, and the inventors intend to practice the invention beyond the specific description herein. Therefore, the invention includes all modifications and equivalents to the subject matter described in the appended claims as permitted by applicable law. Furthermore, unless otherwise stated herein or clearly contradicted by the context, any combination of the foregoing elements in all possible variations is included in the invention.

Claims

1. A fluid distribution system, the fluid distribution system comprising: A first disposable distributor manifold, the first disposable distributor manifold having a first distributor manifold inlet and a plurality of first distributor manifold outlets in fluid communication with the first distributor manifold inlet; The slide includes a pump, and a first disposable dispenser manifold is detachably mounted to the slide and fluidly arranged with the pump to provide supply fluid to the inlet of the first dispenser manifold; A first distributor valve assembly includes a plurality of valves mounted to a slide plate and arranged together with a first disposable distributor manifold, such that each outlet of the first distributor manifold can be independently shut off by a corresponding valve in the first distributor valve assembly. A set of disposable dispensing manifolds, the set of disposable dispensing manifolds corresponding to the number of first dispenser manifold outlets, each disposable dispensing manifold having a dispensing manifold inlet, a plurality of dispensing manifold outlets in fluid communication with the dispensing manifold inlet, and a sterile fluid connector configured to fluidly connect the dispensing manifold inlet to one of the plurality of first dispenser manifold outlets; A second disposable distributor manifold has a second distributor manifold inlet and a plurality of second distributor manifold outlets in fluid communication with the second distributor manifold inlet. The second disposable distributor manifold is detachably mounted to a distributor slide plate. One of the plurality of second distributor manifold outlets is in fluid communication with a first distributor manifold inlet. The second distributor manifold inlet is fluidly arranged with a pump for delivering supply fluid through the second disposable distributor manifold to the first distributor manifold inlet. The second distributor valve assembly includes a plurality of valves mounted to a slide plate and arranged together with a second disposable distributor manifold, such that each outlet of the second distributor manifold can be independently shut off by a corresponding valve in the second distributor valve assembly.

2. The fluid distribution system according to claim 1, wherein, The first disposable dispenser manifold is one of a set of first disposable dispenser manifolds corresponding to the number of outlets of the second dispenser manifolds. Each first disposable dispenser manifold has a sterile fluid connector configured to fluidly connect the inlet of the first disposable dispenser manifold to one of the plurality of outlets of the second dispenser manifolds.

3. The fluid distribution system according to any one of claims 1 to 2, wherein, One of the set of disposable manifolds is mounted to the slide plate, and the fluid distribution system further includes: A filling valve device comprising a plurality of valves, the plurality of valves of the filling valve device being mounted to a slide plate and arranged together with a disposable filling valve device, such that each of the filling manifold outlets can be independently shut off by a corresponding valve in the filling valve device.

4. The fluid distribution system according to claim 3, wherein, The plurality of valves of the filling valve device are arranged at intervals along a vertical axis.

5. The fluid distribution system according to claim 3, wherein, The plurality of valves of the filling valve assembly are arranged at intervals along a horizontal axis.

6. The fluid distribution system according to any one of claims 1 to 2, wherein the fluid distribution system further comprises: A distribution tower, wherein one of the set of disposable filling manifolds is installed in the distribution tower; A filling valve device comprising a plurality of valves, wherein the plurality of valves of the filling valve device are installed to the distribution tower and arranged together with a disposable filling manifold installed to the distribution tower, such that each of the filling manifold outlets can be independently shut off by a corresponding valve in the filling valve device.

7. The fluid distribution system according to claim 6, wherein, The dispensing tower includes a tower and a trolley, with the tower extending from the trolley, and one of the set of disposable dispensing manifolds and a dispensing valve device installed on the tower.

8. The fluid distribution system according to claim 6, wherein, The distribution tower includes a gantry comprising a first column and a second column, and a beam extending between the upper ends of the first column and the second column, wherein one of the set of disposable filling manifolds and the filling valve device are mounted to the beam.

9. The fluid distribution system according to any one of claims 1 to 8, wherein the fluid distribution system further comprises: Multiple disposable containers, each having an access port that is fluidly connected to a corresponding dispensing manifold outlet via a sterile fluid connector; A control unit includes a processor and a non-transitory computer-readable medium carrying a fluid dispensing program. The processor is arranged together with the computer-readable medium to execute the fluid dispensing program. The processor is electrically in communication with the first distributor valve assembly to selectively operate the valves of the first distributor valve assembly based on instructions from the fluid dispensing program. The fluid dispensing program has an extension module configured to sequentially open a corresponding outlet of the first distributor manifold and close the other first distributor manifold outlets to perform a corresponding sequential series of dispensing operations with a corresponding outlet of the set of single-use dispensing manifolds.

10. A method for aseptically dispensing fluid, the method comprising: The fluid is fed into the distributor manifold inlet of the disposable distributor manifold; The first supply fluid is discharged from the first distributor manifold outlet of the plurality of distributor manifold outlets of the disposable distributor manifold through the first sterile fluid channel to the filling manifold inlet of the first disposable filling manifold; Each portion of the first supply fluid is discharged from a plurality of manifold outlets of the first disposable manifold to a corresponding one of a first set of disposable containers, the first set of disposable containers being aseptically fluid connected to the plurality of manifold outlets of the first disposable manifold; After discharging all portions of the first supply fluid, disconnect the first disposable filling manifold from the disposable dispenser manifold; The second supply fluid is discharged from the second distributor manifold outlet of the plurality of distributor manifold outlets of the disposable distributor manifold through the second sterile fluid channel to the filling manifold inlet of the second disposable filling manifold; Each portion of the second supply fluid is discharged from a plurality of manifold outlets of the second disposable manifold to a corresponding one of a second set of disposable containers, the second set of disposable containers being aseptically fluid connected to the plurality of manifold outlets of the second disposable manifold; Wherein, the disposable distributor manifold includes a first disposable distributor manifold, and wherein discharging the first supply fluid from the first distributor manifold outlet of a plurality of distributor manifold outlets of the disposable distributor manifold comprises: The first supply fluid is fed into the inlet of the second disposable dispenser manifold, which is inserted in the first sterile fluid channel between the first dispenser manifold outlet and the inlet of the first disposable filling manifold, one of the plurality of dispenser manifold outlets. The first supply fluid is discharged from the first distributor manifold outlet of the plurality of distributor manifold outlets of the second disposable distributor manifold through the first sterile fluid channel to the filling manifold inlet of the first disposable filling manifold.

11. The method according to claim 10, further comprising: The additional supplied fluid is sequentially discharged from the outlet port of each other dispenser manifold of the disposable dispenser manifold through a corresponding independent sterile fluid channel to the inlet of the corresponding other disposable dispensing manifold; The additional supply of fluid is discharged from the plurality of manifold outlets of each corresponding other disposable manifold to a corresponding one of an additional set of disposable containers, which are aseptically fluid connected to the plurality of manifold outlets of each corresponding other disposable manifold. After discharging the portions of the additional supplied fluid, disconnect each corresponding additional disposable manifold from the disposable dispenser manifold.

12. The method according to claim 11, wherein the method further comprises: The disposable distributor manifold is installed into the filling slide before fluid is fed into the distributor manifold inlet. After the additional supplied fluid has been discharged sequentially from the outlet port of each of the other distributor manifolds of the disposable distributor manifold, the disposable distributor manifold is removed from the filling slide.

13. A method for aseptically dispensing fluid, the method comprising: The first supply fluid is fed into the distributor manifold inlet of the first disposable distributor manifold; The first supply fluid is discharged from the first manifold of the first disposable dispenser manifold through the first sterile fluid channel to the dispenser manifold inlet of the second disposable dispenser manifold. The first supply fluid is discharged from the first distributor manifold outlet of the plurality of distributor manifold outlets of the second disposable distributor manifold through the second sterile fluid channel to the filling manifold inlet of the first disposable filling manifold; Each portion of the first supply fluid is discharged from the plurality of manifold outlets of the first disposable manifold to a corresponding one of the first set of disposable containers, the first set of disposable containers being aseptically fluid connected to the plurality of manifold outlets of the first disposable manifold; After discharging each portion of the first supply fluid, the first disposable filling manifold is disconnected from the second disposable dispenser manifold, and the second disposable filling manifold is connected to the second dispenser manifold outlet of the plurality of dispenser manifold outlets of the second disposable dispenser manifold through a third sterile fluid channel. The second supply fluid is fed into the distributor manifold inlet of the first disposable distributor manifold; The second supply fluid is discharged from the first distributor manifold outlet of the plurality of distributor manifold outlets of the first disposable distributor manifold through the first sterile fluid channel to the distributor manifold inlet of the second disposable distributor manifold. The second supply fluid is discharged from the second distributor manifold outlet of the plurality of distributor manifold outlets of the second disposable distributor manifold through the third sterile fluid passage to the filling manifold inlet of the second disposable filling manifold; Each portion of the second supply fluid is discharged from the plurality of manifold outlets of the second disposable manifold to a corresponding one of the second set of disposable containers, the second set of disposable containers being aseptically fluid connected to the plurality of manifold outlets of the second disposable manifold.

14. The method of claim 13, further comprising: The additional fluid is sequentially discharged from the outlet port of each of the other dispenser manifolds of the second disposable dispenser manifold through the respective independent sterile fluid channel to the filling manifold inlet of the corresponding other disposable dispenser manifold. The additional supplied fluid portions are discharged from the plurality of manifold outlets of each corresponding other disposable manifold to a corresponding one of an additional set of disposable containers, which are aseptically connected to the plurality of manifold outlets of each corresponding other disposable manifold.

15. The method of claim 14, further comprising: After discharging each portion of the additional supplied fluid, disconnect each corresponding additional disposable manifold from the second disposable dispenser manifold. After the additional supplied fluid is discharged sequentially from each of the other dispenser manifold outlet ports of the second disposable dispenser manifold, the second disposable dispenser manifold is disconnected, and the second dispenser manifold outlet of the plurality of dispenser manifold outlets of the first disposable dispenser manifold is connected to the dispenser manifold inlet of the third disposable dispenser manifold via a fourth sterile fluid passage.

16. The method of claim 15, further comprising: The third supply fluid is fed into the distributor manifold inlet of the first disposable distributor manifold; The third supply fluid is discharged from the second distributor manifold outlet of the plurality of distributor manifold outlets of the first disposable distributor manifold through the fourth sterile fluid channel to the distributor manifold inlet of the third disposable distributor manifold. The third supply fluid is discharged from the first distributor manifold outlet of the plurality of distributor manifold outlets of the third disposable distributor manifold through the fifth sterile fluid channel to the filling manifold inlet of the third disposable filling manifold. Each portion of the third supply fluid is discharged from the plurality of manifold outlets of the third disposable manifold to a corresponding one of the third set of disposable containers, which are aseptically fluid connected to the plurality of manifold outlets of the third disposable manifold.

17. The method of claim 16, further comprising: The additional fluid supplied is sequentially discharged from the outlet port of each of the other dispenser manifolds of the third disposable dispenser manifold through a corresponding independent sterile fluid channel to the inlet of the corresponding other disposable dispensing manifold; The portions of the additional fluid supplied are discharged from the plurality of manifold outlets of each corresponding other disposable manifold to a corresponding one of an additional set of disposable containers, which are aseptically connected to the plurality of manifold outlets of each corresponding other disposable manifold.

18. The method of claim 17, further comprising: One of the additional sets of supplied fluids is sequentially discharged from the outlet port of each of the other distributor manifolds from the first disposable distributor manifold into a set of intermediate disposable distributor manifolds.

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