WO2024020342A1

WO2024020342A1 - Liquid patch panel

Info

Publication number: WO2024020342A1
Application number: PCT/US2023/070327
Authority: WO
Inventors: Brandon WHITNEY; Dan SLOMSKI; Jeff Smith; Myo THU; Ivan RAZINKOV
Original assignee: Synthego Corporation
Priority date: 2022-07-20
Filing date: 2023-07-17
Publication date: 2024-01-25

Abstract

A modular liquid patch panel (LPP) for providing one or more fluid pathways between a first processing module and a second processing module for culturing or processing cells, wherein: the first processing module comprises one or more liquid ports, and one or more air ports; and the second processing module comprises one or more liquid ports, and one or more air ports; and the LPP comprises one or more manifolds comprising one or more fluid pathways, a first connector that engages a liquid port on the first processing, module, and a second connector that engages a liquid port on the second processing module such that a fluid pathway is provided from the first processing module, through the LPP, and to the second processing module, and liquid is passed through the fluid pathway by introducing or removing air from the first processing module and/or the second processing module.

Description

LIQUID PATCH PANEL

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63/390,786, as filed July 20, 2022, the contents of which are incorporated herein by reference in its entirety.

BACKGROUND

[0002] Ex-vivo cell culturing allows cells to be grown externally in a nutrient rich solution, which can be used for many applications including experiments on certain cell types, production of biological products (e.g., those produced by the cells), production of cells to be used to treat certain diseases, etc.

[0003] While cell culturing has numerous applications, it is important to keep groups of cells from cross-contaminating one another and from being contaminated by bacteria or other materials. Thus, it would be desirable to have improved systems and methods for processing cells.

SUMMARY OF THE DISCLOSURE

[0004] Various embodiments of the disclosure provide a modular liquid patch panel (LPP) for providing one or more fluid pathways between a first processing module (also referred to herein as a consumable) for culturing or processing cells and a second processing module for culturing or processing cells. The first processing module may include one or more liquid ports for introducing or removing liquid from the first processing module and one or more air ports for introducing or removing air from the first processing module. The second processing module may include one or more liquid ports for introducing or removing liquid from the second processing module and one or more air ports for introducing or removing air from the second processing module. The LPP may include one or more manifolds each of which may include one or more fluid pathways, wherein the one or more manifolds may each include a first connector (e.g. part of a first flow coupler) that engages a liquid port on the first processing module and a second connector (e.g. part of a second flow coupler) that engages a liquid port on the second processing module such that a fluid pathway is provided from the first processing module, through the LPP, and to the second processing module, and liquid is passed through the fluid pathway by introducing or removing air from the first processing module and/or introducing or removing air from the second processing module.

[0005] In some embodiments of the LPP, the one or more manifolds may include one or more liquid routing valves for controlling the flow of liquid through the fluid pathway. In other embodiments, the LPP may provide one or more aseptic liquid pathways (which may be provided at least in part by the flow couplers) between the first processing module and the second processing module. In certain embodiments, the LPP may provide one or more liquid pathways between the first processing module and the second processing module that are isolated from the ambient environment.

[0006] In various embodiments of the LPP, the one or more liquid ports of the first processing module and the second processing module may include an engageable septum, which is engaged and pierced via the first connector or the second connector of the LPP. In particular embodiments of the LPP, the first connector and the second connector may include an engageable septum which sheathes an internal cannula, and when the first connector and second connector engage a liquid port of the first processing module or a liquid port of the second processing module, the cannula may be actuated to pierce the septum of the connector and the septum of the liquid port to establish a liquid connection between the LPP and the first processing module and the second processing module.

[0007] In some embodiments, the LPP may include a first manifold and a second manifold, where the fluid connections between one or more different regions of the first manifold or the second manifold may be selectively changed to adjust the flow of liquid through the LPP. In certain embodiments, the LPP may include one or more multi-position valves that define the one or more different regions, where the position of the one or more multi-position valves may adjust liquid flow through the LPP.

[0008] Various embodiments of the disclosure provide a cell culturing and/or processing system which may include the LPP of any of embodiments disclosed herein. In some embodiments, the cell culturing and/or processing system may include a first processing module including one or more liquid ports for introducing or removing liquid from the first processing module, and one or more air ports for introducing or removing air from the first processing module The cell culturing and/or processing system may also include a second processing module including one or more liquid ports for introducing or removing liquid from the second processing module, and one or more air ports for introducing or removing air from the second processing module. The cell culturing and/or processing system may further include a first actuator coupled to the first connector of the LPP, where the first actuator may be configured to selectively bring the fluid pathway of the LPP into fluid communication with the internal volume of the first processing module by engaging and opening one or more liquid ports of the first processing module via the first connector of the LPP (e.g. using a flow coupler). The cell culturing and/or processing system may additionally include a second actuator coupled to the second connector of the LPP, where the second actuator may be configured to selectively bring the fluid pathway of the LPP into fluid communication with the internal volume of the second processing module by engaging and opening one or more liquid ports of the second processing module via the second connector of the LPP (e.g. using another flow coupler). The cell culturing and/or processing system may also include an air or gas source that is configured to drive liquid from the internal volume of the first processing module, through the fluid pathway of the LPP, and into the internal volume of the second processing module.

[0009] In some embodiments of the cell culturing and/or processing system, the gas source may be a pump. In certain embodiments of the cell culturing and/or processing system, the fluid pathways of the LPP may be isolated from the ambient environment. In particular embodiments of the cell culturing and/or processing system, the first processing module may be a centrifuge container that contains a cell pellet, where liquid from the first processing module that is driven into the second processing module may suspend the cells from the cell pellet into the liquid. [0010] In various embodiments of the cell culturing and/or processing system, the liquid may constitute a first liquid and the gas source may be further configured to drive a second liquid, including the suspended cells, from the second internal volume of the second processing module through a second flow path of the LPP and into a third internal volume of a third processing module that is configured to engage with the LPP.

[0011] In some embodiments of the cell culturing and/or processing system, the second processing module may be a centrifuge container and the liquid that enters the second internal volume of the second processing module may include cells suspended therein. In further embodiments of the cell culturing and/or processing system, the centrifuge container may be configured to be centrifuged to create a cell pellet and supernatant liquid from the liquid that includes the cells suspended therein and the pump may be further configured to drive the supernatant liquid from the second processing module, through the second flow path of the LPP, through the first flow path of the LPP, and into the first internal volume of the first processing module.

[0012] In certain embodiments of the cell culturing and/or processing system, the pump may be further configured to drive gas through a first gas port into the first internal volume of the first processing module to drive the liquid out of the first internal volume of the first processing module. In some embodiments of the cell culturing and/or processing system, when the liquid enters the second internal volume of the second processing module, gas within the second internal volume may be vented out through a second gas port of the second processing module. [0013] In various embodiments of the cell culturing and/or processing system, the pump may be further configured to drive gas out of the second processing module to drive the liquid out of the first internal volume of the first processing module. In some embodiments of the cell culturing and/or processing system, when the liquid exits the first processing module, gas may be directed through the second port into the second internal volume.

[0014] In embodiments of the cell culturing and/or processing system, the LPP may include a third fluid connector, a fourth fluid connector, a third flow path at least partially defined by the third fluid connector, and a fourth flow path at least partially defined by the fourth fluid connector, where the system may further include: a third container including a third barrier that seals a third internal volume of the third container from the ambient environment, and a third port in fluid communication with the third internal volume of the third container; and a third actuator coupled to the third fluid connector, where the third actuator may be configured to selectively bring the third flow path into fluid communication with the second internal volume of the second processing module, and a fourth actuator coupled to the fourth fluid connector, where the fourth actuator may be configured to selectively bring the fourth flow path into fluid communication with the third internal volume of the third container by opening the third barrier. In particular embodiments of the cell culturing and/or processing system, the pump may be further configured to drive at least a portion of the liquid from the second internal volume of the second processing module, through the third flow path, through the fourth flow path, and into the third internal volume of the third container. [0015] In some embodiments of the cell culturing and/or processing system, the cell culture may be positioned within the first internal volume of the first processing module, where the liquid may be spent cell culture media (e.g. cell culture media from which one or more nutrients have been partially or completely consumed or otherwise depleted) having been used to propagate the cells, and the third interior volume of the third container may be empty. In various embodiments of the cell culturing and/or processing system, the second processing module may be a cell processing cartridge that is configured to process cells as the cells flow through the second processing module, such that as the liquid enters the second processing module, cells suspended in the liquid may be subjected to a first process. In certain embodiments of the cell culturing and/or processing system, the third container may be a cell processing cartridge that is configured to process cells as the cells flow through the third container, such that as the portion of the liquid enters the third container, cells suspended in the portion of the liquid may be subjected to a second process that is different than the first process.

[0016] In various embodiments of the cell culturing and/or processing system, the liquid may be designated as a first liquid, and the pump may be further configured to drive second liquid from the first internal volume of the first processing module, through the first flow path of the LPP, through the third flow path of the LPP, and into the third internal volume of the third container.

[0017] In some embodiments of the cell culturing and/or processing system, the liquid may be designated a first liquid, and the pump may be further configured to drive third fluid from the third internal volume of the third container, through the third flow path of the LPP, through the second flow path of the LPP, and into the second internal volume of the second processing module.

[0018] In certain embodiments of the cell culturing and/or processing system, the LPP may include a valve that is configured to change between a first position and a second position, where the valve may be configured to block the liquid from flowing along the fourth flow path when the valve is in the first position, and the valve may be configured to allow the liquid to flow along the fourth flow path when the valve is in the second position.

[0019] In some embodiments of the cell culturing and/or processing system, the first processing module may be removably coupled to the LPP and the second processing module may be removably coupled to the LPP. In certain embodiments of the cell culturing and/or processing system, the first processing module may include a first housing and one or more first liquid connectors each of which define a respective one of the one or more liquid ports of the first processing module, and the second processing module may include a second housing and one or more second liquid connectors each of which define a respective one of the one or more liquid ports of the second processing module, where the LPP may include an LPP housing and a plurality of liquid connectors that include the first connector and the second connector, the plurality of liquid connectors being coupled to the LPP housing, each of the plurality of liquid connectors being configured to be fluidly coupled to a respective liquid connector of the first processing module or the second processing module. In particular embodiments of the cell culturing and/or processing system, each of the plurality of liquid connectors may be configured to be fluidly decoupled from the respective liquid connector of the first processing module or the second processing module. In various embodiments of the cell culturing and/or processing system, each of the one or more liquid connectors of the first processing module, the one or more liquid connectors of the second processing module, and the plurality of liquid connectors of the LPP may be aseptic liquid connectors.

[0020] Some embodiments of the cell culturing and/or processing system may further include a computing device that is configured to cause the first actuator to extend to fluidly couple the LPP to the first processing module, cause the second actuator to extend to fluidly couple the LPP to the second processing module, and cause the gas source to drive liquid from the first processing module and into the second processing module, via the LPP.

[0021] In various embodiments of the cell culturing and/or processing system, the first processing module may be configured to implement a first process on cells that pass through the first processing module and the second processing module may be configured to implement a second process on cells that pass through the second processing module, where the first process and the second process may include at least one of growing cells, culturing cells, concentrating cells, performing cell media exchange for cells, separating cells, electroporating cells, mechanoporating cells, magnetoporating cells, isolating cells, debeading cells, storing cells, collecting cells, washing cells, collecting cells, isolating cells, a cell culture process, or a cell therapy process.

[0022] In certain embodiments of the LPP, the one or more fluid pathways may include a first fluid pathway and a second fluid pathway different from the first fluid pathway, wherein a first fluid flows through the first fluid pathway and a second fluid flows through the second fluid pathway. In various embodiments of the LPP, the first fluid may flow through the first fluid pathway at the same time that the second fluid flows through the second fluid pathway, wherein the first fluid pathway and the second fluid pathway are separate to provide at least one of liquid isolation or contamination avoidance.

[0023] In some embodiments, at least one of the LPP, the first processing module, or the second processing module may be configured for use in an automated manufacturing system. In other embodiments, at least one of the LPP, the first processing module, or the second processing module may be configured for performing at least one of a cell culture process, a cell therapy process, a sterile drug manufacturing process, or a biologic drug manufacturing process.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The following drawings are provided to help illustrate various features of embodiments of the disclosure and are not intended to limit the scope of the disclosure or exclude alternative configurations.

[0025] FIG. 1 shows a Liquid Patch Panel (LPP) consumable including a rigid frame and three manifolds, each containing two liquid connectors and two liquid routing valves.

[0026] FIG. 2 shows an example of a container type consumable (e.g. a cell culture consumable) which includes two liquid input/output ports, a rigid frame that is amenable to robot handling, an air input/output port, and a hollow container for holding one or more of liquid reagents, cells in media, or process waste.

[0027] FIG. 3 shows examples of processing-type consumables (e.g. Liquid Path) where each processing-type consumable includes two liquid input/output ports, two liquid valves for reconfiguring the fluid pathway internal to the processing type consumable, an air input/output port array, a rigid frame that is amenable to robot handling, and one or more integrated reagent storage containers.

[0028] FIG. 4 shows a Liquid Patch Panel assembled to three container type consumables to create a single sealed fluid pathway.

[0029] FIG. 5A shows a Liquid Patch Panel in which the internal fluid routing is indicated using red and blue lines. The connected pathway is shown in blue (including Bus 2) and the unused pathway is shown in red (including Bus 1). FIG. 5A provides a detailed depiction of how fluids move through the LPP by changing positions of valves, while subsequent diagrams simplify this by only showing the net result of the changes in valve positions.

[0030] FIG. 5B shows another internal fluid routing schematic which can be used with various constructions of the LPP disclosed herein, where the various pathways (e.g. Bus 1 and Bus 2) do not share any overlapping segments.

[0031] FIG. 5C shows a single manifold unit of an LPP which depicts an example of how an aseptic liquid connection may be made between the LPP and a consumable.

[0032] FIGS. 6A-6D show a series of steps of media exchange in the LPP using a centrifugation operation:

[0033] FIG. 6A shows Step 1 of the Media Exchange via centrifugation operation. Cells in old media are held in the left container. The center container is a centrifuge type consumable. The right container holds new media. Air is fed into the left consumable’s air input port (red arrow, pointing down) while air is released from the center container (red arrow, pointing up), allowing all cells to be pumped to the center consumable.

[0034] FIG. 6B shows Step 2 of the Media Exchange via centrifugation operation. The center consumable is robotically disconnected, centrifuged, and reconnected. The supernatant is pumped to the left consumable (blue arrow).

[0035] FIG. 6C shows Step 3 of the Media Exchange via centrifugation operation. Following removal of the supernatant in Step 2, the center consumable contains pelleted cells in a very small volume of media. Fresh media is transferred from the right consumable and is used to resuspend the cell pellet. Air is fed into the right container (red arrow, pointing down), air is released from the center container (red arrow, pointing up), and fluid is transferred from the right container to the center container.

[0036] FIG. 6D shows Step 4 of the Media Exchange via centrifugation operation. The center consumable contains resuspended cells in media. These cells are transferred to the right container full of fresh media to complete a media exchange operation using centrifugation.

[0037] FIG. 7 shows a media exchange operation performed without centrifugation. Cells in old media are held in the left container and the center container is empty, while the right container holds fresh media. Media is pumped from the left container to the center container through a port allowing partial withdrawal of the volume. Fresh media is pumped from the right container to the left container to complete the operation. [0038] FTG. 8 shows how the LPP may be configured to perform an operation where the contents of a consumable container may be divided between two other consumables. This may be performed, for example, when it is advantageous to perform operations in multiple parallel work streams to reduce cycle times. This splitting operation is accomplished by reconfiguring the internal valves and liquid connectors of the LPP, where the blue and purple arrows show liquid contents of the right consumable being delivered to the center and left consumables. Red arrows represent airflow used to displace liquid contained in the consumable (left and center consumables, up arrows) or create driving pressures (right consumable, down arrow).

[0039] FIG. 9 shows how the LPP may be configured to perform an operation in which the contents of multiple consumable containers are combined into one consumable. This may be performed when it is disadvantageous to perform operations in parallel. This combining operation is accomplished by reconfiguring the internal valves and liquid connectors of the LPP, where the blue and purple arrows show liquid contents of the right and center consumable being delivered to the left consumable. Red arrows represent airflow used to displace liquid contained in the consumable (center and right, down arrows) or create driving pressures (left, up arrow). [0040] FIG. 10 shows how operations may be performed by combining processing type consumables and container type consumables. This figure shows a fluid processing system involving a container type consumable (left) delivering liquid (blue arrow) to a processing type consumable (center) whose output (purple arrow) is fed to a second container type consumable. Red arrows represent airflow used to displace liquid contained in the consumable or create driving pressures. This may be done in a continuous flow-through type process or in batches. [0041] FIG. 11 shows how operations may be performed by combining multiple processing type consumables with a container type consumable. This figure shows a fluid processing system involving a container type consumable (right) delivering liquid (blue arrow) flowing directly through a processing type consumable (center) to a second processing type consumable (blue arrow, left). Red arrows represent airflow used to displace liquid contained in the consumable or create driving pressures.

[0042] FIG. 12 shows an example of a Rotary Valve body.

[0043] FIG. 13 shows an example of a Slider Valve in darker brown color as it is shown in the final assembly of the consumable shown as the lighter gray color. In this version the valve is designed to move from left to right, allowing and blocking fluid flow through the four main channels.

[0044] FIG. 14 shows an example of a membrane or diaphragm valve and pump system that is actuated by the mechanical actuators from the bottom.

[0045] FIG. 15 is a top view of an LPP (e.g. looking in a downward direction at the device of FIG. 5) showing three rotary valves (e.g. of the type shown in FIG. 13) each of which has an actuator coupled thereto.

[0046] FIG. 16 is a side view of an LPP (e.g. as in FIG. 5) including actuators to operate flow couplers to couple the flow through particular fluid pathways (e.g. Bus 1 or Bus 2).

[0047] FIGS. 17A-17D show steps of an automated process for assembling an LPP- consumable system.

DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE

[0048] The foregoing and other aspects and advantages of the present disclosure will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of illustration one or more exemplary versions. These versions do not necessarily represent the full scope of the disclosure. [0049] Various embodiments of the present disclosure provide a Liquid Patch Panel (LPP) 100 which is a consumable device that enables the fully automated creation of various consumable fluid processing systems when connected to other compatible consumable devices. As shown in FIG. 1, the LPP 100 features a robot handle-able frame 102 encompassing a plurality of manifolds (e.g. three manifolds as shown in the embodiment of FIG. 1) each containing a pair of liquid routing valves 110 and a pair of liquid connectors 104. The liquid connectors 104 may contain flow couplers (see FIGS. 5, 16), such as aseptic liquid connectors, which may be interacted and coupled using an automated instrument. The LPP 100 may be joined to multiple consumables (e.g. as shown in FIGS. 2-4) to form a modular, self-contained system for cell growth and/or processing. As described further below, the consumables include liquid and/or air connection ports that can be engaged with using an automated instruction such that these interfaces allow the consumable to be used in a fully automated manufacturing system. Thus, using embodiments of the LPP such as those disclosed herein, a wide variety of fluid processing systems may be assembled and operated in a fully automated manner by assembling the LPP to various consumables and configuring a selection of the Liquid Patch Panel’s liquid connectors and valves.

[0050] In various embodiments, the LPP 100 may be coupled to various types of consumables 130 including container type consumables, processing type consumables, and/or combination consumables. As shown in FIG. 2, embodiments of a container type consumable 130 may include two liquid input/output ports 132, a rigid robot handle-able frame 134, an air input/output port 136 (or air port), and a hollow container 138 for holding liquid reagents, cells in media, or process waste; while the ports 136 are referred to herein as "air" input/output ports (or "air" ports) 136, these ports 136 may in fact be used to add or remove any gas or mix of gases including but not limited to oxygen, nitrogen, argon, or carbon dioxide, as well as air (e.g. ambient air). Furthermore, while the examples provided herein include two liquid connectors 104 on the LPP 100 and two liquid input/output ports 132 on the consumable 130, in various embodiments the LPP 100 may include any number of liquid connectors 104 (e.g. three, four, five, etc.) and the consumables 130 may include any number of liquid input/output ports 132 (e.g. three, four, five, etc.), generally matching the number of liquid connectors 104 on a one-to- one basis.

[0051] In some embodiments, one type of container type consumable is a Cell Culture Consumable (CCC), which may include a chamber which includes a gas permeable membrane such that it can facilitate exchange of gases (e.g. O2 and CO2) in a cell culture incubator.

[0052] In other embodiments, another type of container type consumable is a Centrifuge Consumable (CFC), which is a container having a geometry that can be centrifuged to produce a concentrate within a certain region of the consumable and which can be extracted by fluid handling procedures.

[0053] FIG. 3 shows several embodiments of processing-type consumables 130 where each processing-type consumable 130 includes two liquid input/output ports 132, two liquid valves 139 for reconfiguring the fluid pathway internal to the processing type consumable 130, an air input/output port array 136, a rigid frame 134 that is amenable to robot handling, and one or more integrated reagent storage containers 138. In various embodiments, the processing type consumables, which may also be referred to as Liquid Paths, may contain valves, microfluidic chips, and/or electrical processing chambers or reactors. [0054] In certain embodiments, other types of container type consumables may be combination consumables, which may include processing systems with storage for large volumes of media or cells.

[0055] In various embodiments, the numbers and types of components (e.g. air and liquid couplers) on the LPP and the consumables which are disclosed herein are for exemplary purposes only and can be varied according to the particular application for which the LPP and consumables are being used.

[0056] As noted above, the consumables 130 are generally robot handle-able, including having a small form-factor and a rigid frame, and may also include features for alignment of the consumable to a robot and instrument docking station, as well as one or more of a barcode, a QR code, or an RFID tag for unique identification of the consumable 130 to the equipment software. Furthermore, each of the consumables 130 may include standardized interfaces to instrumentation, including air, liquid, and electrical connections, as well as provisions for valve actuation, gas exchange, mechanical positioning and alignment, robot gripping, liquid connection cleaning, and/or identification via barcode or other identification mechanisms.

[0057] In certain embodiments, following assembly of the LPP 100 with consumables 130, one or more of the liquid routing valves 110 (see FIGS. 15, 16) and/or flow couplers 160 may be adjusted in order to establish particular fluid paths within the system, where these fluid or liquid pathways may be isolated from the ambient environment (e.g. to maintain sterility). In those embodiments in which the consumables 130 include processing-type consumables, further adjustments may be made to the liquid valves 139 on the consumable 130 (see FIG. 3) to further adjust the fluid flow pathway through the system (see FIGS. 5A, 16). As shown in FIG. 5A, the LPP 100 includes a series of channels (depicted by the red lines, e.g. Bus 1) which can be interconnected using the liquid routing valves 110 and flow couplers 160 to form complete circuits between consumables 130 (depicted by the blue lines, e.g. Bus 2). While the present disclosure depicts rotary valves as an exemplary embodiment for the liquid routing valves 110, as disclosed herein other possible types of valves may be used instead of, or in addition to, rotary valves. Furthermore, while only two liquid channels or buses are depicted in FIG. 5A, in various embodiments the LPP 100 may include more than two such channels or buses which can be used concurrently for different operations (e.g. media exchange, electroporation, or other operations such as those disclosed herein), or in some cases may be used sequentially, and may be kept separate to enact liquid isolation and contamination avoidance (FIG. 5B). FIG. 5B shows an embodiment of an internal fluid routing schematic which can be used with various embodiments of the LPPs 100 disclosed herein, where the various pathways (e.g. Bus 1 and Bus 2) do not share any overlapping segments, where the schematic depicts three manifold units each having four two-way valves (labeled VI -VI 2) and two liquid connectors (labeled ALC1-ALC6). After establishing a particular fluid flow pathway within the system, fluid movement may be initiated and driven using one or both of positive and negative air pressure applied to the air input/output ports 136 of the consumables 130, as discussed further below. As used herein, the term "flow path" refers to any combination of buses and settings of the liquid routing valves 110 and the flow couplers 160 which direct liquid through a particular fluid pathway route in the LPP- consumable system. In one particular example (e.g. similar to the steps shown in FIGS. 6A-6D), a first fluid pathway may be established to transfer cells and media from a first cell culture consumable container to a centrifugation container via the LPP and, following centrifugation, the supernatant from the centrifugation container (which is primarily spent media) may be transferred via the first fluid pathway back to the first cell culture consumable container (e.g. as in FIGS. 6A, 6B). Next, fresh media may be transferred via a second fluid pathway (which is different from the first fluid pathway) from a second cell culture consumable container to the centrifugation container to resuspend the cell pellet, after which the cells resuspended in the fresh media may be transferred via the second fluid pathway to the second cell culture consumable container (e.g. as in FIGS. 6C, 6D).

[0058] In various embodiments, the liquid routing valves 110 may include a system of one or more types of liquid valves such as rotary valves (FIG. 12), slider valves (FIG. 13), and/or membrane/ diaphragm valves (FIG. 14) that could be driven either pneumatically or mechanically such as with a pin actuator, where the membrane may make up only one wall of the liquid channel. In other embodiments, the liquid routing valve 110 may include pinch valves, in which a section of the tubing is compressed by the valve actuator (pneumatically or mechanically); in this case the entirety of the liquid channel within the valve region may be made from a flexible and compressible material such as Silicone or thermoplastic polyurethane (TPU).

[0059] In certain embodiments, the liquid connections that are established between the LPP 100 and the consumables 130 are established using aseptic liquid connections which can be made using components disposed within or otherwise associated with the liquid connectors 104 of the LPP 100 as well as components associated with the liquid input/output ports 132 of the consumables 130.

[0060] For example, in various embodiments aseptic liquid connections may be established by a flow coupler 160 disposed within the liquid connector 104 of the LPP 100 having a male connector including a piercing needle or cannula 162 with a mating connector on the container or processing consumable 130 which is part of the liquid input/output port 132 (FIG. 5C).

[0061] Although there are various ways to implement an aseptic liquid connection, in one embodiment a connector on the LPP side may be formed by a piercing needle or cannula contained in a sealed flexible rubber sheath or engageable septum 164, which may be part of the flow coupler 160 and which may be sterilized prior to use. When the LPP 100 and consumables 130 are assembled into a single structure, the needle or cannula 162 probe is configured to pierce through the sheath on the flow coupler 160 and a rubber barrier or septum 133 on the mating connector (e.g. a rubber barrier that is part of the liquid input/output ports 132) such that a fluidic connection is established between the region inside the needle or cannula 162 probe on the one hand and inside of the mating consumable on the other (represented by two-way arrow in FIG. 5C). In some embodiments, the engageable septum 164 may be brought near or in contact with the septum 133 at the same time that the needle or cannula 162 probe pierces through each of the septa 164, 133 (FIG. 5C, left). Upon completion of the process, the needle or cannula 162 may be withdrawn and each of the septa 164, 133 may reseal to isolate the respective compartments from the ambient environment.

[0062] Prior to or during use, it may be necessary or at least advisable to sterilize the needle or cannula 162 probe prior to initial use or before one or more re-uses. Thus, mechanisms may be provided for sterilizing the needle or cannula 162 probe in a manner that is automated and does not necessarily require operator intervention. Accordingly, in various embodiments, a liquid connection may be completed in a way that is aseptic or free of biological contamination using a number of approaches, including: sealing the connector halves (i.e. the portions associated with the LPP 100 and the consumable 130, respectively) to a chamber where liquid or vaporous (e g. vaporous hydrogen peroxide) decontamination agents may be introduced, followed by flushing agents for removing the sterilant. Sterilant may be introduced to the closed chamber using vacuum or positive pressures; spraying the surfaces of the connectors with a liquid sterilant; irradiating the surfaces of the connectors with UV-C light; and/or removing a barrier which forms a closed and pre-sterilized chamber around the otherwise exposed faces of the liquid connectors immediately prior to mating them (as disclosed above).

[0063] While present disclosure provides exemplary embodiments in which the LPP 100 is coupled to three consumables 130, in various embodiments any number of consumables 130 can be coupled to the LPP 100 including two, three, four, five, six, etc. Furthermore, the present disclosure supports not only automated procedures for initially assembling a system of LPP and consumables but also provides for automated procedures for changing one or more of the consumables from the system, e.g. using a robotic or otherwise automated handling system.

[0064] Embodiments of the systems disclosed herein provide for the fully-automated assembly and operation of LPP-consumable systems which allow aseptic connections to be made by interfacing with connection cleaning systems on the automated equipment and which allow consumables to be connected in any order by rerouting the fluidic handling system by providing a flexible routing system which can be reconfigured via internal fluidic channels and valves to allow multiple types of operations. These operations include:

[0065] - Operations between 2-3 consumables where a first consumable serves as an input

Container and a second consumable serves as a processing consumable, where the processed liquid or cell suspension may be retained in the second consumable/processing module, fed to a third consumable container after the operation, or recirculated and fed back to the original/first consumable container;

[0066] - Operations where contents of two container consumables are simultaneously fed into a single processing consumable;

[0067] - Operations where the contents of one processing consumable is dispensed into two container consumables simultaneously;

[0068] - Operations where the contents of one container consumable is fed into two processing consumables simultaneously;

[0069] - Operations where multiple processing consumables may be connected in series;

[0070] - Operations where multiple container consumables may be connected in series such that a first container consumable may be fed from the excess volume from a second container consumable, e.g. to prevent overfilling of the second container consumable and/or to perform sampling of the second container consumable; [0071] - Flow-through operations where a first consumable serves as a source, a second consumable as the processing consumable, and a third consumable as the final container into which fluid is continuously fed, with fluid moving (intermittently or continuously) from the first consumable and through the second/processing consumable to the third consumable;

[0072] - Media exchange operations where some portion of the contents of a first/input container consumable is transferred to a second container consumable which is used for waste storage and which may be disposed of, while a third container consumable is used to feed fresh media into the original;

[0073] - Media exchange operations where the complete contents of a first container consumable are transferred to a second/centrifugal container consumable. The supernatant from the second/centrifugal container consumable may be transferred back to the first container consumable which can then be disposed. The cell pellet in the second/centrifugal container consumable may then be resuspended using fresh media from a third container consumable and then passed completely to the third container consumable;

[0074] - Operation which is a combination of the contents of two container consumables into a third container consumable;

[0075] - Operation which includes splitting the contents of a first container consumable into second and third container consumables;

[0076] - Continuous exchange of the contents of more than three consumables to allow processing without pauses, with two of the consumables being active and the third consumable being inactive and in the process of being exchanged;

[0077] - Operations to purge internal channels in the LPP by supplying chemical cleaning or disinfecting agent into the LPP via a connected consumable device, which may be performed to lower chances of carryover and cross-contamination; and/or

[0078] - The Processing consumable may contain fluidics which allows separation via passive fluidics or some active fluidics in combination with an analytical readout, which could be optical, electrical, or electro-chemical.

[0079] While these are examples of operations that may be carried out using embodiments of the disclosed procedures, this is simply provided as a list of examples and many other operations may also be carried out using embodiments of the disclosed procedures and thus fall within the scope of the disclosure. [0080] To illustrate the step-by-step procedures that underlie operations such as those listed above, FIGS. 6A-6D show a series of steps performed with an LPP -consumable system to perform media exchange using a centrifugation operation, where spent cell culture media (e.g. cell culture media from which one or more nutrients have been partially or completely consumed or otherwise depleted) may be partly or completely changed during cell culture. While FIGS. 6A-6D illustrate a particular exemplary process, in various embodiments the LPP-consumable systems disclosed herein can perform a wide variety of processes including one or more of processes for growing cells, culturing cells, concentrating cells, performing cell media exchange for cells, separating cells, electroporating cells, mechanoporating cells, magnetoporating cells, isolating cells, debeading cells, storing cells, collecting cells, washing cells, collecting cells, isolating cells, a cell culture process, or a cell therapy process.

[0081] FIG. 6A shows Step 1 of the Media Exchange via centrifugation operation. Cells in old media are held in the left container consumable. The center consumable is a centrifuge type consumable while the right container consumable holds new media. To drive flow of cellcontaining fluid from the left container consumable to the center consumable, air is fed into the left container consumable’s air input/output port (red arrow, pointing down) while air is removed or released from the center consumable (red arrow, pointing up), allowing all cells to be pumped to the center consumable (indicated by blue arrow). Air may be fed into the air input/output port by applying positive pressure to the air input/output port, e.g. using a connected air source (see FIG. 16), and air may be released from the air input/output port by simply opening the port or by applying negative pressure to the air input/output port, e.g. using a connected air source (see FIG. 16).

[0082] FIG. 6B shows Step 2 of the Media Exchange via centrifugation operation. The center consumable is robotically disconnected, centrifuged, and reconnected to the LPP, although in some embodiments the center consumable may be configured to perform centrifugation of the cells in place without being removed. The supernatant is pumped to the left consumable (blue arrow) by feeding air into the air input/output port of the center consumable (red arrow, pointing down) and removing or releasing air from the air input/output port of the left container consumable (red arrow, pointing up). Thus, at the end of Step 2, the cells have been transferred from the left consumable to the center consumable, which is automatically removed and centrifuged and returned to the LPP system (e g. using a robotic handling system), and the resulting supernatant fluid has been transferred from the center consumable to the left consumable.

[0083] FIG. 6C shows Step 3 of the Media Exchange via centrifugation operation. Following removal of the supernatant in Step 2, the center consumable contains pelleted cells in a very small volume of media. Fresh media is transferred from the right consumable and is used to resuspend the cell pellet. Air is fed into the air input/output port of the right container consumable (red arrow, pointing down), air is removed or released from the center container (red arrow, pointing up), and as a result of the air input and removal, fluid is transferred from the right consumable to the center consumable.

[0084] FIG. 6D shows Step 4 of the Media Exchange via centrifugation operation. The center consumable contains resuspended cells in media. Air is fed into the air input/output port of the center consumable (red arrow, pointing down) and removed or released from the air input/output port of the right consumable (red arrow, pointing up). As a result of the air input and removal, the resuspended cells are transferred from the center consumable to the right consumable full of fresh media to complete a media exchange operation using centrifugation. [0085] FIG. 7 shows a media exchange operation performed without centrifugation. Cells bathed in old media are held in the left consumable and the center consumable is empty (where "empty" may mean substantially empty, indicating that it is at least 75% free, at least 90% free, at least 95% free, or at least 99% free of materials such as media, reagents, and/or cells), while the right consumable holds fresh media. Media is pumped/transferred (blue arrow) from the left consumable to the center consumable (using combinations of air input and removal as disclosed above and indicate by red arrows) through a port allowing partial withdrawal of the volume.

Fresh media is pumped/transferred (purple arrow) from the right consumable to the left consumable to complete the operation.

[0086] FIG. 8 shows how the LPP may be configured to perform an operation where the contents of a consumable container may be divided between two other consumables. This may be performed, for example, when it is advantageous to perform operations in multiple parallel work streams to reduce cycle times. This splitting operation is accomplished by reconfiguring the internal valves and liquid connectors of the LPP, where the blue and purple arrows show liquid contents of the right consumable being delivered to the center and left consumables. Red arrows represent airflow used to displace liquid contained in the consumable (left and center consumables, up arrows) or create driving pressures (right consumable, down arrow). [0087] FIG. 9 shows how the LPP may be configured to perform an operation in which the contents of multiple consumable containers are combined into one consumable. This may be performed when it is disadvantageous to perform operations in parallel. This combining operation is accomplished by reconfiguring the internal valves and liquid connectors of the LPP, where the blue and purple arrows show liquid contents of the right and center consumable being delivered to the left consumable. Red arrows represent airflow used to displace liquid contained in the consumable (center and right, down arrows) or create driving pressures (left, up arrow). [0088] FIG. 10 shows how operations may be performed by combining processing type consumables and container type consumables. This figure shows a fluid processing system involving a container type consumable (left) delivering liquid (blue arrow) to a processing type consumable (center) whose output (purple arrow) is fed to a second container type consumable. Red arrows represent airflow used to displace liquid contained in the consumable or create driving pressures. This may be done in a continuous flow-through type process or in batches. [0089] FIG. 11 shows how operations may be performed by combining multiple processing type consumables with a container type consumable. This figure shows a fluid processing system involving a container type consumable (right) delivering liquid (blue arrow) flowing directly through a processing type consumable (center) to a second processing type consumable (blue arrow, left). Red arrows represent airflow used to displace liquid contained in the consumable or create driving pressures.

[0090] FIGS. 15 and 16 provide further details of the construction and operation an exemplary LPP-consumable system. FIG. 15 provides a top view of an LPP 100 (e.g. looking in a downward direction at the device of FIG. 5A) showing three rotary valves 110 (e.g. of the type shown in FIG. 12) each of which may have an actuator 120 coupled thereto. Each of the actuators 120 may be coupled to a controller 200. While FIG. 15 depicts a single rotary valve/actuator unit associated with each of the three manifold units of the LPP 100, in various embodiments a valve/actuator pair may be coupled at each of both the upper and lower positions to direct fluid flow as shown in FIG. 5 A. The actuators 120 operate the valves 110 to determine the route of fluid movement through the LPP. In the embodiment depicted in FIG. 15, the valves 110 are rotary valves and thus the actuators 120 operate by rotating the valves 110 to determine the particular route for the fluid flow (e g. Bus 1 or Bus 2 in FIG. 5 A, or other routes). Tn various embodiments, other types of valves (e.g. slider valves as in FIG. 13 or a membrane or diaphragm valve as in FIG. 14) and suitable actuators may be used instead of, or in addition to, rotary valves. Dashed boxes in FIG. 15 represent locations of consumables 130 (e.g. container type consumables as in FIG. 4) associated with each manifold unit of the LPP 100.

[0091] FIG. 16 shows a diagram of an embodiment of an assembled LPP-consumable system. FIG. 16 is a side view of the system showing an LPP 100 with three manifold units, each of which is coupled to a consumable 130. Each manifold unit of the LPP 100 includes two flow couplers 160 disposed within the liquid connectors 104. Each flow coupler 160 has an associated actuator 140 linked to the flow coupler 160 via a piston 150 to couple fluid flow between consumables 130 through particular fluid pathways (e.g. Bus 1 or Bus 2). The actuators 140 and pistons 150 are shown for the left and right manifold units of the LPP; although these components have been omitted for clarity, the center manifold unit of the LPP may also include actuators, pistons, and other components to operate the flow couplers 160. The flow couplers 160 may be an aseptic liquid connector as described above and shown in FIG. 5C. The actuators 140 may serve to move the flow coupler 160 and/or the needle or cannula 162 into position so as to enter the consumable 130 and establish a fluid flow between the consumable 130 and the flow coupler 160 via the needle or cannula 162.

[0092] FIG. 16 also shows the locations of a liquid routing valve 110 (e.g. a rotary valve) and an actuator 120 for operating the valve 110 (see FIG. 15); for the sake of clarity and simplicity, only a single valve 110 and actuator 120 combination is indicated, however each of the valves 110 would have an associated actuator 120 as shown in FIG. 15. FIG. 16 further shows a gas source 180 (e.g. an air compressor, pump, or tank configured to deliver a gas or mix of gases such as oxygen, nitrogen, argon, carbon dioxide, or ambient air) connected to each of the left and right consumables 130. The gas sources 180 (which may be separate air sources, as shown, or a single air source) are configured to apply positive or negative pressure to the air input/output ports 136 (or to simply release air instead of applying negative pressure).

[0093] Each of the actuators 120, 140 as well as the gas source 180 may be connected (e.g. in a wired or wireless manner) to a controller 200 which coordinates the positions of the valves 110 and the flow couplers 160 (e.g. which may be moved downward by the actuators 140, as indicated by the black arrows in FIG 16) with air flow through the air input/output ports 136 to move fluid between consumables 130. The actuators 120, 140 and the gas source 180 may be continuously coupled to the LPP-consumable system or, alternatively, may be coupled only transiently or intermittently when there is a need to move fluid between consumables 130 and/or to process the contents of the consumables 130.

[0094] In the arrangement shown in FIG. 16, the valves 110 and the flow couplers 160 have been set up in a manner that establishes a fluid connection between the left consumable 130 and the right consumable 130 via Bus 2 such that fluid can be transferred between the two compartments. For example, fluid 170 can be moved from the left consumable 130 to the right consumable 130 (e.g. via the piercing needle or cannulas 162) by applying positive air pressure to the air input/output port 136 of the left consumable 130 and applying negative air pressure to the air input/output port 136 of the right consumable 130 (or simply allowing release of air from the air input/output port 136).

[0095] In various embodiments, the LPP-consumable system (with or without actuators 120, 140, gas source 180, and/or controller 200) may be stored in an incubator, such as a cell culture incubator, which maintains control of one or more of temperature, humidity, or gas levels (e.g. O2 or CO2) in the air. In some embodiments, the LPP-consumable system may be assembled outside of an incubator and may then be transferred to an incubator for various periods of time (e.g. hours, days, weeks, etc.) to promote growth of cells in the consumables 130 after which the LPP-consumable system may be removed from the incubator to process the cells.

[0096] FIGS. 17A-17C show steps of an automated process for assembling an LPP- consumable system. In FIG. 17A, a robotic handling device 190 (or other automated mechanism) locates a series of consumables 130 on a surface (e.g. a surface of an instrument docking station). The robotic handling device 190 may be in communication with a controller 200 as shown in FIGS. 17A and 17B, each device 190 may be self-contained with its own internal controller, or a combination thereof. The robotic handling device 190 may identify the appropriate consumables 130 for a particular system using one or more identification marker associated with the consumables 130, which may include one or more of a barcode, a QR code, or an RFID tag for unique identification of the consumable 130 to the equipment software. The locations onto which the robotic handling device 190 places each of the consumables 130 may be marked in a machine-readable manner which is detected by the robotic handling device 190 and/or each placement location may have mechanisms such as indentations or magnets which help correctly align the consumables 130.

[0097] In FIG. 17B, the robotic handling device 190 places an LPP 100 onto the array of consumables 130. At this time, the robotic handling device 190 helps establish a physical connection between the LPP 100 and the consumables 130, which may be facilitated by magnetic couplings and/or friction fittings between the components which hold the LPP 100 and consumables 130 adjacent to one another and correctly aligned such that the liquid input/output ports 132 of the consumables 130 are lined up with the liquid connectors 104 and flow couplers 160 of the LPP 100.

[0098] FIG. 17C shows the LPP-consumable system produced by the steps of FIGS. 17A and 17B, which can then optionally be transferred to an incubator 210 (if the necessary cells and other components have been loaded into the consumables 130) and/or connected to actuators 120, 140 and/or gas sources 180 in order to correctly set up each of the consumables with materials such as cells, media, and/or reagents. The assembled LPP-consumable system can thus serve as a standalone cell growth and/or processing system which can be used in a fully automated environment. In various embodiments, the consumables 130 may be separated (e.g. from other consumables 130, from the LPP 100 and the actuators 120, 140, and/or from gas sources 180) and handled individually, for example to be placed into or removed from an incubator 210 (FIG. 17D).

[0099] The present disclosure has described one or more preferred claims, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.

[00100] It is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other claims and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings.

[001011 As used herein, unless otherwise limited or defined, discussion of particular directions is provided by example only, with regard to particular claims or relevant illustrations. For example, discussion of “top,” “front,” or “back” features is generally intended as a description only of the orientation of such features relative to a reference frame of a particular example or illustration. Correspondingly, for example, a “top” feature may sometimes be disposed below a “bottom” feature (and so on), in some arrangements or claims. Further, references to particular rotational or other movements (e.g., counterclockwise rotation) is generally intended as a description only of movement relative a reference frame of a particular example of illustration.

[00102] In some claims, aspects of the disclosure, including computerized configurations of methods according to the disclosure, can be implemented as a system, method, apparatus, or article of manufacture using standard programming or engineering techniques to produce software, firmware, hardware, or any combination thereof to control a processor device (e.g., a serial or parallel general purpose or specialized processor chip, a single- or multi-core chip, a microprocessor, a field programmable gate array, any variety of combinations of a control unit, arithmetic logic unit, and processor register, and so on), a computer (e.g., a processor device operatively coupled to a memory), or another electronically operated controller to implement aspects detailed herein. Accordingly, for example, claims of the disclosure can be implemented as a set of instructions, tangibly embodied on a non-transitory computer-readable media, such that a processor device can implement the instructions based upon reading the instructions from the computer-readable media. Some claims of the disclosure can include (or utilize) a control device such as an automation device, a special purpose or general purpose computer including various computer hardware, software, firmware, and so on, consistent with the discussion below. As specific examples, a control device can include a processor, a microcontroller, a field- programmable gate array, a programmable logic controller, logic gates etc., and other typical components that are known in the art for configuration of appropriate functionality (e.g., memory, communication systems, power sources, user interfaces and other inputs, etc.).

[00103] The term “article of manufacture” as used herein is intended to encompass a computer program accessible from any computer-readable device, carrier (e.g., non-transitory signals), or media (e.g., non-transitory media). For example, computer-readable media can include but are not limited to magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips, and so on), optical disks (e.g., compact disk (CD), digital versatile disk (DVD), and so on), smart cards, and flash memory devices (e.g., card, stick, and so on). Additionally it should be appreciated that a carrier wave can be employed to carry computer-readable electronic data such as those used in transmitting and receiving electronic mail or in accessing a network such as the Internet or a local area network (LAN). Those skilled in the art will recognize that many modifications may be made to these configurations without departing from the scope or spirit of the claimed subject matter.

[00104] Certain operations of methods according to the disclosure, or of systems executing those methods, may be represented schematically in the figures or otherwise discussed herein. Unless otherwise specified or limited, representation in the figures of particular operations in particular spatial order may not necessarily require those operations to be executed in a particular sequence corresponding to the particular spatial order. Correspondingly, certain operations represented in the figures, or otherwise disclosed herein, can be executed in different orders than are expressly illustrated or described, as appropriate for particular claims of the disclosure. Further, in some claims, certain operations can be executed in parallel, including by dedicated parallel processing devices, or separate computing devices configured to interoperate as part of a large system.

[00105] As used herein in the context of computer configuration, unless otherwise specified or limited, the terms “component,” “system,” “module,” and the like are intended to encompass part or all of computer-related systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on). [00106] In some configurations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as claims of the disclosure, of the utilized features and implemented capabilities of such device or system.

[00107] As used herein, unless otherwise defined or limited, ordinal numbers are used herein for convenience of reference based generally on the order in which particular components are presented for the relevant part of the disclosure. In this regard, for example, designations such as “first,” “second,” etc., generally indicate only the order in which the relevant component is introduced for discussion and generally do not indicate or require a particular spatial arrangement, functional or structural primacy or order.

[00108] As used herein, unless otherwise defined or limited, directional terms are used for convenience of reference for discussion of particular figures or examples. For example, references to downward (or other) directions or top (or other) positions may be used to discuss aspects of a particular example or figure, but do not necessarily require similar orientation or geometry in all installations or configurations.

[00109] Also as used herein, unless otherwise limited or defined, “or” indicates a nonexclusive list of components or operations that can be present in any variety of combinations, rather than an exclusive list of components that can be present only as alternatives to each other. For example, a list of “A, B, or C” indicates options of: A; B; C; A and B; A and C; B and C; and A, B, and C. Correspondingly, the term “or” as used herein is intended to indicate exclusive alternatives only when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” For example, a list of “one of A, B, or C” indicates options of: A, but not B and C; B, but not A and C; and C, but not A and B. A list preceded by “one or more” (and variations thereon) and including “or” to separate listed elements indicates options of one or more of any or all of the listed elements. For example, the phrases “one or more of A, B, or C” and “at least one of A, B, or C” indicate options of: one or more A; one or more B; one or more C; one or more A and one or more B; one or more B and one or more C; one or more A and one or more C; and one or more of A, one or more of B, and one or more of C. Similarly, a list preceded by “a plurality of’ (and variations thereon) and including “or” to separate listed elements indicates options of multiple instances of any or all of the listed elements. For example, the phrases “a plurality of A, B, or C” and “two or more of A, B, or C” indicate options of: A and B; B and C; A and C; and A, B, and C.

[00110] Furthermore, in those instances where a convention analogous to “at least one of A, B and C, etc.” is used, in general such a construction is intended in the sense of one having ordinary skill in the art would understand the convention (e.g., “a system having at least one of A, B and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together ). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description or figures, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or ‘B or “A and B.”

[00111] This discussion is presented to enable a person skilled in the art to make and use claims of the disclosure. Various modifications to the illustrated examples will be readily apparent to those skilled in the art, and the generic principles herein can be applied to other examples and applications without departing from the principles disclosed herein. Thus, claims of the disclosure are not intended to be limited to claims shown, but are to be accorded the widest scope consistent with the principles and features disclosed herein and the claims below. The following detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected examples and are not intended to limit the scope of the disclosure. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of the disclosure.

[00112] Various features and advantages of the disclosure are set forth in the following claims.

Claims

What is claimed is:

1. A modular liquid patch panel (LPP) for providing one or more fluid pathways between a first processing module for culturing or processing cells and a second processing module for culturing or processing cells, wherein: the first processing module comprises one or more liquid ports for introducing or removing liquid from the first processing module, and one or more air ports for introducing or removing air from the first processing module; and the second processing module comprises one or more liquid ports for introducing or removing liquid from the second processing module, and one or more air ports for introducing or removing air from the second processing module; and the LPP comprises one or more manifolds comprising one or more fluid pathways, wherein the one or more manifolds comprise a first connector that engages a liquid port on the first processing module and a second connector that engages a liquid port on the second processing module such that a fluid pathway is provided from the first processing module, through the LPP, and to the second processing module, and liquid is passed through the fluid pathway by introducing or removing air from the first processing module and/or introducing or removing air from the second processing module.

2. The LPP of claim 1 , wherein the one or more manifolds comprise one or more liquid routing valves for controlling the flow of liquid through the fluid pathway.

3. The LPP of claim 1 or 2, wherein the LPP provides one or more aseptic liquid pathways between the first processing module and the second processing module.

4. The LPP of claim 1 or 2, wherein the LPP provides one or more liquid pathways between the first processing module and the second processing module that are isolated from the ambient environment.

5. The LPP of any of claims 1-4, wherein the one or more liquid ports of the first processing module and the second processing module comprise an engageable septum, which is engaged and pierced via the first connector or the second connector of the LPP.

6. The LPP of claim 5, wherein the first connector and the second connector comprise an engageable septum which sheathes an internal cannula, and when the first connector and second connector engage a liquid port of the first processing module or a liquid port of the second processing module, the cannula may be actuated to pierce the septum of the connector and the septum of the liquid port to establish a liquid connection between the LPP and the first processing module and the second processing module.

7. The LPP of claim 1, wherein the LPP includes a first manifold and a second manifold; and wherein the fluid connections between one or more different regions of the first manifold or the second manifold can be selectively changed to adjust the flow of liquid through the LPP.

8. The LPP of claim 7, wherein the LPP includes one or more multi-position valves that define the one or more different regions; and wherein the position of the one or more multi-position valves adjust liquid flow through the LPP.

9. A cell culturing and/or processing system comprising the LPP of any of the foregoing claims.

10. The cell culturing and/or processing system of claim 9, further comprising a first processing module comprising one or more liquid ports for introducing or removing liquid from the first processing module, and one or more air ports for introducing or removing air from the first processing module; and a second processing module comprising one or more liquid ports for introducing or removing liquid from the second processing module, and one or more air ports for introducing or removing air from the second processing module; and a first actuator coupled to the first connector of the LPP, the first actuator being configured to selectively bring the fluid pathway of the LPP into fluid communication with the internal volume of the first processing module by engaging and opening one or more liquid ports of the first processing module via the first connector of the LPP; a second actuator coupled to the second connector of the LPP, the second actuator being configured to selectively bring the fluid pathway of the LPP into fluid communication with the internal volume of the second processing module by engaging and opening one or more liquid ports of the second processing module via the second connector of the LPP, and a gas source that is configured to drive liquid from the internal volume of the first processing module, through the fluid pathway of the LPP, and into the internal volume of the second processing module.

11. The cell culturing and/or processing system of claim 9, wherein the gas source is a pump.

12. The cell culturing and/or processing system of claim 9, wherein the fluid pathways of the LPP are isolated from the ambient environment.

13. The cell culturing and/or processing system of claim 9, wherein the first processing module is a centrifuge container that contains a cell pellet, and wherein liquid from the first processing module that is driven into the second processing module suspends the cells from the cell pellet into the liquid.

14. The cell culturing and/or processing system of claim 13, wherein the liquid is a first liquid; and wherein the gas source is further configured to drive a second liquid including the suspended cells from the second internal volume of the second processing module, through a second flow path of the LPP, and into a third internal volume of a third processing module that is configured to engage with the LPP. l s. The cell culturing and/or processing system of claim 9, wherein the second processing module is a centrifuge container, and wherein the liquid that enters the second internal volume of the second processing module includes cells suspended therein.

16. The cell culturing and/or processing system of claim 15, wherein the centrifuge container is configured to be centrifuged to create a cell pellet and supernatant liquid from the liquid that includes the cells suspended therein, and wherein the gas source is further configured to drive the supernatant liquid from the second processing module, through the second flow path of the LPP, through the first flow path of the LPP, and into the first internal volume of the first processing module.

17. The cell culturing and/or processing system of claim 9, wherein the gas source is further configured to drive gas through a first air port into the first internal volume of the first processing module to drive the liquid out of the first internal volume of the first processing module.

18. The cell culturing and/or processing system of claim 17, wherein when the liquid enters the second internal volume of the second processing module, gas within the second internal volume is vented out through a second air port of the second processing module.

19. The cell culturing and/or processing system of claim 9, wherein the pump is further configured to drive gas out of the second processing module to drive the liquid out of the first internal volume of the first processing module.

20. The cell culturing and/or processing system of claim 19, wherein when the liquid exits the first processing module, gas is directed through the second port into the second internal volume.

21. The cell culturing and/or processing system of claim 9, wherein the LPP includes a third fluid connector, a fourth fluid connector, a third flow path at least partially defined by the

- so third fluid connector, and a fourth flow path at least partially defined by the fourth fluid connector, and further comprising: a third container including a third barrier that seals a third internal volume of the third container from the ambient environment, and a third port in fluid communication with the third internal volume of the third container; and a third actuator coupled to the third fluid connector, the third actuator being configured to selectively bring the third flow path into fluid communication with the second internal volume of the second processing module, and a fourth actuator coupled to the fourth fluid connector, the fourth actuator being configured to selectively bring the fourth flow path into fluid communication with the third internal volume of the third container by opening the third barrier.

22. The cell culturing and/or processing system of claim 21, wherein the pump is further configured to drive at least a portion of the liquid from the second internal volume of the second processing module, through the third flow path, through the fourth flow path, and into the third internal volume of the third container.

23. The cell culturing and/or processing system of claim 22, wherein the cell culture is positioned within the first internal volume of the first processing module, wherein the liquid is spent cell culture media having been used to propagate the cells, and wherein the third interior volume of the third container is empty.

24. The cell culturing and/or processing system of claim 22, wherein the second processing module is a cell processing cartridge that is configured to process cells as the cells flow through the second processing module, and wherein as the liquid enters the second processing module, cells suspended in the liquid are subjected to a first process.

25. The cell culturing and/or processing system of claim 24, wherein the third container is a cell processing cartridge that is configured to process cells as the cells flow through the third container, and wherein as the portion of the liquid enters the third container, cells suspended in the portion of the liquid are subjected to a second process that is different than the first process.

26. The cell culturing and/or processing system of claim 21, wherein the liquid is a first liquid, and wherein the pump is further configured to drive second liquid from the first internal volume of the first processing module, through the first flow path of the LPP, through the third flow path of the LPP, and into the third internal volume of the third container.

27. The cell culturing and/or processing system of claim 21, wherein the liquid is first liquid, and wherein the pump is further configured to drive third fluid from the third internal volume of the third container, through the third flow path of the LPP, through the second flow path of the LPP, and into the second internal volume of the second processing module.

28. The cell culturing and/or processing system of claim 21, wherein the LPP includes a valve that is configured to change between a first position and a second position, and wherein the valve is configured to block the liquid from flowing along the fourth flow path when the valve is in the first position, and wherein the valve is configured to allow the liquid to flow along the fourth flow path when the valve is in the second position.

29. The cell culturing and/or processing system of claim 9, wherein the first processing module is removably coupled to the LPP; wherein the second processing module is removably coupled to the LPP.

30. The cell culturing and/or processing system of claim 29, wherein the first processing module includes a first housing and one or more first liquid connectors each of which define a respective one of the one or more liquid ports of the first processing module; wherein the second processing module includes a second housing and one or more second liquid connectors each of which define a respective one of the one or more liquid ports of the second processing module; and wherein the LPP includes an LPP housing and a plurality of liquid connectors that include the first connector and the second connector, the plurality of liquid connectors being coupled to the LPP housing, each of the plurality of liquid connectors being configured to be fluidly coupled to a respective liquid connector of the first processing module or the second processing module.

31. The cell culturing and/or processing system of claim 30, wherein each of the plurality of liquid connectors are configured to be fluidly decoupled from the respective liquid connector of the first processing module or the second processing module.

32. The cell culturing and/or processing system of claim 31, wherein each of the one or more liquid connectors of the first processing module, the one or more liquid connectors of the second processing module, and the plurality of liquid connectors of the LPP comprise aseptic liquid connectors.

33. The cell culturing and/or processing system of claim 9, further comprising a computing device being configured to: cause the first actuator to extend to fluidly couple the LPP to the first processing module; cause the second actuator to extend to fluidly couple the LPP to the second processing module; and cause the gas source to drive liquid from the first processing module and into the second processing module, via the LPP.

34. The cell culturing and/or processing system of claim 9, wherein the first processing module is configured to implement a first process on cells that pass through the first processing module; wherein the second processing module is configured to implement a second process on cells that pass through the second processing module; and wherein the first process and the second process include at least one of growing cells, culturing cells, concentrating cells, performing cell media exchange for cells, separating cells, electroporating cells, mechanoporating cells, magnetoporating cells, isolating cells, debeading cells, storing cells, collecting cells, washing cells, collecting cells, isolating cells, a cell culture process, or a cell therapy process.

35. The LPP of claim 1, wherein the one or more fluid pathways comprise a first fluid pathway and a second fluid pathway different from the first fluid pathway, wherein a first fluid flows through the first fluid pathway and a second fluid flows through the second fluid pathway.

36. The LPP of claim 35, where the first fluid flows through the first fluid pathway at the same time that the second fluid flows through the second fluid pathway, wherein the first fluid pathway and the second fluid pathway are separate to provide at least one of liquid isolation or contamination avoidance.

37. The LPP of any of the preceding claims, wherein at least one of the LPP, the first processing module, or the second processing module are configured for use in an automated manufacturing system.

38. The LPP of any of the preceding claims, wherein at least one of the LPP, the first processing module, or the second processing module are configured for performing at least one of a cell culture process, a cell therapy process, a sterile drug manufacturing process, or a biologic drug manufacturing process.