Systems, devices, and methods for fluid transfer within automated cell processing system

Abstract

The present disclosure relates to systems, devices, and methods for automated fluid transfer. In one embodiment, the present disclosure relates to a system for automated fluid transfer, the system comprising: a fluid pump; a fluidic device includes a container for a volume of fluid and a universal collar coupleable to the container, the collar including a plurality of conduits, a sterile liquid transfer port in fluid communication with the plurality of conduits, a fluid pump module in fluid communication with the plurality of conduits, and one or more viewing windows in fluid communication with the plurality of conduits. A fluid pump module including a compressible fluid conduit coupled between an inlet port and an outlet port, each of the inlet port and the outlet port being in fluid communication with the plurality of conduits; and one or more sensors configured to detect the presence of liquid within the sections of the plurality of conduits via the one or more viewing windows.

Description

Technical Field

[0001] This disclosure relates to fluid transfer within an automated cell processing system.

[0002] Cross-references to related applications

[0003] This application claims priority to U.S. Provisional Application No. 63 / 456,388, filed March 31, 2023. All applications are incorporated herein by reference in their entirety. Background Technology

[0004] Cell therapy, in which cells are collected from an individual patient, processed in vitro, and subsequently reinfused into the same patient, has been revolutionary in producing durable and effective clinical responses in patients. Despite its appeal, cell therapy manufacturing processes are complex and often require significant human labor, making large-scale production difficult and susceptible to human error and contamination. While efforts have been made in recent years to automate cell therapy manufacturing (such as automating cell movement between manufacturing steps), traditional cell therapy manufacturing still suffers from numerous inefficiencies. For example, fluid transfer between cell therapy steps and reagent storage devices remains a point of human contact and an introduction point for error and contamination. Given the importance of asepticity in operations such as transferring fluids for sample collection and replenishing culture media, additional systems, devices, and methods are needed for fluid transfer within cell processing systems. Specifically, automated systems, devices, and methods that can be performed aseptically are required. Summary of the Invention

[0005] This disclosure relates throughout to systems, apparatus, and methods for automated fluid transfer within automated cell processing systems. Generally, the fluid apparatus disclosed herein may include: a container for a volume of fluid; and a universal collar capable of being coupled to the container. In some variations, the collar includes: a plurality of conduits; a sterile fluid transfer port in fluid communication with the plurality of conduits; and a fluid pump module including a compressible fluid conduit connected between an inlet port and an outlet port. Each of the inlet port and the outlet port is in fluid communication with the plurality of conduits, and the compressible fluid conduit can be compressed by the fluid pump to control the movement of fluid out of the container. In some variations, the collar may further include one or more sterilization processing ports in fluid communication with the plurality of conduits. A sterilizing agent, which may be one or more of vaporized hydrogen peroxide, ionized hydrogen peroxide, chlorine dioxide, and ethylene oxide, may be provided via the one or more sterilization processing ports. In some variations, the collar may further include one or more air handling ports in fluid communication with the plurality of conduits. The one or more air handling ports may be compressed air handling ports or vents. In some variations, the collar may further include a viewing window allowing optical evaluation of the fluid within the fluid conduits of the collar. In some variations, the sterile fluid transfer port may further include a mechanical seal. In some variations, the collar may further include one or more sterilization ports in fluid communication with the plurality of conduits. In some variations, the mechanical seal of the sterile fluid transfer port and the sterilizing agent supplied via the one or more sterilization ports ensure the sterility of the collar. In some variations, the container includes an opening, and the collar may further include a fluid delivery feature capable of engaging with the opening, wherein the fluid delivery feature is also in fluid communication with the plurality of conduits. A vent may be configured to extend through the opening of the container and be disposed within the container. The vent tube may further include a liquid vent reservoir configured to capture fluid trapped within the vent tube when the fluid device is inverted. An air handling tube may be configured to extend through the opening in the container and be disposed within the container. In some variations, the sterile liquid transfer port may further include a mechanical seal, and the collar may further include one or more sterilization ports in fluid communication with the plurality of conduits, the mechanical seal providing a first mechanism for sterilization, and sterilizing agent supplied via the one or more sterilization ports providing a second mechanism for sterilization.

[0006] Another fluid device for automating fluid transfer may include: a container for a volume of fluid; and a universal collar capable of being coupled to the container. The collar may include: a plurality of tubing; a sterile fluid transfer port in fluid communication with the plurality of tubing; a fluid pump module; an air handling port; and a ball valve coupled to the air handling port. The fluid pump module may include a compressible fluid conduit coupled between an inlet port and an outlet port, each of which is in fluid communication with the plurality of tubing, and the compressible fluid conduit may be configured to be compressed by the fluid pump to control the movement of fluid out of the container. The fluid device may be configured to be positioned in an upright orientation and an inverted orientation, and the ball valve may be configured to prevent the fluid in the container from flowing within the air handling port when the fluid device is in the inverted orientation.

[0007] This document also discloses a method for automating fluid transfer. In some variations, a method for automating fluid transfer includes: inverting a fluid device, the fluid device including a container and a universal collar including a plurality of conduits and a sterile liquid transfer port in fluid communication with the plurality of conduits, by a robot; connecting the sterile liquid transfer port of the inverted fluid device to a corresponding sterile liquid transfer port of a cartridge by the robot; and pumping fluid from the fluid device to the cartridge via the plurality of conduits and the sterile liquid transfer port. In some variations, the method may further include sterilizing the sterile liquid transfer port via one or more sterilization treatment ports of the collar in fluid communication with the plurality of conduits after the connection and before the pumping. In some variations, the method may further include, after the sterilization, actuating a valve of each of the sterile liquid transfer port and the corresponding sterile liquid transfer port by the robot to allow the pumping through them.

[0008] In other variations, a method for automating fluid transfer includes: inverting a fluid device by a robot, the fluid device including a container and a universal collar including a plurality of conduits, a sterile liquid transfer port, and an air handling port, each of the sterile liquid transfer port and the air handling port being in fluid communication with the plurality of conduits; connecting the sterile liquid transfer port of the inverted fluid device to a corresponding sterile liquid transfer port of a cartridge by the robot; pumping at least a portion of fluid from the inverted fluid device to the cartridge via the plurality of conduits and the sterile liquid transfer port; and after the pumping, purging the plurality of conduits using compressed air via the air handling port.

[0009] In other variations, a method for automating fluid transfer includes: inverting a fluid device by a robot, the fluid device including a container and a universal collar including a robot engagement feature, a plurality of conduits, a sterile liquid transfer port, and a plurality of sterilization ports, each of the sterile liquid transfer port and the plurality of sterilization ports being in fluid communication with the plurality of conduits; connecting the sterile liquid transfer port of the inverted fluid device to a corresponding sterile liquid transfer port of a cartridge via the robot; allowing a sterilizing agent to flow through the sterile liquid transfer port via the one or more sterilization ports; and pumping at least a portion of the fluid from the inverted fluid device to the cartridge via the plurality of conduits and the sterile liquid transfer port.

[0010] In other variations, a method for automating fluid transfer includes: filling a fluid device comprising a container and a universal collar, the universal collar including a robotic engagement feature, a plurality of tubing, and a sterile liquid transfer port, while the fluid device is in an upright position; inverting the fluid device by a robot via the robotic engagement feature; connecting the sterile liquid transfer port of the inverted fluid device to a corresponding sterile liquid transfer port of a cartridge via the robot; and pumping at least a portion of the fluid from the fluid device to the cartridge via the plurality of tubing and the sterile liquid transfer device. The pumping may further include: receiving data from a sensor disposed near an observation window of the collar, the sensor being configured to detect the presence of liquid within sections of the plurality of tubing; detecting an air-to-liquid fluid transition based on the received data; operating the fluid pump based on the detected presence of the air-to-liquid fluid transition; detecting a liquid-to-air fluid transition based on the received data; and stopping operation of the fluid pump when the liquid-to-air fluid transition is detected. In some variations, the pumping may further include receiving data about a predetermined volume of fluid to be transferred to the cartridge, wherein the data is received from a sensor disposed near an observation window adjacent to the collar. In some variations, the sensor may be configured to detect the presence of liquid within sections of the plurality of conduits. The air-to-liquid fluid transition may be detected based on the received data, and the fluid pump may be operated to deliver the predetermined volume of fluid. Once the predetermined volume of fluid has been transferred, operation of the fluid pump may be stopped.

[0011] In other variations, a method for automating fluid transfer includes: connecting a sterile liquid transfer port of a fluid device to a corresponding sterile liquid transfer port of a cartridge by a robot; pumping at least a portion of fluid from the fluid device to the cartridge via a plurality of conduits of the fluid device and the sterile liquid transfer port; and, after the pumping, purging the plurality of conduits using compressed air via an air handling port of the fluid device.

[0012] This document also discloses a system for automating fluid transfer. In some variations, a system for automating fluid transfer includes: a fluid pump; a fluid device including a container and a universal collar, the container for a volume of fluid, the universal collar being connectable to the container; and one or more sensors. The universal collar may include: a plurality of tubing; a sterile fluid transfer port in fluid communication with the plurality of tubing; and one or more windows. The one or more sensors may be configured to detect the presence of fluid within sections of the plurality of tubing via the one or more viewing windows. The collar may further include a fluid pump module including a compressible fluid conduit connected between an inlet port and an outlet port, each of the inlet port and the outlet port being in fluid communication with the plurality of tubing, the compressible fluid conduit being configured to be compressed by the fluid pump to control the movement of fluid out of the container. In some variations, the system may further include a processor configured to: receive data from the one or more sensors; detect a fluid transition from air to liquid based on the received data; start the fluid pump; detect a fluid transition from liquid to air; and stop the fluid pump when the fluid transition from liquid to air is detected.

[0013] Additional variations, features, and advantages of the invention will become apparent from the following detailed description and from the practice of the invention. Attached Figure Description

[0014] Figure 1A This is a block diagram illustrating an exemplary variant of a cell processing system.

[0015] Figure 1B This is a block diagram illustrating an exemplary variant of the box.

[0016] Figure 2A This is a block diagram illustrating an exemplary variant of a cell processing system. Figure 2B This is a perspective view of an exemplary variant of the working unit of a cell processing system. Figure 2C This is a perspective view of an exemplary variant of the working unit and box of a cell processing system. Figure 2D This is a block diagram illustrating an exemplary variant of a cell processing system.

[0017] Figure 3A This is a schematic diagram illustrating an exemplary variation of a fluid apparatus with a container and a collar.

[0018] Figure 3B This is a schematic diagram of an exemplary system for automated fluid transfer.

[0019] Figure 4A It is a rendering of a perspective view of an exemplary fluid device used for automated fluid transfer. Figure 4B This is a rendering of a perspective view of an exemplary collar used for automated fluid transfer. Figure 4C This is a top-view rendering of an exemplary collar used for automated fluid transfer. Figure 4D This is an image of the bottom view of an exemplary collar used in an automated fluid transfer device. Figure 4E These are images of illustrative containers and fluid transport features of fluid devices used for automated fluid transfer. Figure 4F It is a perspective rendering of an exemplary container used for automated fluid transfer. Figure 4G This is a rendering of the robotic gripping features of an exemplary fluid handling device and work cell for automated fluid transfer. Figure 4H and Figure 4I This is a rendering of the gripping features of an example robot in a work unit.

[0020] Figure 5A This is a rendering of the first perspective view of an exemplary fluid device used for automated fluid transfer. Figure 5B This is a rendering of a second perspective view of an exemplary fluid device used for automated fluid transfer. Figure 5C This is a top-view rendering of one aspect of an exemplary collar used for automated fluid transfer. Figure 5D This is a rendering of a cross-sectional view of one aspect of an exemplary collar for automated fluid transfer, where the cross-section is the plane between the bottom and top of the fluid device. Figure 5E This is a rendering of the bottom view of an exemplary collar used for automated fluid transfer. Figure 5F This is a rendering of a perspective view of an exemplary collar used for automated fluid transfer. Figure 5G This is a rendering of an illustrative liquid vent pipe for a fluid device used for automated fluid transfer. Figure 5H This is an image of an illustrative liquid vent tube for a fluid device used for automated fluid transfer. Figure 5I It is a perspective rendering of an exemplary container used for automated fluid transfer. Figure 5J This is a rendering of the robotic gripping features of an exemplary fluid handling device and work cell for automated fluid transfer. Figure 5K This is a rendering of the first connection position of the gripper of the robot's gripping feature, which is an exemplary fluid device for connecting the robot's engagement feature and the working unit. Figure 5L This is a rendering of the second connection position of the gripper of the robot's gripping feature, which is an illustrative fluid device for connecting the robot's engagement feature and the working unit.

[0021] Figure 6 This is a flowchart illustrating an exemplary method for automated fluid transfer.

[0022] Figure 7A , Figure 7B , Figure 7C , Figure 7D , Figure 7E and Figure 7F This is a flowchart illustrating an exemplary variation of a method for automating fluid transfer.

[0023] Figure 8 This is a flowchart illustrating an exemplary variation of a method for automating fluid transfer.

[0024] Figure 9 This is a flowchart illustrating another exemplary variation of a method for automating fluid transfer.

[0025] Figure 10 This is a rendering of the bottom view of an exemplary collar for automated fluid transfer, wherein the fluid device includes a ball valve.

[0026] Figure 11A This is a rendering of a transparent view of an exemplary ball valve used with the fluid apparatus described in this article. Figure 11B yes Figure 11A An exploded view of an illustrative ball valve.

[0027] Figure 12A An exemplary variation of the fluid flowing through the ball valve of the fluid device when the fluid device is in an inverted orientation is depicted. Figure 12B An exemplary variation is depicted in which fluid flows through the ball valve of the fluid device when the fluid device is in an upright orientation. Detailed Implementation

[0028] A key limiting factor in cell therapy manufacturing is the lack of automated systems, devices, and methods for performing fluid transfer without contamination and / or the introduction of human error. While devices, including some bottle-sealing devices, integrate tubing within the caps of centrifuge tubes, bottles, flasks, etc., to enable sterile fluid handling, these devices still require human intervention and have not yet been widely integrated into automated cell therapy manufacturing processes.

[0029] Therefore, this disclosure provides systems, apparatus, and methods for automated fluid transfer within automated cell processing systems, with an aim of minimizing the sterility barrier that limits the availability of cell therapies manufactured on a large scale.

[0030] The systems, apparatus, and methods for performing fluid transfer described herein are used in conjunction with cell therapy manufacturing systems or cell processing systems, and exemplary illustrations are shown in […]. Figure 2B As shown in the image. Figure 2BAs shown, cell processing may involve moving a cassette 250 containing cell products between multiple instruments (such as instruments 211, 216, 220, 222) within work unit 202. One or more of these instruments may be configured to engage, attach, or dock with cassette 250 to perform cell processing steps on the cells within cassette 250. In some variations, multiple cell processing steps may be performed within cassette 250. For example, robotic arm 230 may be configured to move cassette 250 between instruments, each instrument configured to perform a different cell processing step when attached to a corresponding module within cassette 250. In some variations, cassette 250 may include any number of modules, such as a bioreactor module, a countercurrent centrifugation (CCE) module, a magnetic cell sorter module, an electroporation module, a sorting module (e.g., a fluorescence-activated cell sorting (FACS) module), an acoustic flow cell module, a microfluidic enrichment module, a spin-seeding module, and / or combinations thereof. In some variations, work unit 202 may process two or more cassettes in parallel. For example, work unit 202 may include multiple instruments, such as instruments 211, 216, 220, and 222, having reception compartments. Each instrument may be configured to dock with a cassette (such as cassette 250) received in the corresponding reception compartment, such that multiple instruments within work unit 202 are available at any given time.

[0031] In addition to and implementing the cell processing steps described above, automated cell processing systems can facilitate automated fluid transfer (which may or may not be sterile fluid transfer) between the cartridge and the system's instruments or other components (such as other cartridges and / or sample collection containers, reagent containers, waste containers, other fluid devices, etc.). For example, as will be described below, the systems, apparatus, and methods of this disclosure can facilitate fluid transfer between the cartridge and a fluid device, which may be a reagent container, sample collection container, waste container, etc.

[0032] I. Cell Processing System

[0033] Figure 1AAn exemplary cell processing system for use with automated fluid transfer devices, systems, and methods is shown. A block diagram of a unit processing system 100 including a working unit 110 and a controller 120 is shown. The working unit 110 may include one or more of the following: an instrument 112, a robot 116 (e.g., a robotic arm), a reagent library 118, a sterile liquid transfer port 132, a sterilizing agent source 129, a fluid source 136, a pump 138, and a sensor 151. A cartridge 114 and a fluid device 142, which can be used within the working unit 110 (and are therefore shown in dashed lines in the figure), are also included. In some variations, the fluid device 142 is a sterile liquid transfer device (SLTD). However, it should be understood that the fluid device 142 can be configured to transfer any fluid (including liquids), whether sterile or not. In some variations, the fluid device 142 may include: a container for storing a fluid (e.g., a liquid); and a collar capable of being coupled to the container and configured to facilitate fluid transfer between the fluid device 142 and another component of the system 100 (e.g., instrument 112 and / or reagent library 118). A robot 116 may be configured to move one or more cartridges 114 and the fluid device 142 within the work unit 110. For example, the robot 116 may be configured to move one or more fluid devices 142 between the reagent library 118 and one or more instruments 112 (e.g., one or more sterile liquid transfer instruments). In some variations, the robot 118 may be configured to position the fluid device 142 in a first orientation within the reagent library 118 and in a second orientation (which may be opposite to the first orientation) when coupled to an instrument 112. For example, the fluid device 142 may be configured to be stored in an upright orientation within the reagent library 118 and may be configured to be coupled to an instrument 112 in an inverted position. As explained herein, an upright orientation may be defined by the relative orientation of the collar and the container of the fluid device 142. In some variations, the fluid device 142 may be in an upright orientation when the collar is above the container, and may be in an inverted orientation when the container is above the collar. The controller 120 may include one or more of a processor 122, a memory 124, a communication device 126, an input device 128, and a display 130.

[0034] The working unit 110 may include a fully or at least partially enclosed housing within which one or more cell processing steps are performed in a fully or at least partially automated process. In some variations, the working unit may be an open system without a housing, which may be configured for use in a cleanroom, biosafety cabinet, or other sterile location. A robot 116 may be used to move the cartridge 114 to reduce manual labor in the cell processing steps, and fluid transfer into and out of the cartridge may also be performed in a fully or partially automated process, as will be described in detail herein. For example, one or more fluids may be stored in a fluid device 142. In some variations, the fluid device is movable within the system 100 by the robot 116. The fluid device and sterile liquid transfer port described herein advantageously enable the automated and metered transfer of fluids to automate cell therapy manufacturing.

[0035] In some variations, robot 116 is configured to move cassette 114 between different instruments to perform cell processing steps in a predetermined sequence. In this way, multiple cassettes 114 can be processed in parallel because different steps of the cell processing sequence can be performed simultaneously on different cassettes.

[0036] A sterile liquid transfer port 132 may be coupled between two or more cartridges 114 to transfer cell products and / or fluids between cartridges 114. Furthermore, the sterile liquid transfer port 132 may be coupled between any set of fluid-carrying components of system 100 (e.g., cartridges 114, reagent reservoirs 118, fluid sources 136, fluid devices 142, etc.). For example, a first sterile liquid transfer port may be coupled between a first cartridge and a corresponding sterile liquid transfer port of a fluid device.

[0037] In some variations, reagent library 118 (or multiple reagent libraries) is used to store reagents, including but not limited to cell culture media, buffers, cytokines, proteins, enzymes, polynucleotides, transfection reagents, non-viral vectors, viral vectors, antibiotics, nutrients, cryoprotectants, solvents, cell materials, and pharmaceutically acceptable excipients. Additionally or alternatively, waste may be stored in the reagent library or in a fluid device within the reagent library. In some variations, samples may be stored in the reagent library or in a fluid device within the reagent library during extraction from one or more cartridges. The reagent library may include one or more temperature-controlled compartments (e.g., freezers, coolers, water baths, heating chambers, or others at, for example, about 80°C, about –20°C, about 4°C, about 25°C, about 30°C, about 37°C, and about 42°C). During cell manufacturing, the temperature in these compartments may be varied to heat or cool the reagents.

[0038] In some variations, reagents, waste, and / or samples extracted during the process may be stored in a fluid device 142 within the reagent storage unit 118. For this purpose, the fluid device 142 may be transferred to a cartridge within the work unit, or the cartridge may be moved to the reagent storage unit 118 by a robot 116 (or manually by an operator). The reagent storage unit 118 may dock with one or more sterile liquid transfer ports on the cartridge, and reagents or materials may be transferred from the fluid device 142 within the reagent storage unit to the cartridge. Optionally, fluid may be added to or removed from the cartridge before, during, or after the addition or removal of reagents or materials. In some variations, the instrument 112 of the work unit 110 includes a sterile liquid transfer instrument similarly configured to automatically transfer fluid to or from a cartridge. The sterile liquid transfer instrument may store reagents via, for example, a robot 116 that moves the fluid device 142, containing the reagents, from the work unit feeder or other location to the sterile liquid transfer instrument. In some variations, robot 116 moves fluid devices 142 from reagent storage tank 118 to a sterile liquid transfer instrument. Reagent storage tank 118 may have automated doors to allow robot 116 access to the fluid devices 142 stored therein. Fluid devices 142 may be configured for pick-up and placement movements performed by robot 116. In some variations, reagent storage tank 118 may include one or more sample pickup areas. For example, robot 116 may be configured to move one or more fluid devices 142, including reagents, to and from one or more sample pickup areas.

[0039] In some variations, the sensor 151 of the working unit 110 includes optical sensors located near various aspects of the sterile fluid transfer instrument. Sensor 151 can be queried during automated fluid transfer to help control the flow of fluid from one fluid device to another. Specifically, the optical sensors may be arranged facing a window of the fluid device to detect the presence or absence of fluid in the fluid conduit of the fluid device. In this way, the controller 120 can deliver a metered volume of fluid from one fluid device to an adjacent fluid device or cassette.

[0040] like Figure 1B As illustrated, cassette 114 may include one or more of a bioreactor 150, a cell separation system 152, an electroporation module 160, a fluid transfer bus 162, a sensor 164, and a sterile liquid transfer port 166, as described in more detail herein. Cell separation system 152 may include one or more of a rotor 154, a flow cell 156, and a magnet 158. In some embodiments, magnet 158 ​​may include one or more magnets and / or an array of magnets. For example, cell separation system 152 may include a first magnet configured to magnetically rotate rotor 154 and a second magnet (e.g., an array of magnets) configured to magnetically separate cells in flow cell 156.

[0041] Any suitable cell treatment can be performed using the systems and apparatus described herein and may include steps such as growth, enrichment, selection, sorting, amplification, activation, transduction, electroporation, and washing. In some variations, the method of treating a solution containing cell products includes the following steps: digesting tissue with an enzymatic reagent to release a selected cell population into the solution; enriching cells using a CCE instrument; washing cells using a CCE instrument; selecting cells in the solution using a selection instrument; sorting cells in the solution using a sorting instrument; differentiating or amplifying cells in a bioreactor; activating cells using an activation reagent; electroporating cells; transducing cells using a vector; and preparing the cell products.

[0042] Figure 2A An exemplary cell processing system for use with the apparatus, systems, and methods described herein is shown. A working unit 203 is shown. This working unit can be divided into an internal zone 204 with a feedthrough inlet 206 and a quality control (QC) instrument 212. An air filter inlet (not shown) provides high-efficiency particulate air (HEPA) filtration to provide ISO 7 or better air quality in the internal zone 204. This air filtration maintains sterile cell processing in an ISO 8 or ISO 9 manufacturing environment. The working unit 203 may also have an air filter at the air outlet to maintain the room's ISO rating. Similar to the references above. Figure 1A The described work unit 203 may further include, within its interior area 104, a bioreactor instrument 214, a cell selection instrument 216 (e.g., a magnetic separation instrument), an electroporation instrument 220, a countercurrent centrifugation (CCE) instrument 222, a sterile fluid transfer instrument 224 (e.g., for facilitating automated fluid transfer), a reagent library 226, and a sterilization system 260. The reagent library 226 is accessible to a user via a sample pickup port 228. A robot 230 (e.g., a support arm, robotic arm, etc.) may be configured to move one or more cartridges 250 from any instrument to any other instrument, move one or more cartridges 250 to and from the reagent library 226, and / or move one or more fluid devices between the reagent library 226 and the sterile fluid transfer instrument 224. In some embodiments, the work unit 203 may include one or more movable barriers 213 (e.g., inlets, doors) configured to facilitate access to one or more instruments within the work unit 203. Figure 2B This is a perspective view of the working unit 205 of the cell processing system. Figure 2C This is a perspective view of the cell processing system, depicting the cartridge 250 introduced into the working unit 205. Multiple cartridges can be inserted into the working unit 205 and undergo one or more cell processing operations in parallel.

[0043] Figure 2D This is a schematic diagram of an embodiment of work unit 200. Work unit 200 may include a housing 202 having four walls, a base, and a top. Work unit 200 may be divided into an internal zone 204 with a feedthrough inlet 206, a biosafety cabinet (BSC) 208, a computing server rack 210 (e.g., controller 120), and quality control (QC) instruments 212. An air filter inlet (not shown) may provide high-efficiency particulate air (HEPA) filtration to provide ISO 7 or better air quality in internal zone 204. Work unit 200 may also have an air filter at the air outlet to maintain the room's ISO rating. Similar to the work unit described above, work unit 200 may further include within its internal area 204 instruments 211 (e.g., located in a general instrument bay), bioreactor instrument 214, cell selection instrument 216 (e.g., magnetic separation instrument, cell selection system), cell sorting instrument 218 (e.g., FACS), electroporation instrument 220, countercurrent centrifugation (CCE) instrument 222, and sterile liquid transfer instrument 224, as well as reagent library 226 and sterilization system 260, which includes one or more of a sterilizing agent source, a fluid source, and a pump. As will be described below, sterilization system 260 may be able to connect to a fluid device for sterilizing sterile liquid transfer ports during automated fluid transfer processes. Reagent library 226 may be accessible via sample pickup port 228. The robot 230 (e.g., a support arm, a robotic arm) may be configured to move one or more cartridges 250 from any instrument to any other instrument, move one or more cartridges 250 to and remove from the reagent library 226, and / or move one or more fluid devices between the reagent library 226 and the sterile liquid transfer instrument 224.

[0044] In some implementations, a human operator may load one or more cartridges 250 into feeder 206. Cartridges 250 may be pre-sterilized, or feeder 206 may sterilize cartridges 250 using ultraviolet (UV) radiation or chemical sterilizing agents provided as sprays or detergents. The chamber of feeder 206 may optionally be configured to automatically spray, wash, irradiate, or otherwise treat cartridges (e.g., with ethanol and / or isopropanol solutions) to maintain the sterility of the internal area 204 (e.g., ISO 7 or better) or the sterility of the biosafety cabinet 208 (e.g., ISO 5 or better). Cartridges 250 may be transferred to biosafety cabinet 208, where the input cell products are provided and loaded into cartridges 250. The user may then move cartridges 250 back to feeder 206 and initiate automated cell processing using a computer processor (e.g., controller 120) in computer server rack 210. Robot 230 can be configured to move box 250 to multiple instruments and stations in a predefined sequence, wherein the components of work unit 200 are controlled by computer processor of computer server rack 210.

[0045] Other suitable cell processing systems and aspects thereof are provided, for example, in U.S. Patent Application Publication No. 17 / 198,134 entitled “Systems and Methods for Cell Processing”, which is incorporated herein by reference.

[0046] A. Work Unit

[0047] i. Robot

[0048] Generally, a robot in a work cell may include any mechanical device capable of moving a box and / or fluid device from one location within the work cell to another. For example, a robot may include a mechanical manipulator (e.g., an arm) that is stationary or attached to a linear or two- or three-dimensional track system. While shown in some figures as fixed in place or relative to the track system, this is not mandatory for the robot. For example, in some variations, the robot includes wheeled devices. Any number of robots, as described herein, may be used within a work cell. For example, in some embodiments, the work cell includes two or more robots of the same or different types (e.g., two robot arms, each independently configured to move boxes between instruments). The robot may also include end effectors for precisely handling different boxes or fluid devices, or for barcode scanning or radio frequency identification tag (RFID) reading.

[0049] The robot used with the cell processing system described herein is capable of moving cartridges between tanks or compartments within the work unit, allowing modules within the cartridges to be coupled to corresponding instruments within the work unit to perform different cell processing steps. Additionally, the robot used with the cell processing system described herein is capable of moving and manipulating fluid devices within the work unit. For example, the robot may be able to move reagent storage fluid devices from the reagent library of the work unit to the sterile liquid transfer instrument of the work unit, enabling automated fluid transfer between the reagent storage fluid devices and cartridges.

[0050] ii. Controller

[0051] In one embodiment, the cell processing system 100 may include a controller 120 (e.g., a computing device) that includes one or more of a processor 122, a memory 124, a communication device 126, an input device 128, and a display 130. The controller 120 may be configured to control (e.g., operate) a work unit 110. The controller 120 may include multiple devices. For example, the work unit 110 may encapsulate one or more components of the controller 120 (e.g., processor 122, memory 124, communication device 126), and one or more components of the controller 120 may be remotely provided to the work unit 110 (e.g., input device 128, display 130).

[0052] iii. Processor

[0053] The processor described herein (e.g., processor 122) can process data and / or other signals to control one or more components of a system. The processor can be configured to receive, process, compile, compute, store, access, read, write, and / or transmit data and / or other signals. Additionally or alternatively, the processor can be configured to control one or more components of a device (e.g., a console, touchscreen, personal computer, laptop computer, tablet computer, server).

[0054] In some embodiments, the processor may be configured to access or receive data and / or other signals from one or more of the work unit 110, server, controller 120, and storage media (e.g., memory, flash drive, memory card, database). In some embodiments, the processor may be any suitable processing device configured to run and / or execute a set of instructions or code, and may include one or more data processors, image processors, graphics processing units (GPUs), physical processing units, digital signal processors (DSPs), analog signal processors, mixed signal processors, machine learning processors, deep learning processors, finite state machines (FSMs), compression processors (e.g., data compression for reducing data rates and / or memory requirements), encryption processors (e.g., for secure wireless data transmission), and / or central processing units (CPUs). The processor may be, for example, a general-purpose processor, a field-programmable gate array (FPGA), an application-specific integrated circuit (ASIC), a processor board, and / or the like. The processor may be configured to run and / or execute application processes and / or other modules, processes, and / or functions associated with the system. Basic device technologies that can provide a variety of component types include, for example, metal-oxide-semiconductor field-effect transistor (MOSFET) technology such as complementary metal-oxide-semiconductor (CMOS), bipolar technology such as emitter-coupled logic (ECL), polymer technologies (e.g., silicon conjugated polymers and metal conjugated polymer-metal structures), hybrid analog and digital, etc.

[0055] The systems, devices, and / or methods described herein can be implemented by software (executing on hardware), hardware, or a combination thereof. Hardware modules can include, for example, general-purpose processors (or microprocessors or microcontrollers), field-programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (executing on hardware) can be expressed in various software languages ​​(e.g., computer code), including Structured Text, TypeScript, C, C++, C#, Java, etc. ® ,Python,Ruby,VisualBasic ® And / or other object-oriented, procedural, or other programming languages ​​and development tools. Examples of computer code include, but are not limited to, microcode or microinstructions, machine instructions (such as those generated by a compiler), code for generating network services, and files containing high-level instructions that are executed by a computer using an interpreter. Additional examples of computer code include, but are not limited to, control signals, encryption code, and compression code.

[0056] iv. Memory

[0057] The cell processing systems and devices described herein may include memory (e.g., memory 124) configured to store data and / or information. In some embodiments, the memory may include one or more of random access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), memory buffers, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), flash memory, volatile memory, non-volatile memory, combinations thereof, etc. In some embodiments, the memory may store instructions to cause a processor to perform modules, processes, and / or functions associated with the device, such as image processing, image display, sensor data, data and / or signal transmission, data and / or signal reception, and / or communication. Some embodiments described herein may be associated with computer storage products having non-transitory computer-readable media (also referred to as non-transitory processor-readable media) having instructions or computer code on which perform various computer-implemented operations. Computer-readable media (or processor-readable media) are non-transient in the sense that they do not inherently include transient propagation signals (e.g., propagating electromagnetic waves carrying information on a transmission medium such as space or cable). Computer code (also referred to as code or algorithm) can be that which is designed and constructed for a particular purpose or one or more. In some embodiments, memory may be configured to store any received data and / or data generated by the controller and / or work unit. In some embodiments, memory may be configured to store data temporarily or permanently.

[0058] v. Input device

[0059] In some embodiments, the input device (e.g., input device 128) may include a display or coupled to a display. The input device can be any suitable device capable of receiving input from a user, such as a keyboard, buttons, a touchscreen, etc. The input device may include at least one switch configured to generate user input. For example, the input device may include a touch surface for the user to provide input corresponding to the user input (e.g., finger contact with a touch surface). Input devices including touch surfaces can be configured to detect contact and movement on the touch surface using any of a variety of touch-sensitive technologies, including capacitive, resistive, infrared, optical imaging, dispersive signaling, acoustic pulse identification, and surface acoustic wave technologies. In embodiments of an input device including at least one switch, the switch may have at least one of, for example, buttons (e.g., hard keys, soft keys), a touch surface, a keyboard, an analog stick (e.g., a joystick), a direction pad, a mouse, a trackball, a dial, a step switch, a rocker switch, a pointing device (e.g., a stylus), a motion sensor, an image sensor, and a microphone. The motion sensor may receive user movement data from the optical sensor and classify user gestures as user input. The microphone can receive audio data and recognize user speech as user input.

[0060] In some embodiments, in addition to a display, the cellular processing system may optionally include one or more output devices, such as, for example, audio devices and haptic devices. The audio device can audibly output any system data, alarms, and / or notifications. For example, the audio device may output an audible alarm when a fault is detected. In some embodiments, the audio device may include at least one of a speaker, a piezoelectric audio device, a magnetostrictive speaker, and / or a digital speaker. In some embodiments, a user may use the audio device and a communication channel to communicate with other users. For example, a user may establish an audio communication channel (e.g., VoIP calling).

[0061] vi. Communication equipment

[0062] In some embodiments, the controller may include a communication device (e.g., communication device 126) configured to communicate with another controller and one or more databases. The communication device may be configured to connect the controller to another system (e.g., the Internet, a remote server, a database, a work unit) via a wired or wireless connection. In some embodiments, the system may communicate with other devices via one or more wired and / or wireless networks. In some embodiments, the communication device may include a radio frequency receiver, a transmitter, and / or an optical (e.g., infrared) receiver and transmitter configured to communicate with one or more devices and / or networks. The communication device may communicate via wired and / or wireless means.

[0063] vii. Display

[0064] Image data can be output on a display of the cell processing system (e.g., display 130). In some embodiments, the display may include at least one of light-emitting diodes (LEDs), liquid crystal displays (LCDs), electroluminescent displays (ELDs), plasma display panels (PDPs), thin-film transistors (TFTs), organic light-emitting diodes (OLEDs), electronic paper / electronic ink displays, laser displays, and / or holographic displays.

[0065] viii. Graphical User Interface

[0066] In some implementations, as noted above, the GUI can be configured for designing the process and monitoring the product. For example, the GUI could be a process design homepage. The GUI can indicate whether a process has not yet been selected or loaded. A creation icon (e.g., "Create Process") can be optional for the user to begin the process design process. In some implementations, one or more of the GUIs described herein may include a search bar.

[0067] B. Box

[0068] The cell processing system described herein may include one or more cartridges having one or more modules configured to interface with one or more instruments within a working unit. References Figure 1B An exemplary box is described.

[0069] Various materials can be used to construct the box and its shell, including metal, plastic, rubber, and / or glass, or combinations thereof. The box, its components, and its shell can be molded, machined, extruded, 3D printed, or any combination thereof. The box may contain commercially available components (e.g., tubing, valves, fittings) that can be attached to or integrated with custom components or devices. The shell of the box may form an additional protective layer to further safeguard the sterility of the cell product.

[0070] In some embodiments, the box module may consist of different parts integrated in a fixed configuration within the box. Additionally or alternatively, the module may be configurable or movable within the box, thereby allowing for the assembly of various box forms. For example, the box may be a single enclosed unit with fixed components for each module, or the box may contain configurable modules coupled by configurable fluid, mechanical, optical, and electrical connections. In some variations, one or more sub-boxes (each containing a set of modules) may be used to perform various cell processing workflows. Modules may be disposed in separate housings or may be integrated into a box or sub-box together with other modules. For simplicity, this disclosure generally illustrates modules as different groups of components; however, it should be noted that these modules may be arranged in any suitable configuration. For example, components for different modules may interpenetrate each other such that each module is defined by a set of connected components that commonly perform a predetermined function. However, the components of each module may or may not be physically grouped within the box. In some implementations, multiple boxes can be used to process a single cell product by transferring the cell product from one box to another box of the same or different types and / or by diverting the cell product into more boxes and / or pooling multiple cell products into fewer boxes.

[0071] Generally, each instrument within a working unit interfaces with one or more corresponding modules on a cartridge. For example, when a cartridge has an electroporation module, the cartridge is moved by a robot to the electroporation instrument within the working unit to perform electroporation on the cells within that cartridge. One advantage of this modular / instrument design is that costly components (e.g., motors, sensors, heaters, lasers, etc.) can remain in the system's instruments, while lower-cost components reside in the cartridge, which can be configured for single-use. Using disposable cartridges eliminates the need for sterilization between uses. Furthermore, having multiple instruments within a working unit further facilitates the parallel use of these instruments when using multiple cartridges within the unit. In contrast, most conventional semi-automated instruments have idle instrument components that cannot be used simultaneously in parallel.

[0072] In some implementations, the cartridge includes sterile liquid transfer ports for transferring fluid into and out of the cartridge. In some variations, the cartridge includes any number of sterile liquid transfer ports and any number or location of fluid paths between the module and the sterile liquid transfer ports.

[0073] The sterile liquid transfer port described herein can form a sterile fluid pathway between a fluid device and a cartridge and / or between a first cartridge and a second cartridge, enabling fluid transfer that can be sterile, fully automated, and precisely metered (e.g., precise control of the volume of fluid transferred). In some variations, a robot can be configured to operate the sterile liquid transfer port to open and close a set of ports and their valves to allow fluid flow between the fluid device and the cartridge and / or between the first cartridge and the second cartridge. Using a robot and controller to operate the sterile liquid transfer port facilitates automation and sterility in cell processing systems.

[0074] Additional aspects of a suitable box are provided, for example, in U.S. Patent Application Publication No. 17 / 198,134 entitled “Systems and Methods for Cell Processing”, which is incorporated herein by reference.

[0075] C. Fluid devices and systems for automated fluid transfer

[0076] Generally, the fluidic devices described herein can be configured to store fluids for automated transfer to another component (such as a cartridge, instrument, or other fluidic device) within a cell processing system. In some variations, the fluidic device for automated fluid transfer may include a portable consumable configured to be moved and manipulated within a work cell using a robot. For example, the robot may be configured to move a fluidic device within the work cell from a reagent storage area to an ISO 7 space, and then to a sterile liquid transfer instrument within the cell processing system, as described above. This fluidic device enables the automated, sterile, and metered transfer of fluids to automate cell therapy manufacturing.

[0077] Turn now Figure 3AThe diagram illustrates an exemplary variant of the fluid device 300. In some embodiments, the fluid device 300 includes a container 310 and a collar 320. The container 310 may include an opening 312 and at least one collar connection feature 303. In some variants, the opening 312 of the container 310 includes an annular seal. The collar 320 may include: one or more robotic engagement features 328; a fluid conduit 322; a sterile liquid transfer port 324; a fluid delivery feature 338 capable of engaging with the opening 312 of the container 310; at least one container connection feature 302 capable of engaging with a corresponding collar connection feature in at least one collar connection feature 303 of the container 310; at least one observation window 336; a fluid pump module 326; a plurality of ports including a sterilization port 330 and at least one air handling port 332; and (optionally) a fluid inlet port 334. In some embodiments, when container 310 is coupled to collar 320, the annular seal of opening 312 of container 310 contacts fluid delivery feature 338 and prevents leakage and / or contamination via the coupling.

[0078] In some embodiments, as described above, the container connection feature 302 can be releasably coupled to the collar connection feature 303 of the container 310. The container connection feature 302 and the collar connection feature 303 are generally designed such that the container can be interchangeably coupled to the collar 320. In this way, the collar 320 can be used with containers 310 of any size and shape. In some variations, a series of containers capable of holding a range of fluid volumes can be used. For example, the container 310 may be capable of holding about 1 ml to about 1 L, or at least about 1 ml, at least about 2 ml, at least about 3 ml, at least about 4 ml, at least about 5 ml, at least about 10 ml, at least about 15 ml, at least about 20 ml, at least about 25 ml, at least about 50 ml, at least about 100 ml, at least about 200 ml, at least about 250 ml, at least about 500 ml, and / or at least about 750 ml. In some variations, the opening 312 of the container may be connected to the fluid delivery feature 338 of the collar 320. For this purpose, the opening 312 and the fluid delivery feature 338 may be connected via a threaded interface, compression fit, press fit, friction fit, Luer fit, or another suitable connection method that allows fluid transfer between the container 310 and the collar 320 without fluid leakage and / or contamination.

[0079] In some embodiments, one or more robotic engagement features 328 of the collar 320 may be capable of being robotically engaged by a work cell to move and otherwise manipulate the fluid device 300 within the work cell. This allows for automated picking and placing of the fluid device 300 within the work cell. (Reference) Figures 4G to 4I and Figures 5J to 5L The manipulation of the fluid device 300 within the work cell is described in more detail. In some variations, one or more robotic engagement features 328 may be at least one recess and / or protrusion within or on the surface of the collar 320. In some embodiments, one or more robotic engagement features 328 of the collar 320 may also be configured or be able to be configured to allow a storage orientation different from that of the reagent magazine in the work cell. For example, one or more robotic engagement features 328 of the collar 320 may be configured to allow the fluid device 300 to be suspended, for example, in an orientation inverted from that of the reagent magazine.

[0080] In some embodiments, the fluid pump module 326 of the collar 320 may be a fluid pump configured to move fluid through the fluid conduit 322 of the collar 320. For example, the fluid pump may be a centrifugal pump or a positive displacement pump. In some variations, the fluid pump module 326 may include a compressible fluid conduit exposed to the external environment of the collar 320. The compressible fluid conduit may be coupled between an outlet port of the collar 320 that delivers fluid to the compressible fluid conduit and an inlet port of the collar 320 that returns fluid to the fluid conduit 322 of the collar 320. Specifically, the compressible fluid conduit may be located close to the outer surface of the collar 320 such that an influencer of the working unit can interact with the compressible fluid conduit to move the fluid therein. For example, the compressible fluid conduit of the collar 320 and the influencer of the working unit may constitute a peristaltic pump. After the fluid device 300 is coupled to, for example, a housing, the influencer within the working unit (which may be a cam mechanism (or the like)) may repeatedly contact the compressible fluid conduit. Repeated contact between the influencer and the compressible fluid conduit results in repeated, controlled compression of the compressible fluid conduit. Based on the influencer's direction of movement, this repeated compression pushes fluid toward the inlet port of the collar 320 and pulls fluid away from the outlet port of the collar 320, ultimately resulting in fluid transfer between the fluid device 300 and the cartridge. However, it is understood that the influencer can also operate in other ways. For example, it can be operated to allow bidirectional movement of fluid within the compressible fluid conduit, and thus bidirectional movement of fluid within the fluid conduit 322 of the collar 320. This bidirectional movement of fluid allows for the possibility of fluid outflow from the fluid device 300, such as for culture medium replenishment, and also allows fluid inflow into the fluid device 300, such as for sample collection.

[0081] In some variations, at least one viewing window 336 may be an aperture, a translucent area, and / or a transparent area, or any other type of viewpoint, providing an advantageous position for at least one segment of the fluid conduit 322 of the collar 320 and allowing assessment of fluid movement within the fluid conduit 322. In some variations, the assessment may be an optical assessment of fluid movement within the fluid conduit 322 performed by a sensor disposed on, for example, a sterile fluid transfer instrument of a work unit. For example, a sensor disposed on a sterile fluid transfer instrument of a work unit may be aligned with at least one viewing window 336 of the collar 320 and may detect a transition from air to liquid within the fluid conduit 322, thereby indicating the start of metering fluid transfer, or may detect a transition from liquid to air within the fluid conduit 322, thereby indicating the evacuation of container 310. In other variations, the assessment of fluid movement within the fluid conduit 322 may be performed by an onboard sensor configured to perform an optical, thermal, or electromagnetic assessment of the fluid conduit 322 to determine the gas-liquid interface therein.

[0082] In some embodiments, the sterile liquid transfer port 324 of the collar 320 may include at least one of a port and a valve, and may form part of a sterile fluid passage between the fluid device 300 and another fluid device and / or cartridge to enable sterile, automated, and precisely metered (e.g., precise control of the volume of fluid transferred) fluid transfer. In some variations, the sterile liquid transfer port 324 may further include a mechanical seal and / or passage for delivering a sterilizing agent within the sterile liquid transfer port 324. In some variations, the mechanical seal may be formed on the surface of the port of the sterile fluid transfer port 324 or as an assembly of the port. Individually or together, the mechanical seal and the sterilizing agent passage help ensure the sterility of the fluid transfer passage. In some variations, as will be described in more detail below, a robot of the work unit (which may be a robot of the sterile liquid transfer instrument) may be configured to operate the sterile liquid transfer port 324 to open and close its set of ports and valves to allow fluid flow between the fluid device 300 and the cartridge and / or another fluid device. Additional details regarding the sterile liquid transfer port and its various aspects are provided, for example, in U.S. Patent Application No. 17 / 331,556, now published as U.S. Patent No. 11,376,587, entitled “FluidConnector,” which is incorporated herein by reference.

[0083] In some variations, the sterilization port 330 and / or at least one air handling port 332 may include valves (e.g., actuable valves, passive valves). For example, the sterilization port 330 may be coupled to a passive valve and may deliver a sterilizing agent from a sterilizing agent source within the work unit to the sterile liquid transfer port 324 of the fluid conduit 322 and the collar 320. In one example, the sterilizing agent source may contain a sterilizing agent such as vaporized hydrogen peroxide, ionized hydrogen peroxide, chlorine dioxide, ethylene oxide, etc. As described throughout, after the sterile liquid transfer port 324 is coupled to a corresponding sterile liquid transfer port of a cartridge, another fluid device, etc., the sterilizing agent may be supplied to the sterile liquid transfer port 324 via the fluid conduit 322. In some variations, sterilizing agent may be supplied to sterile liquid transfer port 324 after actuation of the corresponding port of the connected sterile liquid transfer port (which also translates the mechanical seal away from the fluid passage), but before the corresponding valve of the connected sterile liquid transfer port is connected and fluid is pumped from fluid device 300 to a cartridge, or another fluid device, etc. In this way, sterilizing agent may also be supplied to the interface between the corresponding valves of the connected sterile liquid transfer port before fluid flow. In some variations, a fluid pump may be coupled to a sterilizing agent source and may generate a fluid signal to control the circulation of sterilizing agent in and out of sterile liquid transfer port 324 via sterilization treatment port 332. In some variations, sterilization treatment port 330 and / or at least one air treatment port 332 may be valveless. In some variations, at least one air treatment port 332 may be valved (e.g., a pinch valve) and may provide passage for air to enter or leave fluid device 300 during filling container 310 and / or depleting container 310. In some variations, at least one air handling port 332 may be connected to an air source. In some variations, the air source may include compressed air, which may be used to purge the fluid conduit 322 before and / or after fluid transfer through the fluid conduit 322 of the collar 320. In some variations, at least one air handling port 332 is connected to an in-line filter capable of preventing the introduction of contaminants into the fluid device 300 during filling and / or depleting of the container 310. In some variations, the in-line filter may be a hydrophobic filter.

[0084] In some variations, when the fluid device 300 is in certain orientations, the air handling port 332 with a valve (e.g., a pinch valve) may pose a risk of fluid (e.g., liquid) leakage from the container 310. For example, the fluid device 300 may be configured to be coupled to one or more components of the work unit 350 in various orientations. A first orientation of the fluid device 300 may be an upright orientation, where the collar 320 (and therefore the air handling port 332) is located above the container 310. A second orientation of the fluid device 300 may be an inverted orientation, where the collar 320 (and therefore the air handling port 332) is located below the container 310. When the container 310 carries liquid and the fluid device 300 is in an upright position, gravity prevents the liquid from contacting the interior of the collar 310. Conversely, when the container 310 carries liquid and the fluid device 300 is in an inverted position, gravity can cause the liquid to contact the interior of the collar 310 (e.g., its bottom inner surface and / or internal components). Additionally, in some variations, the valve of air handling port 332 (such as a pinch valve) may need to be switched from an open configuration to a closed configuration (e.g., to isolate an in-line filter), which may take several seconds (e.g., about 0.5s to about 10s, such as about 1s to about 9s, about 1.5s to about 8s, about 2s to about 7s, about 2.5s to about 6s, about 3s to about 5s, or about 3.5s to about 4s, including all ranges and subranges in between). Therefore, when the fluid device is in an inverted orientation and the valve of air handling port 332 needs to be switched from an open configuration to a closed configuration, there is a risk of liquid from container 310 leaking through the valve of air handling port 332. Such leakage may clog the in-line filter (potentially hindering or minimizing the effect of air “purge”) and may also reduce the accuracy of transfer operations and / or cause cross-contamination between subsequent fluid transfers using fluid device 300 due to residual fluid in the valve or filter. Therefore, in some cases, the air handling port 332 with a valve may include a ball valve configured to prevent fluid from traveling through the air handling port 332 and reaching the filter during operation of the fluid device 300 in an inverted orientation. The ball valve prevents fluid flow through a specific fluid passage within the valve leading to the filter, as will be referenced herein. Figures 10 to 12B A detailed explanation.

[0085] In some embodiments, the fluid conduit 322 of the collar 320 can fluidly connect each component of the collar 320 in any suitable combination, including a sterile liquid transfer port 324, a fluid inlet port 334, a fluid pump module 326, a fluid delivery feature 338, a sterilization treatment port 330, and at least one air treatment port 332, as well as a container 310. In some variations, the fluid conduit 322 can be a pipe. In some variations, the fluid conduit 322 can be a channel formed within the body of the collar 320. For example, the channel can be etched into or integrally formed with the surface of the collar 320 body, and a substrate can be coupled to the open surface of the channel to provide a fluid seal. In some variations, the channel can be formed entirely within the body of the collar 320.

[0086] In some variations, the fluid delivery feature 338 of the collar 320 includes a vent, a liquid flow tube, and a fluid port. In some variations, the fluid delivery feature 338, which can be coupled to the opening 312 of the container 310, can be shaped and sized based on the shape and size of the opening 312 of the container 310. In some variations, the vent is configured to extend through the opening 312 of the container 310 and is disposed within the container 310. The vent can extend substantially from the opening 312 into the open volume of the container 310 and can provide an air connection between the container 310 and the external environment of the fluid device 300 via the fluid conduit 322 of the collar 320. In some variations, the vent further includes a liquid vent reservoir configured to capture fluid trapped within the vent when the fluid device 300 is inverted. In some variations, the volume of the liquid vent reservoir is at least larger than the trapping volume of fluid within the vent. In this way, the venting tube and liquid vent reservoir allow the fluid device 300 to be inverted without concern for fluid leakage and / or damage to any components of the fluid device 300 (e.g., air filter). In some embodiments, the liquid flow tube of the fluid delivery feature 338 may be configured to extend through the opening 312 of the container 310 and be disposed within the container 310. The liquid flow tube may extend substantially from the opening 312 into the open volume of the container 310. The liquid flow tube may provide a liquid connection between the container 310 and the external environment of the fluid device 300. For example, the liquid flow tube may be connected to a fluid inlet port 334 and may allow the filling and / or depletion of liquid within the container 310. In some variations, the fluid port of the fluid delivery feature 338 may include an orifice within the body of the fluid delivery feature 338. The fluid port may fluidly connect the container 310 to a sterile liquid transfer port 324 and / or at least one air handling port 332 via a fluid conduit 322. When the fluid device 300 is inverted, the fluid port can be used to allow fluid to be transferred between container 310 and another fluid device or cartridge via sterile liquid transfer port 324. Similarly, when the fluid device 300 is upright, the fluid port can be used to allow fluid to flow out of container 310 and into, for example, a sample collection fluid device via fluid inlet port 334 and liquid flow tube.

[0087] In some variations, the collar 320 of the fluid device 300 further includes a pressure relief valve at the outlet port of the compressible fluid conduit near the fluid pump module 326. The outlet port may be in further fluid communication with the container 310, allowing fluid to flow into the container 310 in the event of excessive pressure at the outlet port.

[0088] In some variations, the fluid device 300 may be reusable. For example, when the fluid device 300 is used for the automated transfer of fluids associated with a single patient, the fluid device 300 may be reusable. For example, a single fluid device may be used to deliver culture medium or other reagents to a cartridge containing patient cells, and may subsequently be used to retrieve a sample of the cell solution from the cartridge for downstream analysis (such as quality control operations via, for example, a QC instrument in a work unit).

[0089] Turn now Figure 3B A schematic diagram of an exemplary system for automated fluid transfer is provided, the system including... Figure 3A Fluid device 300.

[0090] In some variations, the system 370 for automating fluid transfer includes a working unit 350 and a fluid device 300. The fluid device 300 includes a container 310 and a collar 320, as described above. For simplicity, additional redundant descriptions of the fluid device 300 will be provided only where necessary to aid in the description of the system 370. In some variations, the working unit 350 of the system 370 includes a robot 340, a controller 360, a cam 327, a sterilizing agent source 331, an air source 335, and a sensor 351. In some variations, the sensor 351 may include or otherwise utilize imaging devices utilizing visible light, ultrasound, and fluorescence and / or be configured to sense temperature, moisture, electricity, etc. The robot 340 and controller 360 may be substantially similar to those described in the references above. Figures 1A to 2D As described in working units 110 and 203. Additionally or alternatively, robot 340 and controller 360 may be provided by the sterile liquid transfer instrument of working unit 350.

[0091] In some variations, the fluid device 300 may be moved or otherwise manipulated by the robot 340 of the work unit 350 under the control of the controller 360. The instructions provided by the controller 360 may be influenced by data received from each of the collar 320, cam 327, robot 340, and sensor 351, or a combination thereof, and processed at the controller 360.

[0092] In some variations, data received by controller 360 from collar 320 of fluid device 320 may include data corresponding to the activity of fluid pump module 326, sterile liquid transfer port 324, sterilization treatment port 330, and / or at least one air handling port 332. Data received by controller 360 from cam 327 may include revolutions per minute, direction of rotation, fault detection data, etc. Such data may be used in conjunction with known characteristics of fluid conduit 322 (such as material, length, and diameter) and the compressible fluid conduit of fluid pump module 326 to determine or estimate flow rates entering and / or leaving container 310. This data may include the properties of the fluid to be transferred (e.g., viscosity). Data received by controller 360 from sensor 351 may include optical data obtained via at least one viewing window 336. Optical data may include the absorbance, reflectance, and / or fluorescence of the fluid within fluid conduit 322. Such data may be used by controller 360 to determine transitions from liquid to air and from air to liquid. Data received by the controller 360 from the robot 340 may include position data, identification data related to the affected box and / or fluid device, etc.

[0093] In some variations, where the fluid pump module 326 of the collar 320 includes components of a peristaltic pump, the controller 360 can generate a signal to the cam 327 to control fluid transfer between the fluid device 300 and another fluid device or container by controllably compressing the compressible fluid conduit of the fluid pump module 326. In some variations, the rotational speed and direction of the cam 327 can be controlled to control bidirectional flow and velocity of the fluid. For example, the relationship between the cross-sectional area of ​​the fluid conduit 322 (which may be based on the diameter of the fluid conduit 322), the length of the fluid conduit 322, the rheological properties of the fluid within the fluid conduit 322, and the rotational speed of the cam 327 can be used as a function of time to control the flow rate entering and / or leaving the container 310.

[0094] In some variations, controller 360 signals robot 340 to move and / or manipulate fluid device 300 via one or more robot engagement features 328 of collar 320. Movement and manipulation of the device may include moving fluid device 300 within work unit 350, such as between a reagent storage tank and a sterile liquid transfer instrument of work unit 350, and / or controlling the orientation of fluid device 300. For example, controller 360 may signal robot 340 to position fluid device 300 in a specific orientation, such as an upright or inverted orientation. In some variations, fluid device 300 may be configured to move when stored in a reagent storage tank (e.g., Figure 1A When the reagent storage unit 118 is in an upright orientation, the fluid device 300 may be configured to be connected to an instrument such as a sterile liquid transfer instrument (e.g., Figure 1AWhen the instrument 112 is in an inverted orientation, it transfers fluid to a cartridge that docks with the instrument (e.g., Figure 1B Box 114).

[0095] In some variations, the controller 360 generates and / or transmits additional signals to the robot 340 to manipulate the sterile liquid transfer port 324 of the collar 320 of the fluid device 300, thereby allowing sterile, automated, and precisely metered (e.g., precise control of the volume of fluid transferred) fluid transfer. For example, the signal to the robot 340 may control the configuration of at least one port of the sterile liquid transfer port 324 and a valve. In some variations, and because it involves opening a flow path between the sterile liquid transfer port 324 of the fluid device 300 and a sterile liquid transfer port of another fluid device, the controller 360 may first be configured to generate a port signal to the robot 340 to connect at least one port to a corresponding port of the sterile liquid transfer port of the other fluid device. Connecting at least one port to a corresponding port may include turning the port to an open position. Next, the controller 360 may generate a valve signal to the robot 340 to shift the valve relative to a corresponding valve of the sterile liquid transfer device of the other fluid device. To finally open the fluid passage, the controller 360 may then generate another valve signal to turn the valve and its corresponding valve to an open configuration. Following fluid transfer, a similar control signal can be generated to switch the sterile liquid transfer port 324 of the fluid device 300 to a closed configuration.

[0096] In some variations, the controller 360 may generate and / or transmit signals to the sterilization processing port 330 and / or one or more air handling ports 332 to control the flow of fluid therethrough. As noted above, the sterilization processing port 330 may be coupled to a passive valve and may be configured to facilitate the delivery of sterilizing agent from a sterilizing agent source 331 within the working unit 350 to the fluid conduit 322 and the sterile liquid transfer port 324 of the collar 320. In some variations, the working unit 350 may further include a fluid pump configured to control the inflow and outflow of sterilizing agent from the fluid device 300 based on instructions received from the controller 360. For example, after the fluid device 300 is coupled to another fluid device, but before fluid transfer begins, the sterile liquid transfer port 324 and the fluid conduit 322 may be sterilized. This sterilization may include, under the guidance of the controller 360, the flow of sterilizing agent from the sterilizing agent source 331 into and out of the sterile liquid transfer port 324 via the fluid conduit 322 through the fluid pump.

[0097] In some variations, at least one air handling port 332 is valved (e.g., a pinch valve) and provides passage for air to enter or leave the fluid device 300 during filling and / or depleting of container 310. In some variations, at least one air handling port 332 may be connected to an air source 335 of working unit 350. In some variations, air source 335 may include compressed air that can be used to purge the fluid conduit 322 before and / or after fluid transfer through collar 320. In some variations, working unit 350 may further include a fluid pump configured to control the flow of air from air source 335 into and out of fluid device 300 via at least one air handling port 332 based on instructions received from controller 360. For example, after fluid transfer between fluid device 300 and another fluid device via fluid pump module 326 of collar 320, compressed air may be delivered within fluid conduit 322 to ensure complete fluid transfer. In some variations, the air “purge” may be performed by delivering air to a fluid conduit 322 via at least one air handling port 332. In other variations, the air “purge” may be performed by delivering air through a fluid delivery feature 338 and into a container 310 via at least one air handling port 332. Compressed air may be delivered through the air handling port 332 with a force of about 0.25 psi to about 50 psi (such as about 0.5 psi to about 40 psi, about 0.75 psi to about 30 psi, about 1 psi to about 20 psi, about 2 psi to about 18 psi, about 3 psi to about 16 psi, about 4 psi to about 14 psi, about 5 psi to about 12 psi, about 6 psi to about 10 psi, about 7 psi to about 9 psi, or about 8 psi, including all ranges and subranges therein). For example, the air “purge” may be performed with a force greater than or equal to about 8 psi to clear a filter coupled to the air handling port 332. In some variations, the air “purge” can have a duration of about 1 second to about 5 minutes (such as about 1.5 seconds to about 4 minutes, about 2 seconds to about 3 minutes, about 3 seconds to about 2 minutes, about 4 seconds to about 1 minute, about 5 seconds to about 45 seconds, about 6 seconds to about 30 seconds, about 8 seconds to about 20 seconds, or about 10 seconds to about 15 seconds, including all ranges and subranges in between).

[0098] In some variations, data from each component of the work unit 350 described above can be integrated to perform automated fluid transfer. For example, controller 360 can generate and / or transmit signals to robot 340 to move, invert, and couple fluid device 300 to another fluid device or cassette via one or more robot engagement features 328. Coupled to another fluid device or cassette, fluid device 300 includes juxtaposing corresponding sterile liquid transfer ports. Each of the corresponding sterile liquid transfer ports may include a mechanical seal that is in a sealed contact state when the sterile liquid transfer port is engaged. These mechanical seals help ensure a first mechanism for achieving sterility. Controller 360 can generate and / or transmit signals to robot 340 to actuate the corresponding port of the corresponding sterile liquid transfer port to an open position. Controller 360 can then transmit signals to a fluid pump associated with sterilizing agent source 331 to circulate sterilizing agent within collar 320, and thus within the interface between sterile liquid transfer port 324 and the corresponding sterile liquid transfer port. This helps ensure the achievement of a sterile second mechanism. After the sterilizing agent is removed, the controller 360 can generate and / or transmit a signal to the robot 340 to manipulate the corresponding valve at the appropriate sterile liquid transfer port, thereby opening a fluid passage between the fluid device 300 and another fluid device. With the fluid passage open, the controller 360 can generate and / or transmit a signal to the cam 327 to begin rotation in a specific direction. When the controller 360 receives data from the sensor 351 indicating that a change from air to liquid has been detected by at least one observation window 336, the controller 360 can temporarily stop the cam 327 to determine the specific direction, speed, and duration in which the cam 327 should rotate to generate a controlled fluid flow rate within the fluid conduit 322 of the collar 320 to achieve the desired volume of transferred fluid. After the specific duration has elapsed, or when the controller 360 receives data from the sensor 351 indicating that a change from liquid to air has been detected by at least one window 336, the controller 360 can generate a signal to stop the cam 327. The controller 360 may then generate and / or transmit a signal to the fluid pump associated with the air source 335 to supply air to the fluid conduit 322, thereby purging the line and ensuring the completion of fluid transfer. After this air “purging,” the controller 360 may generate a decoupling signal, causing the robot 340 to disconnect the sterile liquid transfer port 324 of the fluid device 300 from the corresponding sterile liquid transfer port of another fluid device, and to reorient (e.g., reposition the fluid device 300 to an upright orientation) and move the fluid device 300 to another location.

[0099] Turn now Figures 4A to 4I This provides a rendered view of an exemplary fluid handling device for automated fluid transfer. Although references will be made... Figures 4A to 4IThe same reference numerals are used, but not all features will be labeled in every drawing.

[0100] In some embodiments, the fluid device 400 includes a container 410 and a collar 420. For example... Figure 4F As shown, container 410 may include an opening 412 and at least one collar-connecting feature 403. In some variations, the opening 412 of container 410 includes an annular seal. Figures 4A to 4D As shown, the collar 420 may include: one or more robotic engagement features, such as protrusions 429; a fluid conduit 422; a sterile liquid transfer port 424 having a mechanical seal 425; at least one container connection feature 402 capable of being coupled to a corresponding collar connection feature in at least one collar connection feature 403 of the container 410; at least one observation window 436; a fluid pump module 426 having a compressible fluid conduit 467; a plurality of ports including a sterilization port 430 (“9”, “10”) and at least one air handling port 432 (“5”); and a fluid inlet port 434.

[0101] In some variations, the compressible fluid conduit 457 may be connected between the outlet port 415 of the collar 420 that delivers fluid to the compressible fluid conduit 457 and the inlet port 414 of the collar 420 that returns fluid to the fluid conduit 422. For example... Figure 4A As can be seen, the compressible fluid conduit 457 can be close to the outer surface of the collar 420, allowing the influencer of the working unit to interact with the compressible fluid conduit 457 to move the fluid therein. For example, the outer surface of the collar 420 can be bent near the compressible fluid conduit 457, allowing the cam of the working unit to compress the compressible fluid conduit 457.

[0102] In some variations, and such as Figure 4BAs shown, at least one observation window 436 is an aperture that provides an advantageous position for at least one section of the fluid conduit 422 of the collar 420 and allows for optical evaluation of fluid movement within the fluid conduit 422. For example, a sensor disposed on a sterile fluid transfer instrument of the work unit can be aligned with at least one observation window 436 of the collar 420 and can detect a change from air to liquid within the fluid conduit 422, thereby indicating the start of metering fluid transfer, or can detect a change from liquid to air within the fluid conduit 422, thereby indicating the emptying of container 410. In some variations, the sensors can be bubble sensor 1 and bubble sensor 2 disposed within the collar 420. Bubble sensors 1 and 2 can be configured to detect a change from air to liquid within the fluid conduit 422, thereby indicating the start of metering fluid transfer, or can be configured to detect a change from liquid to air within the fluid conduit 422, thereby indicating the emptying of container 410.

[0103] In some variations, the sterile liquid transfer port 424 of the collar 420 may include at least one of a port 417 and a valve (not shown), and may form part of a sterile fluid passage between the fluid device 400 and another fluid device and / or cartridge to enable sterile, automated, and precisely metered (e.g., precise control of the volume of fluid transferred) fluid transfer. Figure 4A , Figure 4B and Figure 4C As shown, the sterile fluid transfer port 424 may include a mechanical seal 425. The mechanical seal 425 helps to provide sterility for the fluid transfer pathway between the fluid device 400 and another fluid device or cartridge. In some variations, a robot of the work unit (which may be a robot of a sterile fluid transfer instrument) may be configured to manipulate the fluid device 400 via a protrusion 429 and alignment feature 418 of the sterile fluid transfer port 424 to couple the fluid device 400 to another fluid device or cartridge. Additionally, the robot may be configured to operate the sterile fluid transfer port 424 to open and close a set of ports and their valves, including at least one of ports 417, to allow fluid flow between the fluid device 400 and the cartridge or another fluid device.

[0104] In some variations, and such as Figure 4A , Figure 4B and Figure 4CAs shown, the sterilization port 430 may be configured (e.g., via sterilizing agent inlet 8) to deliver a sterilizing agent (e.g., vaporized hydrogen peroxide (“VHP”) from a sterilizing agent source within the work unit to the fluid conduit 422 and the sterile liquid transfer port 424 of the collar 420. In some variations, at least one air handling port 432 may provide a pathway for air to enter or leave the fluid device 400 during filling and / or depleting of the container 410. In some variations, at least one air handling port 432 may be connected to an air source (e.g., atmospheric air). In some variations, the air source may include compressed air that can be used to purge the fluid conduit 422 before and / or after fluid transfer through the fluid conduit 422 of the collar 420 (via air purge tube 4). In some variations, at least one air handling port 432 may include an in-line filter. Thus, in some embodiments, the fluid device may advantageously include at least two sterilization means, such as, for example, via a mechanical seal 425 and via delivery of at least one sterilizing agent.

[0105] In some variations, the fluid conduit 422 of the collar 420 can fluidly connect each component of the collar 420 in any suitable combination, including a sterile liquid transfer port 424, a fluid inlet port 434, a fluid pump module 426, a fluid delivery feature 438, a sterilization port 430, and at least one air treatment port 432, as well as a container 510. This fluid conduit may include a transfer tube 6 (fluid input to the fluid pump module 426), a transfer extension 18 (fluid from the container 410), a transfer end 3 (fluid input to the sterile liquid transfer port 424), a sterilization inlet end 8 (leading to the sterile liquid transfer port 424), and a sterilization outlet end 7 (leading out from the sterile liquid transfer port 424). For example... Figures 4A to 4D As shown, fluid conduit 422 can be a pipe.

[0106] In some variations, the fluid conduit 422 of the collar 420 can be fluidly connected to the container 410 via a fluid delivery feature 438, which can be connected to the opening 412 of the container 410, such as... Figure 4E shown. Specifically, Figure 4EA fluid delivery feature 438 (“13 / 14”) is shown connected to the opening 412 of container 410 but disconnected from the remaining fluid conduit 422 of collar 420. The fluid delivery feature 438 includes a vent 442 (“15”), a liquid flow conduit 443 (“17”), and a fluid port 446 (“16”). In some embodiments, the fluid delivery feature 438, capable of engaging with the opening 412 of container 410, may be shaped and sized based on the shape and size of the opening 412 of container 410. For example, the fluid delivery feature 438 may be substantially circular and / or cylindrical. In some variations, the vent 442 is configured to extend through the opening 412 of container 410 and be disposed within container 410. The vent 442 may extend substantially from the opening 412 into the open volume of container 410 and may provide an air connection between container 410 and the external environment of fluid device 400 via the fluid conduit 422 of collar 420. In some variations, the vent 442 further includes a liquid vent reservoir configured to capture fluid trapped within the vent 442 when the fluid device 400 is inverted. In some variations, the volume of the liquid vent reservoir is at least greater than the maximum tamperable volume of fluid within the vent 442. In this way, the vent 442 and the liquid vent reservoir allow the fluid device 400 to be inverted without concern for fluid leakage and / or damage to any components of the fluid device 400 (e.g., saturation of the air filter). In some embodiments, the liquid flow conduit 443 of the fluid delivery feature 438 may be configured to extend through the opening 412 of the container 410 and be disposed within the container 410. The liquid flow conduit 443 may extend substantially from the opening 412 into the open volume of the container 410. The liquid flow conduit 443 may provide a liquid connection between the container 410 and the external environment of the fluid device 400. For example, a liquid flow tube 443 may be connected to a fluid inlet port 434 and may allow the filling and / or depletion of liquid within container 410. In some variations, a fluid port 446 of the fluid delivery feature 438 may include an orifice within the body of the fluid delivery feature 438. The fluid port 446 may fluidly connect container 410 to a sterile liquid transfer port 424 and / or at least one air handling port 432 via a fluid conduit 422. In one variation, when the fluid device 400 is inverted, the fluid port 446 may be used to allow fluid to be transferred out of container 410 via sterile liquid transfer port 424 and into another fluid device or cartridge. In another variation, when the fluid device 400 is upright, the fluid port 446 may be used to allow fluid to flow out of container 410 and into, for example, a sample collection fluid device via fluid inlet port 434 and liquid flow tube 443.

[0107] In some variations, the collar 420 of the fluid device 400 further includes a pressure relief valve (not shown) at the outlet port 415 of the compressible fluid conduit 457 near the fluid pump module 426. The outlet port 415 may be in further fluid communication with the container 410, such that fluid may flow into the container 410 when excessive pressure is present at the outlet port 415.

[0108] In some variations, the container 410 of the fluid device 400 further includes a user gripping feature 454 to allow a user to manually manipulate the container 410 and / or the fluid device 400 as needed. For example, the user gripping feature 454 allows the user to engage a snap-fit ​​between the container 410 and the collar 420.

[0109] Now for reference Figures 4G to 4I This provides an exemplary rendering of the interaction between a robot working cell and an exemplary fluid device for automated fluid transfer. Specifically, Figures 4G to 4I An exemplary gripping mechanism is provided, by which a fluid device can be manipulated by a robot of a work cell. In some variations, the robot of the work cell may be a robot of a sterile liquid transfer instrument. However, for clarity, the gripping described below will generally be performed within the work cell, where the controller (such as...) Figure 3B The controller (360°) controls the gripping.

[0110] like Figure 4G As shown, the engagement or gripping between the robot 440 of the work unit and the fluid device 400 includes a connection between at least one of the robot gripping feature 453 of the robot 440 and the robot engagement feature 428 of the fluid device 400. In some variations, the connection between the robot 440 and the fluid device 400 includes receiving at least one robot engagement feature 428 within a hole in the robot gripping feature 453. Figure 4H As shown in the middle part, at least one robot engagement feature 428 may be received within the opening 473 of the robot gripping feature 453. Figure 4I This is an illustrative rendering of a cross-sectional view of the robot gripping feature 453, showing a first gripper 474 and a second gripper 475 configured to translate relative to the opening 473. Specifically, after at least one robot engagement feature 428 of the fluid device 400 is received within the opening 473 of the robot gripping feature 453, the first gripper 474 and the second gripper 475 can translate toward the opening 473 to grip at least one robot engagement feature 428, and thus grip the fluid device 400. After the grippers 474, 475 engage with the fluid device 400 via at least one robot engagement feature 428, the robot 440 can manipulate (e.g., rotate, translate, invert) the fluid device 400 as needed according to the methods described herein.

[0111] Turn now Figures 5A to 5L This provides a rendered view of another exemplary fluid device for automated fluid transfer. Although references will be made... Figures 5A to 5L The same reference numerals are used, but not all features will be labeled in every drawing.

[0112] In some variations, the fluid device 500 includes a container 510 and a collar 520. For example... Figure 5I As shown, container 510 may include an opening 512 and at least one collar-connecting feature 503. In some variations, the opening 512 of container 510 includes an annular seal. Figures 5A to 5E As shown, the collar 420 may include: one or more robotic engagement features, such as a recess 529; a fluid conduit 522; a sterile liquid transfer port 524 having a mechanical seal 525; a fluid delivery feature 538 capable of being coupled to an opening 512 of a container 510; at least one container coupling feature 502 capable of being coupled to a corresponding collar coupling feature in at least one collar coupling feature 503 of the container 510; at least one observation window 536; a fluid pump module 526 having a compressible fluid conduit; a plurality of ports including a sterilization port 530 and at least one air handling port 532; and a fluid inlet port 534.

[0113] In some variations, a compressible fluid conduit (not shown) may be connected between the outlet port 515 of the collar 520 that delivers fluid to the compressible fluid conduit and the inlet port 514 of the collar 520 that returns fluid to the fluid conduit 522 of the collar 520.

[0114] In some variations, and such as Figure 5B As shown, at least one observation window 536 may be an aperture that provides an advantageous position for at least one section of the fluid conduit 522 of the collar 520 and allows for optical assessment of fluid movement within the fluid conduit 522. For example, a sensor disposed on a sterile liquid transfer instrument of the work unit may be aligned with at least one observation window 536 of the collar 520 and may detect a change from air to liquid within the fluid conduit 522 to indicate the start of metering fluid transfer, or may detect a change from liquid to air within the fluid conduit 522 to indicate the emptying of container 510.

[0115] In some variations, the sterile liquid transfer port 524 of the collar 520 may include at least one of a port 517 and a valve (not shown), and may form part of a sterile fluid passage between the fluid device 500 and another fluid device and / or cartridge to enable sterile, fully automated, and precisely metered (e.g., precise control of the volume of fluid transferred) fluid transfer. Figure 5A , Figure 5B and Figure 5C As shown, the sterile fluid transfer port 524 may include a mechanical seal 525. The mechanical seal 525 may help provide sterility for the fluid transfer pathway between the fluid device 500 and another fluid device or cartridge. In some variations, a robot of the work unit (which may be a robot of a sterile fluid transfer instrument) may be configured to manipulate the fluid device 500 via a recess 529 and alignment feature 518 of the sterile fluid transfer port 525 to couple the fluid device 500 to another fluid device or cartridge. Additionally, the robot may be configured to operate the sterile fluid transfer port 524 to open and close a set of ports and their valves, including at least one of the ports 517, to allow fluid flow between the fluid device 500 and the cartridge or another fluid device.

[0116] In some variations, and such as Figure 5A , Figure 5B and Figure 5C As shown, the sterilization port 530 may be configured to deliver a sterilizing agent (e.g., vaporized hydrogen peroxide (“VHP”)) from a sterilizing agent source within the work unit to the fluid conduit 522 and the sterile liquid transfer port 524 of the collar 520. In some variations, at least one air handling port 532 may provide a pathway for air to enter or leave the fluid device 500 during filling and / or depleting of the container 510. In some variations, at least one air handling port 532 may be connected to an air source (e.g., atmospheric air). In some variations, the air source may include compressed air, which may be used to purge the fluid conduit 522 before and / or after fluid transfer through the collar 520. In some variations, at least one air handling port 532 may include an in-line filter, such as filter 533. Filter 533 may be a hydrophobic filter.

[0117] When a fluid handling unit is in a certain orientation, such as during operation when the fluid handling unit is in an inverted orientation, the valved air handling port described herein may pose a risk of fluid (e.g., liquid) leakage from the container, as referenced above. Figure 3BAs explained herein, in some cases, the valved air handling port may include a ball valve configured to prevent liquid from traveling through the port and reaching the filter when the fluid device is in an inverted orientation. That is, the ball valve prevents fluid flow through a specific fluid passage within the valve leading to the filter. In some variations, the fluid device may be configured to be in an inverted (e.g., container side-up) orientation when coupled to an instrument (e.g., a sterile liquid transfer instrument) in a work unit for fluid transfer operations involving a cartridge mating with the instrument. In some variations, the ball valve may be mounted on a collar of the fluid device. Any suitable mechanism may be used to attach the ball valve to the collar, such as welding (e.g., laser welding), adhesives, fasteners, and / or the like. In some variations, the ball valve and collar may be integrated (e.g., having a single construction). Figure 10 An exemplary ball valve 1002 of this type is shown. As depicted, the ball valve 1002 may be coupled to the manifold 1004 of the fluid device collar 1000 (e.g., on its bottom inner surface).

[0118] Specifically, the ball valve described herein may include a housing having an inlet, a hollow interior, and an outlet (creating a path for fluid to flow toward a filter), and may be configured to carry a ball therein. In some variations, the housing may additionally include a top cover. The housing may be made of any suitable material, such as metal (e.g., aluminum) and / or plastic. In some variations, the housing may be made of metal (e.g., aluminum) and may be machined (with or without a fluid-carrying collar). Additionally, the housing may have any suitable geometry. For example, the housing may have one or more straight sidewalls (e.g., 1, 2, 3, 4, 5 or more straight sidewalls, such as 4 straight sidewalls) and / or one or more circular sidewalls (e.g., 1, 2, 3, 4, 5 or more straight sidewalls, such as 3 circular sidewalls). The hollow interior of the housing may have a constant or varying width, such as from about 1 mm to about 5 mm, such as from about 1.5 mm to about 4.75 mm, from about 2 mm to about 4.5 mm, from about 2.5 mm to about 4.25 mm, or from about 3 mm to about 4 mm (inclusive of all ranges and subranges therein). Furthermore, the height of the housing may be constant or varying, and may be from about 1 mm to about 20 mm, such as from about 1.5 mm to about 15 mm, from about 2 mm to about 10 mm, from about 2.5 mm to about 9 mm, or from about 3 mm to about 8 mm, from about 3.5 mm to about 7 mm, from about 4 mm to about 6 mm, or from about 4.5 mm to about 5 mm (inclusive of all ranges and subranges therein). In some variations, one or both of the inlet and outlet of the housing may extend from the surface of the housing, such as from the bottom surface of the housing. For example, one or both of the inlet and outlet may have an exterior extending from the housing and an interior cavity passing through it. The exterior of the inlet and / or outlet may be any suitable shape, such as cylindrical or rectangular. In some variations, the exterior of the inlet and / or outlet may have a constant or varying height of 1 mm to approximately 10 mm, such as approximately 1.5 mm to approximately 9 mm, approximately 2 mm to approximately 8 mm, approximately 2.5 mm to approximately 7 mm, or approximately 3 mm to approximately 6 mm, approximately 3.5 mm to approximately 5 mm, or approximately 4 mm to approximately 4.5 mm (inclusive of all ranges and subranges therebetween). Furthermore, the interior of the inlet and / or outlet may have a constant or varying width or diameter between approximately 1 mm and approximately 5 mm, such as approximately 1.5 mm to approximately 4.75 mm, approximately 2 mm to approximately 4.5 mm, approximately 2.5 mm to approximately 4.25 mm, or approximately 3 mm to approximately 4 mm (inclusive of all ranges and subranges therebetween). In some variations, a portion (e.g., at least a portion) of the interior of one or both of the inlet and outlet may be tapered. For example, the outlet may have an interior having a first portion, a second portion, and a tapered portion, the first portion having a first width or diameter, and the second portion having a second, smaller width or diameter.The first width or diameter may be between about 3 mm and about 4 mm, such as about 3.7 mm, and the second width or diameter may be between about 1 mm and about 2 mm, such as about 1.6 mm. Alternatively, the outlet may have an inner cavity having a first portion and a second portion, the first portion having a width or diameter and the second portion having a smaller width or diameter, extending directly from the first portion.

[0119] Furthermore, the ball valve housing can be configured to carry the ball within the outlet of the housing (such as within a first portion of the outlet cavity, e.g., having the maximum width or diameter). In some variations, the diameter of the ball may be approximately equal to or smaller than the first width or diameter of the first portion of the outlet cavity, and approximately equal to or larger than the second width or diameter of a second (e.g., lower) portion of the cavity. Thus, the ball can be configured to be positioned between the first and second portions of the outlet cavity when the fluid device is in an inverted orientation, thereby partially (e.g., at least partially) blocking fluid flow through the outlet cavity (and thus preventing fluid leakage onto the in-line filter). Additionally, the ball can be made of any suitable material, such as metal, plastic, or rubber (e.g., silicone).

[0120] In some variations, the housing may further include a ball stop to hold the ball in position within the outlet lumen when the fluid device is in an upright (e.g., container side-down) orientation. The ball stop may be shaped to allow fluid flow through the outlet lumen when the fluid device is in both upright and inverted orientations, while preventing movement of the ball within the hollow interior of the housing. Specifically, the ball stop may include one or more conduits, such as multiple conduits, extending through the ball stop to allow airflow around the ball when the fluid device is in an inverted orientation, thereby allowing an air “purge” process during operation when the fluid device is inverted. The multiple conduits of the ball stop may include 2, 3, 4, 5, or more than 5 fluid conduits. In some variations, the ball stop may have multiple legs, such as 2, 3, 4, 5, or more than 5 legs, and one or more of the legs (e.g., each leg) may include a conduit extending therethrough. The legs may have a length approximately equal to or less than half the radius or width of the outlet lumen. In some variations, the ball stop can be configured to press-fit into the outlet cavity.

[0121] Figure 11A and Figure 11B A variation of the ball valve 1100 is shown in more detail. Figure 11A In the image, the transparent view of ball valve 1100 is depicted in an inverted orientation. Figure 11B In the exploded view of ball valve 1100, it is depicted with an inverted orientation. (See diagram below.) Figure 11A and Figure 11BAs shown, the housing 1102 of the ball valve 1100 includes a top cover 1104, an inlet 1106, a hollow interior 1108, an outlet 1110, a ball stop 1112, and a ball 1114. The ball stop 1112 includes a plurality of conduits 1213, such as three conduits extending through the ball stop 1112. Figure 11A As shown, in the inverted orientation state, ball 1114 is located between the first part 1116 and the second part 1118 of outlet 1110, because the inner diameter of the first part 1116 is larger than the inner diameter of the second part 1118.

[0122] Similarly, Figure 12A An illustration shows the fluid flow path through the ball valve 1200 when the fluid device 1220 with the ball valve 1200 is in the inverted position. As shown, in the inverted position, the container 1222 of the fluid device 1220 is positioned above the collar 1224 of the fluid device 1220. In this position, fluid (e.g., a liquid) can flow through the inlet 1206 of the housing 1202, the hollow interior 1208, and the ball stop 1212 (e.g., via its conduit 1213). However, the ball 1214 prevents fluid from leaving the outlet 1210, thereby preventing fluid leakage to the filter or other components coupled to the outlet 1210. Conversely, Figure 12B The diagram illustrates the fluid flow path through the ball valve 1200 when the fluid device 1220 is in the upright position. As shown, in the upright position, the container 1222 of the fluid device 1220 is located below the collar 1224 of the fluid device 1220. In this position, fluid (e.g., liquid) can flow through the inlet 1206 of the housing 1202, the hollow interior 1208, and the ball stop 1212 (e.g., via its conduit 1213). Additionally, because the ball 1210 is positioned on the ball stop 1212, fluid (e.g., air) can exit through the outlet 1210.

[0123] Back Figures 5A to 5L In some variations, the fluid conduit 522 of the collar 520 can fluidly connect each component of the collar 520 in any suitable combination, including a sterile liquid transfer port 524, a fluid inlet port 534, a fluid pump module 526, a fluid delivery feature 538, a sterilization port 530, and at least one air handling port 532, as well as the container 510. Figure 5D (A cross-sectional view of the main body of the collar 520 is provided) and Figure 5E(A plan view of the bottom of the collar 520 is shown.) As illustrated, the fluid conduit 522 can be a channel 563 formed within the body of the collar 520. For example, the channel 563 can be etched into the surface of the body of the collar 520, and a substrate 562 can be coupled to the open surface of the channel 563 to provide a fluid seal. The channel 563 can be in any combination to fluidly connect each component of the collar 520 within the collar 520 and to the container 510.

[0124] For example, such as Figure 5D and Figure 5E As shown, the fluid conduit 522 can form a three-dimensional network of channels 563, allowing fluid to move within, enter, and exit the collar 520 while maintaining feasible form factors and simplicity of user interaction. Channel 563 includes: a sterilization process channel 566 connected to at least one sterilization processing port 530 and a sterile liquid transfer port 524; a venting channel 564 connected to a venting tube (e.g., venting tube 542); an air handling channel 565 connected to at least one air handling port 532, the volume of container 510, and the sterile liquid transfer port 524; a pressure relief channel 567 connected to, for example, a fluid pump module 526 and the volume of container 510; a user fluid channel 568 connected to a fluid inlet port 534 and the volume of container 510; and a delivery fluid channel 569 connected to the volume of container 510 and the sterile liquid transfer port 524 and configured to enable automated fluid transfer between fluid devices.

[0125] In some variations, the fluid delivery feature 538 of the collar 520 includes a vent 542, a liquid flow line 546, a fluid port 543, a pressure relief port 548, and an annular seal 539. In some embodiments, the fluid delivery feature 538, which can be threadedly connected to the opening 512 of the container 510, can be shaped and sized based on the shape and size of the opening 512 of the container 510. For example, the fluid delivery feature 538 can be substantially circular and / or cylindrical. Furthermore, in addition to the annular seal of the opening 512 of the container 510, the annular seal 539 of the fluid delivery feature 538 can minimize (if not eliminate) fluid leakage and the resulting potential contamination.

[0126] In some variations, the vent 542 is configured to extend through the opening 512 of the container 510 and be disposed within the container 510. The vent 542 may extend substantially from the opening 512 into the open volume of the container 510 and may provide an air connection between the container 510 and the external environment of the fluid device 500 via a fluid conduit 522 of the collar 520. In some variations, the vent 542 further includes a vent reservoir 544 configured to capture fluid trapped within the vent 542 when the fluid device 500 is inverted. In some variations, the volume of the vent reservoir 544 is at least greater than the maximum entrapment volume of fluid within the vent 542. In this way, the vent 542 and the vent reservoir 544 allow the fluid device 500 to be inverted without concern for fluid leakage and / or damage to any components of the fluid device 500, such as an air filter. Additional rendering of vent pipe 542 and its various aspects. Figure 5G and Figure 5H As shown in the diagram. In some embodiments, the vent 542 includes a vent reservoir 544, a vent deflector 545, and a tube extending from the vent reservoir 544. When the fluid device 500 is inverted, the fluid volume trapped within the vent 542 flows toward the vent deflector 545, while air (indicated by the green arrow) flows in the opposite direction. Figure 5H As shown, fluid flowing toward the vent deflector 545 contacts the vent deflector 545 and is deflected to the side away from the orifice of the vent deflector 545, and enters the vent reservoir 544's entrapment space. In this way, the vent 542 of the fluid delivery feature 538 of the collar 520 of this disclosure prevents blockage of the vent 542 and / or the air filter otherwise connected to the fluid conduit 522, and thus allows air to backfill the container 510 during fluid transfer.

[0127] In some variations and return to Figure 5A , Figure 5B and Figure 5F The liquid flow tube 546 of the fluid delivery feature 538 may be configured to extend through the opening 512 of the container 510 and be disposed within the container 510. The liquid flow tube 546 may extend substantially from the opening 512 into the open volume of the container 510. The liquid flow tube 546 may provide a liquid connection between the container 510 and the external environment of the fluid device 500. For example, the liquid flow tube 546 may be connected to the fluid inlet port 534 and may allow the filling and / or depletion of liquid within the container 510.

[0128] In some variations, the fluid port 543 of the fluid delivery feature 538 may include an aperture within the body of the fluid delivery feature 538. The fluid port 543 may fluidly connect the container 510 to a sterile liquid transfer port 524 and / or at least one air handling port 532 via a fluid conduit 522. In one variation, when the fluid device 500 is inverted, the fluid port 543 may be used to allow fluid to be transferred out of the container 510 via the sterile liquid transfer port 524 and into another fluid device or cartridge. In another variation, when the fluid device 500 is upright, the fluid port 543 may be used to allow fluid to flow out of the container 510 and into, for example, a sample collection fluid device via a fluid inlet port 534 and a liquid flow tube 546.

[0129] In some variations, the collar 520 of the fluid device 500 further includes a pressure relief valve at the outlet port 515 of the compressible fluid conduit near the fluid pump module 526. The outlet port 515 may be further fluidly connected to the container 510 via a pressure relief valve 548, allowing fluid to flow into the container 510 when excessive pressure is present at the outlet port 515.

[0130] In some variations, the container 510 of the fluid device 500 further includes a user gripping feature 554 to allow a user to manually manipulate the container 510 and / or the fluid device 500 as needed. For example, the user gripping feature 554 allows the user to engage a snap-fit ​​between the container 510 and the collar 520.

[0131] Now for reference Figures 5J to 5L This provides an exemplary rendering of the interaction between a robot working cell and an exemplary fluid device for automated fluid transfer. Specifically, Figures 5J to 5L An exemplary gripping mechanism is provided, by which a fluid device can be manipulated by a robot of a work cell. In some variations, the robot of the work cell may be a robot of a sterile liquid transfer instrument. However, for clarity, the gripping described below will generally be performed within the work cell, where the controller (such as...) Figure 3B The controller (360°) controls the gripping.

[0132] like Figure 5J As shown, the engagement or gripping between the robot 540 of the work unit and the fluid device 500 includes the robot gripping feature 553 of the robot 540 and the robot engagement feature of the fluid device 500 (composed of...). Figure 5AThe connection between at least one robot engagement feature (indicated by reference numeral 529 in the accompanying drawings), wherein the robot engagement feature is a recess, opening, etc., is a joint between the robot 540 and the fluid device 500. In some variations, the connection between the robot 540 and the fluid device 500 includes sliding contact between the first gripper 574 and the second gripper 575 of the robot gripping feature 553 within corresponding robot engagement features, such as... Figure 5K and Figure 5L This is better illustrated in the text. Specifically, as shown in the image. Figure 5K As shown, a first engagement position of grippers 574, 575 and corresponding robot engagement features 528 is illustrated. In the first engagement position, the first gripper 574 and the second gripper 575 enter the opening defined by the corresponding robot engagement feature 528. After insertion into the respective opening, the first gripper 574 and the second gripper 575 can translate in opposite directions toward a second engagement position, thereby engaging the grippers 574, 575 with the surface of the corresponding robot engagement feature 528 and gripping the fluid device 500. After the grippers 574, 575 engage with the fluid device 500 via at least one robot engagement feature 528, as... Figure 5L As shown, robot 540 can manipulate (e.g., rotate, translate, invert) fluid device 500 as needed according to the methods described herein.

[0133] II. Automated Fluid Transfer Methods

[0134] This article also describes methods for fluid transfer, such as automated fluid transfer within a cell processing system.

[0135] First, refer to Figure 6 Method 600 describes a framework for automating fluid transfer.

[0136] Method 600 may include, firstly, at step 602, connecting a sterile liquid transfer port of a fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. The connection may include movement and / or manipulation of the fluid device by a robot relative to the other fluid device or cartridge. For example, alignment features of the sterile liquid transfer port may be used by the robot to align and connect the sterile liquid transfer port. In some variations, the robot may move and manipulate the fluid device relative to a sterile liquid transfer instrument of a work unit (where another fluid device or cartridge is connected).

[0137] Initially, the corresponding port of the sterile liquid transfer port can be in a closed configuration, wherein a mechanical seal disposed on the surface of the corresponding port provides a primary seal. At step 604, the robot can actuate the corresponding port of the sterile liquid transfer port to the open position.

[0138] At step 606, the sterilizing agent may flow into the sterile liquid transfer port of the fluid device via a fluid conduit. Specifically, the sterilizing agent source of the working unit may be connected to the sterilization treatment port of the collar of the fluid device, and the sterilizing agent may circulate within the fluid conduit and the sterile liquid transfer port. In some variations, the sterilizing agent may circulate within the fluid conduit of the fluid device and within the interface formed by the corresponding port of the connected sterile liquid transfer port, which is actuated to the open position at step 604. In some variations, the sterilizing agent may circulate within the fluid conduit and the sterile liquid transfer port for a residence time of up to about 10 minutes, or about 1 minute to about 10 minutes, about 2 minutes to about 9 minutes, about 3 minutes to about 8 minutes, about 4 minutes to about 7 minutes, and about 5 minutes to about 6 minutes (inclusive of all ranges and sub-values). In some variations, the sterilizing agent may include vaporized hydrogen peroxide at concentrations between about 50% and about 70%, between about 55% and about 65%, between about 56% and about 64%, between about 57% and about 63%, between about 58% and about 62%, and between about 59% and about 61% (inclusive of all ranges and sub-values ​​therebetween).

[0139] Generally speaking, sterilization of sterile liquid transfer ports may include one or more steps of dehumidification, conditioning, purification, sterilization (using a sterilizing agent) and ventilation (e.g., air circulation).

[0140] In some variations, step 606 may further include dehumidifying the sterile liquid transfer port of the sterile liquid transfer device. For example, pressurized hot air may optionally be circulated within the sterile liquid transfer port via at least one air handling port to remove residual fluid, moisture, and raise the temperature of the inner surface of the sterile liquid transfer port.

[0141] At step 608, the robot can actuate a valve within a sterile liquid transfer port. Actuation of the valve within the sterile liquid transfer port shifts the fluid passage between them to an open position. In some variations, the valves can be translated relative to each other. Step 608 may include translating a valve of a sterile liquid transfer port of a fluid device relative to a valve of a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, the valve may include a spring-loaded shut-off valve configured to actuate to an open position upon contact with an opposing valve, thereby allowing fluid communication between the sterile liquid transfer ports. In some variations, each valve in the valves may include a corresponding engagement feature, such as a thread, configured to facilitate engagement between the valves. For example, once a valve of a sterile liquid transfer port of a fluid device is translated to contact a valve of a corresponding sterile liquid transfer device of another fluid device or cartridge, the engagement feature of the valve can be engaged (e.g., locked) by rotating (e.g., twisting) one of the valves to engage its respective threads with each other. Conversely, one of the valves can be rotated in the opposite direction to disengage (e.g., unlock).

[0142] After the valve is turned to the open position to enable fluid transfer between sterile fluid transfer ports, fluid transfer can begin at step 610. For example, the contents (e.g., fluid, biological material) of a fluid device and another fluid device or cartridge can be transferred through the sterile fluid transfer port. The rate and direction of fluid transfer can be determined by the fluid conduit, the fluid pump module of the fluid device's collar, and the corresponding cam of the working unit that communicates with the controller of the working unit.

[0143] After the desired volume of fluid has been transferred, the fluid conduit and sterile liquid transfer port may be purged at step 612. In some variations, compressed air may be supplied to the fluid conduit and sterile liquid transfer port via at least one air handling port of the fluid device's collar. By purging the fluid conduit and sterile liquid transfer port, method 600 ensures that the entire desired volume of fluid has been transferred.

[0144] To initiate the separation of the sterile fluid transfer ports at step 614, the valves may be translated away from each other. In some variations, the robot may be configured to manipulate the sterile fluid transfer ports to turn the valves to the closed position and / or translate the valves away from each other, which may occur simultaneously or independently. The valves in the closed position prevent fluid flow through the sterile fluid transfer ports. Subsequently, the robot may be configured to turn the ports of the sterile fluid transfer ports to the closed position. Therefore, at step 616, the fluid passage between the sterile fluid transfer ports is closed, and the sterile fluid transfer ports can be separated.

[0145] Additional details regarding the sterile liquid transfer port and its various aspects are provided, for example, in U.S. Patent Application No. 17 / 331,556 entitled “Fluid Connector,” which is incorporated herein by reference.

[0146] Now for reference Figure 7A , Figure 7B , Figure 7C , Figure 7D , Figure 7E and Figure 7F The following will describe flowcharts illustrating exemplary variations of methods for automated fluid transfer. It should be understood that combinations of the methods described below are also possible without departing from the spirit of this disclosure. Furthermore, it should be understood that each of the methods described below can be implemented in conjunction with, in place of, or independently of the sterile fluid transfer instrument of the work unit, by the controller of the work unit and the sterile fluid transfer instrument of the work unit.

[0147] Figure 7AThis is a flowchart of an exemplary method 700A for automating fluid transfer, in which fluid is transferred from one fluid device to another or to a cartridge. Such fluid transfer may be necessary for supplying culture medium, for example, to a cartridge containing a bioreactor module.

[0148] Initially, method 700A provides a fluid device pre-filled with fluid. The fluid device may be filled by a user inside a biosafety cabinet outside the work unit, for example, or by a commercial fluid supplier. At step 705 of method 700A, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 710, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within the work unit and / or within the sterile liquid transfer instrument of the work unit. Connecting the sterile liquid transfer port may include ports and valves actuated by the robot, as referenced above. Figure 6 As described. At step 715, fluid can be transferred from one fluid device to another fluid device or cartridge. Specifically, the cam of the working unit can be configured to engage the fluid pump module of the fluid device to control the movement of fluid flowing out of the fluid device and into another fluid device or cartridge via a sterile liquid transfer port.

[0149] Figure 7B This is a flowchart of an exemplary method 700B for automating fluid transfer, in which fluid is transferred from one fluid device to another or a cartridge. Such fluid transfer may be necessary for supplying culture medium, for example, to a cartridge containing a bioreactor module.

[0150] Initially, method 700B provides a fluid device pre-filled with fluid. The fluid device may be filled by a user inside a biosafety cabinet outside the work unit, for example, or by a commercial fluid supplier. At step 705 of method 700B, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 710, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within the work unit and / or within the sterile liquid transfer instrument of the work unit. Connecting the sterile liquid transfer port may include ports and valves actuated by the robot, as referenced above. Figure 6As described. At step 715, fluid can be transferred from one fluid device to another fluid device or cartridge. Specifically, the cam of the working unit can be configured to engage the fluid pump module of the fluid device to control the movement of fluid flowing out of the fluid device and into another fluid device or cartridge via a sterile liquid transfer port. At step 725, after the fluid transfer via the fluid pump module of the fluid device, compressed air can be supplied to the fluid conduit and sterile liquid transfer port of the fluid device to purge the collar of the fluid to be transferred.

[0151] Figure 7C This is a flowchart of an exemplary method 700C for automating fluid transfer, in which fluid is transferred from one fluid device to another or a cartridge. Such fluid transfer may be necessary for supplying culture medium, for example, to a cartridge containing a bioreactor module.

[0152] Initially, method 700C provides a fluid device pre-filled with fluid. The fluid device may be filled by a user inside a biosafety cabinet outside the work unit, for example, or by a commercial fluid supplier. At step 705 of method 700C, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 710, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within the work unit and / or within the sterile liquid transfer instrument of the work unit. In some variations, the connection includes actuating a corresponding port of the connected sterile liquid transfer port, each corresponding port including a corresponding mechanical seal. At step 711, and before the valve of the connected sterile liquid transfer port is actuated by the robot, sterilizing agent from a sterilizing agent source within the work unit may circulate within the sterile liquid transfer port and fluid conduit of the fluid device via a sterilization processing port of the fluid device. In some variations, circulation may include allowing the sterilizing agent to flow within an interface formed by the actuation port of the connected sterile liquid transfer port. After circulation and removal of the sterilizing agent from the sterile liquid transfer port and fluid conduit of the fluid device, an automated fluid transfer from one fluid device to another fluid device or cartridge may be performed at step 715 of method 700C. Specifically, a cam of the working unit may be configured to engage the fluid pump module of the fluid device to control the movement of fluid flowing out of the fluid device via the sterile liquid transfer port and into another fluid device or cartridge.

[0153] Figure 7D This is a flowchart of an exemplary method 700D for automated fluid transfer, in which fluid is transferred from another fluid device or cartridge to another fluid device. Such fluid transfer may be necessary for obtaining cell solution samples for in-process testing, obtaining waste liquid for disposal, etc.

[0154] Initially, method 700D provides an empty fluid device. At step 705 of method 700D, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 710, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within a work unit and / or within a sterile liquid transfer instrument of the work unit. In some variations, the connection includes actuating a corresponding port of the connected sterile liquid transfer port, each corresponding port including a corresponding mechanical seal. At step 711, and before the valve of the connected sterile liquid transfer port is actuated by the robot, sterilizing agent from a sterilizing agent source within the work unit may circulate within the sterile liquid transfer port and fluid conduit of the fluid device via a sterilization processing port of the fluid device. In some variations, circulation may include allowing the sterilizing agent to flow within an interface formed by the actuation port of the connected sterile liquid transfer port. After circulating and removing the sterilizing agent from the sterile liquid transfer port and fluid conduit of the fluid device, an automated fluid transfer from another fluid device or cartridge to the fluid device can be performed at step 716 of method 700C. Specifically, the cam of the working unit can be configured to engage the fluid pump module of the fluid device to control the movement of fluid from another fluid device or cartridge into the fluid device via the sterile liquid transfer port.

[0155] In some variations, method 700D may be performed after 700A, 700B, 700C and / or 700E (described below), wherein fluid transferred from one fluid device to another fluid device or cartridge and fluid transferred from another fluid device or cartridge to another fluid device are associated with the same patient.

[0156] Figure 7E This is a flowchart of an exemplary method 700E for automated fluid transfer, in which a fluid device is filled with fluid, and the fluid is subsequently transferred from one fluid device to another fluid device or cartridge. Such fluid transfer may be necessary for supplying culture medium, for example, to a cartridge containing a bioreactor module. Furthermore, after the fluid transfer, the fluid device may be purged to ensure complete fluid transfer.

[0157] Initially, method 700E provides an empty fluid device. At step 701, the fluid device may be filled with fluid to be transferred to another fluid device or cartridge. The fluid device may be filled via, for example, a fluid inlet port of a collar of the fluid device. Filling may occur before or after the fluid device is introduced into the work unit. The amount of fluid filled may be based on a predetermined volume required by the other fluid device or cartridge. After filling, at step 705, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 710, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within the work unit and / or within the sterile liquid transfer instrument of the work unit. In some variations, the connection includes actuating a corresponding port of the connected sterile liquid transfer port, each of the corresponding ports including a corresponding mechanical seal. At step 711, and before the valve of the connected sterile liquid transfer port is actuated by the robot, sterilizing agent from a sterilizing agent source within the working unit may circulate within the sterile liquid transfer port and fluid conduit of the fluid device via the sterilization treatment port of the fluid device. In some variations, circulation may include allowing the sterilizing agent to flow within an interface formed by the actuation port of the connected sterile liquid transfer port. After circulation and removal of the sterilizing agent from the sterile liquid transfer port and fluid conduit of the fluid device, an automated fluid transfer from the fluid device to another fluid device or cartridge may be performed at step 715 of method 700E. Specifically, a cam of the working unit may be configured to engage the fluid pump module of the fluid device to control the movement of fluid flowing out of the fluid device via the sterile liquid transfer port and into another fluid device or cartridge. At step 725, after the fluid transfer via the fluid pump module of the fluid device, compressed air may be supplied to the fluid conduit and sterile liquid transfer port of the fluid device to purge the collar of the fluid to be transferred.

[0158] Figure 7F This is a flowchart of an exemplary method 700F for automated fluid transfer, in which the fluid device is initially empty and fluid is transferred from another fluid device or cartridge to the fluid device. Such fluid transfer may be necessary for obtaining cell solution samples for in-process testing, obtaining waste liquid for disposal, etc. Furthermore, after fluid transfer, the fluid device can be purged to ensure complete fluid transfer.

[0159] Initially, method 700F provides an empty fluid device. At step 705, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 710, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within a work unit and / or within a sterile liquid transfer instrument of the work unit. In some variations, the connection includes actuating a corresponding port of the connected sterile liquid transfer port, each of the corresponding ports including a corresponding mechanical seal. At step 711, and before the valve of the connected sterile liquid transfer port is actuated by the robot, sterilizing agent from a sterilizing agent source within the work unit may circulate within the sterile liquid transfer port and fluid conduit of the fluid device via a sterilization processing port of the fluid device. In some variations, circulation may include allowing the sterilizing agent to flow within an interface formed by the actuation port of the connected sterile liquid transfer port. After circulating and removing the sterilizing agent from the sterile liquid transfer port and fluid conduit of the fluid device, an automated fluid transfer from one fluid device or cartridge to another fluid device or cartridge can be performed at step 715 of method 700E. Specifically, a cam of the working unit can be configured to engage the fluid pump module of the fluid device to control the movement of fluid from another fluid device or cartridge into the fluid device via the sterile liquid transfer port. At step 725, after the fluid transfer via the fluid pump module of the fluid device, compressed air can be supplied to the fluid conduit and sterile liquid transfer port of the fluid device to purge the collar of the fluid to be transferred.

[0160] In some variations, method 700F may further include infusing air into the container of the fluid device after the fluid transfer, so as to force the transferred fluid out of the fluid device via a fluid inlet port, such as a collar of the fluid device. This subsequent transfer of fluid from the fluid device can be performed when the fluid device is in any orientation (such as an upright position).

[0161] In some variations, the exemplary method of automated fluid transfer described herein further includes controlling fluid movement within the fluid device using at least one observation window of the fluid device's collar, as well as sensors and controllers of the working unit. In this way, the flow rate of the fluid transfer can be controlled such that a known volume of fluid is transferred into and from the fluid device.

[0162] therefore, Figure 8 and Figure 9 The flowcharts are other exemplary variations of methods for automating fluid transfer, where a target transfer volume and data from sensors are used to control the fluid transfer. It should be understood that each method described below can be controlled by a controller of the work unit, either in conjunction with or independently of the work unit's sterile fluid transfer instrument.

[0163] First refer to Figure 8 Method 800 relates to automated fluid transfer at a controlled rate when substantially all contents of a fluid device are to be transferred.

[0164] Initially, method 800 provides an empty fluid device. At step 801, the fluid device may be filled with fluid to be transferred to another fluid device or cartridge. Filling may occur before or after the fluid device is introduced into the work unit. The amount of fluid filled may be based on a predetermined volume required by the other fluid device or cartridge. After filling, at step 805, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 810, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within the work unit and / or within the sterile liquid transfer instrument of the work unit. In some variations, the connection includes actuating a corresponding port of the connected sterile liquid transfer port, each of the corresponding ports including a corresponding mechanical seal. At step 811, and before the valve of the connected sterile liquid transfer port is actuated by the robot, sterilizing agent from a sterilizing agent source within the work unit may circulate within the sterile liquid transfer port and fluid conduit of the fluid device via a sterilization processing port of the fluid device. In some variations, circulation may include allowing the sterilizing agent to flow within an interface formed by an actuation port of a connected sterile liquid transfer port. After circulation and removal of the sterilizing agent from the sterile liquid transfer port and fluid conduit of the fluid device, automated fluid transfer from one fluid device to another fluid device or cartridge can be initiated. Specifically, a cam of the working unit may be configured to engage the fluid pump module of the fluid device to initiate the movement of fluid within the fluid device. At step 813, data may be received by a controller from a sensor at least one viewing window near the collar of the fluid device. As previously described, at least one viewing window may have an advantageous position over at least one section of the fluid conduit of the collar of the fluid device. The data received from the sensor may be processed at step 814 to detect when a fluid transition from air to liquid occurs within the visible section of the fluid conduit. When this transition is detected, and as long as the liquid remains detected by the sensor, the fluid pump module and the cam may operate in a manner that transfers fluid from one fluid device to another fluid device or cartridge at a controlled flow rate. For example, the cam may operate at a speed of 60 revolutions per minute. Taking into account the cross-sectional area and length of the fluid conduit and the rheological properties of the fluid, the rotational speed of the cam can correspond to a fluid transfer rate of 100 mL per minute. At step 816, data received from the sensor can indicate another fluid transition, this time from liquid to air. When a liquid-to-air transition is detected, it can be assumed that the container of the fluid device is empty. Therefore, at step 817, the fluid pump module and the cam can be stopped. In some variations, as described above... Figure 7B , Figure 7E and Figure 7F As described, after fluid pumping is stopped at step 817, compressed air may be supplied to the fluid conduit and sterile liquid transfer port of the fluid device to purge the collar of the fluid to be transferred.

[0165] Now for reference Figure 9 Method 900 relates to automated fluid transfer at a controlled rate and when the target volume to be transferred is smaller than the fluid volume within the fluid device.

[0166] Initially, method 900 provides an empty fluid device. At step 901, the fluid device may be filled with fluid. Filling may occur before or after introducing the fluid device into the work unit. The amount of fluid filled may be based on a target volume required by another fluid device or cartridge. For example, the volume of fluid filled may be larger than the target volume to be transferred to another fluid device or cartridge, thereby ensuring that sufficient volume is transferred even if a certain volume of fluid is trapped within the fluid device. After filling, at step 905, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement features. At step 910, the robot may connect a sterile liquid transfer port of the fluid device to a corresponding sterile liquid transfer port of another fluid device or cartridge. In some variations, this connection may be made within the work unit and / or within the sterile liquid transfer instrument of the work unit. In some variations, the connection includes actuating a corresponding port of the connected sterile liquid transfer port, each of the corresponding ports including a corresponding mechanical seal. At step 911, and before the valve of the connected sterile liquid transfer port is actuated by the robot, sterilizing agent from a sterilizing agent source within the working unit may circulate within the sterile liquid transfer port and fluid conduit of the fluid device via the sterilization processing port of the fluid device. In some variations, circulation may include allowing the sterilizing agent to flow within an interface formed by the actuation port of the connected sterile liquid transfer port. After circulation and removal of the sterilizing agent from the sterile liquid transfer port and fluid conduit of the fluid device, automated fluid transfer from the fluid device to another fluid device or cartridge may begin. Specifically, a cam of the working unit may be configured to engage the fluid pump module of the fluid device to initiate the movement of fluid within the fluid device. Simultaneously or separately from step 911, at step 912, the target volume or predetermined volume to be transferred may be obtained by the controller of the working unit. After activating the fluid pump module and cam to initiate the movement of fluid within the fluid conduit of the fluid device, at step 913, data may be received by the controller from a sensor at least one viewing window near the collar of the fluid device. As previously described, at least one observation window may have an advantageous position over at least one section of the fluid conduit of the fluid device's collar. Data received from the sensor may be processed at step 914 to detect when a fluid transition from air to liquid occurs within the visible section of the fluid conduit. When the transition is detected, the fluid pump module and cam may operate to transfer fluid from one fluid device to another fluid device or cartridge at a controlled fluid rate and for a controlled duration, such that the volume transferred is equal to the target volume received at step 912. For example, the cam may operate at a specific rotational speed for a specific duration based on the target volume, the dimensions of the fluid conduit, and the rheological properties of the fluid. A temporary stop of the fluid pump module and cam may also occur before step 915 to ensure the accuracy and precision of the metered fluid transfer. After the specific duration has elapsed, the fluid pump module and cam may stop at step 917.In some variations, as mentioned above. Figure 7B , Figure 7E and Figure 7F As described, after fluid pumping is stopped at step 917, compressed air may be supplied to the fluid conduit and sterile liquid transfer port of the fluid device to purge the collar of the fluid to be transferred.

[0167] All references cited in this article are incorporated herein by reference.

[0168] Throughout this application, the term "about" is used to indicate a value that includes inherent error variations in the apparatus or method used to determine that value, or variations present in the sample being measured. Unless otherwise stated or otherwise apparent from the context, the term "about" means within 10% of the reported value (unless the value would exceed 100% of the possible value or be less than 0%). When used in conjunction with a range or series of values, the term "about" applies to the endpoints of the range or each value listed in the series, unless otherwise stated. As used in this application, the terms "about" and "approximately" are used as equivalents.

[0169] While embodiments of the invention have been shown and described herein, those skilled in the art will understand that such embodiments are provided by way of example only. Many variations, modifications, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in carrying out the invention. The following claims are intended to define the scope of the invention, and the methods and structures within the scope of these claims, as well as their equivalents, are thereby covered.

Claims

1. A fluid device for use in automated fluid transfer, the fluid device comprising: A container for a given volume of fluid; and Universal collar, the universal collar being capable of being coupled to the container, the collar comprising... Multiple catheters, A sterile liquid transfer port, which is in fluid communication with the plurality of catheters, and A fluid pump module includes a compressible fluid conduit connected between an inlet port and an outlet port, each of the inlet port and the outlet port being in fluid communication with the plurality of conduits, the compressible fluid conduit being configured to be compressed by the fluid pump to control the movement of fluid flowing out of the container.

2. The fluid device according to claim 1, wherein the collar further comprises a robotic engagement feature.

3. The fluid device according to claim 2, wherein the robot engagement feature is capable of being engaged by a robot to manipulate the fluid device.

4. The fluid device of claim 1, wherein the robot engagement feature comprises one or more recesses and / or protrusions located within the surface of the collar.

5. The fluid device according to claim 1, wherein the collar is releasably connected to the container via corresponding features provided on the collar and the container.

6. The fluid device of claim 1, wherein the fluid capacity of the container is in the range of about 1 ml to about 1 liter.

7. The fluid apparatus of claim 1, wherein the control of the movement of the fluid includes bidirectional movement control.

8. The fluid device of claim 1, wherein the collar further comprises one or more sterilization ports in fluid communication with the plurality of conduits.

9. The fluid device of claim 8, wherein the sterilizing agent provided via the one or more sterilization ports comprises one or more of vaporized hydrogen peroxide, ionized hydrogen peroxide, chlorine dioxide, and ethylene oxide.

10. The fluid device of claim 8, wherein the one or more sterilization ports are valved.

11. The fluid device of claim 8, wherein the one or more sterilization ports are connected to one or more passive valves.

12. The fluid device of claim 1, wherein the collar further comprises one or more air handling ports in fluid communication with the plurality of conduits.

13. The fluid device of claim 12, wherein the one or more air handling ports are compressed air handling ports.

14. The fluid device of claim 1, wherein the collar further comprises a valve for preventing air from being introduced into the fluid during the fluid transfer.

15. The fluid device of claim 12, wherein the one or more air handling ports are vents.

16. The fluid device of claim 12, wherein the collar further comprises a hydrophobic filter capable of being coupled to the one or more air handling ports.

17. The fluid apparatus of claim 1, wherein the collar further comprises a fluid inlet port for filling the container after the collar and the container are coupled.

18. The fluid device of claim 1, wherein the collar further includes an observation window that allows for optical evaluation of fluid within the fluid conduit of the collar.

19. The fluid device of claim 1, wherein the sterile liquid transfer port further comprises a mechanical seal.

20. The fluid device of claim 19, wherein the collar further includes one or more sterilization ports in fluid communication with the plurality of conduits, and wherein the mechanical seal of the sterile liquid transfer port and a sterilizing agent supplied via the one or more sterilization ports ensure the sterility of the collar.

21. The fluid device of claim 1, wherein the collar further comprises a pressure relief valve located at the outlet port of the compressible fluid conduit of the fluid pump module, and wherein the outlet port is further in fluid communication with the container such that liquid flows into the container when excessive pressure is present at the outlet port.

22. The fluid device of claim 1, wherein the container includes an opening, and wherein the collar further includes a fluid delivery feature capable of being coupled to the opening and in fluid communication with the plurality of conduits.

23. The fluid device of claim 22, wherein the fluid delivery feature of the collar includes a vent tube configured to extend through the opening of the container and disposed within the container.

24. The fluid device of claim 23, wherein the vent further comprises a liquid vent reservoir configured to capture fluid trapped within the vent when the fluid device is inverted.

25. The fluid apparatus of claim 24, wherein the volume of the liquid vent reservoir is greater than the volume of the vent pipe within the container.

26. The fluid device of claim 23, wherein the fluid delivery feature further comprises a liquid flow tube configured to extend through the opening of the container and disposed within the container.

27. The fluid device of claim 26, wherein the collar further comprises one or more air handling ports, and the one or more air handling ports are in fluid communication with the liquid flow tube.

28. The fluid device of claim 23, wherein the fluid delivery feature further comprises a flow port in fluid communication with the container and the sterile liquid transfer port.

29. The fluid device of claim 1, wherein the sterile liquid transfer port further comprises a mechanical seal, and the collar further comprises one or more sterilization ports in fluid communication with the plurality of conduits, the mechanical seal providing a first mechanism for achieving sterilization, and a sterilizing agent provided via the one or more sterilization ports providing a second mechanism for achieving sterilization.

30. A method for automating fluid transfer, the method comprising: A fluid device inverted by a robot, the fluid device comprising a container and a universal collar, the universal collar comprising multiple tubing and a sterile liquid transfer port, the sterile liquid transfer port being in fluid communication with the multiple tubing; The robot connects the sterile liquid transfer port of the inverted fluid device to the corresponding sterile liquid transfer port of the cartridge. as well as Fluid is pumped from the fluid device to the cartridge via the plurality of catheters and the sterile liquid transfer port.

31. The method of claim 30, wherein the method further comprises After the connection and before the pumping, the sterile liquid transfer port is sterilized via one or more sterilization treatment ports that are in fluid communication with the plurality of conduits through the collar.

32. The method of claim 30, wherein the method further comprises After sterilization, the robot actuates the valves of each of the sterile liquid transfer ports and the corresponding sterile liquid transfer ports to allow the pumping.

33. The method of claim 30, wherein the inversion includes The robot engagement feature of the collar of the fluid device is engaged by the robot.

34. A method for automating fluid transfer, the method comprising: A fluid device inverted by a robot, the fluid device comprising a container and a universal collar, the universal collar comprising a plurality of tubing, a sterile liquid transfer port and an air handling port, each of the sterile liquid transfer port and the air handling port being in fluid communication with the plurality of tubing; The robot connects the sterile liquid transfer port of the inverted fluid device to the corresponding sterile liquid transfer port of the cartridge. At least a portion of the fluid is pumped from the inverted fluid device into the cartridge via the plurality of catheters and the sterile liquid transfer port; as well as After the pumping, compressed air is used to purge the plurality of ducts via the air handling port.

35. A method for automating fluid transfer, the method comprising: A robot-inverted fluid device, the fluid device comprising a container and a universal collar, the universal collar comprising a robot engagement feature, a plurality of conduits, a sterile liquid transfer port and a plurality of sterilization ports, each of the sterile liquid transfer port and the plurality of sterilization ports being in fluid communication with the plurality of conduits; The robot connects the sterile liquid transfer port of the inverted fluid device to the corresponding sterile liquid transfer port of the cartridge. The sterilizing agent is allowed to flow through the sterile liquid transfer port via the one or more sterilization treatment ports. as well as At least a portion of the fluid is pumped from the inverted fluid device to the cartridge via the plurality of catheters and the sterile liquid transfer port.

36. A method for automating fluid transfer, the method comprising: When the fluid device is in an upright position, it is filled with a fluid device comprising a container and a universal collar, the universal collar including a robotic engagement feature, multiple conduits, and a sterile liquid transfer port; The fluid device is inverted by a robot via the robot engagement feature; The robot connects the sterile liquid transfer port of the inverted fluid device to the corresponding sterile liquid transfer port of the cartridge. as well as At least a portion of the fluid is pumped from the fluid device to the cartridge via the plurality of catheters and the sterile liquid transfer device.

37. The method of claim 36, wherein the method further comprises The plurality of conduits within the collar are purged via the air handling port of the collar.

38. The method of claim 36, wherein the filling is performed via the fluid inlet port of the collar.

39. The method of claim 36, wherein the pumping further comprises Data is received from a sensor located near the observation window of the collar, the sensor being configured to detect the presence of liquid within sections of the plurality of conduits; Detecting the fluid transition from air to liquid based on the received data; The fluid pump is operated based on the presence of the detected air-to-liquid fluid transition; Detecting the fluid transition from liquid to air based on the received data; and When a fluid transition from liquid to air is detected, operation of the fluid pump is stopped.

40. The method of claim 36, wherein the pumping further comprises Receive data regarding a specified volume of fluid to be transferred to the box; Data is received from a sensor located near the observation window of the collar, the sensor being configured to detect the presence of liquid within sections of the plurality of conduits; Detecting the fluid transition from air to liquid based on the received data; The fluid pump is operated based on the detected presence of the air-to-liquid fluid transition and the received data on the specified volume of fluid. and Once the specified volume of fluid has been transferred, stop operating the fluid pump.

41. A system for automating fluid transfer, the system comprising: Fluid pump; Fluid apparatus, the fluid apparatus comprising Container, the container being used for a certain volume of fluid, and Universal collar, the universal collar being capable of being coupled to the container, the collar comprising... Multiple catheters, A sterile liquid transfer port, which is in fluid communication with the plurality of catheters. A fluid pump module includes a compressible fluid conduit connected between an inlet port and an outlet port, each of the inlet port and the outlet port being in fluid communication with a plurality of conduits, the compressible fluid conduit being configured to be compressed by the fluid pump to control the movement of fluid flowing out of the container. One or more viewing windows; and One or more sensors are configured to detect the presence of liquid within sections of the plurality of conduits via the one or more observation windows.

42. The system of claim 41, further comprising: Processor, the processor is configured to Receive data from the one or more sensors; Detecting fluid transitions from air to liquid based on received data; Start the fluid pump; Detecting fluid transitions from liquid to air; and When the fluid transition from liquid to air is detected, the fluid pump is stopped.

43. A system for automating fluid transfer, the system comprising: Fluid pump; robot; and Fluid apparatus, the fluid apparatus comprising Container, the container being used for a certain volume of fluid, and Universal collar, the universal collar being capable of being coupled to the container, the collar comprising... A robot engagement feature, which can be engaged by the robot. Multiple catheters, A sterile liquid transfer port, which is in fluid communication with the plurality of catheters. A fluid pump module includes a compressible fluid conduit connected between an inlet port and an outlet port, each of the inlet port and the outlet port being in fluid communication with a plurality of conduits, the compressible fluid conduit being configured to be compressed by the fluid pump to control the movement of fluid flowing out of the container.

44. A method for automating fluid transfer, the method comprising: The robot connects the sterile liquid transfer port of the fluid device to the corresponding sterile liquid transfer port of the cartridge. At least a portion of the fluid is pumped from the fluid device to the cartridge via a plurality of conduits of the fluid device and the sterile liquid transfer port; as well as After the pumping, compressed air is used to purge the plurality of conduits via the air handling port of the fluid device.

45. A fluid device for automating fluid transfer, the fluid device comprising: A container for a given volume of fluid; and Universal collar, capable of being coupled to the container, the collar comprising: Multiple catheters; A sterile liquid transfer port, wherein the sterile liquid transfer port is in fluid communication with the plurality of catheters; A fluid pump module includes a compressible fluid conduit connected between an inlet port and an outlet port, each of the inlet port and the outlet port being in fluid communication with a plurality of conduits, the compressible fluid conduit being configured to be compressed by the fluid pump to control the movement of fluid flowing out of the container; Air handling port; and A ball valve is coupled to the air handling port, wherein the fluid device is configured to be positioned in an upright orientation and an inverted orientation, and wherein the ball valve is configured to prevent the fluid in the container from flowing within the air handling port when the fluid device is in the inverted orientation.

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