Fluid dispensing system with disposable manifold fluid recovery assembly

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-references to related applications

[0002] This patent application claims priority to U.S. non-provisional patent application No. 17 / 934,486, filed September 22, 2022, entitled "Fluid Dispensing System with Disposable Manifold Fluid Recovery Assembly," and U.S. non-provisional patent application No. 63 / 295,490, filed December 30, 2021, entitled "Fluid Dispensing System with Disposable Manifold Fluid Recovery Assembly," 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] In traditional systems, after the dispensing sequence has been executed, the fluid can remain in the manifold of the fluid dispensing system. For a typical drug solution, the cost per milliliter can be several thousand dollars. In some cases, the operator may manually manipulate the manifold to force fluid from the manifold into "odd" containers for each change. These containers are "odd" because their volume is different from the customer-filled container, and therefore the fluid in these containers is often discarded for offline analysis or not included in the final drug formulation. This is not only a costly loss but also reduces the amount of drug produced in the final formulation and the number of drug doses used to treat patients per batch.

[0007] There remains a need in the art for single-use applications related to dispensing fluids from a supply to a number of smaller containers. For example, there continues to be a need in the art to provide additional solutions to aliquot liquids in a sterile manner to a large number of outlets, as well as to containers such as bags and bottles, while reducing the amount of fluid wasted during the filling operation.

[0008] It is to be understood that this background description is for illustrative purposes only, and should not be taken as indicative of any SUMMARY

[0009] The present disclosure relates, in one aspect, to embodiments of a fluid dispensing system. In one embodiment, the fluid dispensing system includes a pump, a disposable fill manifold, a fill valve arrangement, and a control unit.

[0010] The pump is adapted to selectively produce a flow of fluid. The disposable fill manifold includes a fill manifold inlet, a plurality of fill manifold outlets, and a fill manifold body conduit. The fill manifold inlet is in fluid communication with each of the plurality of fill manifold outlets through the fill manifold body conduit. The fill manifold inlet is arranged with the pump for delivering a supply fluid to the disposable fill manifold, the fill manifold outlets include at least one standard fill outlet and one underfill outlet. The fill valve arrangement includes a plurality of valves arranged with the disposable fill manifold such that each of the fill manifold outlets is independently occludable by a respective one of the fill valve arrangement valves.

[0011] The control unit includes a processor and a non-transitory computer readable medium carrying a fluid dispensing program. The processor is arranged with the computer readable medium to execute the fluid dispensing program. The processor is in electrical communication with the pump and the fill valve arrangement to selectively operate the pump and the valves of the fill valve arrangement based on instructions of the fluid dispensing program. The fluid dispensing program has a container fill module configured to discharge a target fill volume amount of the supply fluid out of each of the standard fill outlets of the fill manifold outlets, to discharge an underfill volume amount of the supply fluid out of the underfill outlet of the fill manifold outlets, and to discharge a fill manifold volume amount of the supply fluid from the fill manifold body conduit out of the underfill outlet of the fill manifold outlets. The underfill volume amount is less than the target fill volume amount

[0012] In another aspect, the present disclosure is directed to embodiments of a technique for aseptically dispensing a fluid. In one embodiment, a method for aseptically dispensing a fluid includes: advancing a supply liquid into a fill manifold inlet of a disposable fill manifold. Expelling a fill portion of the supply fluid from all but a reserved fill manifold outlet of a plurality of fill manifold outlets of the disposable fill manifold into a disposable container in aseptic fluid connection with the fill manifold outlets, respectively. After expelling the fill portion, expelling an underfill portion of the supply fluid from the reserved fill manifold outlet of the fill manifold outlets into the disposable container in aseptic fluid connection with the reserved fill manifold outlet. The underfill portion is less than the fill portion. After expelling the underfill portion, expelling a fill manifold volume of the supply fluid from a body conduit of the disposable fill manifold out the reserved fill manifold outlet of the fill manifold outlets into the disposable container in aseptic fluid connection with the reserved fill manifold outlet.

[0013] Further and alternative aspects and features of the disclosed principles will be appreciated from the following detailed description and the accompanying drawings. As will be appreciated, the fluid dispensing system and method for aseptically dispensing a fluid disclosed herein can be implemented in other and different embodiments, and modifications can be made in the various aspects. Accordingly, it is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the scope of the appended claims. BRIEF DESCRIPTION OF DRAWINGS

[0014] Figure 1 is a perspective view of an embodiment of a fluid dispensing system constructed in accordance with the principles of the present disclosure, in the form of an embodiment of a dispenser skid constructed in accordance with the principles of the present disclosure.

[0015] Figure 2 is a perspective view of an embodiment of a dispenser skid of Figure 1 is a front view of the dispenser skid of

[0016] Figure 3 is a perspective view of another embodiment of a dispenser skid of Figure 1 and a perspective view of an embodiment of a work station configured to hold a plurality of disposable containers for receiving aliquoted portions of fluid from the fluid dispensing system.

[0017] Figure 4 is a front view of the dispenser skid of Figure 3 and the work station.

[0018] Figure 5 is a perspective view of another embodiment of a dispenser skid of Figure 1 and a perspective view of another embodiment of a work station configured to hold a plurality of disposable containers for receiving aliquoted portions of fluid from the fluid dispensing system.

[0019] Figure 6 is Figure 5 a front view of the dispenser sled and the workstation of

[0020] Figure 7 is a perspective view of another embodiment of a fluid dispensing system including an embodiment of a dispenser sled and an embodiment of a dispensing tower having a disposable prime manifold of the fluid dispensing system mounted thereto, and a perspective view of another embodiment of a workstation configured to hold a plurality of disposable containers for receiving aliquoted portions of fluid from the fluid dispensing system, constructed in accordance with the principles of the present disclosure.

[0021] Figure 8 is Figure 7 a front view of the dispenser sled, the dispensing tower, and the workstation of

[0022] Figure 9 is Figure 7 another front view of the dispensing tower of

[0023] Figure 10 is Figure 7 a perspective view of the dispensing tower of

[0024] Figure 11 is a perspective view of another embodiment of a fluid dispensing system including an embodiment of a dispenser sled, Figure 7 a dispensing tower of and another embodiment of a dispensing tower having a disposable prime manifold of the fluid dispensing system mounted thereto, and a perspective view of another embodiment of a workstation configured to hold a plurality of disposable containers for receiving aliquoted portions of fluid from the fluid dispensing system, constructed in accordance with the principles of the present disclosure.

[0025] Figure 12 Figure 11 is a top view of the dispenser sled, the dispensing tower, and the workstation of

[0026] Figures 13-21 is a schematic diagram of an embodiment of a fluid dispensing system constructed in accordance with the principles of the present disclosure, showing a series of fluid recovery steps of an embodiment of a method of aseptically dispensing a fluid in accordance with the principles of the present disclosure.

[0027] It is to be understood that the figures are not necessarily drawn to scale, that the embodiments disclosed are to be considered in a descriptive sense and not a restrictive sense, and that the disclosed embodiments are illustrative of the broader principles of the present disclosure. It is to be further understood that the principles of the present disclosure can be used in other embodiments not specifically described herein. DETAILED DESCRIPTION

[0028] Embodiments of fluid dispensing systems constructed in accordance with the principles of the present disclosure are suitable for use with embodiments of methods of aseptically dispensing fluids that follow the principles of the present disclosure. Embodiments of fluid dispensing systems constructed in accordance with the principles of the present disclosure can be used in biopharmaceutical environments, as well as in other industrial applications where different fluids, solutions, reagents, and / or chemicals are stored for metering to processing stations.

[0029] For example, embodiments of fluid dispensing systems constructed in accordance with the principles of the present disclosure are suitable for use in bioprocessing systems where supplies of fluids are dispensed into a plurality of containers for bioprocess applications. Embodiments of fluid dispensing systems constructed in accordance with the principles of the present disclosure can be used to perform applications related to batch filling in the production of pharmaceutical drugs. Embodiments of fluid dispensing systems constructed in accordance with the principles of the present disclosure can be used to perform applications related to formulation, filling, and other applications related to aliquoting liquids in an aseptic manner.

[0030] In embodiments, the fluid dispensing system includes a scalable series of disposable manifolds that are in fluid communication with each other in a closed, aseptic system. In embodiments, the fluid dispensing system includes two, three, or more disposable manifolds that are connected together in series to effectively increase the number of containers that can be filled in an aseptic manner by the most upstream disposable manifold to be greater than the number of outlets present therein. Thus, the number of containers that can be filled using a fluid dispensing system constructed in accordance with the principles of the present disclosure is scalable to meet the specific parameters of a given application.

[0031] In embodiments, the fluid dispensing system includes a disposable dispenser manifold that is suitable for and sequentially aseptically fluidly connected to a set of disposable filling manifolds corresponding to the number of dispenser manifold outlets. In embodiments, each manifold includes replaceable components that are installed into the fluid dispensing system for single use in a bioprocess application and are unloaded for disposal after their intended single use. In embodiments, the fluid dispensing system includes an upstream disposable dispenser manifold that is suitable for and sequentially aseptically fluidly connected to a set of intermediate disposable dispenser manifolds corresponding to the number of dispenser manifold outlets of the upstream disposable dispenser manifold. The system further includes a plurality of sets of disposable filling manifolds, where each respective set of disposable filling manifolds corresponds to the number of dispenser manifold outlets of a respective one of the set of intermediate dispenser manifolds.

[0032] In embodiments, the fluid dispensing system is incorporated into a dispenser skid that includes at least one disposable dispenser manifold and a set of disposable prime manifolds adapted to be placed in fluid communication with one of a plurality of dispenser manifold outlets. In other embodiments, the fluid dispensing system is incorporated into a dispenser skid and one or more dispensing towers, wherein the dispensing towers are adapted to receive one of a set of disposable prime manifolds.

[0033] Embodiments of a fluid dispensing system constructed in accordance with the principles of the present disclosure are configured as a relatively compact solution to enable a scalable range of different fluid dispensing scenarios for intended use in bioprocess applications. Embodiments of a fluid dispensing system constructed in accordance with the principles of the present disclosure can include a fluid supply, at least one disposable dispenser manifold, a set of disposable prime manifolds each having a prime manifold inlet adapted to be in fluid communication with one of a plurality of dispenser manifold outlets, and a plurality of containers corresponding to the product of the number of prime manifold outlets and the number of disposable prime manifolds in the set. Multiple sets of containers can be individually primed with each of the set of disposable prime manifolds in a relatively small footprint (particularly relative to conventional dispensing towers configured for similar bioprocess applications) to store fluids for predetermined bioprocess applications therein. The containers can be delivered on demand to a storage area (e.g., a workstation supporting a plurality of bioprocess container bags for bioprocess applications (e.g., chromatography / tangential flow filtration (TFF) applications). Embodiments of a fluid dispensing system constructed in accordance with the principles of the present disclosure can be used to replace conventional systems for similar bioprocess applications that use a disposable manifold once per use to prime no more than the number of outlets of the disposable manifold.

[0034] Embodiments of a fluid dispensing system constructed in accordance with the principles of the present disclosure are configured to drain fluid volumes from the body of a disposable prime manifold into a reserved fill container of a set of fill containers, thus forming part of the "usable" customer product fluid. Embodiments of a fluid dispensing system constructed in accordance with the principles of the present disclosure are configured to perform a specific automated method in which fluid from the above-described multiplier manifold is completely recovered into a recovery bag after each manifold change and reintroduced into the system to fill and charge the newly installed manifold. Thus, there will be only one "different class" volume in the recovery bag after a batch is completed (per the above-described case scenario) (as opposed to each individual fill sequence in conventional techniques).

[0035] Embodiments of a fluid dispensing system constructed according to the principles of the present disclosure include a control unit programmed with a fluid dispensing program having a container fill module configured to expel a target fill volume amount of supply fluid from each standard fill outlet of a fill manifold outlet, expel an underfill volume amount of supply fluid from an underfill outlet of a fill manifold outlet, and expel a fill manifold volume amount of supply fluid from a fill manifold body conduit to the underfill outlet of the fill manifold outlet. The underfill volume amount is less than the target fill volume amount.

[0036] In dispensing applications of bulk products, air is entrapped in the flow path and in the final filled container, which has the risk of negatively impacting the process. Air in the flow path can reduce the ability of the system to accurately dispense fluid, thereby increasing variability of the dispense and adversely affecting downstream formulation processes. Air in the final container can reduce product quality because some products can be sensitive to oxygen and / or reduce the efficiency of the process of freezing fluid in these containers. Embodiments of a fluid dispensing system constructed according to the principles of the present disclosure include a control unit programmed with a fluid dispensing program to automatically remove air trapped in the manifold, thereby improving the accuracy and consistency of the fluid dispensing process.

[0037] Turning now to the drawings, Figure 1 and Figure 2 An embodiment of a fluid dispensing system 50 constructed according to the principles of the present disclosure is shown incorporated into a dispenser slide 52 constructed according to the principles of the present disclosure, the fluid dispensing system including an upstream disposable dispenser manifold 53, an intermediate disposable dispenser manifold 54, and a disposable fill manifold 55, fluidly connected in series. The dispenser slide 52 includes a pump 57 (see Figure 3 configured to draw fluid from a fluid supply (not shown) and deliver the fluid to the serially connected manifolds 53-55.

[0038] In the embodiment shown, each of the manifolds 53-55 includes a replaceable portion that is installed into the dispenser slide 52 for a bioprocess application and then removed for disposal. After completing its intended use in a bioprocess application, the respective manifold 53-55 is able to be disconnected from the dispenser slide 52 according to a predetermined hierarchy and replaced with another disposable manifold of similar construction.

[0039] In embodiments, fluid dispensing system 50 can be used with any suitable fluid that can be stored in a suitable container, such as a tank, that is in fluid communication with pump 57, for example. In embodiments, fluid dispensing system 50 constructed in accordance with the principles of the present disclosure can include at least two disposable manifolds 54, 55 that are fluidly connected together in series.

[0040] Intermediate disposable dispenser manifold 54 is one of a set of intermediate disposable dispenser manifolds 54 that have substantially the same construction and are configured to be installed in sequence onto dispenser slide 52. Similarly, disposable prime manifold 55 is one of a set of disposable prime manifolds 55 that have substantially the same construction and are configured to be installed in sequence onto dispenser slide 52. The illustrated fluid dispensing system 50 is configured to receive fluid from a supply, such as a buffer solution for an intended bioprocess application, such as chromatography, TFF, etc., before replacing upstream disposable dispenser manifold 53 and opening the closed system (six outlets for each of a set of twenty disposable prime manifolds 55 x five outlets for each of a set of four intermediate disposable dispenser manifolds 54 x four outlets of upstream disposable dispenser manifold 53) and to dispense fluid into up to one hundred and twenty containers in sequence by using the set of disposable prime manifolds 55 and disposable dispenser manifolds 54 in sequence.

[0041] In other embodiments, fluid dispensing system 50 can be configured to prime a different maximum number of containers in the closed system before needing to be opened to continue dispensing fluid to more containers. In embodiments, the set of intermediate disposable dispenser manifolds 54 can include at least one manifold that is structurally different from at least one other manifold of the set (e.g., a different number of outlets), and in embodiments, the set of disposable prime manifolds 55 can include at least one manifold that is structurally different from at least one other manifold of the set (e.g., a different number of outlets).

[0042] Referring to Figure 2 Each of upstream disposable dispenser manifold 53, intermediate disposable dispenser manifold 54, and disposable prime manifold 55 can have a similar structure. In the illustrated embodiment, each manifold 53-55 includes a plumbing arrangement that interconnects the various ports of the manifold and is associated with control valves to control the flow of fluid through the manifold. In embodiments, the plumbing arrangement includes a plurality of flexible lines that are adapted to be selectively occluded by pinch valves mounted thereon from the outside. In embodiments, the flexible plumbing can be made of any suitable material, such as silicone, thermoplastic elastomer (TPE), etc.

[0043] In embodiments, the manifolds 53-55 can be made of any suitable material and can include suitable tubing defining fluid conduits therethrough. In embodiments, the manifolds 53-55 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., Pall's Presto Aseptic Connectors and Presto Aseptic Disconnectors) available from Pall Corporation, New York, NY. The manifolds 53-55 in the figures are made of tubing that can be selectively occluded by pinch valves.

[0044] The upstream disposable dispenser manifold 53 is removably mounted to the dispenser sled 52. The upstream disposable dispenser manifold 53 has an upstream dispenser manifold inlet 60 and a plurality of upstream dispenser manifold outlets 61, 62, 63, 64 in fluid communication with the upstream dispenser manifold inlet through the hollow body conduit of the manifold 53. The illustrated upstream disposable dispenser manifold 53 includes four upstream dispenser manifold outlets 61-64. In other embodiments, the number of upstream dispenser manifold outlets 61-64 can be different. The upstream dispenser manifold inlet 60 is fluidly arranged with the pump 57 mounted to the dispenser sled 52 through suitable tubing and connectors to deliver a fluid supply to the series of manifolds 53-55.

[0045] The intermediate disposable dispenser manifold 54 is removably mounted to the dispenser sled 52. The intermediate disposable dispenser manifold 54 has an intermediate dispenser manifold inlet 70 and a plurality of intermediate dispenser manifold outlets 71, 72, 73, 74, 75 in fluid communication with the intermediate dispenser manifold inlet 70 through the hollow body conduit of the manifold 54. The intermediate dispenser manifold inlet 70 is in fluid communication with one of the upstream dispenser manifold outlets (in this case, the fourth dispenser manifold outlet 64). The illustrated intermediate disposable dispenser manifold 54 includes five intermediate dispenser manifold outlets 71-75. In other embodiments, the number of intermediate dispenser manifold outlets 71-75 can be different.

[0046] ​The intermediate disposable dispenser manifold 54 is one of a set of intermediate disposable dispenser manifolds 54. The set of intermediate disposable dispenser manifolds 54 corresponds to the number of upstream dispenser manifold outlets 61-64 (in this case, four). Each intermediate disposable dispenser manifold 54 has a sterile fluid connector 77 configured to fluidly connect the intermediate dispenser manifold inlet 70 with one of the upstream dispenser manifold outlets. In embodiments, each of the set of intermediate disposable dispenser manifolds 54 has a similar structure. In embodiments, at least one of the set of intermediate disposable dispenser manifolds 54 can have a different structure than at least one other intermediate disposable dispenser manifold in the set, for example, a different number of intermediate dispenser manifold outlets than at least one other intermediate disposable dispenser manifold in the set of intermediate disposable dispenser manifolds 54.

[0047] In embodiments, the dispensing manifolds 53, 54 are curved, which makes the length of all the connecting tubes substantially similar. This configuration can make the length and footprint of the manifolds relatively compact, while simplifying the manufacturing process of the manifolds.

[0048] The disposable prime manifold 55 is removably mounted to the dispenser sled 52. The disposable prime manifold 55 has one prime manifold inlet 80 and a plurality of prime manifold outlets 81, 82, 83, 84, 85, 86 that are in fluid communication with the prime manifold inlet 80 through a hollow body conduit of the manifold 55. The prime 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 prime manifold 55 includes six prime manifold outlets 81-86. In other embodiments, the number of prime manifold outlets 81-86 can be different.

[0049] In embodiments, the prime manifold outlets 81-86 include at least one standard fill outlet and one underfill fill outlet for use with a container fill module of a fluid dispensing program to conserve fluid. In the illustrated embodiment, the disposable prime manifold 55 includes five standard fill outlets 81-85, and the bottommost outlet includes an underfill fill outlet 86. The container fill module can be configured to expel a target fill volume amount of supply fluid out of each standard fill outlet 81-85 of the prime manifold outlets 81-86, an underfill volume amount of supply fluid out of the underfill fill outlet 86 of the prime manifold outlets 81-86, and a prime manifold volume amount of supply fluid from the prime manifold body conduit of the disposable prime manifold 55 out of the underfill fill outlet 86 of the prime manifold outlets 81-86. The underfill volume amount is less than the target fill volume amount. In embodiments, the underfill volume amount, in combination with the prime manifold volume amount, is substantially the same as the target fill volume amount.

[0050] The disposable prime manifold 55 is one of a set of disposable prime manifolds 55. In embodiments, the set of disposable prime manifolds 55 corresponds to the product of the number of outlets of each of the two or more dispenser manifolds connected in series upstream of the prime manifold inlet. In embodiments where there is only one disposable dispenser manifold connected in series with the prime manifold inlet, the set of disposable prime manifolds 55 can correspond to the number of dispenser manifold outlets of the single dispenser manifold. In the illustrated embodiment, the set of disposable prime manifolds 55 includes twenty disposable prime manifolds 55, which corresponds to the product of the number of intermediate dispenser manifold outlets (five) and the number of upstream dispenser manifold outlets (four). In embodiments, the set of disposable prime manifolds 55 corresponds to at least the number of intermediate dispenser manifold outlets. Each disposable prime manifold has a sterile fluid connector 87 configured to fluidly connect the prime manifold inlet 80 with one of the plurality of intermediate dispenser manifold outlets 71-75.

[0051] In embodiments, each of the set of disposable prime manifolds 55 has a similar structure. In embodiments, at least one of the set of disposable prime manifolds 55 can have a different structure than at least one other of the set of disposable prime manifolds, such as a different number of prime manifold outlets than at least one other of the set of disposable prime manifolds 55.

[0052] Referring to Figure 2 , the illustrated fluid dispensing system 50 includes a valve 90 associated with each outlet of the manifolds 53-55 Figure 2 The upstream dispenser valve arrangement 91 includes a plurality of valves 90 mounted to the slide plate 52 and arranged with the upstream disposable dispenser manifold 53 such that each of the upstream dispenser manifold outlets 61-64 can be independently occluded by a respective one of the valves 90 of the upstream dispenser valve arrangement 91. The intermediate dispenser valve arrangement 92 includes a plurality of valves 90 mounted to the slide plate 52 and arranged with the intermediate disposable dispenser manifold 54 such that each of the intermediate dispenser manifold outlets 71-75 can be independently occluded by a respective one of the valves 90 of the intermediate dispenser valve arrangement 92. The prime valve arrangement 93 includes a plurality of valves 90 mounted to the slide plate 52 and arranged with the disposable prime manifold 55 such that each of the prime valve outlets 81-86 can be independently occluded by a respective one of the valves 90 of the prime valve arrangement 93.

[0053] In embodiments, the valve devices 91-93 can comprise any suitable valve adapted to selectively occlude the outlet associated therewith. In the illustrated embodiment, the valve devices 91-93 comprise pinch valves adapted to effectively occlude the manifold outlet associated therewith by occluding the manifold's tubing to control fluid flow within the system. The valves 90 are secured to the skid 52 and provide means for removably mounting the manifolds 53-55 to the skid 52. In other embodiments, different types of valves can be used, such as solenoid valves, as will be readily familiar to those skilled in the art. In embodiments, the valves 90 can be operated by a suitable source, such as a pneumatic source or an electrical source. In embodiments, a control unit can be used to coordinate operation of the valves 90 of the valve devices 91-93, which is suitably programmed to operate the desired fluid dispensing sequence or sequences.

[0054] Referring to Figure 1 , the dispenser skid 52 includes a first fill valve device 93 and a second fill valve device 94. The first fill valve device 93 is disposed on one side of the dispenser skid 52 that includes the upstream and intermediate dispenser manifolds 53, 54. The second fill valve device 94 is disposed on the other side of the dispenser skid 52.

[0055] The valves of the first fill valve device 93 are disposed in spaced relation to one another along a vertical axis. The disposable fill manifolds 55 are mounted to the dispenser skid 52 such that the valves of the first fill valve device 93 are associated with each fill manifold outlet, respectively. This arrangement is particularly useful when filling containers stored in the work station 100 in the configuration shown. Figure 3

[0056] The valves of the second fill valve device 94 are disposed in spaced relation to one another along a horizontal axis. As shown, the disposable fill manifolds 55' can be mounted to the dispenser skid 52 such that the valves of the second fill valve device 94 are associated with each fill manifold outlet, respectively. This arrangement is particularly useful when filling containers stored in the work station 100' in the configuration shown. Figure 5 Figure 5 Referring to

[0057] In embodiments, the fluid dispensing system 50 can include means for removing air trapped within the manifolds 53-55 to improve the accuracy and consistency of the fluid dispensing process. In the illustrated embodiment, an air filter 96 and a vent conduit 97 are provided. The vent conduit 97 is in fluid communication with the manifolds 53-55 through a vent junction 98 associated with the disposable fill manifolds 55. The air filter 96 is in fluid communication with the body conduit of the fill manifolds 55 and the body conduits of the upstream and intermediate disposable dispenser manifolds 53, 54 through the vent conduit 97. Figure 2

[0058] ​​​In embodiments, the air filter 96 is configured to filter particulate matter. In embodiments, the air filter 96 acts as a sterile barrier between the product fluid within the manifold and the surrounding atmosphere. The air filter substantially prevents non-sterile air from entering the manifold flow path at any time during installation or handling.

[0059] The vent conduit 97 includes a vent liquid sensor 99 and a vent valve 101 to protect the air filter 96 from exposure to liquid. The vent liquid sensor 99 is configured to generate a liquid detection signal in response to detecting liquid in the vent conduit 97. The control unit 120 is in electrical communication with the vent liquid sensor 99 to receive the liquid detection signal emitted therefrom. The vent valve 101 is disposed with the vent conduit 97 to selectively occlude the vent conduit 97. The vent valve 101 is interposed between the vent liquid sensor 99 and the air filter 96. The vent liquid sensor 99 is interposed between the vent junction 98 and the vent valve 101. The vent valve 101 is operatively disposed with the control unit 120 such that the control unit can selectively operate the vent valve 101. In embodiments, the control unit 120 is configured to stop operation of the pump 57 and / or close the vent valve 101 in response to receiving the liquid detection signal to prevent the filter 96 from becoming wetted with fluid during priming of the dispensing manifold.

[0060] In embodiments, the control unit 120 is configured to perform a priming operation. In embodiments, the control unit 120 is configured to open the vent valve 101 to open the vent conduit 97, operate the pump 57 to deliver a flow of fluid to the disposable prime manifold 55, while closing all of the prime manifold outlets 81-86, such that the body of the prime manifold 55 is filled with fluid and air in the manifolds 53-55 is displaced to the vent conduit 97 through the vent junction 98. The control unit 120 can be configured to stop operation of the pump 57 and / or close the vent valve 101 in response to receiving the liquid detection signal, thereby indicating that the body of the disposable prime manifold 55 is filled with fluid above the vent junction 98.

[0061] In embodiments, the vent junction 98 is located at a relative high point of a series of manifolds 53-55 fluidly connected together. In embodiments, the dispenser manifolds 53, 54 are configured such that fluid moves through these manifolds toward the fill manifold 55 in a substantially sloped trajectory from the upstream dispenser manifold inlet 60 to the fill manifold inlet 80 (in embodiments, to the vent junction 98). In embodiments, the body of the dispenser manifolds 53, 54 extends along a sloped path that is at least 0.5° from horizontal. The control unit 120 can be configured such that as liquid is introduced into the upstream dispenser manifold inlet 60 and flows through the manifolds 53-55, the liquid displaces air from the current flow path, thereby pushing the air toward the air filter 96 and out of the series of manifolds 53-55 during a priming operation.

[0062] In embodiments, the control unit 120 is configured to perform an underfill operation. In embodiments, the control unit 120 is configured to send a supply of fluid into the fill manifold inlet 80 of the disposable fill manifold 55 and to sequentially discharge a target fill volume of fluid from each of the standard fill outlets 81-85 of the disposable fill manifold 55 into a disposable container to which it is aseptically fluidly connected, respectively. Upon sequential discharge of the target fill volume, an underfill volume of fluid is discharged from the underfill outlet 86 of the disposable fill manifold 55 into a disposable container to which it is aseptically fluidly connected. In embodiments, the underfill volume is less than the target fill volume. In embodiments, the underfill volume, in combination with the volume of fluid discharged from the fill manifold 55, is substantially the same as the target fill volume. In embodiments, the underfill outlet 86 of the disposable fill manifold 55 can be the lowest outlet in the direction of gravity.

[0063] Upon discharge of the underfill volume, the control unit 120 can be configured to discharge fluid from the body conduit of the fill manifold 55 out the underfill outlet 86 into a disposable container to which it is aseptically fluidly connected. The control unit 120 can be configured to open the vent valve 101 during the discharge.

[0064] In embodiments, a fill manifold discharge valve 102 can be provided upstream of the vent junction 98 to selectively occlude the fill manifold inlet 80 during a fill manifold discharge operation to further facilitate discharge of fluid from the body of the fill manifold 55 out the underfill outlet 86. The fill manifold discharge valve 102 is operatively arranged with the control unit 120 such that the control unit can selectively operate the fill manifold discharge valve 102. In embodiments, the control unit 120 is configured to close the fill manifold discharge valve 102 during a fill manifold discharge to help maintain consistency in the volume of fluid discharged from the fill manifold 55 during the discharge operation.

[0065] In embodiments, the low level drain sensor 103 can be associated with the body of the fill manifold 55 proximate and above the low fill outlet 86, such that the level in the body of the fill manifold 55 can be monitored to help determine when a fill manifold drain operation is complete. The low level drain sensor 103 is configured to generate a low level fill manifold drain signal in response to detecting that the liquid in the fill manifold 55 is below a predetermined low level (corresponding to the completion / approaching completion of a drain operation).

[0066] The control unit 120 is in electrical communication with the low level drain sensor 103 to receive the low level fill manifold drain signal. In embodiments, the control unit 120 can be configured to stop a fill manifold drain operation in response to receiving the low level fill manifold drain signal. In embodiments, the control unit 120 can be configured to open the fill manifold drain valve 102 and close the vent valve 101 in response to receiving the low level fill manifold drain signal. The location of the low level drain sensor 103 can help ensure that the fill manifold drain operation is stopped before all fluid is drained from the fill manifold 55 to help prevent air from also being delivered to a disposable container connected to the low fill outlet 86.

[0067] In embodiments, the fluid dispensing system 50 can include means for recovering fluid from one or more of the manifolds 53-55 that would otherwise be retained in the manifolds 53-55 or drained to a disposable container being filled in a fill operation. In the illustrated embodiment, the fluid dispensing system 50 includes means for recovering fluid from one or more of the dispenser manifolds 53, 54, the means including a recovery conduit 106, a recovery container 107, and a recovery pump 108.

[0068] The recovery conduit 106 includes a sterile fluid reserve passage that is in fluid communication with the dispenser manifolds 53, 54 and is adapted to be in fluid communication with the recovery container 107 (see also Figure 1 ). The recovery conduit 106 includes a recovery valve 109. The recovery valve 109 is disposed with the sterile fluid reserve passage 106 such that the sterile fluid reserve passage 106 can be occluded by the recovery valve 109. The recovery valve 109 is operatively disposed with the control unit 120 such that the control unit 120 can selectively operate the recovery valve 109.

[0069] The recovery container 107 can be placed in fluid communication with the dispenser manifolds 53, 54 through the sterile fluid reserve passage provided by the recovery conduit 106. The recovery container storage chamber 116 is mounted on the dispenser skid 52 (see also Figure 1). The recovery container storage chamber 116 is configured to receive the recovery container 107 therein. The recovery container storage chamber 116 is positioned such that, in the direction of gravity acting on the fluid in the dispenser manifold 53, 54, the recovery container 107 is disposed below the dispenser manifold 53, 54 and the air filter 96.

[0070] The recovery high level sensor 117 and the recovery low level sensor 118 can be associated with the storage chamber 116 such that a respective predetermined maximum and minimum fluid volume in the recovery container can be monitored (see also Figure 13 ), to help avoid overfilling the recovery container and / or inadvertently drawing air into the system. With reference to Figure 13 , the recovery high level sensor 117 is arranged with the recovery container 107 and is configured to generate a high recovery level signal in response to detecting that the liquid in the recovery container 107 is at a predetermined high level, corresponding to the predetermined maximum fluid volume in the recovery container. The recovery low level sensor 116 is arranged with the recovery container 107 and is configured to generate a low recovery level signal in response to detecting that the liquid in the recovery container 107 is below a predetermined low level, corresponding to the predetermined minimum fluid volume in the recovery container. The control unit 120 is in electrical communication with the high and low recovery level sensors 117, 118 to receive the high and low recovery level signals therefrom, respectively.

[0071] With reference to Figure 2 , in embodiments, the recovery pump 108 is in fluid communication with the recovery container 107 through the recovery conduit 106 and a fluid supply conduit 119 fluidly connected with the upstream dispenser manifold inlet 60. The recovery pump is adapted to selectively generate a recovery fluid flow from the recovery container to the upstream dispenser manifold inlet 60 to include a portion of the supply fluid dispensed through the manifold 53-55.

[0072] In embodiments, the control unit 120 can be configured to automatically drain fluid from the dispenser manifold 53, 54 to the recovery container 107 through the recovery conduit 106. In embodiments, the control unit 120 is configured to open the vent valve 101 to allow air to enter the dispenser manifold 54, 53 from outside the air filter 96 and to open the recovery valve 109. In embodiments, the control unit 120 can be configured to close the vent valve 101 and to close the recovery valve 109 in response to receiving the high recovery level signal to stop the fluid draining operation of the dispenser manifold. In embodiments, a recovery liquid sensor can be provided in the recovery conduit 106 upstream of the recovery container 107 so as to provide a signal to the control unit when the recovery level sensor detects that no more fluid is passing through the recovery conduit 106 to the recovery container 107, so that the control unit 120 can stop the draining operation of the dispenser manifold.

[0073] In embodiments, the control unit 120 can be configured to automatically direct fluid from the recovery container 107 back into the series of manifolds 53-55 during a fill operation. In embodiments, the control unit 120 can be configured to operate the recovery pump 108 to draw recovery fluid from the recovery container 107 to the upstream dispenser manifold inlet 60. In embodiments, the control unit 120 can be configured to supply fluid into the upstream dispenser manifold inlet 60 by introducing recovery fluid from the recovery container 107, such that at least a portion of the supplied fluid comprises recovery fluid from the recovery container 107. In embodiments, the control unit 120 can be configured to operate the recovery pump 108 and at least one other pump 57 during a fill operation. In embodiments, the control unit 120 can be configured to stop operation of the recovery pump 108 during a fluid fill operation in response to receiving a low recovery level signal.

[0074] Referring to Figure 1 The dispenser skid 52 includes a cart 105, a cabinet 110, disposable manifolds 53-55, and valve assemblies 91-94. The cabinet 110 is mounted to the top of the cart 105 and is configured to house hydraulic and automation equipment for the liquid dispensing system 50. The manifolds 53-55 include disposable manifolds that are removably mounted to the cabinet 110 such that the manifolds 53-55 are operatively arranged with valves of the valve assemblies 91-93 mounted to the cabinet 110.

[0075] The cart 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 with one wheel 114 rotatably connected at each corner of the base 112. In embodiments, the base 112 can be generally square.

[0076] The cabinet 110 is mounted to the base 112 of the cart 105. In embodiments, the cabinet 110 includes storage units for automation and hydraulic equipment and is made of a suitable metal, such as stainless steel. The cabinet 110 defines an interior cavity that can be suitably configured to store and support components of the liquid dispensing system. Valves of the valve assemblies 91-94 can be supported by the cabinet 110. In the illustrated embodiment, a clamping portion of each valve extends from an outer surface of the cabinet 110 in association with a manifold outlet, respectively.

[0077] Referring to Figure 3In embodiments, the cabinet 110 houses therein the control unit 120 and at least one pump 57. The pump 57 is in operable relationship with the control unit 120 such that the control unit 120 can selectively operate the pump 57. The pump 57 is adapted to selectively generate a flow of fluid to deliver a supply of fluid to the manifolds 53-55. In embodiments, the pump 57 can be any suitable pump capable of generating a flow of fluid through the manifolds to be delivered to the disposable container 125 connected to the fill manifold 55 and meeting the specifications of the intended application. In embodiments, the pump 57 comprises a variable displacement pump. In embodiments, the fluid dispensing system 50 comprises a plurality of pumps that can be used to deliver one or more types of fluid to the manifolds 53-55.

[0078] In embodiments, the control unit 120 can comprise any suitable device configured to control the operation of at least one component of the liquid dispensing system 50 in performing a filling operation. In embodiments, the control unit 120 comprises 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 operably 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 by the display device 125.

[0079] The processor 121 can be configured as a controller to selectively operate at least one component of the fluid dispensing system 50, such as the pump 57 and the valve arrangement. In embodiments, the processor 121 is in electrical communication with the pump and the valve arrangement to selectively operate the valve based on instructions of the fluid dispensing program.

[0080] In embodiments, the controller and the processor 121 can comprise separate devices, and the controller can be arranged in operable communication with the processor 121. In embodiments, the controller can comprise user input and / or interface devices having one or more user-actuated mechanisms (e.g., one or more buttons, slide bars, rotatable knobs, keyboards, and mice) adapted to generate one or more user-actuated input control signals. In embodiments, the controller can be configured to include one or more other user-actuated mechanisms to provide various other control functions of the fluid dispensing system, as will be appreciated by those skilled in the art. The controller can be associated with a display device 125 adapted to display a graphical user interface. The graphical user interface can be configured to function as both a user input device and a display device in embodiments. In embodiments, the display device 125 can comprise a touch screen device adapted to receive input signals from a user touching different portions of the display screen. In embodiments, the controller can be in the form of a smartphone, tablet, personal digital assistant (e.g., a wireless mobile device), notebook computer, desktop computer, or other type of device.

[0081] In embodiments, the fluid dispensing program has a scaling module configured to sequence through a series of valve open and closed conditions to perform a fill sequence in accordance with the principles of the present disclosure. For example, the scaling module can be configured to open a respective one of the upstream dispenser manifold outlets and the intermediate dispenser manifold outlets, and close the other of the upstream dispenser manifold outlets and the intermediate dispenser manifold outlets, to perform a respective sequential series of fill operations using a respective one of the set of disposable fill manifolds. The scaling module can sequence the opening of each of the intermediate dispenser manifold outlets with the one of the upstream dispenser manifold outlets in an open state, then close the one of the upstream dispenser manifold outlets and place a second one of the upstream dispenser manifold outlets in an open state while the other is closed. The scaling module can coordinate the sequential filling operations of the remaining valves in a similar manner. In embodiments, the scaling module includes logic for scaling the fill sequence to the number of containers required for a given closed system fill operation.

[0082] In embodiments, the fluid dispensing program is configured to perform at least one fluid recovery operation to efficiently utilize fluid that would otherwise remain in the manifolds 53-55 or fluid that is not discharged into a disposable container filled during a fill operation. In embodiments, the fluid dispensing program is configured to perform at least one of a fluid recovery operation in the form of a disposable container underfill operation, a manifold drain operation, and a manifold prime operation.

[0083] For example, in embodiments, the fluid dispensing procedure includes a container fill module configured to automatically perform at least one fluid recovery operation. In embodiments, the fluid dispensing procedure includes a container fill module configured to perform a fluid recovery operation in the form of a single-use container underfill fill operation. In embodiments, the container fill module is configured to perform a single-use container underfill fill operation including expelling a target fill volume amount of supply fluid from each standard fill outlet 81-85 of the fill manifold outlet 81-86, expelling an underfill volume amount of supply fluid from an underfill outlet 86 of the fill manifold outlet 81-86, and expelling a fill manifold volume amount of supply fluid from a fill manifold body conduit of the single-use fill manifold 55 to the underfill outlet 86 of the fill manifold outlet 81-86. The underfill volume amount is less than the target fill volume amount. In embodiments, the underfill volume amount in combination with the fill manifold volume amount is substantially the same as the target fill volume amount.

[0084] In embodiments, the container fill module is configured to perform an underfill fill operation of a single-use container including passing supply fluid to a fill manifold inlet 80 of a single-use fill manifold 55. A target fill volume amount of fluid is sequentially expelled from each standard fill outlet 81-85 of the fill manifold outlet 81-86 to a single-use container to which it is aseptically fluidly connected, respectively. After the target fill volume amount is sequentially expelled, an underfill volume amount of fluid is expelled from an underfill outlet 86 to a single-use container to which it is aseptically fluidly connected. After the underfill volume amount is expelled, a fill manifold volume amount of fluid is expelled from a fill manifold body conduit 55 to the underfill outlet 86 to a single-use container to which it is aseptically fluidly connected. In embodiments, the underfill portion in combination with the fill manifold volume amount is substantially the same as the fill portion. In embodiments, the vent valve 101 is open during the venting to facilitate the expulsion of fluid from the body conduit of the fill manifold 55. In embodiments, the container fill module is configured to expel the fill portion at substantially the same time.

[0085] In embodiments, the fluid dispensing program is configured to perform a fluid recovery operation in the form of a manifold venting operation. In embodiments, the fluid dispensing program includes a dispenser manifold venting module configured to cause fluid to be drained from at least one of the dispenser manifolds 53, 54 into the sterile fluid reserve channel 106 to the recovery reservoir 107 when executed by the processor. In embodiments, venting dispenser manifold fluid includes draining fluid remaining in the upstream disposable dispenser manifold 53 and the intermediate disposable dispenser manifold 54. In embodiments, venting dispenser manifold fluid includes opening the vent valve 101 and opening at least one recovery valve 109 arranged with the recovery conduit 106. In embodiments, the dispenser manifold venting module is configured to cause the vent valve 101 to close and the recovery valve 109 arranged with the recovery conduit 106 to close when executed by the processor in response to receiving a high recovery level signal.

[0086] In embodiments, the fluid dispensing program is configured to perform a fluid recovery operation in the form of a manifold priming operation. In embodiments, the fluid dispensing program includes a prime manifold priming module configured to perform a fluid recovery operation in the form of a manifold priming operation. In embodiments, the fluid dispensing program includes a prime manifold priming module configured to prime a disposable prime manifold with a supply fluid of a prime manifold body conduit of the prime manifold. In embodiments, the prime manifold priming module is configured to open the vent valve 101 to move air in the prime manifold body conduit out of the air filter 96 during priming and to place the vent valve 101 in a closed position after the prime manifold body is primed.

[0087] In embodiments, the prime manifold priming module is configured to prime the manifold by introducing recovery fluid in the recovery reservoir 107 through the sterile fluid reserve channel 106 into the dispenser manifold inlet 60 such that at least a portion of the fluid supply includes recovery fluid from the recovery reservoir 107. In embodiments, the prime manifold priming module is configured to operate the recovery pump 108 to draw recovery fluid from the recovery reservoir 107 during the manifold priming operation. In embodiments, the prime manifold priming module is configured to stop operation of the recovery pump and close a recovery valve arranged with the recovery fluid fill channel 106 in response to receiving a low recovery level signal.

[0088] In embodiments, the control unit 120 is in electrical communication with each pump 57 for delivering fluid to the manifold 53-55 and each valve of the valve arrangement 91-94. The control unit 120 is configured to selectively operate the pumps 57 and the valves of the valve arrangement 91-94 in accordance with logic and operating parameters contained in a fluid dispensing program. In embodiments, the control unit 120 is configured to control at least one of a pump speed and a volumetric displacement of the pumps 57 to control an amount of fluid dispensed into a disposable container 125 connected to the fill manifold 55. In the illustrated embodiment, the control unit 120 is configured to independently operate each valve of the different valve arrangements 91-93 to place each valve arrangement in a series of sequential valve conditions to fill a disposable container 125 having a fill quantity greater than a number of fill manifold outlets in any one disposable fill manifold of the set of disposable fill manifolds 55.

[0089] In embodiments, the control unit 120 is configured to selectively operate the pumps 57 in accordance with at least one input signal received from each work station 100 holding a container 125. In embodiments, the control unit 120 is configured to operate the dispenser skid 52 to perform at least one fill sequence.

[0090] In embodiments, the processor 121 comprises a specially programmed processor that can be used to fill a series of disposable containers 125 using at least one dispenser manifold 53, 54 and a set of disposable fill manifolds 55. In the illustrated embodiment, the processor 121 is configured to facilitate control and operation of the fluid dispensing system 50. In embodiments, the processor 121 can 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 the processor 121 comprise the same device.

[0091] In embodiments, the processor 121 is configured to display fluid data received from at least one sensor in electrical communication with the control unit 121 in a display device 125. The fluid data can also be stored in a data storage device 123 operatively arranged with the processor 121.

[0092] In embodiments, the processor 121 can comprise any suitable computing device, such as a microprocessor, a computer mainframe, a digital signal processor, a portable computing device, an electronic organizer, a device controller, a logic device (e.g., a programmable logic device configured to perform processing functions), a digital signal processing (DSP) device, or a computing engine within an appliance. In embodiments, the processor 121 also includes one or more additional input devices (e.g., a keyboard and a mouse).

[0093] The processor 121 can have one or more memory devices associated therewith for storing data and information. The one or more memory devices can 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, the processor 121 is adapted to execute programming stored on the non-transitory computer readable medium 122 to perform various methods, processes and operational modes in a manner consistent with the principles of the present disclosure.

[0094] In embodiments, the non-transitory computer readable medium 122 can contain a fluid dispensing program configured to implement embodiments of methods of dispensing fluid in accordance with the principles of the present disclosure. In embodiments, the fluid dispensing program includes a graphical user interface that can be displayed by the display device 125. The graphical user interface can be used to facilitate a user inputting commands and data to the fluid dispensing program and to display output generated by the fluid dispensing program.

[0095] The fluid dispensing program can be stored on any suitable computer readable storage medium. For example, in embodiments, the fluid dispensing program in accordance with the principles of the present disclosure can be stored in a hard disk, a floppy disk, a CD-ROM drive, a tape drive, a compact flash drive, an optical storage device, a magnetic storage device, etc.

[0096] In embodiments, the processor 121 is in operable communication with a data storage device 123 that includes at least one database containing fluid dispensing data. In embodiments, the fluid dispensing program can be configured to store fluid dispensing data generated during operation of the system in the data storage device 123. In embodiments, the fluid dispensing data can be logically associated with time data in the data storage device such that various data can be retrieved for a given time.

[0097] Referring to Figure 4 The workstation 100 is configured to hold a plurality of disposable containers 125. Each disposable container 125 has an access port 130 that is fluidly connected to a respective one of the fill manifold outlets 81-86 through a sterile fluid disconnect 131 and a sterile fluid connector 132.

[0098] The workstation 100 includes a workstation configured to hold fluid in the disposable containers 125 that are aliquoted from a larger supply by the fluid dispensing system. The workstation 100 includes a cart 140, a frame structure 143, and a weigh scale 145.

[0099] The frame structure 143 is mounted to the dolly 140 and is configured to support the disposable containers 125 in a stacked relationship. The frame structure 143 includes four uprights 147 connected to and spaced apart from respective corners of the dolly 140 and four cross members 148 each extending between two of the uprights 147, such that the frame structure 143 has a rectangular configuration. In the illustrated embodiment, the work station includes six shelves 149 each configured to support at least one disposable container 125, such that the frame structure 143 can support disposable containers 125 in a vertically stacked relationship with one another. In other embodiments, the work station 100 can be configured to support different numbers of disposable containers 125, including such that each of the shelves 149 is configured to support multiple disposable containers 125.

[0100] The recycling container storage compartment 144 is mounted on the frame structure 143 and is configured to receive the recycling container 107 therein. In embodiments, once the closed system is opened after performing an extended fill operation using the serially connected manifolds 53-55, the recycling container 107 can be disconnected from the recycling conduit 106 and stored in the recycling container storage compartment 144 mounted to the frame structure 143. The "different class" volume of fluid left in the recycling container 107 can be associated with the disposable containers filled during use of that particular recycling container 107. Rather than a different class volume amount being generated during performance of a fill operation using each of the set of disposable fill manifolds 55, the recycling container 107 can be the only different class volume amount generated after use of the entire set of fill manifolds 55.

[0101] The dolly 140 includes a base and a plurality of wheels rotatably attached to the base. In the illustrated embodiment, the base is rectangular with a wheel rotatably attached to each corner of the base. In embodiments, the base can be substantially square. The base of the dolly 140 is mounted to the bottom of the frame structure 143. The dolly 140 is positionable on the weigh scale 145 such that the weigh scale 145 supports the weight of the dolly 140 (and thus also the frame structure 143 and the containers 125 stored therein).

[0102] In embodiments, the load scale 145 can be any suitable scale suitable for weighing a load in a range corresponding to the intended fluid application. In embodiments, the load scale 145 includes a suitable load sensor that generates an electrical signal indicative of the measured weight. The load scale 145 can be configured to generate a weight signal and can be placed in electrical communication 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 the control unit 120 to verify that the intended amount of fluid is dispensed into the container 125 stored in the workstation 100. In embodiments, the control unit 120 can be configured to convert the measured weight of the fluid into a volumetric measurement of such fluid.

[0103] In other embodiments, a workstation suitable for use with a fluid dispensing system constructed in accordance with the principles of the present disclosure can have a different structure. For example, in other embodiments, the volume / weight of the container 125 can be monitored using other techniques, as would be understood by one skilled in the art, such as a fill level sensor. In embodiments, the fill level sensor is configured to generate a fill level signal indicative of the amount of material within the storage volume of the disposable container detected by the fill level sensor. Each fill level sensor can be in electrical communication with the control unit so that the control unit can use the fill level signal as a feedback loop. In embodiments, a capacitive fill level sensor can be used to measure the fill level of a fluidic medium or solid material disposed within the storage volume of the container. In embodiments, the capacitive fill level sensor can be a suitable commercially available strip sensor, such as can be obtained from Balluff Ltd., that can detect the fill level along a strip over a predetermined length, such as 850 millimeters. In embodiments, the capacitive fill level sensor used to measure the fill level can be configured to form a measurement impedance in response to being within a detection range of the material stored within the disposable container, the ohmic component of the measurement impedance, and in particular the capacitive component therein, reflecting a measurement of the fill level of the material within the container that can be used to generate the fill level signal.

[0104] Each disposable container 125 is in fluid connection with a respective one of the fill manifold outlets 81-86 of the distributor skid 52 by a flexible line extending between each container 125 and the fill manifold outlet 81-86 associated therewith, and selectively maintained in fluid communication by a respective sterile connector 132. In embodiments, the sterile connectors 132 can be any suitable connector, such as commercially available sterile connectors familiar to those skilled in the art. In embodiments, the tubing placing the containers 125 in fluid communication with the associated fill manifold outlets 81-86 is adapted to be selectively occluded by a pinch valve mounted to the exterior thereof, and in embodiments includes flexible tubing made of any suitable material, such as silicone, thermoplastic elastomer (TPE), or the like.

[0105] In embodiments, the disposable containers 125 include any suitable container configured to store an intended volume of material for an intended application. In embodiments, the disposable containers 125 include "2D" (or "two-dimensional") bioprocess container bags, as familiar to those skilled in the art.

[0106] In the illustrated embodiment, the disposable containers 125 include 2D bioprocess container bags made of flexible film material. The bioprocess container bags 125 can include two or more ports and tubing with connected ends configured to receive material within the interior storage volume of the bag, and / or to expel material from the bag. In other embodiments, the bioprocess container bags 125 include at least one other port configured for use as a sampling port. In embodiments, the bioprocess container bags 125 can define a predetermined size storage volume therein, such as a volume in the range of one liter to twenty liters. In other embodiments, the storage volume can be a different size, such as one hundred liters. In embodiments, the bioprocess container bags 125 include suitable commercially available disposable bioprocess container bags, such as the brand name Allegro® bioprocess container bags available from Pall Corporation of Washington, New York. TM 2D bioprocess container bags.

[0107] In embodiments, the biocontainer bag 125 can comprise at least a pair of flexible panels connected together. The flexible panels fit together to define an internal storage volume configured to hold a predetermined volume of material (e.g., one hundred liters). In embodiments, each panel is made of a suitable plastic material. For example, in embodiments, each panel is made of a low density polyethylene (LDPE) fluid contact portion, and an outer film with an ethylene-vinyl alcohol copolymer (EvOH) gas barrier inner film. In embodiments, the biocontainer bag can be made of a material that meets at least one of the following requirements: USP <88> Biological Reactivity Tests for Class VI - 50°C plastics, which tests for - monitoring the effects of systemic toxicity, histological irritation, and biocompatibility of implants of biocontainer extracts; USP <87> Biological Reactivity Tests (in vitro) for plastics (cytotoxicity); and ISO 10993 Biological Evaluation of Medical Devices (Section 4 (hemolysis), Section 5 (cytotoxicity), Section 6 (implant testing), Section 10 (irritation and sensitization testing), and Section 11 (acute systemic toxicity)) of ISO 10993 Biological Evaluation of Medical Devices (Section 8.2.2).

[0108] Referring to Figure 5 In embodiments, the fluid dispensing system 50' includes a disposable fill manifold 55' mounted to the dispenser sled 52 such that the valves of the second fill valve arrangement 94 are respectively associated with each of the fill manifold outlets 81', 82', 83', 84', 85', 86'. The valves of the second fill valve arrangement 94 are disposed in spaced relation to one another along a horizontal axis. With this arrangement, the fill manifold outlets 81'-86' can be disposed above the work station 100' in the configuration shown in Figure 5 and 6 .

[0109] Figure 5 and Figure 6 The work station 100' shown in includes a cart 140, a frame structure 143', and a weigh scale 145. The frame structure 143' is mounted to the cart 140 and is configured to support one or more biocontainer cases. The frame structure 143' includes an upright structure configured to hold the cases in place and form a pair of handle portions 152 adapted to be grasped when moving the work station 100' over a surface on which the wheels of the cart 140 are located. The work station 100' includes a work station configured to hold fluid in at least one disposable case from which the fluid dispensing system 50' aliquots fluid from a larger supply. Figure 5 The work station 100' can otherwise be similar to the work station 100 of Figure 3 .

[0110] Referring toFigures 7-10 In embodiments, a fluid dispensing system 250 constructed in accordance with the principles of the present disclosure includes at least one disposable fill manifold 255 and at least one fill valve device 293 mounted to a dispensing tower 295 separate from a dispenser skid 252. The illustrated dispensing tower 295 includes a cart 305 and a fill tower 310. The fill tower 310 extends from the cart 305. In Figure 7 and Figure 8 In the illustrated embodiment, two of the set of disposable fill manifolds 255, 255' are mounted to the fill tower of the dispensing tower. In embodiments, the fill valve device 293 is mounted to the tower 310 and can be associated with one of the disposable fill manifolds 255 mounted to the fill tower 310 such that the valves of the fill valve device 293 are respectively associated with each of the fill manifold outlets. The fill manifold outlets of the disposable fill manifold 255 can be placed in fluid communication with a respective plurality of disposable containers that can be supported by the workstations 300, 301.

[0111] In embodiments, after the first of the disposable fill manifolds 255 mounted to the fill tower 310 is used for a fill operation, the other of the disposable fill manifolds 255' mounted to the fill tower 310 can be associated with the fill valve device 293 mounted to the fill tower 310 and the other intermediate dispenser manifold outlet of the intermediate disposable dispenser manifold 254. The other disposable fill manifold 255' mounted to the fill tower 310 can then be used with another set of disposable containers in a second fill operation.

[0112] Referring to Figure 9 and Figure 10 , the fill tower 310 of the dispensing tower 295 is illustrated with a fill valve device 293 and a disposable fill manifold 255 mounted thereto. The fill tower 310 includes a housing 315 that can support a plurality of valves including the fill valve device 293 such that the clamping portions of the valves extend from an outer surface of the housing 315. As Figure 9 illustrated, the clamping portions 297 can be associated with a respective one of the fill manifold outlets 281 (only one of which is labeled).

[0113] Referring to Figure 11 and 12 In embodiments, an embodiment of a fluid dispensing system 450 constructed in accordance with the principles of the present disclosure includes at least one disposable fill manifold 455 and at least one fill valve device 493 mounted to a dispensing tower 497 separate from a dispenser skid 452. In Figure 11 and Figure 12 In the illustrated embodiment, a pair of dispensing towers 495, 497 are provided. In embodiments, the fluid dispensing system 450 includes a plurality of dispensing towers configured to support a plurality of different disposable containers filled by the fluid dispensing system.

[0114] In the illustrated embodiment, one of the distribution towers 495 is structurally similar to the distribution tower 295 of Figures 7-10 The other distribution tower 497 includes a gantry 505 that includes first and second upright columns 507, 508 and a beam 509 extending between the upper ends of the first and second upright columns 507, 508. Each of the upright columns 507, 508 includes a trolley at its base that is configured to facilitate movement of the gantry 505. One of the set of disposable prime manifolds 455 and prime valve assemblies 493 is mounted to the beam.

[0115] Referring to Figure 11 , in embodiments, the prime manifold inlet of the disposable prime manifold can be placed in fluid communication with one of the intermediate distributor manifold outlets of the disposable intermediate distributor manifold 454 mounted to the distributor sled 452. The prime manifold outlets of the disposable prime manifold 455 can be placed in fluid communication with a respective plurality of disposable containers that can be supported by the workstations 500, 501, respectively.

[0116] In embodiments, the prime manifold inlet of the disposable prime manifold 456 mounted to the prime tower 510 can be placed in fluid communication with another of the intermediate distributor manifold outlets of the disposable intermediate distributor manifold 454 mounted to the distributor sled 452. The prime manifold outlets of the disposable prime manifold 456 can be placed in fluid communication with another set of disposable containers that can be supported by the workstations 500, 501 or other differently configured workstations (e.g., the workstation shown) respectively. Figure 7

[0117] In other embodiments, fluid distribution systems constructed in accordance with the principles of the present disclosure can include different equipment configured to hold supply fluids for delivery to manifolds for distributed proportional dispensing in a plurality of disposable containers. For example, in other embodiments, fluid distribution systems constructed in accordance with the principles of the present disclosure can include at least one tower configured to hold one or more tanks filled with fluids for use in the fluid distribution system. In other embodiments, fluid distribution systems constructed in accordance with the principles of the present disclosure can include one or more canisters filled with fluids for use in the system.

[0118] In other embodiments of fluid distribution systems constructed in accordance with the principles of the present disclosure, the structure of the fluid distribution system can take alternative forms. For example, in embodiments, the distribution towers can be replaced by tanks. In other embodiments, the fluid distribution system can be scaled up to accommodate larger capacities or scaled down for laboratory use. In embodiments, the fluid distribution system can include disposable manifolds constructed of rigid plastic structures. In embodiments, fluid distribution systems constructed in accordance with the principles of the present disclosure can be used to process a variety of liquids to meet the requirements of desired applications.​

[0119] In embodiments of a method of using a fluid dispensing system following the principles of the present disclosure, a fluid dispensing system constructed according to the principles of the present disclosure is used to deliver portions of fluid to a series of disposable containers discussed herein. In embodiments, a method of using a fluid dispensing system following the principles of the present disclosure can be used with any embodiment of a fluid dispensing system according to the principles discussed herein, which can include embodiments of a dispenser skid having at least one disposable dispenser manifold according to the principles of the present disclosure.

[0120] In embodiments, a method of 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 port of a plurality of dispenser manifold outlet ports of the disposable dispenser manifold through a first aseptic fluid passageway to a fill manifold inlet of a first disposable fill manifold. Portions of the first supply fluid are each discharged from a plurality of fill manifold outlet ports of the first disposable fill manifold to a respective one of a first set of disposable containers that are each aseptically fluidly connected to the plurality of fill manifold outlet ports of the first disposable fill manifold. After discharging the portions of the first supply fluid, the first disposable fill manifold is disconnected from the disposable dispenser manifold.

[0121] A second supply fluid is discharged from a second dispenser manifold outlet port of the plurality of dispenser manifold outlet ports of the disposable dispenser manifold through a second aseptic fluid passageway to the fill manifold inlet of a second disposable fill manifold. Portions of the second supply fluid are each discharged from a plurality of fill manifold outlet ports of the second disposable fill manifold to a respective one of a second set of disposable containers that are each aseptically fluidly connected to the plurality of fill manifold outlet ports of the second disposable fill manifold.

[0122] In embodiments, the method further includes sequentially discharging additional supplies of fluid from each other dispenser manifold outlet of the disposable dispenser manifold through a respective independent aseptic fluid passageway to a fill manifold inlet of a respective other disposable fill manifold. Portions of the additional supplies of fluid are each discharged from a plurality of fill manifold outlet ports of each respective other disposable fill manifold to a respective one of an additional set of disposable containers that are each aseptically fluidly connected to the plurality of fill manifold outlet ports of each respective other disposable fill manifold. After discharging the portions of the additional supplies of fluid, respectively, each respective other disposable fill manifold is disconnected from the disposable dispenser manifold.

[0123] In embodiments, the method further includes installing the disposable dispenser manifold to the fill skid prior to delivering fluid into the dispenser manifold inlet of the disposable dispenser manifold. The disposable dispenser manifold is removed from the fill skid after sequentially discharging the additional supplies of fluid from each other dispenser manifold outlet of the disposable dispenser manifold.

[0124] In embodiments, the disposable dispenser manifold includes a first disposable dispenser manifold. In embodiments, a first supply fluid is discharged from a first one of a plurality of dispenser manifold outlet ports of the disposable dispenser manifold by passing the first supply fluid into a dispenser manifold inlet of a second disposable dispenser manifold. A second disposable dispenser manifold of the first sterile fluid pass is interposed between the first one of the plurality of dispenser manifold outlet ports of the first disposable dispenser manifold and a fill manifold inlet of the first disposable fill manifold, and the first supply fluid is discharged from the first one of the plurality of dispenser manifold outlet ports of the second disposable dispenser manifold through the first sterile fluid pass to the fill manifold inlet of the first disposable fill manifold.

[0125] In other embodiments, a method of sterile dispensing a fluid includes passing a first supply fluid into a dispenser manifold inlet of a first disposable dispenser manifold. The first supply fluid is discharged from a first one of a plurality of dispenser manifold outlet ports of the first disposable dispenser manifold through a first sterile fluid pass to a dispenser manifold inlet of a second disposable dispenser manifold. The first supply fluid is discharged from a second one of the plurality of dispenser manifold outlet ports of the second disposable dispenser manifold through a second sterile fluid pass to a fill manifold inlet of a first disposable fill manifold. Portions of the first supply fluid are respectively discharged from a plurality of fill manifold outlet ports of the first disposable fill manifold to respective ones of a first set of disposable containers that are respectively sterile fluidly connected to the plurality of fill manifold outlet ports of the first disposable fill manifold.

[0126] After the portions of the first supply fluid are discharged, the first disposable fill manifold is disconnected from the second disposable dispenser manifold, and a second disposable fill manifold is connected to a second one of the plurality of dispenser manifold outlet ports of the second disposable dispenser manifold through a third sterile fluid pass. A second supply fluid is passed into the dispenser manifold inlet of the first disposable dispenser manifold. The second supply fluid is discharged from the first one of the plurality of dispenser manifold outlet ports of the first disposable dispenser manifold through the first sterile fluid pass to the dispenser manifold inlet of the second disposable dispenser manifold. The second supply fluid is discharged from the second one of the plurality of dispenser manifold outlet ports of the second disposable dispenser manifold through the third sterile fluid pass to the fill manifold inlet of the second disposable fill manifold. Portions of the second supply fluid are respectively discharged from the plurality of fill manifold outlet ports of the second disposable fill manifold to respective ones of a second set of disposable containers that are respectively sterile fluidly connected to the plurality of fill manifold outlet ports of the second disposable fill manifold.

[0127] In embodiments, the method further includes sequentially discharging additional supplies of fluid from each other dispenser manifold outlet of the second disposable dispenser manifold through a respective, independent sterile fluid pathway to a respective other disposable prime manifold prime manifold inlet. Portions of the additional supplies of liquid are respectively discharged from a plurality of prime manifold outlet ports of each respective other disposable prime manifold to a respective one of an additional set of disposable containers that are respectively sterile fluidly connected to the plurality of prime manifold outlet ports of each respective other disposable prime manifold.

[0128] In embodiments, the method further includes disconnecting each respective other disposable prime manifold from the second disposable dispenser manifold after the respective portions of the additional supplies of fluid are respectively discharged. In embodiments, the method further includes disconnecting the second disposable dispenser manifold after the additional supplies of fluid are sequentially discharged from each other dispenser manifold outlet of the second disposable dispenser manifold and connecting a second one of the plurality of dispenser manifold outlet ports of the first disposable dispenser manifold to a dispenser manifold inlet of a third disposable dispenser manifold through a fourth sterile fluid pathway.

[0129] In embodiments, the method further includes delivering a third supply of fluid to the dispenser manifold inlet of the first disposable dispenser manifold. The third supply of fluid is discharged from the second one of the plurality of dispenser manifold outlet ports of the first disposable dispenser manifold to the dispenser manifold inlet of the third disposable dispenser manifold through the fourth sterile fluid pathway. The third supply of fluid is discharged from a first one of the plurality of dispenser manifold outlet ports of the third disposable dispenser manifold to the prime manifold inlet of the third disposable prime manifold through a fifth sterile fluid pathway. Portions of the third supply of liquid are respectively discharged from a plurality of prime manifold outlet ports of the third disposable prime manifold to a respective one of a third set of disposable containers that are respectively sterile fluidly connected to the plurality of prime manifold outlet ports of the third disposable prime manifold.

[0130] In embodiments, the method further includes sequentially discharging additional supplies of fluid from each other dispenser manifold outlet port of the third disposable dispenser manifold through a respective, independent sterile fluid pathway to a respective other disposable prime manifold prime manifold inlet. Portions of the additional supplies of liquid are respectively discharged from a plurality of prime manifold outlet ports of each respective other disposable prime manifold to a respective one of an additional set of disposable containers that are respectively sterile fluidly connected to the plurality of prime manifold outlet ports of each respective other disposable prime manifold.

[0131] In embodiments, the method further includes sequentially discharging respective ones of an additional set of supplies of fluid from each other dispenser manifold outlet of the first disposable dispenser manifold to a set of intermediate disposable dispenser manifolds.

[0132] In another embodiment of a method of aseptically dispensing a fluid in accordance with the principles of the present disclosure, the method includes discharging a supply of fluid from different ones of a plurality of dispenser manifold outlet ports of a disposable dispenser manifold in sequence, each dispenser manifold outlet port being in fluid communication with a fill manifold inlet of a respective one of a corresponding plurality of disposable fill manifolds by a respective aseptic fluid conduit, wherein the discharging of the supply of fluid in sequence is performed by operating the valve arrangement to open the dispenser manifold outlet ports in sequence through a series of different conditions including, for each dispenser manifold outlet port, the dispenser manifold outlet being open while the other dispenser manifold outlet ports are occluded.

[0133] In an embodiment, for each disposable fill manifold, a portion of the supply of fluid received from one of the dispenser manifold outlet ports in fluid communication therewith is discharged from each of the plurality of fill manifold outlet ports into a respective one of a set of disposable containers to which it is aseptically fluidly connected. In an embodiment, the supply of fluid is discharged in sequence by operating the valve arrangement to open each of the aseptic fluid conduits in sequence while the other aseptic fluid conduits are occluded.

[0134] In another embodiment of a method of aseptically dispensing a fluid in accordance with the principles of the present disclosure, the method includes delivering a supply of fluid to a fill manifold inlet of a disposable fill manifold. A fill portion of the supply of fluid is discharged from all but a reserved one of a plurality of fill manifold outlets of the first disposable fill manifold into disposable containers to which it is respectively aseptically fluidly connected. After the fill portion is discharged, an underfill portion of the supply of fluid is discharged from the reserved one of the fill manifold outlets into a disposable container to which it is aseptically fluidly connected. The underfill portion is less than the fill portion. After the underfill portion is discharged, a fill manifold volume of the supply of fluid is discharged from a main conduit of the disposable fill manifold from the reserved one of the fill manifold outlets into a disposable container to which it is aseptically fluidly connected. In an embodiment, the underfill portion in combination with the fill manifold volume together is substantially the same as the fill portion.

[0135] In an embodiment, delivering the supply of fluid to the fill manifold inlet includes priming a main conduit of the disposable fill manifold with a fill manifold volume, moving air in the main conduit out of a vent conduit in fluid communication with the main conduit during priming, and closing the vent conduit after priming. In an embodiment, discharging the fill portion includes discharging each fill portion in sequence. In an embodiment, discharging the fill manifold volume of the supply of fluid remaining in the main conduit of the disposable fill manifold includes opening the vent conduit in fluid communication with the main conduit and replacing the fill manifold volume with air in the main conduit during discharge.

[0136] In embodiments, the method further includes delivering the supply fluid into a dispenser manifold inlet of the disposable dispenser manifold. The supply fluid is discharged from a first one of the plurality of dispenser manifold outlets of the disposable dispenser manifold through the first sterile liquid fill channel to a fill manifold inlet of the disposable fill manifold. After discharging a fill manifold volume of the supply fluid remaining in the disposable fill manifold, the disposable container is disconnected from the disposable fill manifold. A dispenser manifold volume of the supply fluid is drained from the disposable dispenser manifold into the sterile liquid reserve channel into a recovery container in sterile fluid communication therewith. The dispenser manifold volume includes fluid remaining in a main conduit of the disposable dispenser manifold.

[0137] In embodiments, delivering the supply fluid into a dispenser manifold inlet of the disposable dispenser manifold includes introducing recovery fluid from the recovery container into the dispenser manifold inlet through the sterile fluid reserve channel, such that at least a portion of the supply fluid includes recovery fluid from the recovery container. In embodiments, discharging a dispenser manifold volume of the supply fluid remaining in the main conduit of the disposable dispenser manifold includes (i) opening a vent conduit in fluid communication with the main conduit of the disposable dispenser manifold, and (ii) opening at least one recovery valve arranged with the first sterile fluid fill channel to discharge fluid to the recovery container.

[0138] In embodiments, the disposable dispenser manifold includes an intermediate disposable dispenser manifold, and the method further includes delivering the supply fluid into a dispenser manifold inlet of an upstream disposable dispenser manifold. The supply fluid is discharged from a first one of the plurality of dispenser manifold outlets of the upstream disposable dispenser manifold through the sterile dispenser fluid channel to the dispenser manifold inlet of the intermediate disposable dispenser manifold. In embodiments, discharging a dispenser manifold volume of the supply fluid includes discharging fluid remaining in the disposable dispenser manifold and the upstream disposable dispenser manifold. In embodiments, the recovery container is disposed below the disposable dispenser manifold and the upstream disposable dispenser manifold in a direction of gravity on the dispenser manifold volume.

[0139] In embodiments, the disposable fill manifold includes a first disposable fill manifold, the supply fluid includes a first supply fluid, and the method further includes disconnecting the first disposable fill manifold from the disposable dispenser manifold after a fill portion of the first supply fluid is discharged and an underfill fill portion is discharged. In embodiments, the method further includes recovering / discharging any remaining fluid in the fill manifold body to a last outlet port and in combination with the underfill fill portion to constitute a full discharge portion prior to the fill manifold being disconnected.

[0140] In embodiments, the fill manifold inlet of the second disposable fill manifold is connected by a second sterile fluid fill channel to a second one of the plurality of dispenser manifold outlets of the disposable dispenser manifold. A second supply fluid is sent into the dispenser manifold inlet of the disposable dispenser manifold. In embodiments, sending the second supply fluid includes introducing a recycle fluid from a recycle reservoir into the dispenser manifold inlet through the sterile liquid reservoir channel, such that at least a portion of the second supply fluid comprises the recycle fluid from the recycle reservoir. The second supply fluid is discharged from the second one of the plurality of dispenser manifold outlets of the disposable dispenser manifold through the second sterile liquid fill channel to the fill manifold inlet of the second disposable fill manifold. A fill portion of the second supply fluid is discharged from all but one of the plurality of fill manifold outlets of the second disposable fill manifold to the respective one of the plurality of disposable containers to which it is sterilely connected. After the fill portion is discharged, an underfill portion of the second supply fluid is discharged from the one of the plurality of fill manifold outlets of the second disposable fill manifold to the one of the plurality of disposable containers to which it is sterilely connected. After the underfill portion is discharged, the remaining fill volume of the second supply fluid in the body conduit of the second disposable fill manifold is discharged from the one of the plurality of fill manifold outlets of the second disposable fill manifold to the one of the plurality of disposable containers to which it is sterilely connected.

[0141] Referring to Figures 13-21 , an embodiment of a fluid dispensing system 650 constructed according to the principles of the present disclosure is shown, which system undergoes a series of fluid recycle sequences. In Figures 13-21 , dashed lines depict the fluid flow paths through the system 650 according to the particular operation being performed.

[0142] Figures 13-18 A first fluid recycle sequence in the form of an underfill operation is described. Referring to Figure 13 , the system 650 can be primed by sending a supply fluid 651 from a source container to the manifolds 653, 654, 655. The vent conduit 697 above the fill manifold 655 is open, such that air is pushed out of the series of manifolds 653-655. In Figure 14 , the vent valve 701 is closed in response to liquid reaching the liquid sensor 699 in the vent conduit 697. Figure 15 and 16 show sequential filling of the first and second standard fill outlets 681, 682 of the fill manifold 655, with each container 725 to which it is connected being filled to a target volume. Referring to Figure 16 , sequential filling can occur at the remainder of the standard fill ports 683-686. Referring to Figure 17 , an underfill volume is discharged through the underfill outlet 686 of the fill manifold 655 to a disposable container 725 to which it is in fluid communication. Referring toFigure 18 Fluid in the fill manifold 655 is drained from the main body of the fill manifold through the underfill outlet 686 into the bottommost container 725, so that each container in the rack 700 contains the target volume. During the drain operation of the fill manifold 655, the vent conduit 697 is open.

[0143] Figure 19 and 20 A second fluid recovery sequence in the form of a dispenser manifold drain operation is described. Referring to Figure 19 After filling the disposable containers stored in the work station 700, the containers are disconnected from the fill manifold 655. The vent conduit 697 is opened, and the fluid in the dispenser manifolds 653, 654 is allowed to drain (by gravity) through the recovery conduit 106 into the recovery container 107. Referring to Figure 20 Once the dispenser manifold drain operation is complete, the vent conduit 697 can be closed, and a new disposable fill manifold 655’ can be connected to a different outlet of the intermediate dispenser manifold 654.

[0144] Figure 21 A third fluid recovery sequence in the form of a manifold prime operation is described, in which fluid from the recovery container 107 is used to prime the manifolds 653, 654. Once the fluid in the recovery container 107 reaches a low level sensor 118, as Figure 21 shown, the system 650 can provide a fresh fluid supply from the original fluid source 651.

[0145] Referring to Figures 13-21 In embodiments, the fluid dispensing system 650 can include a suitable integrity testing device 735 configured to perform an integrity test on at least one component of the system 650. In embodiments, the integrity testing device 735 is configured to perform an integrity test on at least one of the manifolds 653-655. Various integrity testing instruments are suitable for use in accordance with embodiments of the present disclosure, such as the PALLTRONIC Flowstar IV filter integrity tester, or the PALLTRONIC Flowstar IV filter integrity tester MUX extension, or the PALLTRONIC Flowstar LGR tester, or the PALLTRONIC AquaWIT IV filter integrity testing system from Pall Corporation of Washington, New York. In embodiments, the integrity testing device 735 is configured to perform one of a leak test and a pressure decay test on at least one of the disposable manifolds 653-655.

[0146] In embodiments, the fluid dispensing system is configured to provide a closed system usable for an "X" group fill sequence, where the "X" group fill sequence is equal to the number of outlets of the first dispenser manifold. In embodiments, the fluid dispensing system is configured to provide a closed system usable for an "X" and "Y" product group fill sequence, where the "X" group fill sequence is equal to the number of outlets in the first dispenser manifold and the "Y" group sequence is equal to the number of outlets in a second dispenser manifold in series with the first dispenser manifold.

[0147] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.

[0148] The terms "a" and "an" and "the" and the like convey the understanding that the both the singular and plural are meant unless the context clearly dictates otherwise. The terms "comprising," "having," "including," and "containing" are to be construed as open-ended terms (i.e., meaning "including, but not limited to,") unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated in the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., "such as") provided herein, is intended merely to better illuminate the application and does not pose a limitation on the scope of the application unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the application.

[0149] Preferred embodiments of this application are described herein, including the best mode known to the inventors of practicing the application. Variations of these preferred embodiments can become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the application to embrace all such modifications and equivalents. Accordingly, the application includes all modifications and equivalents that can come within the scope of the claims appended hereto and encompasses all such modifications as fall within the scope of the appended claims. In addition, any combination of the elements from any of the aspects of the application described above is encompassed by the application.

Claims

1. A fluid distribution system, the fluid distribution system comprising: A pump adapted to selectively generate a fluid flow; A disposable filling manifold, comprising a filling manifold inlet, a plurality of filling manifold outlets, and a filling manifold main conduit, wherein the filling manifold inlet is in fluid communication with each of the plurality of filling manifold outlets via the filling manifold main conduit, the filling manifold inlet is arranged together with a pump for supplying fluid to the disposable filling manifold, and the filling manifold outlets include at least one standard fill outlet and a short fill outlet; A filling valve device comprising a plurality of valves arranged together with a single-use filling manifold, such that each outlet of the filling manifold can be independently shut off by a corresponding valve of the filling valve device; 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 in electrical communication with a pump and a filling valve assembly to selectively operate valves of the pump and the filling valve assembly based on instructions from the fluid dispensing program. The fluid dispensing program has a container filling module configured to discharge a target filling volume of supply fluid to each standard filling outlet of the filling manifold outlet, discharge a short filling volume of supply fluid to a short filling outlet of the filling manifold outlet, and discharge a filling manifold volume of supply fluid from the filling manifold main conduit to a short filling outlet of the filling manifold outlet, wherein the short filling volume is less than the target filling volume.

2. The fluid distribution system according to claim 1, wherein the fluid distribution system further comprises: Multiple disposable containers, each having an access port, the access port being fluidly connected to a corresponding dispensing manifold outlet via a sterile fluid connector; The container filling module of the fluid distribution procedure is configured to perform the following steps when executed by the processor: The supply fluid is fed into the manifold inlet of the disposable filling manifold; The fluid of the target filling volume is sequentially discharged from each standard filling outlet of the disposable filling manifold into a disposable container that is respectively connected to each standard filling outlet in a sterile fluid connection. After the target filling volume is discharged in sequence, the fluid of the short filling volume is discharged from the short filling outlet of the disposable filling manifold to a disposable container that is in sterile fluid connection with the short filling outlet. After the underfill volume is discharged, the fluid of the filling manifold volume is discharged from the underfill outlet of the filling manifold main conduit into a disposable container that is in sterile fluid connection with the underfill outlet.

3. The fluid distribution system according to claim 1 or 2, wherein the fluid distribution system further comprises: A ventilation duct, which is in fluid communication with the main duct of the filling manifold; A ventilation valve is arranged together with a ventilation duct to selectively block the ventilation duct, and the ventilation valve is operatively arranged together with a control unit.

4. The fluid distribution system according to claim 3, wherein the fluid distribution system further comprises: A ventilation liquid sensor is disposed in a ventilation duct and configured to generate a liquid detection signal in response to detecting liquid in the ventilation duct. A control unit communicates electrically with the ventilation liquid sensor to receive the liquid detection signal from the ventilation liquid sensor. An air filter is provided, which is arranged together with a ventilation duct, and a ventilation valve is inserted between the ventilation liquid sensor and the air filter; The control unit is configured to stop the operation of the pump and / or close the vent valve in response to receiving a liquid detection signal.

5. The fluid distribution system according to claim 3, wherein, The fluid dispensing procedure includes a manifold filling module configured to perform the following steps when executed by a processor: The main conduit of the disposable manifold is filled with the supply fluid of the manifold volume; During the filling of the main manifold duct, air is removed from the main manifold duct and the ventilation valve is in the open position. After filling the main manifold conduit, place the ventilation valve in the closed position to block the ventilation conduit.

6. The fluid distribution system according to claim 1 or 2, wherein the fluid distribution system further comprises: A disposable dispenser manifold, comprising a dispenser manifold inlet, a plurality of dispenser manifold outlets, and a dispenser manifold body conduit, wherein the dispenser manifold inlet is in fluid communication with each of the plurality of dispenser manifold outlets via the dispenser manifold body conduit, one of the plurality of dispenser manifold outlets is in sterile fluid connection with the dispensing manifold inlet, and the dispenser manifold inlet is arranged together with a pump to deliver supply fluid to the disposable dispensing manifold through the one of the dispenser manifold outlets; A distributor valve assembly comprising a plurality of valves arranged together with a disposable distributor manifold, such that each outlet of the distributor manifold can be independently shut off by a corresponding valve in the distributor valve assembly.

7. The fluid distribution system according to claim 6, wherein the fluid distribution system further comprises: A recovery container and a sterile fluid storage channel, wherein the recovery container is in fluid communication with the main conduit of the dispenser manifold through the sterile fluid storage channel; The fluid dispensing procedure includes a distributor manifold discharge module, which is configured, when executed by the processor, to discharge the supply fluid of the distributor manifold volume in the distributor manifold main conduit into a sterile fluid storage channel and reach a recovery container.

8. The fluid distribution system according to claim 7, wherein the fluid distribution system further comprises: Ventilation duct, which is in fluid communication with the main body duct of the distributor manifold; A ventilation valve, which is arranged together with a ventilation duct to selectively block the ventilation duct, and a control unit is operably arranged together; A recovery valve is arranged together with a sterile fluid reservoir channel, such that the sterile fluid reservoir channel can be closed by the recovery valve, and the recovery valve is operatively arranged together with a control unit. In the direction in which gravity acts on the fluid in the distributor manifold, the recovery container is positioned below the vent valve and the disposable distributor manifold. The distributor manifold discharge module is configured, when executed by the processor, to open the ventilation valve to allow air to enter the distributor manifold body duct from the outside of the ventilation duct, and to open the recovery valve arranged with the first sterile fluid filling channel.

9. The fluid distribution system according to claim 8, wherein the fluid distribution system further comprises: A high liquid level sensor is disposed together with a recovery container and configured to generate a high recovery liquid level signal in response to detecting that the liquid in the recovery container is at a predetermined high liquid level. The control unit communicates electrically with the high liquid level sensor to receive the high recovery liquid level signal from the high liquid level sensor. The distributor manifold discharge module is configured to, when executed by the processor, close the vent valve and the recovery valve arranged together with the first sterile fluid filling channel in response to receiving a high recovery level signal.

10. The fluid distribution system according to claim 6, wherein, The disposable dispenser manifold includes an intermediate disposable dispenser manifold, and the system further includes: An upstream disposable dispenser manifold includes an upstream dispenser manifold inlet, a plurality of upstream dispenser manifold outlets, and an upstream dispenser manifold main conduit. The upstream dispenser manifold inlet is in fluid communication with each of the plurality of upstream dispenser manifold outlets through the upstream dispenser manifold main conduit. One of the plurality of upstream dispenser manifold outlets is in sterile fluid connection with the dispenser manifold inlet of an intermediate disposable dispenser manifold. The upstream dispenser manifold inlet is arranged together with a pump for delivering supply fluid to the disposable dispensing manifold. An upstream distributor valve assembly includes multiple valves arranged together with an upstream disposable distributor manifold, such that each outlet of the upstream distributor manifold can be independently shut off by a corresponding valve in the upstream distributor valve assembly.

11. A method for aseptically dispensing fluid, the method comprising: The supply fluid is fed into the manifold inlet of the disposable filling manifold; The filling portion of the supply fluid is discharged from all dispensing manifold outlets of the disposable dispensing manifold, except for the reserved dispensing manifold outlet, into disposable containers that are respectively connected to the sterile fluid at the dispensing manifold outlet; After the filled portion is discharged, the supply fluid of the underfilled portion is discharged from the reserved filling manifold outlet in the filling manifold outlet to a disposable container connected to the sterile fluid of the reserved filling manifold outlet. The underfilled portion is smaller than the filled portion. After the underfill portion is discharged, the supply fluid of the manifold volume is discharged from the main conduit of the disposable manifold to the reserved manifold outlet in the manifold outlet, reaching the disposable container that is connected to the reserved manifold outlet for sterile fluid.

12. The method according to claim 11, wherein, The supply fluid for the remaining manifold volume in the main conduit of the discharge manifold includes: opening the manifold vent, which is in fluid communication with the main conduit, and replacing the manifold volume with air from the main conduit during discharge.

13. The method according to claim 12, wherein, The process of supplying fluid into the filling manifold inlet includes filling the main conduit of the disposable filling manifold with the filling manifold volume, removing air from the main conduit during filling and fluidly communicating with the manifold vent, and closing the manifold vent after filling.

14. The method according to any one of claims 11 to 13, wherein, Discharging the filler involves discharging each filler section in sequence.

15. The method according to any one of claims 11 to 13, wherein, The combination of the underfill portion and the filling manifold volume is basically the same as that of the filling portion.

16. The method according to any one of claims 11 to 13, the method further comprising: The supply fluid is fed into the distributor manifold inlet of the disposable distributor manifold; The supply fluid is discharged from the first distributor manifold outlet of the multiple distributor manifold outlets of the disposable distributor manifold through the first sterile fluid filling channel to the filling manifold inlet of the disposable filling manifold. After draining the remaining supply fluid from the disposable dispenser manifold, disconnect the disposable container from the disposable dispenser manifold. The supply fluid volume of the dispenser manifold is discharged from the disposable dispenser manifold into the sterile fluid reservoir channel to reach the recovery container connected to the sterile fluid reservoir channel.

17. The method according to claim 16, wherein, The dispenser manifold inlet for supplying fluid into a disposable dispenser manifold includes introducing recycled fluid from a recycling container through a sterile fluid reserve channel into the dispenser manifold inlet, such that at least a portion of the supplied fluid includes recycled fluid from the recycling container.

18. The method according to claim 16, wherein, The supply fluid for discharging the remaining dispenser manifold volume in the main conduit of the disposable dispenser manifold includes: opening a manifold vent that is in fluid communication with the main conduit of the disposable dispenser manifold, and opening at least one recovery valve arranged in conjunction with a first sterile fluid filling channel.

19. The method of claim 16, wherein, The disposable dispenser manifold includes an intermediate disposable dispenser manifold, and the method further includes: The supply fluid is fed into the distributor manifold inlet of the upstream disposable distributor manifold; The supply fluid is discharged from the first of the multiple dispenser manifold outlets of the upstream disposable dispenser manifold through the sterile dispenser fluid channel to the dispenser manifold inlet of the intermediate disposable dispenser manifold. The supply fluid of the discharge manifold volume includes the fluid remaining in the disposable manifold and the upstream disposable manifold, and wherein, in the direction of gravity acting on the fluid in the manifold, the recovery container is positioned below the disposable manifold and the upstream disposable manifold.

20. The method of claim 16, wherein, The disposable filling manifold includes a first disposable filling manifold, and the supply fluid includes a first supply fluid, the method further comprising: After the first supply fluid is discharged from the filled portion and the underfill portion, disconnect the first disposable filling manifold from the disposable dispenser manifold; The inlet of the second disposable dispensing manifold is connected to the second dispensing manifold outlet among the plurality of dispensing manifold outlets of the disposable dispensing manifold via a second sterile fluid filling channel. The second supply fluid is fed into the dispenser manifold inlet of the disposable dispenser manifold, wherein feeding the second supply fluid includes introducing recycled fluid from the recycling container through a sterile fluid reserve channel into the dispenser manifold inlet, such that at least a portion of the second supply fluid includes recycled fluid from the recycling container. 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 filling channel to the filling manifold inlet of the second disposable filling manifold. The filling portion of the second supply fluid is discharged from all the multiple manifold outlets of the second disposable manifold, except for the retained manifold outlet, into disposable containers that are respectively connected to the sterile fluid of the manifold outlet; After the filling portion is discharged, the insufficient filling portion of the second supply fluid is discharged from the reserved filling manifold outlet in the filling manifold outlet of the second disposable filling manifold to the disposable container connected to the sterile fluid of the reserved filling manifold outlet. After the underfill portion is discharged, the remaining manifold volume of the second supply fluid in the main conduit of the second disposable manifold is discharged to the reserved manifold outlet in the manifold outlet of the second disposable manifold, reaching the disposable container that is in sterile fluid connection with the reserved manifold outlet.

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