Method and device for remotely operated-scheduleable- intelligent-automated-bioreactor-feeder

Abstract

An apparatus for automated delivery of fluids to a vessel of a bioprocessing device includes a support structure and a plurality of valves located on or in the support structure, each of the valves being selectively openable and closeable and configured for receiving and selectively opening and closing a fluid line, each fluid line having at least one dedicated valve of the plurality. The apparatus further includes a pump located on or in the support structure, the pump configured to receive a fluid line to or from a valve of the plurality and selectively pump fluid into the vessel. The apparatus is controllable to automatically open or close the plurality of valves and activate the pump to deliver a quantity of fluid to the vessel.

Description

METHOD AND DEVICE FOR REMOTELY OPERATED-SCHEDULEABLE- INTELLIGENT-AUTOMATED-BIOREACTOR-FEEDER BACKGROUND TECHNICAL FIELD

[0001] Embodiments of the invention relate generally to cellular processing, and, more particularly, to apparatus, systems, and methods for the automated delivery of fluids to a vessel, e.g., a flexible bag, of a bioprocessing device to facilitate processing of biological materials. DISCUSSION OF ART

[0002] Cellular processing devices such as bioreactors, mixers, and fermenters are often employed to carry out biochemical and / or biological processes and / or manipulate liquids and other products of such processes. Such devices often include flexible or collapsible single-use disposable bags / vessels that are supported by an outer rigid structure, such as a tank or platform. The vessels are filled with the desired fluid for processing. The fluid within the vessels may require mixing or agitation to prevent settling of particulates at the bottom of the vessel which may be accomplished through the use of, e.g., rotatable impeller or a rocking mechanism.

[0003] Fluids typically introduced into vessels include liquids, such as cell culture media, feeds, supplements, serum, salt solutions, buffers, and water, as well as gases such as air, oxygen, carbon dioxide, nitrogen, or mixtures thereof. Fluids are added to establish and maintain suitable growth and / or reaction conditions for producing a product from cellular material within the vessel.

[0004] Fluids, e.g., cell culture media, are typically pumped from a fluid source into the vessel through fluid lines using a pump, e.g., a peristaltic pump. This process is manual, however, and the addition of fluids can be challenging for a variety of reasons.

[0005] For example, in fed-batch processing, the number of fluids and fluid lines that run into and out of the bioreactor vessel is substantial, e.g., 2 – 4 (or more) separate feeds / lines. Fluids are also fed into the vessel using volumetric processes or gravimetric processes, e.g., they are added / pumped in by weight rather than by volume, which involves the use of multiple load cells / scales. As a result, fed-batch processing is user intensive and involves manually unclamping tubing to allow flow of fluids, monitoring the weight of fluids being added to the bioreactor, and manually turning on / off the pumps used for feeding.

[0006] In addition to the general challenges associated with manual fed-batch processing, the number or type of lines that may be connected to the vessel itself may be incompatible with the number and / or type of lines required, e.g., vessels may only be equipped with a single or few input ports. This may be a particular concern with smaller capacity vessels (e.g., those with working volumes of about 2.5 L to about 10 L) which, as will be appreciated, have limited surface area for inputs / ports.

[0007] Moreover, with smaller scale single-use bench-top bioreactors, usable bench space is at a premium. Complex manual fed batch systems with multiplescales and external pumps may occupy most or all available space, which is generally undesirable.

[0008] The issues presented by known manually operated systems and processes can potentially result in feeding errors and lack of repeatability. Further, the use of known systems / processes is labor intensive requiring near continuous monitoring. As such, one or more standby users are often required to potentially fill in for the user originally tasked with carrying out the process. Known systems and processes may also be challenging to use with bioreactors and vessels.

[0009] In order to increase efficiency, convenience, and ease of use, and reduce equipment complexity, a need exists for an apparatus, system, and method that allows for the simplified and automated delivery of fluids to a vessel, e.g., bioreactor bag. BRIEF DESCRIPTION

[0010] Certain embodiments commensurate in scope with the originally claimed subject matter are summarized below. These embodiments are not intended to limit the scope of the claimed subject matter, but rather these embodiments are intended only to provide a brief summary of the possible embodiments. Indeed, the disclosure may encompass a variety of forms that may be similar to or different from the embodiments set forth below.

[0011] According to an aspect of the invention, an apparatus for automated delivery of fluids to a vessel of a bioprocessing device includes a support structure and a plurality of valves located on or in the support structure, each of the valvesbeing selectively openable and closeable and configured for receiving and selectively opening and closing a fluid line, each fluid line having at least one dedicated valve of the plurality. The apparatus further includes a pump located on or in the support structure, the pump configured to receive a fluid line to or from a valve of the plurality and selectively pump fluid into the vessel. The apparatus may further include a controller operatively connected to the plurality of valves and the pump and wherein the controller is programmed to automatically open or close the plurality of valves and activate the pump to deliver a quantity of fluid to the vessel.

[0012] In an embodiment, the fluid lines from two or more valves of the plurality are multiplexed into the pump.

[0013] In an embodiment, the plurality of valves includes a first valve and a second valve, the first and second valves may be in series and configured to receive and selectively open and close the same fluid line.

[0014] In an embodiment, the apparatus may include a plurality of pumps, each pump of the plurality being fluidly connectible to a valve from the plurality of valves via a fluid line.

[0015] In an embodiment, the apparatus may include a discharge valve located downstream of the pump and configured to receive and selectively open and close a fluid line from the pump to allow fluid to flow into the flexible bag.

[0016] In an embodiment, the support structure may be a housing and the pump and plurality of valves are located on an exterior of the housing.

[0017] In an embodiment, the housing may be configured to selectively receive pumps of varying sizes and / or flow rates.

[0018] According to an aspect of the invention, a method of delivering fluids to a vessel of a bioprocessing device includes connecting a fluid line from a fluid receptacle to at least one valve and a pump, the at least one valve and pump being located on or in a support structure and being operatively connected to a controller. The method further includes connecting the fluid line to a vessel to that the vessel is fluidly connected to the receptacle. The method also includes initiating a fluid delivery protocol via the controller whereby the controller opens the valve and activates the pump to deliver a quantity of fluid to the vessel.

[0019] In an embodiment, connecting the fluid line to at least one valve includes connecting the fluid line to a pair of valves that are in series and are configured to receive and selectively open and close the fluid line.

[0020] In an embodiment, the step of connecting a fluid line from a fluid receptacle to at least one valve and a pump includes connecting multiple fluid lines to separate valves and to at least one pump, each of the multiple fluid lines being connected to a separate fluid receptacle, and wherein the at least one pump is connected to the vessel.

[0021] In an embodiment, during the step of initiating a fluid delivery protocol, the controller opens at least one valve and activates at least one pump to deliver quantities of fluids from one or more of the separate fluid receptacles to the vessel.

[0022] In an embodiment, the method further includes opening a separate discharge valve that is downstream of the pump to allow the fluid to flow into the vessel.

[0023] In an embodiment, the controller closes the valve and deactivates the pump after the quantity of fluid has been delivered to the vessel.

[0024] In an embodiment, the fluid delivery protocol is selected from a plurality of protocols via the controller.

[0025] In an embodiment, the fluid delivery protocol may be scheduled, initiated, and / or controlled by a user.

[0026] In an embodiment, the fluid delivery protocol may be remotely scheduled, initiated, and / or controlled by a user.

[0027] In an embodiment, the method may further includes generating a user alarm in response to the detection of a no feed, overfill, and / or system error scenario.

[0028] In an embodiment, the method may further include deactivating the pump and / or closing the valve or the separate discharge valve to prevent overfilling independent of whether the quantity of fluid has been delivered.

[0029] According to an aspect of the invention, a system for automated delivery of fluids to a flexible bag of a bioprocessing device includes a support structure and a plurality of valves located on or in the support structure, each of the valves being selectively openable and closeable and configured for receiving and selectively opening and closing a fluid line, each fluid line having at least one dedicated valve of the plurality. The system further includes a pump located on orin the support structure, the pump configured to receive a fluid line to or from a valve of the plurality and selectively pump fluid into the flexible bag. The system additionally includes a one or more fluid lines, each of the fluid lines configured for attachment to at least one dedicated valve of the plurality, the fluid lines may be multiplexed into a single pump line which is configured to be connected to the pump. The system further includes a controller operatively connected to the plurality of valves and the pump, the controller being programmed to automatically open or close the plurality of valves and activate the pump to deliver a quantity of fluid to the flexible bag.

[0030] In an embodiment, the plurality of valves includes a first valve and a second valve that are in series and are dedicated to one fluid line, the first valve and second valve configured selectively open and close the fluid line.

[0031] In an embodiment, the system further comprises a discharge valve that is downstream of the pump to allow the fluid to flow into the flexible bag.

[0032] Features which are described in the context of separate aspects and embodiments of the invention may be used together and / or be interchangeable. Similarly, features described in the context of a single embodiment may also be provided separately or in any suitable sub-combination. BRIEF DESCRIPTION OF THE FIGURES

[0033] The present invention will be better understood from reading the following description of non-limiting embodiments, with reference to the attached drawings, wherein below:

[0034] FIG.1 is a perspective view of a bioprocessing device, e.g., a bioreactor, suitable for use with embodiments of the invention.

[0035] FIG.2 is a perspective view of a bioreactor that includes an apparatus for automated delivery of fluids to a vessel according to an embodiment of the invention.

[0036] FIG.3 is a front perspective view of the apparatus of FIG.2 along with an HMI which may be used to control the apparatus.

[0037] FIG.4 is a rear perspective view of the apparatus of FIG.2 with the back of the apparatus opened to depict controller electronics and the like according to an embodiment of the invention.

[0038] FIG.5 is a simplified illustration of multiplexed fluid line manifold for use with the apparatus of FIG.2, according to an embodiment of the invention.

[0039] FIG.6 is an illustration of a user interface which contains a simplified schematic of an embodiment of the invention that includes multiple apparatus operatively connected to a single reactor.

[0040] FIG.7 is a flowchart of a method of automated delivery of fluids according to an embodiment of the invention. DETAILED DESCRIPTION

[0041] Reference will be made below in detail to exemplary embodiments of the invention, examples of which are illustrated in the accompanying drawings.Wherever possible, the same reference characters used throughout the drawings refer to the same or like parts.

[0042] As used herein, the term “flexible” or “collapsible” refers to a structure or material that is pliable, or capable of being bent without breaking, and may also refer to a material that is compressible or expandable. An example of a flexible structure is a bag formed of polyethylene film.

[0043] A “vessel,” as the term is used herein, means a flexible bag, a flexible container, a semi-rigid container, or a rigid container, as the case may be. The term “vessel” as used herein is intended to encompass bioreactor vessels having a wall or a portion of a wall that is flexible, single-use flexible bags, as well as other containers or conduits commonly used in biological or biochemical processing, including, for example, cell culture / purification (e.g., chromatography) systems, fermentation systems, mixing systems, media / buffer preparation systems, and filtration / purification systems.

[0044] As used herein, the term “bag” means a flexible or semi-rigid container or vessel used, for example, as a bioreactor or mixer for the contents within.

[0045] While depicted for use in connection with small-scale or bench top bioreactors and reactor vessels, e.g., those with working volumes of about 2.5 L to about 10 L, embodiments may be suitable for use with all reactor vessels requiring the input of fluids. Indeed, embodiments may be used with bioreactors with working volumes ranging up to 2000 L or greater. Other embodiments may beutilized in connection with bioprocessing devices generally and are not limited to bioreactors.

[0046] Embodiments may be utilized with stirred tank or rocking platform bioreactors and are not limited in this regard. Certain embodiments may be suitable for use with mixers and fermenters and other material processing devices.

[0047] Embodiments are described and depicted for use in connection with gravimetric fed-batch processing. However, embodiments may be suitable for use with other processes such as volumetric fed-batch and perfusion processes. Indeed, embodiments may be suitable for use with batch, continuous, or other bioprocessing techniques, in addition to fed-batch.

[0048] Embodiments are likewise not limited to the delivery of any specific fluid or substance, e.g., cell media, and may be used in connection with a wide variety of biological and chemical processes. Certain embodiments may be utilized in other industries where automated control and pumping of multiple feed lines is desirable.

[0049] Referring now to FIG.1, a bioprocessing device, e.g., bioreactor 100, suitable for use with embodiments of the invention is depicted. As shown, the bioreactor 100 includes a structural support, i.e., tank 104, which may be formed, for example, from stainless steel, polymers, composites, glass, or other metals and may be rectangular or cylindrical in shape. The tank 104 has an open top 105 that allows access to an interior that is configured to receive a vessel, e.g., a flexible, single-use bag 102. The bioreactor 100 also has a frame 106 that surrounds the tank 104.

[0050] The bag 102 includes a rotatable agitator or impeller assembly (not shown) that, in use, is magnetically coupled to a drive motor 110. The bag 102 further includes one or more ports for the addition of fluids (gases and liquids), for the connection of sample lines, sensors / probes, e.g., temperature and pH, as well as for a drain line. Generally, probe ports (not shown) are located on a lower portion of the bag and are accessed through an opening / window in the tank 104, while fluid ports are located at an upper portion of the bag 102 and are accessed via the open top 105 of the tank 104.

[0051] The bioreactor 100 further includes an instrument tower 108 which houses gas flow control equipment, such as mass flow controllers, transmitters for sensors, antifoam control systems, among other equipment.

[0052] In use, the bioreactor 100 will often have a substantial number of lines (more than those depicted in FIG.1) that run to and from the bag 102. In addition, a plurality of scales / load cells and external pumps are often utilized. As a result, fed- batch processing is labor / user intensive and involves manually clamping and unclamping of numerous fluid lines to allow flow of fluids, monitoring the weight of fluids, and manually actuating the pumps used for feeding. These issues may be compounded with small-scale bioreactors and vessels e.g., those with working volumes of about 2.5 L to about 10 L, which have limited space for ports and pumps and are often placed on laboratory benches which are surface area limited.

[0053] Turning now to FIG.2, the bioreactor 100 of FIG.1 is depicted along with an apparatus 120 for the automated delivery of fluids according to anembodiment of the invention. In particular, the bioreactor 100 and instrument tower 108 of FIG.1 are shown on bench 112. The bench 112 further includes four scales 116 on which fluid receptacles 114 are located, with one fluid receptacle 114 per scale 116. As will be appreciated, the scales 116 are utilized in connection with gravimetric feeding. In other embodiments utilizing volumetric feeding, flow sensors and transmitters (not shown) may be employed.

[0054] In the depicted embodiment, four fluid lines 118 run from the fluid receptacles 114 to the apparatus 120 allowing fluids to be pumped into the bag 102 (FIG.1). A human machine interface (HMI) 123 which may be utilized to control the apparatus 120 is also located on the bench 112.

[0055] While not to scale, FIG.2 illustrates the limited space available in bench top reactor applications. The figure further illustrates that apparatus 120 provides beneficial fluid line management from the fluid receptacles 114 to the bioreactor 100 and, in embodiments, has a relatively small footprint. As discussed in greater detail below, however, the apparatus 120 is not limited to any particular size, shape, configuration or location of use.

[0056] Referring now to FIG.3, the apparatus 120 includes a support structure, e.g., housing 121, having a plurality of valves 150, a pump 130, a discharge valve 132, and an emergency stop button 140, all located on its exterior. Each of the plurality of valves 150 is selectively openable and closeable and is configured for receiving and selectively opening / closing a fluid line 118. Each fluid line 118 has at least one dedicated valve from the plurality of valves 150.

[0057] In embodiments, the valves 150 are pinch valves but, in certain embodiments, other valve types may be utilized without departing from the scope of the invention. In specific embodiments, the plurality of valves 150 may be solenoid operated, i.e., a solenoid is energized to move a plunger to pinch the fluid line 118. In other embodiments, the plurality valves 150 may be pneumatic. In certain embodiments, the plurality of valves 150 may of mixed types, sizes, and / or configurations.

[0058] The housing 121 may also include a plurality of tube holders 154. As will be appreciated, the tube holders 154 secure the fluid lines 118 in place on a substantially exterior of the housing 121 and generally provide organization to the fluid lines 118 when connected to the plurality of valves 150. The tube holders 154 may be in a variety of locations and certain embodiments may exclude such holders without departing from the invention.

[0059] In embodiments, the housing 121 may be manufactured from a rigid material, e.g., metals, polymers, composites and may be a variety of shapes and sizes. While the housing 121 is illustrated as having a hollow interior cavity, in particular embodiments, the valves and pumps may be simply mounted via, e.g., fasteners, to a front surface / exterior of a sheet of material, e.g., metal, and control electronics may be mounted on a back or rear surface.

[0060] As will be appreciated, the housing 121 may be unitary or an assembly of multiple panels / components. In embodiments, the housing 121 may be manufactured using a variety of techniques / processes and the invention is notlimited in this regard. In embodiments, the housing 121 also includes a plurality of friction limiting feet 152 which prevent slippage or movement of the apparatus 120 on bench and facilitates movement of the apparatus 120 by creating a hand hold.

[0061] As shown, in an embodiment, the plurality of valves 150 may include one or more first valves 150A and one or more second valves 150B. Adjacent first valves 150A and second valves 150B form a pair of valves that are in series and that are dedicated to a single fluid line 118. The valve pair is configured to selectively open and close the fluid line 118. The use of first and second valves 150A, 150B on a single fluid line 118 adds redundancy to ensure that fluid flows are stopped and started properly.

[0062] While shown with paired valves, other embodiments may utilize a single valve per fluid line 118 without departing from the scope of the invention. In yet other embodiments, more than two valves may be used on a single fluid line 118.

[0063] The embodiment of FIG.2 and FIG.3 includes four fluid lines 118, each of which is operatively connected to a fluid source, e.g., fluid receptacle 114. Each fluid line 118 has at least one dedicated valve of the plurality of valves 150 and, as depicted, each fluid line 118 may be connected to a pair of valves, e.g., first and second valves 150A, 150B. While shown with four fluid lines 118, embodiments may be used with fewer than four fluid lines. Certain embodiments may include a plurality of valves 150 sufficient to connect more than four lines.

[0064] As will be appreciated, fluid lines 118 may be manufactured from a variety of suitable materials, e.g., silicone, etc., and may have a variety of durometers. The invention is not limited to specific fluid line sizes or materials.

[0065] Referring to FIG.3 and FIG.5, in an embodiment, the four fluid lines 118 may be multiplexed into a single pump fluid line 122, which runs to the pump 130 and then to the bag 102. More specifically, each fluid line 118 is connected to a tube holder 154 and then run into a valve of the plurality of valves 150. As depicted, the fluid line 118 may be connected to paired first and second valves 150A, 150B.

[0066] Once past the valves 150A, 150B, the fluid lines 118 are multiplexed into a single pump line 122 via an L connector 129 and three T connectors 128. Intermediate lines 119 are used between the L connector 129 and the T connectors 128. The fluid lines 118 and intermediate lines 119 may be selectively removable from the connectors or may be welded to or otherwise part of the connectors. Other multiplexing solutions, connectors, or fluid flow architectures may be utilized without departing from the scope of the invention.

[0067] In embodiments, the fluid lines 118 may be preassembled into a sterilized, single use multiplexed arrangement that is configured for attachment to at least one dedicated valve 150 of the apparatus 120.

[0068] As depicted, the pump line 122 enters the pump 130, which is configured to selectively pump fluid from the fluid receptacles 114 into the bag 102 of the bioreactor 100. The pump 130 is illustrated as a peristaltic pump, however, inembodiments, other pump types may be utilized, e.g., centrifugal pumps and the like. The pump 130 may be a constant speed pump or variable speed.

[0069] The pump line 122 is then passed to a discharge valve 132 located downstream of the pump 130 and then to the bag 102. The discharge valve 132 functions as, among other things, a safeguard to ensure that fluid is added only when desired / scheduled. In embodiments, the discharge valve 132 is a pinch valve.

[0070] Embodiments of the invention include a single pump 130 mounted on the housing 121. In certain embodiments, the pump 130 may be selectively removable from the housing 121 such that the apparatus may be used with pumps of varying sizes and / or flow rates, or other properties, depending on the size of the bioreactor or other considerations.

[0071] In yet other embodiments, a plurality of pumps may be utilized. That is, the housing 121 may include two or more pumps 130, each of which may be fluidly connectible to a valve from the plurality of valves 150 via a fluid line 118. In this regard, each pump 130 may be directly connected to a single fluid line 118 and / or fluid receptacle 114 (without multiplexing) or connected to multiple fluid receptacles 114 via multiplexed fluid lines 118. In such embodiments, the plurality of pumps may be mounted to the housing 121 in a vertical arrangement such that each of the pumps is in proximity to (e.g., adjacent to) an individual valve 150 (or pair valves). As will be appreciated, other pump configurations and locations may be possible without departing from the scope of the invention.

[0072] Referring now to FIG.4, the housing 121 has an interior cavity 160 that may be accessed by opening a door 162 which may include one or more latches 164 to secure the same. As shown, the back or rear surface of the plurality of valves 150 (e.g., first valve 150A and second valve 150B) is accessible. In embodiments, the plurality of valves 150 may be operatively connected to control electronics / controller 200 that are mounted on a reverse side of the door 162.

[0073] In certain embodiments, the controller 200 includes one or more programmable logic controllers (PLCs) that are operatively (e.g. electronically) connected to the plurality of valves 150, the pump 130, and the discharge valve 132. While the controller 200 is illustrated as located within the housing 121, in other embodiments the controller 200 may be external to the apparatus 120.

[0074] The controller 200 is programmed to automatically open or close the plurality of valves 150 and activate the pump 130 to deliver a quantity of fluid to the flexible bag 102. In embodiments, the controller 200 utilizes digital inputs and outputs to control operation of the apparatus 120. For example, the controller 200 may receive digital inputs to run a feeding protocol and that the emergency stop button is functional. The controller 200 in turn may output digital signals to the pinch valves 150, discharge valve 132, and the pump 130 to run the protocol. The controller 200 may also receive analog inputs from the scales 116 or flow sensor (not shown) or bioreactor or receiving device.

[0075] In embodiments, the controller 200 may receive data from a variety of sources, e.g., sensors. For example, the controller 200 may receive metabolitemeasurements, cell counts, conductivity, pH, or other data regarding the contents of the vessel, e.g., flexible bag. In particular examples, the sensors are in contact with the contents of the flexible bag and signals generated from the sensors is transmitted (e.g., wired or wirelessly) to the controller. The controller 200 may be directly or operatively connected to sensors gathering such data. The data may then be used to determine, e.g., compute / calculate, among other things, an appropriate amount / volume of fluid to be transferred to the vessel. It may also be used to provide an indication to a user that a parameter has or has not been met and that corrective action should be taken.

[0076] Referring now to FIG.6 an exemplary user interface (UI) 300 for controlling apparatus 120 is depicted. In embodiments, the UI 300 may be accessed directly through the HMI 123 (FIGS.2 and 3), through a remote desktop via the internet, and / or through a mobile application.

[0077] As shown, in certain embodiments, multiple apparatus 120 may be connected to a single reactor 310. Moreover, one or more apparatus 120 may be manually operated if desired, though, as will be appreciated, automated operation is likely to be utilized.

[0078] In this regard, embodiments allow for user schedulable feed regimes. That is, a user may select the day / time of discharge, as well as the source / type and / or quantity of fluid to be discharged to the vessel. In certain embodiments, the duration of fluid discharge, flow rate, and other variables may be user scheduled.Feed regimes using apparatus 120 may be remotely initiated, adjusted, and / or controlled by a user.

[0079] In embodiments, the apparatus 120 may be utilized to establish closed loop control of bioprocessing operations such as feeding based on metabolite measurements, cell counts, conductivity, pH, or other data. That is, the apparatus 120 may be utilized to automatically feed or otherwise regulate vessel contents to maintain a desired state or set point without user interaction.

[0080] The apparatus 120 may also be used as an add-on module for a bioreactor to enable perfusion control or other modes of bioreactor operation, such as concentrated fed-batch processing. It is anticipated that embodiments may be suitable for use with a wide variety of existing bioprocessing devices that utilize EtherNet / IP (or other) communication protocols.

[0081] In certain embodiments, the apparatus 120 may be utilized to deliver fluids from a vessel to a downstream container. In such embodiments, the apparatus 120 may, for example, be used for transfer, filling, and / or sampling of fluid from a bioprocessing device to a target container or other device. As will be appreciated, in certain embodiments, multiple apparatus 120 may be networked to a single bioprocessing device to control the delivery of fluids both to and from the device.

[0082] Turning now to FIG.7, a flowchart depicting a method of delivering fluids according to an embodiment is illustrated. The method 400 involves a step of assessing whether the receiving device, e.g., the bioreactor 100 is ready to receive media (or other fluids). The system then assesses at step 404 whether it’s time tostart feeding media to the bag 102, and whether any other media is being fed 406. Assuming no other media is being fed, the valves 150 are opened, as is the discharge valve 132, and the pump 130 is started (step 408).

[0083] At step 410, the pump 130 is stopped once the preconfigured amount (by weight / volume) of media has been fed into the bag 102. The method (steps 404 – 412) is then repeated for all other media in sequence pursuant to the selected delivery protocol. As described in step 414, once this is complete, the process is stopped. While FIG.7 and the associated text herein describe the transfer and control of media to a bioreactor, the method is not so limited. Other types of fluids (e.g., buffers) can be transferred to other types of vessels and vessels (e.g., mixers) using the aforementioned methodology.

[0084] Embodiments of the invention contemplate methods of delivering fluids to a vessel, e.g., flexible bag 102. In a specific embodiment, such methods include connecting a fluid line 118 from a fluid receptacle 114 to at least one valve 150 and a pump 130, the at least one valve 150 and pump 130 being located on or in the support structure, e.g., housing 121, and being operatively connected to a controller. The method further includes connecting the fluid line 118 to a flexible bag 102 to that the flexible bag 102 is fluidly connected to the receptacle 114. The method also includes initiating a fluid delivery protocol via the controller whereby the controller opens a valve of the at least one valve 150 and activates the pump 130 to deliver a quantity of fluid to the flexible bag 102.

[0085] In an embodiment, connecting the fluid line 118 to at least one valve 150 includes connecting the fluid line 118 to a pair of valves 150A, 150B that are in series and are configured to receive and selectively open and close the fluid line 118.

[0086] In an embodiment, the step of connecting a fluid line 118 from a fluid receptacle 114 to at least one valve 150 and a pump 130 includes connecting multiple fluid lines 118 to separate valves 150 and to at least one pump 130, each of the multiple fluid lines 118 being connected to a separate fluid receptacle 114, and wherein the at least one pump 130 is connected to the flexible bag 102.

[0087] In an embodiment, during the step of initiating a fluid delivery protocol, the controller opens at least one valve 150 and activates at least one pump 130 to deliver quantities of fluids from one or more separate fluid receptacles 114 to the flexible bag 102.

[0088] In an embodiment, the method further includes opening a separate discharge valve 132 that is downstream of the pump 130 to allow the fluid to flow into the flexible bag 102.

[0089] In an embodiment, the controller closes the valve 150 and deactivates the pump 130 after the quantity of fluid has been delivered to the flexible bag 102.

[0090] In certain embodiments, the method further includes deactivating the pump 130 and / or closing the valve 150 and / or the separate discharge valve 132 to prevent overfilling the flexible bag 102, independent of whether the quantity of fluid has been delivered.

[0091] In an embodiment, the method further includes generating a user alarm in response to the detection of a no feed, overfill, and / or system error scenario.

[0092] In an embodiment, the fluid delivery protocol may be selected from a plurality of protocols via the controller. As will be appreciated, the protocols may vary based on a variety of variables include the size of the vessel / bag, the biological or other process being run in the bag, the number of feed / fluid lines to be utilized, etc.

[0093] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural of said elements or steps, unless such exclusion is explicitly stated. Furthermore, references to “one embodiment” of the present invention are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features. Moreover, unless explicitly stated to the contrary, embodiments “comprising,” “including,” or “having” an element or a plurality of elements having a particular property may include additional such elements not having that property.

[0094] While the dimensions and types of materials described herein are intended to define the parameters of the invention, they are by no means limiting and are exemplary embodiments. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description.

[0095] The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to whichsuch claims are entitled. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.”

[0096] Moreover, in the following claims, terms such as “first,” “second,” “upper,” “lower,” “bottom,” “top,” etc. are used merely as labels, and are not intended to impose numerical or positional requirements on their objects. Further, the limitations of the following claims are not written in means-plus-function format and are not intended to be interpreted as such, unless and until such claim limitations expressly use the phrase “means for” followed by a statement of function void of further structure.

[0097] This written description uses examples to disclose several embodiments of the invention, including the best mode, and also to enable one of ordinary skill in the art to practice the embodiments of invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to one of ordinary skill in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.

Claims

CLAIMS: What is claimed is:

1. An apparatus for automated delivery of fluids to a vessel of a bioprocessing device, the apparatus comprising: a support structure; a plurality of valves located on or in the support structure, each of the plurality of valves being selectively openable and closeable and configured for receiving and selectively opening and closing a fluid line, each fluid line having at least one dedicated valve of the plurality of valves; a pump located on or in the support structure, the pump configured to receive a fluid line to or from a valve of the plurality of valves and selectively pump fluid into the vessel; and a controller operatively connected to the plurality of valves and the pump; wherein the controller is programmed to automatically open or close the plurality of valves and activate the pump to deliver a quantity of fluid to the vessel.

2. The apparatus of claim 1, wherein fluid lines from two or more valves of the plurality of valves are multiplexed into the pump.

3. The apparatus of claim 1, wherein the plurality of valves includes a first valve and a second valve that are in series and are dedicated to one fluid line, the first valve and second valve configured selectively open and close the fluid line.

4. The apparatus of claim 1, wherein the apparatus includes a plurality of pumps, each pump of the plurality of pumps being fluidly connectible to a valve from the plurality of valves via a fluid line.

5. The apparatus of claim 1, further comprising a discharge valve located downstream of the pump and configured to receive and selectively open and close a fluid line from the pump to allow fluid to flow into the vessel.

6. The apparatus of claim 1, wherein the support structure is a housing and the pump and plurality of valves are located on an exterior of the housing.

7. The apparatus of claim 6, wherein the housing is configured to selectively receive pumps of varying sizes and / or flow rates.

8. A method of delivering fluids to a vessel of a bioprocessing device comprising steps of: connecting a fluid line from a fluid receptacle to at least one valve and a pump, the at least one valve and pump being located on or in a support structure and being operatively connected to a controller; connecting the fluid line to a vessel to that the vessel is fluidly connected to the fluid receptacle; and initiating a fluid delivery protocol via the controller whereby the controller opens a valve of the at least one valve and activates the pump to deliver a quantity of fluid to the vessel.

9. The method of claim 8, wherein connecting the fluid line to at least one valve includes connecting the fluid line to a pair of valves that are in series and are configured to receive and selectively open and close the fluid line.

10. The method of claim 8, wherein connecting a fluid line from a fluid receptacle to at least one valve and a pump comprises: connecting multiple fluid lines to separate valves and the pump, each of the multiple fluid lines being connected to a separate fluid receptacle, and wherein the pump is connected to the vessel.

11. The method of claim 10, wherein when initiating a fluid delivery protocol, the controller opens at least one valve and activates the pump to deliver quantities of fluids from at least one of the separate fluid receptacles to the vessel.

12. The method of claim 8, further comprising: opening a separate discharge valve that is downstream of the pump to allow the fluid to flow into the vessel.

13. The method of claim 8 wherein the controller closes the valve and deactivates the pump after the quantity of fluid has been delivered to the vessel.

14. The method of claim 8 wherein the fluid delivery protocol is selected from a plurality of protocols via the controller.

15. The method of claim 8 wherein the fluid delivery protocol may be scheduled, initiated, and / or controlled by a user.

16. The method of claim 8 wherein the fluid delivery protocol may be remotely scheduled, initiated, and / or controlled by a user.

17. A system for automated delivery of fluids to a flexible bag of a bioprocessing device, the system comprising: a support structure; a plurality of valves located on or in the support structure, each of the plurality of valves being selectively openable and closeable and configured for receiving and selectively opening and closing a fluid line, each fluid line having at least one dedicated valve of the plurality of valves; a pump located on or in the support structure, the pump configured to receive a fluid line to or from a valve of the plurality of valves and selectively pump fluid into the flexible bag; a plurality of fluid lines, each of the fluid lines configured for attachment to at least one dedicated valve of the plurality of valves, the fluid lines being multiplexed into a single pump line which is configured to be connected to the pump; and a controller operatively connected to the plurality of valves and the pump; wherein the controller is programmed to automatically open or close the plurality of valves and activate the pump to deliver a quantity of fluid to the flexible bag.

18. The system of claim 17 wherein the plurality of valves includes a first valve and a second valve that are in series and are dedicated to one fluid line, the first valve and second valve configured selectively open and close the fluid line.

19. The system of claim 17 further comprising:a discharge valve that is downstream of the pump to allow the fluid to flow into the flexible bag.

Images