Systems, devices, and methods for fluid transfer within automated cell processing systems.
Automated fluid transfer systems with sterilization features and robotic control address inefficiencies and contamination risks in cell therapy manufacturing, enhancing scalability and efficiency.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- CELLARES CORP
- Filing Date
- 2024-03-28
- Publication Date
- 2026-05-19
AI Technical Summary
Conventional cell therapy manufacturing processes face inefficiencies and risks of contamination and human error due to manual fluid transfer between steps, which are difficult to automate.
The development of automated fluid transfer systems and methods within cell processing systems, utilizing a general-purpose collar with conduits, sterilization ports, and fluid pumps to ensure sterile fluid transfer, facilitated by robotic manipulation and sensor-controlled fluid movement.
Minimizes contamination and human error in fluid transfer, enabling scalable and efficient cell therapy production by automating the process.
Smart Images

Figure 2026515589000001_ABST
Abstract
Description
Technical Field
[0001] (Field of the Invention) The present disclosure relates to fluid transfer within an automated cell processing system.
[0002] (Cross - Reference to Related Applications) This application claims priority to U.S. Provisional Patent Application No. 63 / 456,388, filed Mar. 31, 2023. All applications are hereby incorporated by reference in their entirety.
Background Art
[0003] Cell therapies that collect cells from individual patients, process them ex vivo, and then return them to the same patient are revolutionary for producing durable and effective clinical responses in patients. Although cell therapy manufacturing is attractive, it is difficult to "scale up" and is a complex, often labor - intensive process that is prone to human error and contamination. Efforts have recently been made to automate cell therapy manufacturing, such as automating the movement of cells between manufacturing steps, but conventional cell therapy manufacturing still includes many inefficiencies. For example, fluid transfer between cell therapy steps and reagent storage devices is still a point of human contact and an entry point for errors and contamination. Considering the importance of sterility in fluid transfer for sample collection, media replenishment, etc., additional systems, devices, and methods for fluid transfer within a cell processing system are desirable. In particular, automated systems, devices, and methods, as well as methods that can be implemented in a sterile manner, are desirable.
Summary of the Invention
[0004] This disclosure relates, in general, to systems, devices, and methods for automated fluid transfer within automated cell processing systems. Generally, the fluid devices disclosed herein may comprise a container for a certain volume of fluid and a general-purpose collar that can be coupled to the container. In some modifications, the collar comprises a fluid pump module having a plurality of conduits, a sterilization fluid transfer port fluid-communicating with the plurality of conduits, and a compressible fluid tube coupled between an inlet port and an outlet port. Each of the inlet and outlet ports may fluid-communicate with the plurality of conduits, and the compressible fluid tube may be compressed by the fluid pump to control the movement of the fluid out of the container. In some modifications, the collar may further comprise one or more sterilization ports fluid-communicating with the plurality of conduits. A sterilizer, which may be one or more of vaporized hydrogen peroxide, ionized hydrogen peroxide, chlorine dioxide, and ethylene oxide, may be supplied through the one or more sterilization ports. In some modifications, the collar may further comprise one or more air treatment ports fluid-communicating with the plurality of conduits. One or more air handling ports may be compressed air handling ports or vents. In some modifications, the collar may further comprise a viewing window that allows for optical evaluation of the fluid in the fluid conduit of the collar. In some modifications, the sterilization fluid transfer port may further comprise a mechanical seal. In some modifications, the collar may further comprise one or more sterilization ports that are in fluid communication with multiple conduits. In some modifications, the mechanical seal of the sterilization fluid transfer port and the sterilizer provided through one or more sterilization ports ensure the sterilization of the collar. In some modifications, the container may comprise an opening, and the collar may further comprise a fluid transport mechanism that can be coupled to the opening, and the fluid transport mechanism may also be in fluid communication with multiple conduits. A vent may extend through the opening of the container and be configured to be disposed within the container. The vent may further comprise a liquid vent reservoir configured to capture fluid trapped within the vent when the fluid device is inverted. An air handling tube may extend through the opening of the container and be configured to be disposed within the container.In some modifications, the sterilization fluid transfer port may further comprise a mechanical seal, the collar may further comprise one or more sterilization ports communicating with multiple conduits and fluids, the mechanical seal provides a first mechanism for achieving sterilization, and the sterilization agent delivered through one or more sterilization ports provides a second mechanism for achieving sterilization.
[0005] Another fluid device for automated fluid transfer may comprise a container for a certain amount of fluid and a general-purpose collar that can be coupled to the container. The collar may include a plurality of conduits, a sterile fluid transfer port that is in fluid communication with the plurality of conduits, a fluid pump module, an air treatment port, and a ball valve coupled to the air treatment port. The fluid pump module may include a compressible fluid tube coupled between an inlet port and an outlet port, each of which may be in fluid communication with the plurality of conduits, and the compressible fluid tube 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 through the air treatment port when the fluid device is in the inverted orientation.
[0006] Methods for automated fluid transfer are also disclosed herein. In some variations, the method for automated fluid transfer includes, by a robot, inverting a fluid device comprising a container and a general-purpose collar having a plurality of conduits and a sterile fluid transfer port having fluid communication with the plurality of conduits; by a robot, connecting the sterile fluid transfer port of the inverted fluid device to a corresponding sterile fluid transfer port of a cartridge; and pumping fluid from the fluid device to the cartridge through the plurality of conduits and sterile fluid transfer ports. In some variations, the method may further include sterilizing the sterile fluid transfer port via one or more sterile processing ports of the collar having fluid communication with the plurality of conduits after connection and before pumping. In some variations, the method may further include, after sterilization, the robot activating the valves of the sterile fluid transfer port and the corresponding sterile fluid transfer port to enable pumping through them.
[0007] In other variations, a method for automated fluid transfer may include, by a robot, inverting a fluid device comprising a container and a general-purpose collar having a plurality of conduits, a sterile fluid transfer port, and an air treatment port, each of which is in fluid communication with the plurality of conduits; connecting the sterile fluid transfer port of the inverted fluid device to a corresponding sterile fluid transfer port of a cartridge by the robot; pressurizing at least a portion of the fluid from the inverted fluid device to the cartridge through the plurality of conduits and the sterile fluid transfer port; and, after pressurizing, purging the plurality of conduits using compressed air through the air treatment port.
[0008] In other variations, a method for automated fluid transfer includes inverting a fluid device comprising a container and a general-purpose collar having a robot engagement mechanism, a plurality of conduits, a sterilizing agent transfer port, and a plurality of sterilization ports, each of which has a sterilizing agent transfer port and a plurality of sterilization ports in fluid communication with the plurality of conduits; connecting the sterilizing agent transfer port of the inverted fluid device to a corresponding sterilizing agent transfer port of a cartridge by the robot; flowing a sterilizing agent through the sterilizing agent transfer port via one or more sterilization ports; and pressurizing at least a portion of the fluid from the inverted fluid device to the cartridge via the plurality of conduits and sterilizing agent transfer ports.
[0009] In other variations, a method for automated fluid transfer includes filling a fluid device, which comprises a container and a general-purpose collar having a robotic engagement mechanism, a plurality of conduits, and a sterile fluid transfer port, when the fluid device is in an upright position; inverting the fluid device via the robotic engagement mechanism by a robot; connecting the sterile fluid transfer port of the inverted fluid device to a corresponding sterile fluid transfer port of a cartridge by a robot; and pumping at least a portion of the fluid from the fluid device to the cartridge via the plurality of conduits and the sterile fluid transfer device. Pumping may further include receiving data from a sensor positioned close to a viewing window of the collar and configured to detect the presence of liquid in compartments of the plurality of conduits; detecting the presence of a fluid transition from air to liquid based on the received data; operating a fluid pump based on the detected presence of a fluid transition from air to liquid; detecting a fluid transition from liquid to air based on the received data; and stopping the operation of the fluid pump when a fluid transition from liquid to air is detected. In some variations, pumping may further include receiving data on a specified amount of fluid to be transferred to a cartridge, the data being received from a sensor positioned near a color viewing window. In some variations, the sensor may be configured to detect the presence of liquid in compartments of multiple conduits. The fluid transition from air to liquid may be detected based on the received data, and the fluid pump may operate to deliver a specified amount of fluid. Once the specified amount of fluid has been transferred, the operation of the fluid pump may be stopped.
[0010] In other variations, a method for automated fluid transfer includes, by means of a robot, connecting the sterile fluid transfer port of a fluid device to the corresponding sterile fluid transfer port of a cartridge; pressurizing at least a portion of the fluid from the fluid device to the cartridge through multiple conduits and sterile fluid transfer ports of the fluid device; and, after pressurizing, purging the multiple conduits using compressed air through the air treatment port of the fluid device.
[0011] Systems for automated fluid transfer are also disclosed herein. In some modifications, the system for automated fluid transfer comprises a fluid pump, a fluid device having a container for a certain amount of fluid and a general-purpose collar that can be coupled to the container, and one or more sensors. The general-purpose collar may comprise a plurality of conduits, a sterile fluid transfer port that is in fluid communication with the plurality of conduits, and one or more windows. One or more sensors may be configured to detect the presence of liquid in the compartments of the plurality of conduits through one or more viewing windows. The collar may further comprise a fluid pump module having a compressible fluid tube coupled between an inlet port and an outlet port, each of the inlet and outlet ports being in fluid communication with the plurality of conduits, and the compressible fluid tube is configured to be compressed by the fluid pump to control the movement of fluid out of the container. In some modifications, the system may further comprise a processor configured to receive data from one or more sensors and, based on the received data, detect a fluid transition from air to liquid and start the fluid pump, detect a fluid transition from liquid to air, and stop the fluid pump when a fluid transition from liquid to air is detected.
[0012] Further variations, features, and advantages of the present invention will become apparent from the following detailed description and through the implementation of the invention. [Brief explanation of the drawing]
[0013] [Figure 1A] This is a block diagram of an exemplary modified example of a cell processing system. [Figure 1B] This is a block diagram illustrating an example of a modified cartridge. [Figure 2A] This is a block diagram of an exemplary modified example of a cell processing system. [Figure 2B] This is a perspective view of an exemplary modified working cell of a cell processing system. [Figure 2C] This is a perspective view of an exemplary modified working cell and cartridge of a cell processing system. [Figure 2D] This is a block diagram of an exemplary modified example of a cell processing system. [Figure 3A] Schematic diagrams of exemplary variants of a fluid device showing a container and color. [Figure 3B] Schematic diagram of an exemplary system for automatic fluid transfer. [Figure 4A] Drawing of a perspective view of an exemplary fluid device for automatic fluid transfer. [Figure 4B] Drawing of a perspective view of an exemplary color of a fluid device for automatic fluid transfer. [Figure 4C] Drawing of a top view of an exemplary color of a fluid device for automatic fluid transfer. [Figure 4D] Image of a bottom view of an exemplary color of a fluid device for automatic fluid transfer. [Figure 4E] Image of a diagram of an exemplary container and fluid transport mechanism of a fluid device for automatic fluid transfer. [Figure 4F] Drawing of a perspective view of an exemplary container of a fluid device for automatic fluid transfer. [Figure 4G] Drawing of an exemplary fluid device for automatic fluid transfer and a robotic gripping mechanism of a robot in a work cell. [Figure 4H] Drawing of an exemplary robotic gripping mechanism of a robot in a work cell. [Figure 4I] Drawing of an exemplary robotic gripping mechanism of a robot in a work cell. [Figure 5A] Drawing of a first perspective view of an exemplary fluid device for automatic fluid transfer. [Figure 5B] Drawing of a second perspective view of an exemplary fluid device for automatic fluid transfer. [Figure 5C] Drawing of a top view of an exemplary aspect of a color of a fluid device for automatic fluid transfer. [Figure 5D] Drawing of a cross-sectional view of an exemplary aspect of a color of a fluid device for automatic fluid transfer, the cross-section being a plane between the bottom and the top of the fluid device. [Figure 5E] Drawing of a bottom view of an exemplary color of a fluid device for automatic fluid transfer. [Figure 5F] It is a drawing of a perspective view of an exemplary color of a fluid device for automatic fluid transfer. [Figure 5G] It is a drawing of an exemplary liquid vent tube of a color of a fluid device for automatic fluid transfer. [Figure 5H] It is an image of an exemplary liquid vent tube of a color of a fluid device for automatic fluid transfer. [Figure 5I] It is a drawing of a perspective view of an exemplary container of a fluid device for automatic fluid transfer. [Figure 5J] It is a drawing of an exemplary fluid device for automatic fluid transfer and a robotic gripping mechanism of a robot in a work cell. [Figure 5K] It is a drawing of a first connection position between a robotic engagement mechanism of an exemplary fluid device and a clamp of a robotic gripping mechanism of a robot in a work cell. [Figure 5L] It is a drawing of a second connection position between a robotic engagement mechanism of an exemplary fluid device and a clamp of a robotic gripping mechanism of a robot in a work cell. [Figure 6] It is a flowchart of an exemplary method for automatic fluid transfer. [Figure 7A] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 7B] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 7C] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 7D] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 7E] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 7F] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 8] It is a flowchart of an exemplary variation of a method for automatic fluid transfer. [Figure 9] It is a flowchart of another exemplary variation of a method for automatic fluid transfer. [Figure 10]This is an illustrative color bottom view drawing of a fluid device for automatic fluid transfer, the fluid device including a ball valve. [Figure 11A] This specification shows a perspective view of an exemplary ball valve for use in the fluid devices described herein. [Figure 11B] Figure 11A is an exploded view of the ball valve. [Figure 12A] This shows an exemplary variation of fluid flow through a ball valve in a fluid device when the fluid device is in an inverted orientation. [Figure 12B] This shows an exemplary variation of fluid flow through a ball valve in a fluid device when the fluid device is oriented vertically. [Modes for carrying out the invention]
[0014] A major limiting factor in cell therapy manufacturing is the absence of automated systems, devices, and methods for performing fluid transfers without introducing contamination and / or human error. While devices, including certain vial closure devices, incorporate tubing into the caps of centrifuge tubes, vials, flasks, etc., to enable the handling of sterile fluids, these devices still require human intervention and, to date, have not been incorporated on a large scale into automated cell therapy manufacturing processes.
[0015] Accordingly, this disclosure provides systems, devices, and methods for automated fluid transfer within automated cell processing systems to minimize the sterile barrier that significantly limits the availability of manufactured cell therapies.
[0016] The systems, devices, and methods for carrying out fluid transfer described herein are for use in cell therapy manufacturing systems or cell processing systems, an exemplary figure of which is shown in Figure 2B. As shown in Figure 2B, cell processing may involve moving a cartridge 250 containing cell products between several instruments such as instruments 211, 216, 220, and 222 in a working cell 202. One or more instruments may be configured to couple, engage with, or interface with the cartridge 250 to perform cell processing steps on the cells in the cartridge 250. In some modifications, multiple cell processing steps may be performed within the cartridge 250. For example, a robotic arm 230 may be configured to move the cartridge 250 between instruments, each instrument being configured to perform different cell processing steps when coupled to a corresponding module in the cartridge 250. In some variations, cartridge 250 may comprise any number of modules, such as a bioreactor module, a counterflow centrifugal elutriation (CCE) module, a magnetic cell sorting module, an electroporation module, a sorting module (e.g., a fluorescence-activated cell sorting (FACS) module), an acoustic flow cell module, a microfluidic concentration module, a spinoculation module, and / or a combination thereof. In some variations, the working cell 202 may process two or more cartridges in parallel. For example, the working cell 202 may comprise multiple instruments such as instruments 211, 216, 220, and 222, each having a receiving bay. Each instrument may be configured to interface with a cartridge, such as cartridge 250, received in its respective receiving bay, so that multiple instruments within the working cell 202 may be in use at any given time.
[0017] In addition to the cell processing steps described above, and to enable them, an automated cell processing system may facilitate automated fluid transfer (which may or may not be sterile fluid transfer) between a cartridge and other cartridges and / or equipment or other components of the system, such as sample collection containers, reagent containers, waste containers, and other fluid devices. For example, as described below, the systems, devices, and methods of the present disclosure may facilitate fluid transfer between a cartridge and fluid devices, which may include reagent containers, sample collection containers, waste containers, and the like.
[0018] I. Cell Processing Systems An exemplary cell processing system for use in automated fluid transfer devices, systems, and methods is shown in Figure 1A. A block diagram of cell processing system 100 comprising a working cell 110 and a controller 120 is shown. The working cell 110 may comprise one or more of the following: equipment 112, robot 116 (e.g., robotic arm), reagent storage unit 118, sterile fluid transfer port 132, sterilizer source 129, fluid source 136, pump 138, and sensor 151. A cartridge 114 and fluid device 142 may be used within the working cell 110 (and are therefore shown here by dashed lines). In some modifications, the fluid device 142 is a sterile liquid transfer device (SLTD). However, it should be understood that the fluid device 142 may 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 that can be coupled to the container and is configured to assist in the transfer of the fluid between the fluid device 142 and another component of the system 100 (e.g., an instrument 112 and / or a reagent storage unit 118). The robot 116 may be configured to move one or more cartridges 114 and the fluid device 142 within the work cell 110. As an example, the robot 116 may be configured to move one or more fluid devices 142 between the reagent storage unit 118 and one or more instruments 112 (e.g., one or more sterile fluid transfer instruments). In some variations, the robot 118 may be configured to position the fluid device 142 in a first orientation within the reagent storage unit 118 and, when coupled to the instrument 112, in a second orientation (which may be opposite to the first orientation). For example, the fluid device 142 may be configured to be stored in an upright orientation within the reagent storage section 118 and to be connectable to the instrument 112 in an inverted position. As described herein, the upright orientation may be determined by the relative orientation of the collar and the container of the fluid device 142. In some modifications, the fluid device 142 may be upright when the collar is above the container of the fluid device 142, and may be in an inverted orientation when the container is above the collar of the fluid device 142.The controller 120 may include one or more of the following: a processor 122, memory 124, communication device 126, input device 128, and display 130.
[0019] The working cell 110 may comprise a fully or at least partially sealed housing within which one or more cell processing steps are carried out by fully or at least partially automated processes. In some modifications, the working cell may be an open system without an enclosure, which may be configured for use in a cleanroom, biosafety cabinet, or other sterile location. The cartridge 114 may be moved using a robot 116 to reduce manual labor in the cell processing steps, and the transfer of fluids in and out of the cartridge may also be carried out by fully or partially automated processes, as described in detail herein. For example, one or more fluids may be stored in a fluid device 142. In some modifications, the fluid device may be moved within the system 100 by a robot 116. The fluid devices and sterile fluid transfer ports described herein may advantageously enable the transfer of fluids in an automated metering manner for automating cell therapy production.
[0020] In some variations, the robot 116 is configured to move cartridges 114 between different instruments and perform a predetermined sequence of cell processing steps. In this way, different steps of the cell processing sequence can be performed simultaneously on different cartridges, so that multiple cartridges 114 can be processed in parallel.
[0021] The sterile fluid transfer port 132 can be coupled between two or more cartridges 114 to transfer cell products and / or fluids between the cartridges 114. Furthermore, the sterile fluid transfer port 132 can be coupled between any set of fluid-carrying components of the system 100 (e.g., cartridges 114, reagent storage unit 118, fluid source 136, fluid device 142, etc.). For example, a first sterile fluid transfer port can be coupled between a first cartridge and the corresponding sterile fluid transfer port of a fluid device.
[0022] In some modifications, the reagent storage unit 118 (or more reagent storage units) 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, cryoprotective substances, solvents, cell materials, and pharmaceutically acceptable excipients. Additionally or alternatively, waste can be stored in the reagent storage unit or in a fluid device within the reagent storage unit. In some modifications, samples being processed, extracted from one or more cartridges, can be stored in the reagent storage unit or in a fluid device within the reagent storage unit. The reagent storage unit may comprise one or more controlled temperature compartments (e.g., a freezer, condenser, water bath, heating chamber, or others, e.g., about -80°C, about -20°C, about 4°C, about 25°C, about 30°C, about 37°C, and about 42°C). The temperatures within these compartments can be varied during the cell manufacturing process to heat or cool the reagents.
[0023] In some modifications, reagents, waste, and / or extracted samples during processing may be stored in a fluid device 142 within a reagent storage unit 118. For this purpose, the fluid device 142 may be transferred to a cartridge in a working cell, 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 interface with one or more sterile fluid transfer ports on the cartridge, and reagents or materials may be transferred from the fluid device 142 in the reagent storage unit into 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 modifications, the equipment 112 of the working cell 110 includes a sterile fluid transfer device similarly configured to transfer fluid in and out of the cartridge in an automated manner. The sterile fluid transfer device may store reagents, for example, by a robot 116 that moves the fluid device 142 containing reagents from a feedthrough in the working cell or other location to the sterile fluid transfer device. In some variations, the robot 116 moves the fluid device 142 from the reagent storage unit 118 to a sterile fluid transfer device. The reagent storage unit 118 may have an automatic door to allow the robot 116 to access the fluid device 142 stored inside. The fluid device 142 may be configured for pick-and-place movement by the robot 116. In some variations, the reagent storage unit 118 may have one or more sample pickup areas. For example, the robot 116 may be configured to move one or more fluid devices 142 containing reagents to and from one or more of the sample pickup areas.
[0024] In some variations, the working cell 110's sensor 151 comprises an optical sensor positioned close to the side of the sterile fluid transfer equipment. Sensor 151 can be queryed during an automated fluid transfer procedure to assist in the controlled flow of fluid from one fluid device to another fluid device or cartridge. In particular, the optical sensor may be positioned to have a field of view of the window of the fluid device in order 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 amount of fluid from one fluid device to an adjacent fluid device or cartridge.
[0025] As shown in Figure 1B, the cartridge 114 may comprise one or more of the following, as described in more detail herein: a bioreactor 150, a cell separation system 152, an electroporation module 160, a fluid transfer bus 162, a sensor 164, and a sterile fluid transfer port 166. The cell separation system 152 may comprise one or more of the following: a rotor 154, a flow cell 156, and a magnet 158. In some embodiments, the magnet 158 may comprise one or more magnets and / or a magnet array. For example, the cell separation system 152 may comprise a first magnet configured to magnetically rotate the rotor 154 and a second magnet (e.g., a magnet array) configured to magnetically separate cells in the flow cell 156.
[0026] Any suitable cell processing may be carried out using the systems and devices described herein and may include steps such as proliferation, concentration, selection, sorting, expansion, activation, transduction, electroporation, and washing. In some variations, a method for processing a solution containing cell products includes the steps of digesting tissue using an enzymatic reagent to release a selected cell population into a 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 growing cells in a bioreactor, activating cells using an activation reagent, electroporating cells, transduction of cells using a vector, and finishing the cell products.
[0027] Figure 2A shows an exemplary cell processing system for use in the devices, systems, and methods described herein. The figure shows a working cell 203. The working cell may be divided into an internal zone 204 having access to a feedthrough 206 and quality control (QC) equipment 212. An air filtration inlet (not shown) may provide high-efficiency particulate air (HEPA) filtration to provide ISO 7 or better air quality in the internal zone 204. This air filtration can maintain sterile cell processing in an ISO 8 or ISO 9 manufacturing environment. The working cell 203 may have an air filter at the air outlet to maintain the ISO rating of the room. Similar to the working cell described above with reference to Figure 1A, the working cell 203 may further include, inside the internal zone 104, a bioreactor instrument 214, a cell selection instrument 216 (e.g., a magnetic separation instrument), an electroporation instrument 220, a countercurrent centrifuge elutriation (CCE) instrument 222, a sterile fluid transfer instrument 224 (e.g., to facilitate automated fluid transfer), a reagent storage unit 226, and a sterilization system 260. The reagent storage unit 226 may be accessible to the user through a sample pickup port 228. A robot 230 (e.g., a support arm, a 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 storage unit 226, and / or move one or more fluid devices between the reagent storage unit 226 and the sterile fluid transfer instrument 224. In some embodiments, the working cell 203 may include one or more movable barriers 213 (e.g., access doors) configured to facilitate access to one or more of the instruments within the working cell 203. Figure 2B is a perspective view of the working cell 205 of the cell processing system. Figure 2C is a perspective view of the cell processing system showing cartridges 250 introduced into the working cell 205. Multiple cartridges can be inserted into the working cell 205 and undergo one or more cell processing operations in parallel.
[0028] Figure 2D is a schematic diagram of one embodiment of the work cell 200. The work cell 200 may comprise an enclosure 202 having four walls, a base, and a roof. The work cell 200 may be divided into an internal zone 204 with access to a feedthrough 206, a biosafety cabinet (BSC) 208, a computing server rack 210 (e.g., controller 120), and quality control (QC) equipment 212. An air filtration inlet (not shown) may provide high-efficiency particulate air (HEPA) filtration to provide ISO 7 or better air quality in the internal zone 204. The work cell 200 may also have an air filter at the air outlet to maintain the ISO rating of the room. Similar to the working cell described above, the working cell 200 may further include, inside the internal zone 204, instruments 211 (e.g., located in a general-purpose 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 elutriation (CCE) instrument 222, and sterile fluid transfer instrument 224, together with a reagent storage unit 226 and a sterilization system 260 comprising one or more of a sterilizing agent source, a fluid source, and a pump. As described below, the sterilization system 260 may be connectable to a fluid device to sterilize the sterile fluid transfer port during the automated fluid transfer process. The reagent storage unit 226 may be accessible through a sample pickup port 228. The robot 230 (e.g., support arm, robot arm) may be configured to move one or more cartridges 250 from any device to any other device, move one or more cartridges 250 to and from the reagent storage unit 226, and / or move one or more fluid devices between the reagent storage unit 226 and the sterile fluid transfer device 224.
[0029] In some embodiments, a human operator may load one or more cartridges 250 into the feedthrough 206. The cartridges 250 may be pre-sterilized, or the feedthrough 206 may sterilize the cartridges 250 using ultraviolet (UV) light or a chemical sterilizer provided as a spray or washing solution. The feedthrough 206 chamber may optionally be configured to automatically spray, wash, irradiate, or otherwise treat the cartridges (e.g., with an ethanol and / or isopropyl alcohol solution) to maintain the sterility of the internal zone 204 (e.g., ISO 7 or higher) or the biosafety cabinet 208 (e.g., ISO 5 or higher). The cartridges 250 may be passed to a biosafety cabinet 208 into which input cell products are provided and into which the cartridges 250 are loaded. The user can then return the cartridges 250 to the feedthrough 206 and initiate automated cell processing using a computer processor (e.g., controller 120) in a computer server rack 210. The robot 230 may be configured to move the cartridge 250 in a predetermined order to multiple devices and stations using components of a work cell 200 controlled by a computer processor in a computer server rack 210.
[0030] Other suitable cell processing systems and embodiments thereof are provided, for example, in U.S. Patent Application No. 17 / 198,134, published as U.S. Patent Application Publication No. 2021 / 0283565, entitled "Systems and Methods for Cell Processing," which is incorporated herein by reference.
[0031] A. Working cell i. Robot In general, the robot in a work cell may be equipped with any mechanical device capable of moving cartridges and / or fluid devices from one position to another within the work cell. For example, the robot may be equipped with a mechanical manipulator (e.g., an arm) that is in a fixed position or mounted on a linear rail or a two-dimensional or three-dimensional rail system. In some figures, the robot is shown as being fixed in place or to a rail system, but this is not required. For example, in some modifications, the robot may be equipped with a wheeled device. Any number of robots may be used within a work cell as described herein. For example, in some embodiments, the work cell may be equipped with two or more robots of the same or different types (e.g., two robotic arms configured independently for moving cartridges between devices). The robot may also be equipped with end effectors for precisely handling different cartridges or fluid devices, or for barcode scanning or reading radio-frequency identification (RFID) tags.
[0032] A robot for use in the cell processing system described herein can move cartridges between slots or bays within the working cell so that modules within the cartridge can be coupled to corresponding equipment within the working cell to perform different cell processing steps. Furthermore, a robot for use in the cell processing system described herein can move and operate fluid devices within the working cell. For example, a robot may be able to move a reagent storage fluid device from the reagent storage section of the working cell to the sterile fluid transfer equipment of the working cell so that automated fluid transfer can be performed between the reagent storage fluid device and the cartridge.
[0033] ii. Controller In an embodiment, the cell processing system 100 may include a controller 120 (e.g., a computing device) comprising one or more of the following: a processor 122, memory 124, communication device 126, input device 128, and display 130. The controller 120 may be configured to control (e.g., operate) the working cell 110. The controller 120 may comprise multiple devices. For example, the working cell 110 may house one or more components of the controller 120 (e.g., the processor 122, memory 124, and communication device 126), while one or more components of the controller 120 may be provided remotely to the working cell 110 (e.g., the input device 128 and display 130).
[0034] iii. Processor A processor described herein (e.g., processor 122) can process data and / or other signals to control one or more components of a system. A processor may be configured to receive, process, compile, compute, store, access, read, write, and / or transmit data and / or other signals. Additionally or alternatively, a processor may be configured to control one or more components of a device (e.g., a console, a touchscreen, a personal computer, a laptop, a tablet, a server).
[0035] In some embodiments, the processor may be configured to access or receive data and / or other signals from one or more of the working cell 110, the server, the 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 operate 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 to reduce data rate and / or memory requirements), cryptographic processors (e.g., for secure wireless data transfer), 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 similar. The processor may be configured to operate and / or perform application processes and / or processes and / or functions associated with other modules, systems, and other modules. The underlying device technology may be provided by various component types, such as metal-oxide semiconductor field-effect transistor (MOSFET) technology like complementary metal-oxide semiconductor (CMOS), bipolar technology like emitter-coupled logic (ECL), polymer technology (e.g., silicone-conjugated polymers, and metal-conjugated polymer-metal structures), and analog and digital mixed technologies.
[0036] The systems, devices, and / or methods described herein may be implemented by software (running on hardware), hardware, or a combination thereof. Hardware modules may include, for example, general-purpose processors (or microprocessors or microcontrollers), field-programmable gate arrays (FPGAs), and / or application-specific integrated circuits (ASICs). Software modules (running on hardware) may be expressed in various software languages (e.g., computer code), including structured text, TypeScript, C, C++, C#, Java®, Python, Ruby, Visual Basic®, 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 used to generate web services, and files containing high-level instructions 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.
[0037] iv. Memory The cell processing systems and devices described herein may include a memory (e.g., memory 124) configured to store data and / or information. In some embodiments, the memory may include one or more of the following: random access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), memory buffer, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), flash memory, volatile memory, non-volatile memory, or combinations thereof. In some embodiments, the memory may store instructions causing a processor to execute 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 relate to computer storage products with a non-temporary computer-readable medium (which may also be referred to as a non-temporary processor-readable medium) having instructions or computer code for performing various computer implementation operations. Computer-readable media (or processor-readable media) are non-transient in the sense that they do not contain transient propagating signals themselves (e.g., propagating electromagnetic waves that carry information on a transmission medium such as space or a cable). Computer code (which may also be called code or algorithms) may be designed and constructed for one or more specific purposes. In some embodiments, memory may be configured to store any received data, as well as data generated by the controller and / or working cells. In some embodiments, memory may be configured to store data temporarily or permanently.
[0038] v. Input devices In some embodiments, the input device, for example, input device 128, may include a display or be coupled to a display. The input device may be any suitable device capable of receiving input from a user, such as a keyboard, buttons, or a touchscreen. 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 to the touch surface). An input device including a touch surface may be configured to detect contact and movement on the touch surface using any of a plurality of touch sensitivity techniques, including capacitive, resistive, infrared, optical imaging, dispersed signaling, acoustic pulse recognition, and surface acoustic wave techniques. In embodiments of an input device including at least one switch, the switch may have at least one of the following: a button (e.g., a hard key, a soft key), a touch surface, a keyboard, an analog stick (e.g., a joystick), a directional pad, a mouse, a trackball, a jog dial, a step switch, a rocker switch, a pointer device (e.g., a stylus), a motion sensor, an image sensor, and a microphone. Motion sensors can receive user movement data from optical sensors and classify user gestures as user input. Microphones can receive acoustic data and recognize user voice as user input.
[0039] In some embodiments, the cell processing system may optionally include one or more output devices in addition to a display, such as an audio device and a haptic device. The acoustic device may audibly output any system data, alarms, and / or notifications. For example, the acoustic device may output an audible alarm when a malfunction is detected. In some embodiments, the acoustic device may include at least one of a speaker, a piezoelectric acoustic device, a magnetostrictive speaker, and / or a digital speaker. In some embodiments, a user may communicate with other users using the acoustic device and communication channels. For example, a user may form a voice communication channel (e.g., a VoIP call).
[0040] vi. Communication devices 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 cell) 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 practical forms, the communication device may include a radio frequency receiver, transmitter, and / or 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.
[0041] vii. Display Image data can be output onto a display of the cell processing system (e.g., display 130). In some embodiments, the display may include at least one of the following: 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.
[0042] viii. Graphical User Interface In some embodiments, as described above, the GUI may be configured for designing processes and monitoring their output. For example, the GUI may be a process design homepage. The GUI may indicate that no process is selected or loaded. A create icon (e.g., "Create Process") may be available for the user to initiate the process design process. In some embodiments, one or more of the GUIs described herein may include a search bar.
[0043] B. Cartridge The cell processing systems described herein may comprise one or more cartridges having one or more modules configured to interface with one or more instruments in a working cell. An exemplary cartridge is illustrated with reference to Figure 1B.
[0044] Various materials may be used to construct the cartridge and cartridge housing, including metal, plastic, rubber, and / or glass, or combinations thereof. The cartridge, its components, and its housing may be manufactured by molding, machining, extrusion, 3D printing, or any combination thereof. The cartridge may contain commercially available components (e.g., tubes, valves, fittings), which may be attached to or integrated with custom components or devices. The cartridge housing may constitute an additional encapsulation layer to further protect the sterility of the cell products.
[0045] In some embodiments, a cartridge module may consist of separate compartments that are fixedly incorporated within the cartridge. Additionally or alternatively, modules may be configurable or movable within the cartridge, allowing for the assembly of various types of cartridges. For example, a cartridge may be a single closed unit with fixed components for each module, or a cartridge may include configurable modules coupled by configurable fluidic, mechanical, optical, and electrical connections. In some modifications, one or more subcartridges, each containing a set of modules, may be used to perform various cell processing workflows. Modules may each be housed in a separate housing, or they may be incorporated together with other modules into a cartridge or subcartridge. While this disclosure generally presents modules as separate groups of components for simplicity, it should be noted that these modules may be arranged in any preferred configuration. For example, components for different modules may be scattered amongst themselves, such that each module is defined by a set of connected components that collectively perform a predetermined function. However, the components of each module may or may not be physically grouped within the cartridge. In some embodiments, a single cell product may be processed using multiple cartridges, by transferring the cell product from one cartridge to another cartridge of the same or different type, and / or by dividing the cell product into more cartridges, and / or by pooling multiple cell products into fewer cartridges.
[0046] Generally, each instrument within a working cell can interface with its respective module on a cartridge. For example, if a cartridge has an electroporation module, the cartridge is moved by a robot to the electroporation instrument within the working cell to perform electroporation on the cells in the cartridge. One advantage of such a segmented module / instrument design is that expensive components (e.g., motors, sensors, heaters, lasers, etc.) can be kept within the system's instruments, while less expensive components reside in cartridges that can be configured for single use. Using disposable cartridges eliminates the need to sterilize cartridges between uses. Furthermore, having multiple instruments within a working cell further facilitates the parallel use of those instruments when multiple cartridges are used within the working cell. In contrast, most conventional semi-automatic instruments have instrument components that are idle and cannot be used simultaneously in parallel.
[0047] In some embodiments, the cartridge includes sterile fluid transfer ports for the transfer of fluid into and out of the cartridge. In some modifications, the cartridge includes any number of sterile fluid transfer ports and any number or positions of fluid paths between the module and the sterile fluid transfer ports.
[0048] The sterile fluid transfer ports described herein can form sterile fluid paths between a fluid device and a cartridge, and / or between a first cartridge and a second cartridge, enabling the transfer of a sterile, fully automated, and precisely metered fluid (e.g., precise control of the flow rate transferred). In some modifications, a robot may be configured to operate the sterile fluid transfer port to open and close the port and its set of valves, thereby enabling fluid flow between the fluid device and the cartridge and / or between the first cartridge and the second cartridge. By using a robot and controller to operate the sterile fluid transfer port, the automation and sterilization of the cell processing system can be facilitated.
[0049] Further embodiments of preferred cartridges are provided, for example, in U.S. Patent Application No. 17 / 198,134, published as U.S. Patent Application Publication No. 2021 / 0283565, entitled "Systems and Methods for Cell Processing," which is incorporated herein by reference.
[0050] C. Fluid devices and systems for automated fluid transfer In general, the fluid devices described herein may be configured to store fluids for automated transfer to other components of a cell processing system, such as cartridges, instruments, or other fluid devices. In some variations, the fluid device for automated fluid transfer may comprise a portable consumable configured to be moved and operated within a working cell using a robot. For example, the robot may be configured to move the fluid device within the working cell from a reagent storage unit to an ISO7 space, or to a sterile fluid transfer device within the cell processing system, such as the fluids described above. The fluid device may enable the transfer of fluids in an automated sterile metering manner for automating the production of cell therapies.
[0051] Referring here to Figure 3A, schematic diagrams of exemplary variations of the fluid device 300 are shown. In some embodiments, the fluid device 300 comprises a container 310 and a collar 320. The container 310 may comprise an opening 312 and at least one collar coupling mechanism 303. In some variations, the opening 312 of the container 310 comprises an annular seal. The collar 320 may comprise one or more robotic engagement mechanisms 328, a fluid conduit 322, a sterilization fluid transfer port 324, a fluid transport mechanism 338 that can be coupled to the opening 312 of the container 310, at least one container coupling mechanism 302 that can be coupled to a corresponding one of the at least one collar coupling mechanism 303 of the container 310, at least one viewing 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 access port 334. In some embodiments, the annular seal of the opening 312 of the container 310 comes into contact with the fluid transport mechanism 338 when the container 310 is coupled to the collar 320, preventing leakage and / or contamination through the coupling.
[0052] In some embodiments, as described above, the container coupling mechanism 302 can be releasably coupled to the collar coupling mechanism 303 of the container 310. The container coupling mechanism 302 and the collar coupling mechanism 303 can be universally designed so 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 modifications, various containers capable of holding various flow rates 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 modifications, the opening 312 of the container may be coupled to the fluid transport mechanism 338 of the collar 320. For this purpose, the opening 312 and the fluid transport mechanism 338 may be coupled by a threaded interface, compression fit, press fit, friction fit, Luer fit, or by another preferred coupling method that allows fluid transfer between the container 310 and the collar 320 without fluid leakage and / or contamination.
[0053] In some embodiments, one or more robotic engagement mechanisms 328 of the collar 320 are engageable by a robot of the work cell, allowing the fluid device 300 to be moved and manipulated in a different manner within the work cell. This enables automated pick-and-place of the fluid device 300 within the work cell. The manipulation of the fluid device 300 within the work cell is described in more detail with reference to Figures 4G-4I and 5J-5L. In some modifications, one or more robotic engagement mechanisms 328 may be at least one recess and / or protrusion in or on the surface of the collar 320. In some embodiments, one or more robotic engagement mechanisms 328 of the collar 320 may also be configured to allow different storage orientations with respect to the reagent storage section of the work cell. For example, one or more robotic engagement mechanisms 328 of the collar 320 may be configured to allow the fluid device 300 to be suspended, for example, in an inverted orientation with respect to the reagent storage section.
[0054] 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 tube exposed to the external environment of the collar 320. The compressible fluid tube may be coupled between an outlet port of the collar 320 that delivers fluid to the compressible fluid tube and an inlet port of the collar 320 that returns fluid to the fluid conduit 322 of the collar 320. In particular, the compressible fluid tube may be close to the outer surface of the collar 320, and as a result, an affector of the working cell may interact with the compressible fluid tube to move fluid into it. For example, the compressible fluid tube of the collar 320 and the affector of the working cell may constitute a peristaltic pump. After the fluid device 300 is coupled, for example, to a cartridge, an affector in the working cell, which may be a cam mechanism (or equivalent), may repeatedly contact the compressible fluid tube. Repeated contact between the affector and the compressible fluid tube results in repeated, controllable compression of the compressible fluid tube. Based on the direction of the affector's movement, this repeated compression pushes the fluid toward the inlet port of the collar 320 and draws the fluid away from the outlet port of the collar 320, ultimately resulting in the transfer of fluid between the fluid device 300 and the cartridge. However, it will be understood that the affector can be operated in other ways as well. For example, the affector may operate to allow bidirectional movement of fluid in the compressible fluid tube, and therefore in the fluid conduit 322 of the collar 320. This bidirectional movement of fluid allows for the possibility of draining fluid from the fluid device 300 for purposes such as culture medium replenishment, and for flowing fluid into the fluid device 300 for purposes such as sample collection.
[0055] In some variations, at least one viewing window 336 may be an opening, a translucent area and / or a transparent area, or any other type of observation point that provides a good view of at least one section of the fluid conduit 322 of the color 320, enabling evaluation of fluid movement within the fluid conduit 322. In some variations, the evaluation may be an optical evaluation of fluid movement within the fluid conduit 322, performed, for example, by a sensor positioned on the sterile fluid transfer device of the working cell. For example, a sensor positioned on the sterile fluid transfer device of the working cell may be aligned with at least one viewing window 336 of the color 320 and may detect a transition from air to liquid within the fluid conduit 322, thereby indicating the start of metered fluid transfer, or it may detect a transition from liquid to air within the fluid conduit 322, thereby indicating that the container 310 is empty. In other variations, the evaluation of fluid movement within the fluid conduit 322 may be performed by an onboard sensor configured to perform an optical, thermal, or electromagnetic evaluation of the fluid conduit 322 and to determine the internal air-liquid interface.
[0056] In some embodiments, the sterile fluid transfer port 324 of the collar 320 may comprise at least one of ports and valves and may form part of a sterile fluid path 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 amount of fluid transferred) fluid transfer. In some modifications, the sterile fluid transfer port 324 may further comprise a mechanical seal and / or path for the sterilizer delivered within the sterile fluid transfer port 324. In some modifications, the mechanical seal may be formed on the surface of the port of the sterile fluid transfer port 324 or as a component thereof. Separately or together, the mechanical seal and sterilizer path help ensure the sterilization of the fluid transfer path. In some modifications, as described in more detail below, a robot in a working cell, which may be a robot of the sterile fluid transfer equipment, may be configured to operate the sterile fluid transfer port 324 to open and close its set of ports and valves, thereby enabling fluid flow between the fluid device 300 and the cartridge and / or other fluid devices. Further details relating to the sterile fluid transfer port and its embodiments are provided, for example, in U.S. Patent Application No. 17 / 331,556, currently issued as U.S. Patent No. 11,376,587, entitled “Fluid Connector,” which is incorporated herein by reference.
[0057] In some modifications, the sterilization port 330 and / or at least one air handling port 332 may be equipped with a valve (e.g., an operating valve, a passive valve). For example, the sterilization port 330 may be coupled to a passive valve and may also deliver a sterilizer from a sterilizer source in the working cell to the sterilizer transfer port 324 of the fluid conduit 322 and collar 320. In one example, the sterilizer source may contain sterilizers such as vaporized hydrogen peroxide, ionized hydrogen peroxide, chlorine dioxide, or ethylene oxide. As described throughout, the sterilizer may be supplied to the sterilizer transfer port 324 via the fluid conduit 322 after the sterilizer transfer port 324 has been coupled to a corresponding sterilizer transfer port such as a cartridge or another fluid device. In some modifications, the sterilizer may be supplied to the sterilizer transfer port 324 after the corresponding port of the connected sterilizer transfer port is activated, which also translates the mechanical seal away from the fluid path, but this is before the corresponding valve of the connected sterilizer transfer port is activated and the fluid is pumped from the fluid device 300 to a cartridge, other fluid device, etc. In this way, the sterilizer can be supplied to the interface between the corresponding valves of the connected sterilizer transfer port before the fluid flows. In some modifications, a fluid pump may be coupled to the sterilizer source and can generate fluid signals to control the circulation of the sterilizer in and out of the sterilizer transfer port 324 via the sterilization port 332. In some modifications, the sterilization port 330 and / or at least one air treatment port 332 may be valveless. In some modifications, at least one air treatment port 332 may be valved (e.g., a pinch valve) and may provide a path for air to enter and exit the fluid device 300 during the filling of the container 310 and / or the depletion of the container 310. In some modifications, at least one air treatment port 332 may be connected to an air source. In some modifications, the air source may include compressed air, which may be used to purge the fluid conduit before and / or after the fluid is transported through the fluid conduit 322 of the collar 320. In some modifications, at least one air treatment port 332 may be connected to an in-line filter capable of preventing contaminants from entering the fluid device 300 during the filling of the container 310 and / or during the depletion of the container 310.In some variations, the inline filter can be a hydrophobic filter.
[0058] In some variations, the air handling port 332, which has a valve (e.g., a pinch valve), may risk leaking fluid (e.g., liquid) from the container 310 when the fluid device 300 is in a particular orientation. For example, the fluid device 300 may be configured to be coupled to one or more components of the work cell 350 in various orientations. A first orientation of the fluid device 300 may be an upright orientation, where the collar 320 (and thus the air handling port 332) may be above the container 310. A second orientation of the fluid device 300 may be an inverted orientation, where the collar 320 (and thus the air handling port 332) may be below the container 310. When the container 310 contains liquid and the fluid device 300 is in an upright position, gravity may prevent the liquid from coming into contact with the inside of the collar 310. Conversely, when the container 310 contains liquid and the fluid device 300 is in the inverted position, gravity may cause the liquid to come into contact with the interior of the collar 310 (e.g., the bottom inner surface and / or its internal components). In addition, in some modifications, valves such as the pinch valve of the air processing port 332 may need to transition from an open configuration to a closed configuration (e.g., to isolate an inline filter), and this transition may take several seconds (approximately 0.5 to 10 seconds, e.g., approximately 1 to 9 seconds, approximately 1.5 to 8 seconds, approximately 2 to 7 seconds, approximately 2.5 to 6 seconds, approximately 3 to 5 seconds, or approximately 3.5 to 4 seconds, etc. (including the entire range and partial ranges in between)). Therefore, when the fluid device is in the inverted orientation and the valve of the air processing port 332 needs to transition from an open configuration to a closed configuration, there may be a risk of liquid leaking out of the container 310 through the valve of the air processing port 332. This leakage could clog the inline filter (potentially blocking or minimizing the effect of air "purging"), reduce the accuracy of the transfer operation, and / or result in cross-contamination between subsequent fluid transfers using the fluid device 300 due to residual fluid in the valve or filter. Therefore, in some examples, the valved air processing port 332 may include a ball valve configured to prevent fluid from moving through the air processing port 332 to the filter while the fluid device 300 is operating in an inverted orientation.The ball valve may be configured to prevent fluid from flowing through specific fluid paths within the valve to the filter, as described in detail with reference to Figures 10 to 12B provided herein.
[0059] In some embodiments, the fluid conduits 322 of the collar 320 can fluidly connect each of the components of the collar 320, including the sterilization fluid transfer port 324, the fluid access port 334, the fluid pump module 326, the fluid transport mechanism 338, the sterilization port 330, and at least one air handling port 332, to the container 310 in any preferred combination. In some modifications, the fluid conduits 322 may be tubes. In some modifications, the fluid conduits 322 may be channels formed within the body of the collar 320. For example, the channels may be etched onto the surface of the body of the collar 320 or integrally formed with that surface, and a substrate may be coupled to the open surface of the channel to provide a fluid seal. In some modifications, the channels may be formed entirely within the body of the collar 320.
[0060] In some variations, the fluid transport mechanism 338 of the collar 320 comprises a vent pipe, a liquid flow pipe, and a fluid port. In some variations, the fluid transport mechanism 338, which can be coupled to the opening 312 of the container 310, may be molded and sized based on the shape and size of the opening 312 of the container 310. In some variations, the vent pipe is configured to extend through the opening 312 of the container 310 and to be disposed within the container 310. The vent pipe may extend substantially from the opening 312 into the opening volume of the container 310 and may 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 pipe further comprises a liquid vent reservoir configured to capture fluid trapped within the vent pipe when the fluid device 300 is inverted. In some variations, the volume of the liquid vent reservoir is at least greater than the amount of fluid that can be trapped within the vent pipe. In this way, the vent pipe and liquid vent reservoir allow the fluid device 300 to be inverted without concern for fluid leakage and / or damage to any component of the fluid device 300 (e.g., an air filter). In some embodiments, the liquid flow pipe of the fluid transport mechanism 338 may be configured to extend through the opening 312 of the container 310 and to be disposed within the container 310. The liquid flow pipe may extend substantially from the opening 312 into the opening volume of the container 310. The liquid flow pipe may provide a liquid connection between the container 310 and the external environment of the fluid device 300. For example, the liquid flow pipe may be connected to a fluid access port 334, which may allow the filling and / or depletion of the liquid in the container 310. In some modifications, the fluid port of the fluid transport mechanism 338 may have an opening within the body of the fluid transport mechanism 338. The fluid port may fluidly connect the container 310 to a sterilization fluid transfer port 324 and / or at least one air processing port 332 via a fluid conduit 322. The fluid port may be used when the fluid device 300 is inverted to allow fluid transfer between the container 310 and another fluid device or cartridge via the sterile fluid transfer port 324.Similarly, when the fluid device 300 is upright, the fluid port can be used to allow fluid to flow from the container 310 to, for example, a sample collection fluid device, via the fluid access port 334 and the liquid flow tube.
[0061] In some variations, the collar 320 of the fluid device 300 further comprises a pressure relief valve located adjacent to the outlet port of the compressible fluid tube of the fluid pump module 326. The outlet port may further fluidize into a vessel 310, and as a result, fluid may flow into the vessel 310 when excessive pressure is present at the outlet port.
[0062] In some variations, the fluid device 300 is reusable. For example, the fluid device 300 may be reusable when it is used for the automated transfer of fluids associated with a single patient. For example, a single fluid device can be used to provide culture medium or other reagents to a cartridge containing patient cells, and then a sample of the cell solution can be recovered from the cartridge for downstream analysis (e.g., quality control operations via QC equipment on the working cell).
[0063] Referring now to Figure 3B, a schematic diagram of an exemplary system for automated fluid transfer, including the fluid device 300 shown in Figure 3A, is provided.
[0064] In some variations, the system 370 for automated fluid transfer comprises a work cell 350 and a fluid device 300. The fluid device 300 comprises a container 310 and a collar 320, as described above. For brevity, any additional redundant description of the fluid device 300 is provided only if necessary to supplement the description of the system 370. In some variations, the work cell 350 of the system 370 comprises a robot 340, a controller 360, a cam 327, a sterilizer source 331, an air source 335, and a sensor 351. In some variations, the sensor 351 may comprise an imaging device utilizing visible light, ultrasound, and fluorescence, and / or a device configured to sense temperature, moisture, electricity, etc., or may be used otherwise. The robot 340 and controller 360 may be substantially the same as those described above with reference to the work cells 110 and 203 in Figures 1A to 2D. Additionally or alternatively, the robot 340 and controller 360 may be provided by the sterile fluid transfer equipment for the work cell 350.
[0065] In some variations, the fluid device 300 may be moved by the robot 340 of the work cell 350 under the control of the controller 360, or otherwise operated. The commands provided by the controller 360 may be influenced by data received from each or a combination thereof from the color 320, cam 327, robot 340, and sensor 351 and processed in the controller 360.
[0066] In some variations, the data received by the controller 360 from the color 320 of the fluid device 320 may include data corresponding to the activity of the fluid pump module 326, the sterilization fluid transfer port 324, the sterilization processing port 330, and / or at least one air processing port 332. The data received by the controller 360 from the cam 327 may include revolutions per minute, direction of rotation, fault detection data, etc. Such data can be used in conjunction with known properties of the fluid conduit 322, such as material, length, and diameter, as well as the compressible fluid tube of the fluid pump module 326, to determine or estimate the flow rate into and / or out of the container 310. This data may include properties of the fluid being transferred (e.g., viscosity). The data received by the controller 360 from the sensor 351 may include optical data acquired through at least one viewing window 336. The optical data may include absorbance, reflectance, and / or fluorescence of the fluid in the fluid conduit 322. Such data can be used by the controller 360 to determine transitions from liquid to air and from air to liquid. The data received by the controller 360 from the robot 340 may include position data, identification data regarding the affected cartridge and / or fluid device, and so on.
[0067] In some variations, the fluid pump module 326 of the collar 320 comprises components of a peristaltic pump, and the controller 360 can control fluid transfer between the fluid device 300 and another fluid device or cartridge by generating signals to the cam 327 to controllably compress the compressible fluid tube of the fluid pump module 326. In some variations, the rotational speed and direction of the cam 327 can be controlled to control the bidirectional flow and flow rate 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 in 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.
[0068] In some variations, the controller 360 transmits signals to the robot 340 to move and / or operate the fluid device 300 via one or more robot engagement mechanisms 328 of the collar 320. Movement and operation of the device may include moving the fluid device 300 within the work cell 350, for example, between the reagent storage unit of the work cell 350 and the sterile fluid transfer device of the work cell 350, and / or controlling the orientation of the fluid device 300. For example, the controller 360 may transmit signals to the robot 340 to position the fluid device 300 in a specific orientation, such as upright or inverted orientation. In some variations, the fluid device 300 may be configured to be in an upright orientation when stored in the reagent storage unit (e.g., the reagent storage unit 118 in Figure 1A). In some variations, the fluid device 300 may be in an inverted orientation when coupled to equipment such as a sterile fluid transfer device (e.g., equipment 112 in Figure 1A) and configured to transfer fluid to a cartridge interfaced with the equipment (e.g., cartridge 114 in Figure 1B).
[0069] In some modifications, the controller 360 generates and / or transmits further signals to the robot 340 to operate the sterilization fluid transfer port 324 of the collar 320 of the fluid device 300, enabling sterilized, automated, and precisely metered (e.g., precise control of the amount of fluid transferred) fluid transfer. For example, a signal to the robot 340 may control the configuration of at least one port and valve of the sterilization fluid transfer port 324. In some modifications, because it relates to opening a flow path between the sterilization fluid transfer port 324 of the fluid device 300 and the sterilization fluid transfer port of another fluid device, the controller 360 may first generate a port signal to the robot 340 to couple at least one port to the corresponding port of the sterilization fluid transfer port of the other fluid device. Coupler of at least one port to the corresponding port may include moving the port to the open position. The controller 360 can then generate a valve signal to the robot 340 to translate a valve to the corresponding valve of the sterilization fluid transfer device of the other fluid device. To finally open the fluid path, the controller 360 may then generate another valve signal to switch the valve and its corresponding valve to an open configuration. After fluid transfer, a similar control signal can be generated to switch the sterile fluid transfer port 324 of the fluid device 300 to a closed configuration.
[0070] In some variations, the controller 360 may generate signals and / or transmit signals to the sterilization port 330 and / or one or more air treatment ports 332 to control the flow of fluid through them. As described above, the sterilization port 330 may be coupled to a passive valve and may be configured to facilitate the delivery of sterilizer from the sterilizer source 331 in the working cell 350 to the fluid conduit 322 and sterilizer transfer port 324 of the collar 320. In some variations, the working cell 350 may further include a fluid pump configured to control the flow of sterilizer into and out of the fluid device 300 based on commands received from the controller 360. For example, the sterilizer transfer port 324 and fluid conduit 322 can be sterilized after the fluid device 300 has been coupled to another fluid device, but before fluid transfer has begun. This sterilization may include flowing sterilizer from the sterilizer source 331 through the fluid conduit 322 into and out of the sterilizer transfer port 324, under the guidance of the controller 360 via the fluid pump.
[0071] In some modifications, at least one air handling port 332 is valved (e.g., a pinch valve) and may provide a path for air to enter and exit the fluid device 300 during filling and / or depletion of the container 310. In some modifications, at least one air handling port 332 may be connected to an air source 335 of the work cell 350. In some modifications, the air source 335 may contain compressed air, which may be used to purge the fluid conduit 322 before and / or after the fluid is transferred through the fluid conduit 322 of the collar 320. In some modifications, the work cell 350 may further include a fluid pump configured to control the flow of air from the air source 335 to enter and exit the fluid device 300 via at least one air handling port 332 based on commands received from the controller 360. For example, after transferring fluid between the fluid device 300 and another fluid device via the fluid pump module 326 of the collar 320, compressed air can be delivered into the fluid conduit 322 to ensure complete transfer of the fluid. In some variations, this air "purge" can be carried out by delivering air to the fluid conduit 322 via at least one air processing port 332. In other variations, this air "purge" can be carried out by delivering air into the container 310 through the fluid transport mechanism 338 via at least one air processing port 332. Compressed air can be delivered through the air processing port 332 at 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 and partial ranges in between). For example, air "purge" can be carried out at about 8 psi or higher to remove clogging from a filter coupled to the air processing port 332.In some variations, the air "purge" may have durations ranging from approximately 1 second to 5 minutes, such as approximately 1.5 seconds to 4 minutes, approximately 2 seconds to 3 minutes, approximately 3 seconds to 2 minutes, approximately 4 seconds to 1 minute, approximately 5 seconds to 45 seconds, approximately 6 seconds to 30 seconds, approximately 8 seconds to 20 seconds, or approximately 10 seconds to 15 seconds (including all and partial ranges in between).
[0072] In some modifications, data from each of the components of the work cell 350 described above may be integrated to carry out automatic fluid transfer. For example, the controller 360 may generate signals to move, invert, and couple the fluid device 300 to another fluid device or cartridge via one or more robot engagement mechanisms 328, and / or send signals to the robot 340. Coupled the fluid device 300 to another fluid device or cartridge involves juxtaposing the respective sterile fluid transfer ports. Each of the respective sterile fluid transfer ports may be provided with a mechanical seal that makes a sealed contact when the sterile fluid transfer port is connected. These mechanical seals help ensure the sterilization of the first mechanism. The controller 360 may generate signals to activate the corresponding port of each sterile fluid transfer port to the open position, and / or send signals to the robot 340. The controller 360 may then send signals to a fluid pump associated with the sterile fluid source 331 to circulate the sterile fluid within the collar 320, and thus within the interfaces between the sterile fluid transfer ports 324 and each sterile fluid transfer port. This may help ensure the sterilization of the second mechanism. After the sterilizer is removed, the controller 360 may operate the corresponding valves of each sterilizing fluid transfer port to generate a signal to open a fluid path between the fluid device 300 and other fluid devices, and / or send a signal to the robot 340. With the fluid path open, the controller 360 may generate a signal to start rotation in a specific direction, and / or send a signal to the cam 327. When the controller 360 receives data from the sensor 351 indicating that an air-to-liquid transition has been detected via at least one viewing window 336, the controller 360 may immediately stop the cam 327 to determine a specific direction, a specific speed, and a specific duration for the cam 327 to rotate in order to generate a controlled fluid flow rate in the fluid conduit 322 of the collar 320 to achieve a desired amount of fluid to be transferred.After a certain duration has elapsed, or when the controller 360 receives data from the sensor 351 indicating that a transition from liquid to air has been detected through at least one window 336, the controller 360 may generate a signal to stop the cam 327. The controller 360 may then generate a signal to supply air to the fluid conduit 322 to purge the line and ensure the completion of the fluid transfer, and / or send a signal to the fluid pump associated with the air source 335. After this air "purge", the controller 360 may generate a separation signal so that the robot 340 separates the sterile fluid transfer port 324 of the fluid device 300 from the corresponding sterile fluid transfer port of another fluid device, reorients it (e.g., repositions the fluid device 300 to an upright orientation), and moves the fluid device 300 to another location.
[0073] Referring here to Figures 4A to 4I, illustrative diagrams of fluid devices for automated fluid transfer are provided. Similar reference numerals are used when referring to Figures 4A to 4I, but not all features are mentioned in each figure.
[0074] In some embodiments, the fluid device 400 comprises a container 410 and a collar 420. As shown in Figure 4F, the container 410 may comprise an opening 412 and at least one collar coupling mechanism 403. In some modifications, the opening 412 of the container 410 comprises an annular seal. As shown in Figures 4A to 4D, the collar 420 may comprise one or more robotic engagement mechanisms, such as a projection 429, as well as a fluid conduit 422, a sterilization fluid transfer port 424 having a mechanical seal 425, at least one container coupling mechanism 402 that can be coupled to a corresponding one of the at least one collar coupling mechanism 403 of the container 410, at least one viewing window 436, a fluid pump module 426 having a compressible fluid tube 467, sterilization ports 430 ("9", "10") and at least one air handling port 432 ("5"), as well as a fluid access port 434.
[0075] In some variations, the compressible fluid tube 457 may be coupled between the outlet port 415 of the collar 420, which delivers fluid to the compressible fluid tube 457, and the inlet port 414 of the collar 420, which returns fluid to the fluid conduit 422 of the collar 420. As seen in Figure 4A, the compressible fluid tube 457 may be close to the outer surface of the collar 420, and as a result, the affector of the working cell may interact with the compressible fluid tube 457 to move fluid into it. For example, the outer surface of the collar 420 may be curved close to the compressible fluid tube 457 so that the cam of the working cell can compress the compressible fluid tube 457.
[0076] In some modifications, as shown in Figure 4B, at least one viewing window 436 is an opening that provides a field of view of at least one section of the fluid conduit 422 of the color 420, enabling optical evaluation of fluid movement within the fluid conduit 422. For example, a sensor placed on the sterile fluid transfer equipment of a working cell may be aligned with at least one viewing window 436 of the color 420 and may detect the transition from air to liquid in the fluid conduit 422, thereby indicating the start of metered fluid transfer, or detect the transition from liquid to air in the fluid conduit 422, thereby indicating that the container 410 is empty. In some modifications, the sensors may be bubble sensors 1 and 2 placed within the color 420. Bubble sensors 1 and 2 may be configured to detect the transition from air to liquid in the fluid conduit 422, thereby indicating the start of metered fluid transfer, or detect the transition from liquid to air in the fluid conduit 422, thereby indicating that the container 410 is empty.
[0077] In some modifications, the sterile fluid transfer port 424 of the collar 420 may comprise at least one of a port 417 and a valve (not shown) and may form part of a sterile fluid path 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 amount of fluid transferred) fluid transfer. As shown in Figures 4A, 4B, and 4C, the sterile fluid transfer port 424 may comprise a mechanical seal 425. The mechanical seal 425 helps to provide sterility in the fluid transfer path between the fluid device 400 and the other fluid device or cartridge. In some modifications, a robot in the working cell, which may be a robot of the sterile fluid transfer equipment, may be configured to operate the fluid device 400 via the projection 429 and alignment mechanism 418 of the sterile fluid transfer port 424 and to couple the fluid device 400 to the other fluid device or cartridge. Furthermore, the robot may be configured to operate the sterilization fluid transfer port 424 to open and close a set of ports and valves, including at least one of the ports 417, thereby enabling fluid flow between the fluid device 400 and the cartridge or another fluid device.
[0078] In some modifications, as shown in Figures 4A, 4B, and 4C, the sterilization port 430 may be configured to deliver a sterilizer (e.g., vaporized hydrogen peroxide, VHP) from a sterilizer source in the working cell to the fluid conduit 422 and sterilizer transfer port 424 of the collar 420 (e.g., via the sterilizer input 8). In some modifications, at least one air treatment port 432 may provide a path for air to enter and exit the fluid device 400 during the filling and / or depletion of the container 410. In some modifications, at least one air treatment port 432 may be connected to an air source (e.g., the atmosphere). In some modifications, the air source may include compressed air, which may be used to purge the fluid conduit (via the air purge pipe 4) before and / or after the fluid is transferred through the fluid conduit 422 of the collar 420. In some modifications, at least one air treatment port 432 may be equipped with an in-line filter. Therefore, in some embodiments, the fluid device may advantageously include at least two sterilization means, for example, via a mechanical seal 425 and via the delivery of at least one sterilizing agent.
[0079] In some variations, the fluid conduit 422 of the collar 420, which may include a transfer pipe 6 (fluid input to the fluid pump module 426), a transfer extension 18 (fluid from the container 510), a transfer end 3 (fluid injected into the sterilization fluid transfer port 424), a sterilization input 8 (entering the sterilization fluid transfer port 424), and a sterilization output 7 (exiting the sterilization fluid transfer port 424), can fluidically connect each of the components of the collar 420, including the sterilization fluid transfer port 424, a fluid access port 434, a fluid pump module 426, a fluid transport mechanism 438, a sterilization processing port 430, and at least one air processing port 432, as well as the container 410, in any preferred combination. As shown in Figures 4A to 4D, the fluid conduit 422 may be a tube.
[0080] In some modifications, the fluid conduit 422 of the collar 420 may be fluidically coupled to the container 410 via a fluid transport mechanism 438 that can be coupled to the opening 412 of the container 410, as shown in Figure 4E. In particular, Figure 4E shows a fluid transport mechanism 438 ("13 / 14") that is connected to the opening 412 of the container 410 but separate from the rest of the fluid conduit 422 of the collar 420. The fluid transport mechanism 438 comprises a vent pipe 442 ("15"), a liquid flow pipe 443 ("17"), and a fluid port 446 ("16"). In some embodiments, the fluid transport mechanism 438 that can be coupled to the opening 412 of the container 410 may be molded and sized based on the shape and size of the opening 412 of the container 410. For example, the fluid transport mechanism 438 may be substantially circular and / or cylindrical. In some modifications, the vent pipe 442 is configured to extend through the opening 412 of the container 410 and to be disposed within the container 410. The vent pipe 442 may extend substantially from the opening 412 into the opening volume of the container 410 and may provide an air connection between the container 410 and the external environment of the fluid device 400 via the fluid conduit 422 of the collar 420. In some modifications, the vent pipe 442 further comprises a liquid vent reservoir configured to capture the fluid trapped within the vent pipe 442 when the fluid device 400 is inverted. In some modifications, the volume of the liquid vent reservoir is at least greater than the amount of fluid that can be trapped within the vent pipe 442. In this way, the vent pipe 442 and the liquid vent reservoir allow the inversion of the fluid device 400 without concern for fluid leakage and / or damage to any component of the fluid device 400 (e.g., saturation of the air filter). In some embodiments, the liquid flow tube 443 of the fluid transport mechanism 438 may be configured to extend through the opening 412 of the container 410 and be disposed within the container 410. The liquid flow tube 443 may extend substantially from the opening 412 into the opening volume of the container 410. The liquid flow tube 443 may provide a liquid connection between the container 410 and the external environment of the fluid device 400. For example, the liquid flow tube 443 may be connected to a fluid access port 434, which may allow filling and / or depletion of the liquid in the container 410.In some modifications, the fluid port 446 of the fluid transport mechanism 438 may have an opening within the body of the fluid transport mechanism 438. The fluid port 446 may fluidly connect the container 410 to the sterile fluid transfer port 424 and / or at least one air processing port 432 via the fluid conduit 422. In one modification, the fluid port 446 may be used when the fluid device 400 is inverted to allow fluid transfer out of the container 410 via the sterile fluid transfer port 424 into another fluid device or cartridge. In another modification, when the fluid device 400 is upright, the fluid port 446 may be used to allow fluid to flow from the container 410 into, for example, a sample collection fluid device, via the fluid access port 434 and the liquid flow conduit 443.
[0081] In some modifications, the collar 420 of the fluid device 400 further comprises a pressure relief valve (not shown) adjacent to the outlet port 415 of the compressible fluid tube 457 of the fluid pump module 426. The outlet port 415 may further fluidize into a vessel 410, and as a result, fluid may flow into the vessel 410 when excessive pressure is present at the outlet port 415.
[0082] In some variations, the container 410 of the fluid device 400 further comprises a user gripping mechanism 454 to allow the user to manually operate the container 410 and / or the fluid device 400, if necessary. For example, the user gripping mechanism 454 may allow the user to perform a snap-fit between the container 410 and the collar 420.
[0083] Referring next to Figures 4G to 4I, exemplary drawings of engagement between a robot in a work cell and an exemplary fluid device for automated fluid transfer are provided. In particular, Figures 4G to 4I provide an exemplary gripping mechanism in which the fluid device can be operated by the robot in the work cell. In some modifications, the robot in the work cell may be a robot of a sterile fluid transfer device. However, for clarity, the gripping described below is generally performed within a work cell and controlled by a controller (such as controller 360 in Figure 3B).
[0084] As shown in Figure 4G, engagement or gripping between the robot 440 of the work cell and the fluid device 400 includes coupling between the robotic gripping mechanism 453 of the robot 440 and at least one of the robotic engagement mechanisms 428 of the fluid device 400. In some modifications, coupling between the robot 440 and the fluid device 400 includes receiving at least one robotic engagement mechanism 428 within the opening of the robotic gripping mechanism 453. As partially shown in Figure 4H, at least one robotic engagement mechanism 428 may be received within the opening 473 of the robotic gripping mechanism 453. Figure 4I is a cross-sectional view of an exemplary drawing of the robotic gripping mechanism 453, showing a first clamp 474 and a second clamp 475 configured to translate relative to the opening 473. Specifically, after at least one robot engagement mechanism 428 of the fluid device 400 is received within the opening 473 of the robot gripping mechanism 453, the first clamp 474 and the second clamp 475 can translate toward the opening 473 to grip at least one robot engagement mechanism 428, and thus the fluid device 400. After the clamps 474, 475 are engaged with the fluid device 400 via at least one robot engagement mechanism 428, the robot 440 can manipulate the fluid device 400 as required by the methods described herein (e.g., rotate, translate, reverse).
[0085] Referring here to Figures 5A to 5L, diagrams of another exemplary fluid device for automated fluid transfer are provided. Similar reference numerals are used in Figures 5A to 5L, but not all features are mentioned in each figure.
[0086] In some variations, the fluid device 500 comprises a container 510 and a collar 520. As shown in Figure 5I, the container 510 may comprise an opening 512 and at least one collar coupling mechanism 503. In some variations, the opening 512 of the container 510 comprises an annular seal. As shown in Figures 5A to 5E, the collar 420 may comprise one or more robotic engagement mechanisms, such as a recess 529, as well as a fluid conduit 522, a sterilization fluid transfer port 524 having a mechanical seal 525, a fluid transport mechanism 538 that can be coupled to the opening 512 of the container 510, at least one container coupling mechanism 502 that can be coupled to one of the corresponding one of the at least one collar coupling mechanisms 503 of the container 510, at least one viewing window 536, a fluid pump module 526 having a compressible fluid tube, a sterilization port 530 and at least one air handling port 532, as well as a fluid access port 534.
[0087] In some variations, a compressible fluid tube (not shown) may be coupled between the outlet port 515 of the collar 520, which delivers fluid to the compressible fluid tube, and the inlet port 514 of the collar 520, which returns fluid to the fluid conduit 522 of the collar 520.
[0088] In some variations, as shown in Figure 5B, at least one viewing window 536 may be an opening that provides a field of view of at least one section of the fluid conduit 522 of the color 520, enabling optical evaluation of fluid movement within the fluid conduit 522. For example, a sensor positioned on the sterile fluid transfer device of a working cell may be aligned with at least one viewing window 536 of the color 520 and may detect a transition from air to liquid in the fluid conduit 522, thereby indicating the start of metered fluid transfer, or it may detect a transition from liquid to air in the fluid conduit 522, thereby indicating that the container 510 is empty.
[0089] In some modifications, the sterile fluid transfer port 524 of the collar 520 may comprise at least one of the port 517 and a valve (not shown) and may form part of a sterile fluid path 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 amount of fluid transferred) fluid transfer. As shown in Figures 5A, 5B, and 5C, the sterile fluid transfer port 524 may comprise a mechanical seal 525. The mechanical seal 525 may help provide sterility in the fluid transfer path between the fluid device 500 and another fluid device or cartridge. In some modifications, a robot of the working cell, which may be a robot of the sterile fluid transfer equipment, may be configured to operate the fluid device 500 via the recess 529 and alignment mechanism 518 of the sterile fluid transfer port 525 and to couple the fluid device 500 to another fluid device or cartridge. Furthermore, the robot may be configured to operate the sterilization fluid transfer port 524 to open and close a set of ports and their valves, including at least one of the ports 517, thereby enabling fluid flow between the fluid device 500 and the cartridge or other fluid device.
[0090] In some modifications, as shown in Figures 5A, 5B, and 5C, the sterilization port 530 may be configured to deliver a sterilizer (e.g., vaporized hydrogen peroxide ("VHP")) from a sterilizer source in the working cell to the fluid conduit 522 and sterilizer transfer port 524 of the collar 520. In some modifications, at least one air treatment port 532 may provide a path for air to enter and exit the fluid device 500 during the filling and / or depletion of the container 510. In some modifications, at least one air treatment port 532 may be connected to an air source (e.g., the atmosphere). In some modifications, the air source may include compressed air, which may be used to purge the fluid conduit before and / or after the fluid is transferred through the fluid conduit 522 of the collar 520. In some modifications, at least one air treatment port 532 may include an in-line filter, such as a filter 533. The filter 533 may be a hydrophobic filter.
[0091] As described above with reference to Figure 3B, the valved air handling ports described herein may risk leaking fluid (e.g., liquid) from the container when the fluid device is in a specific orientation, such as during operation of the fluid device in an inverted orientation. Therefore, in some examples, the valved air handling ports described herein may include a ball valve configured to prevent fluid from moving through the port to the filter when the fluid device 300 is operating in an inverted orientation. That is, the ball valve can prevent fluid from flowing through a specific fluid path in the valve to the filter. In some modifications, the fluid device may be configured to be in an inverted orientation (e.g., container side up) when coupled to equipment in a working cell (e.g., sterile fluid transfer equipment) for fluid transfer operations with a cartridge interfaced with the equipment. In some modifications, the ball valve may be mounted on the collar of the fluid device. The ball valve can be mounted to the collar using any preferred mechanism such as welding (e.g., laser welding), adhesive, or fasteners. In some modifications, the ball valve and collar may be integrated (e.g., a single structure). An exemplary such ball valve 1002 is shown in Figure 10. As shown in the figure, the ball valve 1002 can be coupled to the manifold 1004 of the fluid device collar 1000 (for example, on its bottom inner surface).
[0092] In particular, the ball valve described herein may include a housing having an inlet, a hollow interior, and an outlet (creating a path for fluid flow toward a filter), and may be configured to carry a ball inside. In some modifications, the housing may further include a top cover. The housing may be made of any preferred material such as metal (e.g., aluminum) and / or plastic. In some modifications, the housing may be constructed of metal (e.g., aluminum) and may be machined (with or without a collar for the fluid device). Furthermore, the housing may have any preferred shape. For example, the housing may have one or more straight sidewalls (e.g., one, two, three, four, five, or more than five straight sidewalls, e.g., four straight sidewalls) and / or one or more rounded sidewalls (e.g., one, two, three, four, five, or more than five straight sidewalls, e.g., three rounded sidewalls). The hollow interior of the housing may have a constant or variable width, for example, about 1 mm to about 5 mm, for example, about 1.5 mm to about 4.75 mm, about 2 mm to about 4.5 mm, about 2.5 mm to about 4.25 mm, or about 3 mm to about 4 mm (including all and partial ranges in between). Furthermore, the height of the housing may be constant or variable, and may be about 1 mm to about 20 mm, for example, about 1.5 mm to about 15 mm, about 2 mm to about 10 mm, about 2.5 mm to about 9 mm, or about 3 mm to about 8 mm, about 3.5 mm to about 7 mm, about 4 mm to about 6 mm, or about 4.5 mm to about 5 mm (including all and partial ranges in between). In some modifications, one or both of the inlet and outlet of the housing may extend from its surface, such as from the bottom of the housing. For example, one or both of the inlet and outlet may have an exterior extending from the housing and a lumen through it. The exterior of the inlet and / or outlet may be any preferred shape, such as cylindrical or rectangular. In some modifications, the exterior of the inlet and / or outlet may have a constant or variable height of 1 mm to about 10 mm, for example, about 1.5 mm to about 9 mm, about 2 mm to about 8 mm, about 2.5 mm to about 7 mm, or about 3 mm to about 6 mm, about 3.5 mm to about 5 mm, or about 4 mm to about 4.5 mm (including all and partial ranges in between).Furthermore, the lumens of the inlet and / or outlet may have a constant or variable width, i.e., diameter, of about 1 mm to about 5 mm, for example, about 1.5 mm to about 4.75 mm, about 2 mm to about 4.5 mm, about 2.5 mm to about 4.25 mm, or about 3 mm to about 4 mm (including all and partial ranges in between). In some modifications, a portion (e.g., at least a portion) of one or both of the lumens of the inlet and outlet may be tapered. As an example, the outlet may have a lumen comprising a first portion having a first width, i.e., diameter, a second portion having a smaller width, i.e., diameter, and a tapered portion. The first width, i.e., diameter may be about 3 mm to about 4 mm, for example, about 3.7 mm, and the second width, i.e., diameter may be about 1 mm to about 2 mm, for example, about 1.6 mm. As another example, the outlet may have a lumen comprising a first portion having a first width, i.e., diameter, and a second portion having a smaller width, i.e., diameter, may extend directly from the first portion.
[0093] Furthermore, the housing of the ball valve may be configured to support a ball within the outlet of the housing, for example, within a first portion of the outlet lumen (e.g., having the widest width, i.e., diameter). In some modifications, the diameter of the ball may be approximately equal to or smaller than the first width, i.e., diameter of the first portion of the outlet lumen, and approximately equal to or larger than the second width, i.e., diameter of the second (e.g., lower) portion of the lumen. Thus, the ball may be configured to fit between the first and second portions of the outlet lumen when the fluid device is inverted orientation, and thus partially (e.g., at least partially) block the fluid flow through the outlet lumen (thus preventing fluid from leaking onto the inline filter). Furthermore, the ball may be made of any preferred material such as metal, plastic, or rubber (e.g., silicone).
[0094] In some variations, the housing may further include a ball stopper to maintain the position of the ball in the outlet lumen when the fluid device is oriented upright (e.g., with the container side down). The ball stopper may be molded to allow fluid flow through the outlet lumen while preventing the ball from moving within the hollow interior of the housing when the fluid device is oriented upright and inverted. In particular, the ball stopper may include one or more conduits, such as a plurality of conduits extending through the ball stopper, allowing airflow around the ball when the fluid device is inverted, and thus enabling an operating air "purge" procedure when the fluid device is inverted. The plurality of conduits in the ball stopper may include two, three, four, five, or more than five fluid conduits. In some variations, the ball stopper may have a plurality of legs, such as two, three, four, five, or more than five legs, one or more of which may include a conduit extending through the ball stopper. The legs may have a length approximately equal to or shorter than half the radius, i.e., width, of the outlet lumen. In some modifications, the ball stopper may be configured to be press-fitted into the outlet lumen.
[0095] Figures 11A and 11B show more detailed modifications of the ball valve 1100. Figure 11A shows a perspective view of the ball valve 1100 in an inverted orientation. Figure 11B shows an exploded view of the ball valve 1100 in an inverted orientation. As shown in both Figures 11A and 11B, the housing 1102 of the ball valve 1100 includes an upper cover 1104, an inlet 1106, a hollow interior 1108, an outlet 1110, a ball retainer 1112, and a ball 1114. The ball retainer 1112 includes several conduits 1213, such as three conduits extending through the ball retainer 1112. As shown in Figure 11A, in the inverted orientation, the ball 1114 rests between the first portion 1116 and the second portion 1118 of the outlet 1110 because the first portion 1116 has a larger inner diameter than the second portion 1118 of the outlet 1110.
[0096] Similarly, Figure 12A shows the fluid path through the ball valve 1200 when the fluid device 1220 having the ball valve 1200 is in the inverted position. As shown, in the inverted position, the vessel 1222 of the fluid device 1220 is above the collar 1224 of the fluid device 1220. In this position, the fluid (e.g., liquid) can flow through the inlet 1206 of the housing 1202, the hollow interior 1208, and the ball stopper 1212 (e.g., through its conduit 1213). However, the ball 1214 prevents the fluid from flowing out of the outlet 1210, thereby preventing the fluid from leaking onto a filter or other component coupled to the outlet 1210. Conversely, Figure 12B shows the fluid path through the ball valve 1200 when the fluid device 1220 is in the upright position. As shown, in the upright position, the vessel 1222 of the fluid device 1220 is below the collar 1224 of the fluid device 1220. In this position, the fluid (e.g., liquid) can flow through the inlet 1206 of the housing 1202, the hollow interior 1208, and the ball stopper 1212 (e.g., through its conduit 1213). Furthermore, since the ball 1210 is stationary on the ball stopper 1212 in this position, the fluid (e.g., air) can exit through the outlet 1210.
[0097] Returning to Figures 5A to 5L, in some modifications, the fluid conduits 522 of the collar 520 can fluidly connect each of the components of the collar 520, including the sterilization fluid transfer port 524, the fluid access port 534, the fluid pump module 526, the fluid transport mechanism 538, the sterilization port 530, and at least one air handling port 532, to the container 510 in any preferred combination. As shown in Figure 5D, which provides a cross-sectional view of the body of the collar 520, and Figure 5E, which shows a plan view of the bottom of the collar 520, the fluid conduits 522 can be channels 563 formed within the body of the collar 520. For example, the channels 563 may be etched onto the surface of the body of the collar 520, and a substrate 562 may be coupled to the open surface of the channels 563 to provide a fluid seal. The channels 563 can fluidly connect each of the components of the collar 520 within the collar 520 to the container 510 in any preferred combination.
[0098] For example, as shown in Figures 5D and 5E, the fluid conduit 522 can form a three-dimensional network of channels 563 that allows fluid to move within and out of the collar 520, while maintaining a feasible form factor and simplicity of user interaction. Channel 563 includes a sterilization channel 566 connected to at least one sterilization port 530 and a sterilization fluid transfer port 524; a ventilation channel 564 connected to a vent pipe (e.g., a vent pipe 542); an air treatment channel 565 connected to at least one air treatment port 532, a container 510 of a certain volume, and a sterilization fluid transfer port 524; a pressure relief channel 567 connected to, for example, a fluid pump module 526 and a container 510 of a certain volume; a user fluid channel 568 connected to a fluid access port 534 and a container 510 of a certain volume; and a transport fluid channel 569 connected to a container 510 of a certain volume and a sterilization fluid transfer port 524, wherein the transport fluid channel 569 is configured to enable automatic fluid transfer between one fluid device and another fluid device.
[0099] In some variations, the fluid transport mechanism 538 of the collar 520 comprises a vent pipe 542, a liquid flow pipe 546, a fluid port 543, a pressure relief port 548, and an annular seal 539. In some embodiments, the fluid transport mechanism 538, which can be coupled to the opening 512 of the container 510 by screwing, can be molded and sized based on the shape and size of the opening 512 of the container 510. For example, the fluid transport mechanism 538 may 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 transport mechanism 538 can minimize, if not eliminate, fluid leakage and the resulting potential contamination.
[0100] In some modifications, the vent pipe 542 is configured to extend through the opening 512 of the container 510 and to be disposed within the container 510. The vent pipe 542 may extend substantially from the opening 512 into the opening 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 the fluid conduit 522 of the collar 520. In some modifications, the vent pipe 542 further comprises a vent pipe reservoir 544 configured to capture the fluid trapped within the vent pipe 542 when the fluid device 500 is inverted. In some modifications, the volume of the vent pipe reservoir 544 is at least greater than the amount of fluid that can be trapped within the vent pipe 542. In this way, the vent pipe 542 and the vent pipe reservoir 544 allow the inversion of the fluid device 500 without concern for fluid leakage and / or damage to any component of the fluid device 500 (e.g., an air filter). Additional drawings of the vent pipe 542 and its embodiments are shown in Figures 5G and 5H. In some embodiments, the vent pipe 542 comprises a vent pipe reservoir 544, a vent pipe deflector 545, and a pipe extending from the vent pipe reservoir 544. When the fluid device 500 is reversed, the amount of fluid confined within the vent pipe 542 flows toward the vent pipe deflector 545, while air (indicated by the green arrow) flows in the opposite direction. As shown in Figure 5H, the confined amount of fluid flowing toward the vent pipe deflector 545 comes into contact with the vent pipe deflector 545 and is deflected laterally away from the opening of the vent pipe deflector 545 into the trapping space of the vent pipe reservoir 544. In this manner, the vent pipe 542 of the fluid transport mechanism 538 of the collar 520 of the present disclosure prevents the vent pipe 542 from being blocked and / or the air filter otherwise coupled to the fluid conduit 522 from being blocked, and thus allows air to be refilled into the container 510 during fluid transport.
[0101] In some variations, returning to Figures 5A, 5B, and 5F, the liquid flow tube 546 of the fluid transport mechanism 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 opening 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 a fluid access port 534, which may allow filling and / or depletion of the liquid in the container 510.
[0102] In some modifications, the fluid port 543 of the fluid transport mechanism 538 may have an opening within the body of the fluid transport mechanism 538. The fluid port 543 may fluidly connect the container 510 to the sterilization fluid transfer port 524 and / or at least one air processing port 532 via the fluid conduit 522. In one modification, the fluid port 543 may be used when the fluid device 500 is inverted to allow fluid transfer out of the container 510 via the sterilization fluid transfer port 524 and into another fluid device or cartridge. In another modification, when the fluid device 500 is upright, the fluid port 543 may be used to allow fluid to flow from the container 510 into, for example, a sample collection fluid device, via the fluid access port 534 and the liquid flow conduit 546.
[0103] In some variations, the collar 520 of the fluid device 500 further comprises a pressure relief valve adjacent to the outlet port 515 of the compressible fluid tube of the fluid pump module 526. The outlet port 515 may further fluidize into a vessel 510 via a pressure relief valve 548, and as a result, fluid may flow into the vessel 510 when excessive pressure is present at the outlet port 515.
[0104] In some variations, the container 510 of the fluid device 500 further comprises a user gripping mechanism 554 to allow the user to manually operate the container 510 and / or the fluid device 500, if necessary. For example, the user gripping mechanism 554 may allow the user to perform a snap-fit between the container 510 and the collar 520.
[0105] Next, referring to Figures 5J to 5L, exemplary drawings of engagement between a robot in a work cell and an exemplary fluid device for automated fluid transfer are provided. In particular, Figures 5J to 5L provide exemplary gripping mechanisms in which the fluid device can be operated by the robot in the work cell. In some modifications, the robot in the work cell may be a robot of a sterile fluid transfer device. However, for clarity, the gripping described below is generally performed within the work cell and controlled by a controller (such as controller 360 in Figure 3B).
[0106] As shown in Figure 5J, engagement or gripping between the robot 540 of the work cell and the fluid device 500 includes a coupling between the robotic gripping mechanism 553 of the robot 540 and at least one of the robotic engagement mechanisms (shown as reference numeral 529 in Figure 5A) of the fluid device 500, where the robotic engagement mechanism is a recess, an opening, etc. In some modifications, the coupling between the robot 540 and the fluid device 500 includes sliding contact between a first clamp 574 and a second clamp 575 of the robotic gripping mechanism 553, as better shown in Figures 5K and 5L. In particular, the first coupling position of the clamps 574, 575 and their respective robotic engagement mechanisms 528 is shown in Figure 5K. In the first coupling position, the first clamp 574 and the second clamp 575 engage with the opening defined by their respective robotic engagement mechanisms 528. After being inserted into their respective openings, the first clamp 574 and the second clamp 575 translate in opposite directions toward the second coupling position, thereby engaging the clamps 574 and 575 with the surfaces of their respective robot engagement mechanisms 528 and gripping the fluid device 500. As shown in Figure 5L, after the clamps 574 and 575 are engaged with the fluid device 500 via at least one robot engagement mechanism 528, the robot 540 can manipulate the fluid device 500 as required by the methods described herein (e.g., rotating, translating, reversing).
[0107] II. Automatic fluid transfer method This specification also describes methods for fluid transfer, such as automated fluid transfer within cell processing systems.
[0108] First, a framework for automated fluid transfer will be described with reference to Method 600 in Figure 6.
[0109] Method 600 may first include, in step 602, connecting the sterile fluid transfer port of a fluid device to a corresponding sterile fluid transfer port of another fluid device or cartridge. Connecting may include moving and / or manipulating one fluid device relative to another fluid device or cartridge by a robot. For example, a sterile fluid transfer port alignment mechanism may be used by a robot to align and connect the sterile fluid transfer ports. In some modifications, the robot may move and manipulate the fluid device relative to the sterile fluid transfer equipment of a working cell to which the other fluid device or cartridge is connected.
[0110] Initially, the corresponding port of the sterile fluid transfer port may be in a closed configuration, and a mechanical seal disposed on the surface of the corresponding port provides a primary seal. In step 604, the robot can actuate the corresponding port of the sterile fluid transfer port to the open position.
[0111] In step 606, the sterilizer may flow into the sterilizer transfer port of the fluid device via the fluid conduit. In particular, the sterilizer source of the working cell may be coupled to the sterilization port of the color of the fluid device, and the sterilizer may circulate within the fluid conduit and the sterilizer transfer port. In some modifications, the sterilizer may circulate within the fluid conduit of the fluid device and within the interface formed by the corresponding port of the connected sterilizer transfer port, which is activated and opened in step 604. In some modifications, the sterilizer may circulate within the fluid conduit and the sterilizer transfer port for residence times of up to about 10 minutes, or about 1 to about 10 minutes, about 2 to about 9 minutes, about 3 to about 8 minutes, about 4 to about 7 minutes, and about 5 to about 6 minutes (including all ranges and partial values in between). In some variations, the sterilizer may contain vaporized hydrogen peroxide at concentrations of approximately 50%–70%, approximately 55%–65%, approximately 56%–64%, approximately 57%–63%, approximately 58%–62%, and approximately 59%–61% (including all ranges and partial values in between).
[0112] Generally, sterilization of a sterile fluid transfer port may involve one or more steps of dehumidification, conditioning, decontamination, sterilization (using a sterilizing agent), and ventilation (e.g., air circulation).
[0113] In some variations, step 606 may further include dehumidifying the sterile fluid transfer port of the sterile fluid transfer device. For example, pressurized hot air may optionally circulate through at least one air treatment port within the sterile fluid transfer port to remove residual fluid, moisture, and raise the temperature of the inner surface of the sterile fluid transfer port.
[0114] In step 608, the robot may actuate valves in the sterile fluid transfer ports. The actuateate of valves in the sterile fluid transfer ports moves the fluid path between them to the open position. In some modifications, the valves may be translated relative to one another. Step 608 may include translating the valve of the sterile fluid transfer port of a fluid device relative to the valve of the corresponding sterile fluid transfer port of another fluid device or cartridge. In some modifications, the valves may include a spring-loaded shutoff that is configured to actuate to the open position when it comes into contact with the opposing valve, thereby enabling fluid communication between the sterile fluid transfer ports. In some modifications, each of the multiple valves may include a corresponding engagement mechanism, such as threading, configured to facilitate coupling between the valves. For example, when the valve of the sterile fluid transfer port of a fluid device is translated and comes into contact with the valve of the corresponding sterile fluid transfer device of another fluid device or cartridge, the valve engagement mechanism may be coupled (e.g., locked) by rotating (e.g., twisting) one of the valves and engaging their individual threads with each other. Conversely, one of the valves can be rotated in the opposite direction to disengage (e.g., unlock) the valve.
[0115] After translating the valve to the open position to allow fluid transfer between the sterile fluid transfer ports, fluid transfer can be initiated in step 610. For example, the contents of a fluid device and other fluid devices or cartridges (e.g., fluid, biological material) can be transferred through the sterile fluid transfer ports. The speed and direction of fluid transfer can be determined by the fluid conduit, the fluid pump module of the fluid device collar, and the corresponding cam of the working cell communicating with the controller of the working cell.
[0116] After the desired amount of fluid has been transferred, in step 612, the fluid conduit and sterile fluid transfer port can be purged. In some modifications, compressed air may be supplied to the fluid conduit and sterile fluid transfer port via at least one air treatment port on the collar of the fluid device. By purging the fluid conduit and sterile fluid transfer port, method 600 ensures that the entire desired amount of fluid has been transferred.
[0117] In step 614, the valves may be translated so that they move away from each other in order to initiate the disengagement of the sterile fluid transfer ports. In some modifications, the robot may be configured to operate the sterile fluid transfer ports to move the valves to the closed position and / or translate the valves away from each other, which may be done simultaneously or independently. The valves in the closed position block the flow of fluid through the sterile fluid transfer ports. The robot may then be configured to move the ports of the sterile fluid transfer ports to the closed position. Thus, in step 616, the fluid path between the sterile fluid transfer ports may be closed and the sterile fluid transfer ports separated.
[0118] Further details relating to the sterilization fluid transfer port and its embodiments are provided, for example, in U.S. Patent Application No. 17 / 331,556, entitled “Fluid Connector,” which is incorporated herein by reference.
[0119] Referring here to Figures 7A, 7B, 7C, 7D, 7E, and 7F, flow diagrams of exemplary modifications of the method for automated fluid transfer are shown. 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 may be carried out by the controller of the working cell, either in conjunction with, or instead of, the sterile fluid transfer equipment of the working cell, or independently thereof.
[0120] Figure 7A is a flow diagram of an exemplary method 700A for automated fluid transfer, in which a fluid is transferred from one fluid device to another fluid device or cartridge. Such fluid transfer may be necessary, for example, to supply a culture medium for a bioreactor module inside a cartridge.
[0121] First, Method 700A provides a fluid device pre-filled with fluid. The fluid device may be filled, for example, by a user in a biosafety cabinet outside the working cell, or by a commercial fluid supplier. In step 705 of Method 700A, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 710, the robot may connect the sterile fluid transfer port of the fluid device to a corresponding sterile fluid transfer port of another fluid device or cartridge. In some modifications, this connection may be made within the working cell and / or within the sterile fluid transfer equipment of the working cell. Connecting the sterile fluid transfer ports may involve the robot operating the ports and valves of the sterile fluid transfer ports, as described above with reference to Figure 6. In step 715, the fluid may be transferred from the fluid device to another fluid device or cartridge. Specifically, a cam in the working cell may be configured to engage with the fluid pump module of the fluid device to control the movement of fluid out of the fluid device and into the other fluid device or cartridge via the sterile fluid transfer port.
[0122] Figure 7B is a flow diagram of an exemplary method 700B for automated fluid transfer, in which a fluid is transferred from one fluid device to another fluid device or cartridge. Such fluid transfer may be necessary, for example, to supply a culture medium for a bioreactor module inside a cartridge.
[0123] First, Method 700B provides a fluid device pre-filled with fluid. The fluid device may be filled, for example, by a user in a biosafety cabinet outside the working cell, or by a commercial fluid supplier. In step 705 of Method 700B, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 710, the robot may connect the sterile fluid transfer port of the fluid device to a corresponding sterile fluid transfer port of another fluid device or cartridge. In some modifications, this connection may be made within the working cell and / or within the sterile fluid transfer equipment of the working cell. Connecting the sterile fluid transfer ports may include the operation of the ports and valves of the sterile fluid transfer ports by the robot, as described above with reference to Figure 6. In step 715, the fluid may be transferred from the fluid device to another fluid device or cartridge. Specifically, a cam in the working cell may be configured to engage with the fluid pump module of the fluid device to control the movement of fluid out of the fluid device and into the other fluid device or cartridge via the sterile fluid transfer port. In step 725, after the fluid is transferred via the fluid pump module of the fluid device, compressed air can be supplied to the fluid conduit and sterile fluid transfer port of the fluid device to purge the collar of the transferred fluid.
[0124] Figure 7C is a flow diagram of an exemplary method 700C for automated fluid transfer, in which a fluid is transferred from one fluid device to another fluid device or cartridge. Such fluid transfer may be necessary, for example, to supply a culture medium for a bioreactor module inside a cartridge.
[0125] First, Method 700C provides a fluid device pre-filled with fluid. The fluid device may be filled, for example, by a user in a biosafety cabinet outside the working cell, or by a commercial fluid supplier. In step 705 of Method 700C, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 710, the robot may connect the sterile fluid transfer port of the fluid device to a corresponding sterile fluid transfer port of another fluid device or cartridge. In some modifications, this connection may be made within the working cell and / or within the sterile fluid transfer equipment of the working cell. In some modifications, this connection includes the operation of the corresponding port of the connected sterile fluid transfer port, each of which includes a corresponding mechanical seal. In step 711, prior to the robot's operation of the valve of the connected sterile fluid transfer port, the sterilizer from a sterilizer source in the working cell may be circulated through the sterilization port of the fluid device and in the sterile fluid transfer port and the fluid conduit of the fluid device. In some variations, circulation may involve flowing the sterilizer through an interface formed by the activated port of the connected sterilizer transfer port. After circulating the sterilizer and removing it from the sterilizer transfer port and the fluid conduit of the fluid device, automatic fluid transfer from the fluid device to another fluid device or cartridge can be performed in step 715 of method 700C. Specifically, the cam of the working cell may be configured to engage with the fluid pump module of the fluid device to control the movement of fluid out of the fluid device and into another fluid device or cartridge via the sterilizer transfer port.
[0126] Figure 7D is a flow diagram of an exemplary method 700D for automated fluid transfer, in which a fluid is transferred from one fluid device or cartridge to another. Such fluid transfer may be necessary to obtain cell solution samples for in-process testing, or to obtain waste liquid for disposal.
[0127] First, Method 700D provides an empty fluid device. In step 705 of Method 700D, the fluid device can be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 710, the robot may connect the sterilization transfer port of the fluid device to a corresponding sterilization transfer port of another fluid device or cartridge. In some modifications, this connection can be made within a working cell and / or within the sterilization transfer equipment of the working cell. In some modifications, this connection involves the activation of the corresponding port of the connected sterilization transfer port, each of which includes a corresponding mechanical seal. In step 711, prior to the activation of the valve of the connected sterilization transfer port by the robot, the sterilizer from the sterilizer source in the working cell can be circulated through the sterilization port of the fluid device and within the sterilization transfer port and the fluid conduit of the fluid device. In some modifications, the circulation may involve flowing the sterilizer into the interface formed by the activated port of the connected sterilization transfer port. After circulating the sterilizer and removing it from the sterilization fluid transfer port and the fluid conduit of the fluid device, automatic fluid transfer from another fluid device or cartridge to the fluid device can be performed in step 716 of method 700C. Specifically, the cam of the working cell may be configured to engage with the fluid pump module of the fluid device to control the movement of fluid from another fluid device or cartridge to the fluid device via the sterilization fluid transfer port.
[0128] In some modifications, Method 700D may be performed after the implementation of 700A, 700B, 700C, and / or 700E (described below), and the fluids transferred from one fluid device to another fluid device or cartridge and the fluids transferred from another fluid device or cartridge to another fluid device are associated with the same patient.
[0129] Figure 7E is a flow diagram of an exemplary method 700E for automated fluid transfer, in which a fluid device is filled with fluid, and then the fluid is transferred from the fluid device to another fluid device or cartridge. Such fluid transfer may be necessary, for example, to supply a culture medium for a bioreactor module inside a cartridge. Furthermore, after the fluid transfer, the fluid device can be purged to ensure complete fluid transfer.
[0130] First, Method 700E provides an empty fluid device. In 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, for example, through the fluid access port of the fluid device's collar. Filling may be performed before or after introducing the fluid device into a work cell. The amount of fluid to be filled may be based on a predetermined amount required by the other fluid device or cartridge. After filling, in step 705, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 710, the robot may connect the sterile fluid transfer port of the fluid device to a corresponding sterile fluid transfer port of another fluid device or cartridge. In some modifications, this connection may be made within the work cell and / or within the sterile fluid transfer equipment of the work cell. In some modifications, this connection includes the operation of the corresponding ports of the connected sterile fluid transfer ports, each of which includes a corresponding mechanical seal. In step 711, prior to the robot's activation of the valve of the connected sterilization transfer port, the sterilizer from the sterilizer source in the working cell may be circulated through the sterilization port of the fluid device and within the sterilization transfer port and the fluid conduit of the fluid device. In some modifications, circulation may include flowing the sterilizer through the interface formed by the activated port of the connected sterilization transfer port. After circulating the sterilizer and removing it from the sterilization transfer port and the fluid conduit of the fluid device, automatic fluid transfer from the fluid device to another fluid device or cartridge can be performed in step 715 of method 700E. Specifically, a cam in the working cell may be configured to engage with the fluid pump module of the fluid device to control the movement of fluid leaving the fluid device and entering another fluid device or cartridge through the sterilization transfer port. In 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 sterilization transfer port of the fluid device to purge the collar of the fluid being transferred.
[0131] Figure 7F is a flow diagram of 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 to obtain cell solution samples for in-process testing, or to obtain waste liquid for disposal. Furthermore, after the fluid transfer, the fluid device can be purged to ensure complete fluid transfer.
[0132] First, Method 700F provides an empty fluid device. In step 705, the fluid device can be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 710, the robot can connect the sterilization transfer port of the fluid device to a corresponding sterilization transfer port of another fluid device or cartridge. In some modifications, this connection can be made within a working cell and / or within the sterilization transfer equipment of the working cell. In some modifications, this connection involves the activation of the corresponding port of the connected sterilization transfer port, each of which includes a corresponding mechanical seal. In step 711, prior to the activation of the valve of the connected sterilization transfer port by the robot, the sterilizer from the sterilizer source in the working cell can be circulated through the sterilization port of the fluid device and within the sterilization transfer port and the fluid conduit of the fluid device. In some modifications, the circulation may involve flowing the sterilizer into the interface formed by the activated port of the connected sterilization transfer port. After circulating the sterilizer and removing it from the sterilization fluid transfer port and the fluid conduit of the fluid device, automatic fluid transfer from another fluid device or cartridge to another fluid device or cartridge can be performed in step 715 of method 700E. Specifically, the cam of the working cell may be configured to engage with the fluid pump module of the fluid device to control the movement of fluid from another fluid device or cartridge to the fluid device via the sterilization fluid transfer port. In 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 sterilization fluid transfer port of the fluid device to purge the collar of the fluid being transferred.
[0133] In some variations, method 700F may further include, for example, injecting air into the container of the fluid device after fluid transfer to push the transferred fluid out of the fluid device via the fluid access port of the collar of the fluid device. This subsequent transfer of fluid from the fluid device can be carried out when the fluid device is in any orientation, such as an upright position.
[0134] In some modifications, the exemplary methods of automated fluid transfer described herein further include controlling the fluid movement within the fluid device using at least one viewing window of the fluid device's color and sensors and controllers in the working cell. In this way, the flow rate of the fluid transfer can be controlled so that a known amount of fluid is transferred into and out of the fluid device.
[0135] Therefore, Figures 8 and 9 are flow diagrams of other exemplary modifications of the method for automated fluid transfer, where the target transfer volume and data from sensors are used to control the fluid transfer. It should be understood that each of the methods described below can be controlled by a controller of the working cell, either in conjunction with or independently of the sterile fluid transfer equipment of the working cell.
[0136] Referring first to Figure 8, Method 800 relates to automated fluid transfer at a controlled speed when substantially all of the contents of a fluid device are transferred.
[0137] First, Method 800 provides an empty fluid device. In step 801, the fluid device may be filled with fluid to be transferred to another fluid device or cartridge. Filling may be performed before or after introducing the fluid device into the work cell. The amount of fluid to be filled may be based on a predetermined amount required by the other fluid device or cartridge. After filling, in step 805, the fluid device may be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 810, the robot may connect the sterilization fluid transfer port of the fluid device to a corresponding sterilization fluid transfer port of another fluid device or cartridge. In some modifications, this connection may be made within the work cell and / or within the sterilization fluid transfer equipment of the work cell. In some modifications, this connection includes the operation of the corresponding port of the connected sterilization fluid transfer port, each of which includes a corresponding mechanical seal. In step 811, prior to the robot's operation of the valve of the connected sterilization fluid transfer port, the sterilizer from the sterilizer source in the work cell may be circulated through the sterilization port of the fluid device and in the sterilization fluid transfer port and the fluid conduit of the fluid device. In some variations, circulation may involve flowing the sterilizer through an interface formed by the activated port of the connected sterilizer transfer port. After circulating the sterilizer and removing it from the sterilizer transfer port and the fluid conduit of the fluid device, automatic fluid transfer from the fluid device to another fluid device or cartridge can be initiated. Specifically, the cam of the working cell may be configured to engage with the fluid pump module of the fluid device to initiate the movement of fluid within the fluid device. In step 813, data can be received by the controller from a sensor located near at least one viewing window of the color of the fluid device. As previously stated, at least one viewing window may provide a field of view of at least one section of the fluid conduit of the color of the fluid device. The data received from the sensor is processed in step 814 to detect the point in time when the fluid transition from air to liquid occurs within the visible section of the fluid conduit.Upon detecting a transition, the fluid pump module and cam can operate to transfer fluid from one fluid device to another fluid device or cartridge at a controlled flow rate, as long as the liquid remains detected by the sensor. For example, the cam may operate at a speed of 60 revolutions per minute. Considering the cross-sectional area and length of the fluid conduit, as well as the rheological properties of the fluid, the rotational speed of the cam may correspond to a fluid transfer rate of 100 mL per minute. In step 816, the data received from the sensor may indicate another fluid transition, this time from liquid to air. Upon detection of a transition from liquid to air, it can be inferred that the container of the fluid device is empty. Therefore, in step 817, the fluid pump module and cam may stop. In some modifications, as described above in Figures 7B, 7E, and 7F, compressed air may be supplied to the fluid conduit and sterile fluid transfer port of the fluid device after the fluid pumping stops in step 817 to purge the color of the fluid being transferred.
[0138] Referring here to Figure 9, Method 900 relates to automatic fluid transfer at a controlled speed when the target transfer amount is less than the amount of fluid in the fluid device.
[0139] First, method 900 provides an empty fluid device. In step 901, the fluid device can be filled with fluid. Filling may be performed before or after introducing the fluid device into a work cell. The amount of fluid to be filled may be based on a target amount required by another fluid device or cartridge. For example, the amount of fluid to be filled may be greater than the target amount to be transferred to the other fluid device or cartridge, thus ensuring that a sufficient amount is transferred even if a certain amount of fluid is confined within the fluid device. After filling, in step 905, the fluid device can be inverted by a robot engaged with the fluid device via one or more engagement mechanisms of the fluid device. In step 910, the robot may connect the sterile fluid transfer port of the fluid device to a corresponding sterile fluid transfer port of another fluid device or cartridge. In some modifications, this connection may be made within the work cell and / or within the sterile fluid transfer equipment of the work cell. In some modifications, this connection includes the operation of the corresponding ports of the connected sterile fluid transfer ports, each of which includes a corresponding mechanical seal. In step 911, prior to the robot's activation of the valve of the connected sterilization transfer port, the sterilizer from the sterilizer source in the work cell may be circulated through the sterilization port of the fluid device and within the fluid conduit of the fluid device. In some modifications, circulation may include flowing the sterilizer through the interface formed by the activated port of the connected sterilization transfer port. After circulating the sterilizer and removing it from the sterilization transfer port and the fluid conduit of the fluid device, automatic fluid transfer from the fluid device to another fluid device or cartridge can be initiated. Specifically, the cam of the work cell may be configured to engage with the fluid pump module of the fluid device to initiate the movement of fluid within the fluid device. Simultaneously, or separately from step 911, in step 912, the target or specified amount to be transferred can be obtained by the controller of the work cell.After starting the fluid pump module and cam to initiate the movement of fluid within the fluid conduit of the fluid device, in step 913, data can be received by the controller from a sensor located near at least one viewing window of the fluid device's collar. As previously mentioned, at least one viewing window may provide a field of view of at least one section of the fluid conduit of the fluid device's collar. The data received from the sensor is processed in step 914 to detect the point in time when the fluid transition from air to liquid occurs within the visible section of the fluid conduit. Upon detecting the transition, the fluid pump module and cam can operate to transfer fluid from the fluid device to another fluid device or cartridge at a controlled fluid velocity and controlled duration so that the amount transferred is equal to the target amount received in step 912. For example, the cam may operate at a specific rotational speed for a specific duration based on the target amount, the dimensions of the fluid conduit, and the rheological properties of the fluid. A temporary stop of the fluid pump module and cam may occur before the execution of step 915 to ensure accuracy and precision in the metered fluid transfer. After a certain duration has elapsed, the fluid pump module and cam may be stopped in step 917. In some modifications, as described above in Figures 7B, 7E, and 7F, compressed air may be supplied to the fluid conduit and sterile fluid transfer port of the fluid device after the fluid pumping has stopped in step 917 in order to purge the collar of the fluid being transferred.
[0140] All cited references are incorporated herein by reference in their entirety.
[0141] Throughout this application, the term “approximately” is used to indicate that a value includes inherent variations in error in the device or method employed to determine that value, or variations present between samples being measured. Unless otherwise stated or evident from the context, “approximately” means within plus or minus 10 percent of a reported number (except where such a number is greater than 100% of a possible value or less than 0%). When used in conjunction with a range or set of values, the term “approximately” applies to each of the endpoints of the range or the values listed in the set of values, unless otherwise indicated. As used herein, the terms “approximately” and “about” are used synonymously.
[0142] While embodiments of the present invention have been shown and described herein, those skilled in the art will understand that such embodiments are provided only as examples. Those skilled in the art will recall numerous variations, modifications, and substitutions without departing from the present invention. It should be understood that various substitutes for the embodiments of the present invention described herein may be used in carrying out the invention. The following claims define the scope of the present invention, and methods and structures within these claims, as well as their equivalents, are intended to be encompassed thereby.
Claims
1. A fluid device for use in automatic fluid transfer, A container for a certain amount of fluid, A general-purpose collar that can be attached to the aforementioned container, wherein the collar is Multiple conduits, A sterilization liquid transfer port that is in fluid communication with the aforementioned plurality of conduits, A fluid device comprising a fluid pump module having a compressible fluid tube coupled between an inlet port and an outlet port, wherein each of the inlet port and the outlet port is in fluid communication with a plurality of conduits, and the compressible fluid tube is configured to be compressed by a fluid pump to control the movement of fluid out of the container; and a general-purpose collar.
2. The fluid device according to claim 1, wherein the collar further comprises a robot engagement mechanism.
3. The fluid device according to claim 2, wherein the robot engagement mechanism is engaged by a robot and can operate the fluid device.
4. The fluid device according to claim 1, wherein the robot engagement mechanism comprises one or more recesses and / or protrusions within the surface of the collar.
5. The fluid device according to claim 1, wherein the collar is releasably coupled to the container via corresponding mechanisms disposed on the collar and the container.
6. The fluid device according to claim 1, wherein the fluid capacity of the container is in the range of about 1 milliliter to about 1 liter.
7. The fluid device according to claim 1, wherein the control of the movement of the fluid includes bidirectional movement control.
8. The fluid device according to claim 1, wherein the collar further comprises one or more sterilization ports that are in fluid communication with the plurality of conduits.
9. The fluid device according to claim 8, wherein the sterilizer provided through 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 according to claim 8, wherein one or more sterilization ports are equipped with valves.
11. The fluid device according to claim 8, wherein the one or more sterilization ports are coupled to one or more passive valves.
12. The fluid device according to claim 1, wherein the collar further comprises one or more air processing ports that are in fluid communication with the plurality of conduits.
13. The fluid device according to claim 12, wherein the one or more air processing ports are compressed air processing ports.
14. The fluid device according to claim 1, wherein the collar further comprises a valve for preventing the introduction of air into the fluid during the fluid transfer.
15. The fluid device according to claim 12, wherein one or more of the air processing ports are vents.
16. The fluid device according to claim 12, wherein the collar further comprises a hydrophobic filter that can be coupled to one or more air processing ports.
17. The fluid device according to claim 1, wherein the collar further comprises a fluid access port for filling the container after the collar and the container are coupled together.
18. The fluid device according to claim 1, wherein the color further comprises a viewing window that enables optical evaluation of the fluid in the fluid conduit of the color.
19. The fluid device according to claim 1, wherein the sterilization fluid transfer port further comprises a mechanical seal.
20. The fluid device according to claim 19, wherein the collar further comprises one or more sterilization ports that are in fluid communication with the plurality of conduits, and the mechanical seal of the sterilization fluid transfer port and the sterilizer provided through the one or more sterilization ports ensure the sterilization of the collar.
21. The fluid device according to claim 1, wherein the collar further comprises a pressure relief valve at the outlet port of the compressible fluid tube of the fluid pump module, and the outlet port is in further fluid communication with the container so that when excessive pressure is present at the outlet port, liquid flows into the container.
22. The fluid device according to claim 1, wherein the container has an opening, the collar is connectable to the opening, and the device further comprises a fluid transport mechanism that is in fluid communication with the plurality of conduits.
23. The fluid transport mechanism of the color comprises a vent pipe that extends through the opening of the container and is configured to be disposed within the container, according to claim 22.
24. The fluid device according to claim 23, wherein the vent pipe further comprises a liquid vent reservoir configured to capture fluid trapped in the vent pipe when the fluid device is inverted.
25. The fluid device according to claim 24, wherein the volume of the liquid ventilation reservoir is greater than the volume of the ventilation pipe in the container.
26. The fluid device according to claim 23, wherein the fluid transport mechanism further comprises a liquid flow tube that extends through the opening of the container and is configured to be disposed within the container.
27. The fluid device according to claim 26, wherein the collar further comprises one or more air processing ports, and the one or more air processing ports are in fluid communication with the liquid flow tube.
28. The fluid transport mechanism further comprises a flow port that is in fluid communication with the container and the sterilization liquid transport port, according to claim 23.
29. The fluid device according to claim 1, wherein the sterilization fluid transfer port further comprises a mechanical seal, and the collar further comprises one or more sterilization ports having fluid communication with the plurality of conduits, the mechanical seal providing a first mechanism for achieving sterile sterilization, and the sterilization agent provided through the one or more sterilization ports providing a second mechanism for achieving sterilization.
30. A method for automatic fluid transfer, wherein the method is The robot inverts a fluid device comprising a container and a general-purpose collar equipped with multiple conduits and a sterilization liquid transfer port that is in fluid communication with the multiple conduits. The robot connects the inverted sterilization liquid transfer port of the fluid device to the corresponding sterilization liquid transfer port of the cartridge. A method comprising pressurizing fluid from the fluid device to the cartridge through the plurality of conduits and the sterile fluid transfer port.
31. The method according to claim 30, further comprising sterilizing the sterilization fluid transfer port via one or more sterilization ports of the collar that are in fluid communication with the plurality of conduits, after the connection and before the pressurization.
32. The method according to claim 30, further comprising using the robot to activate the valves of the sterilization liquid transfer port and the corresponding sterilization liquid transfer port after the sterilization, thereby enabling the pumping.
33. The aforementioned reversal means, The method according to claim 30, comprising engaging the robot engagement mechanism of the collar of the fluid device with the robot.
34. A method for automatic fluid transfer, wherein the method is A robot inverts a fluid device comprising a container, a general-purpose collar having multiple conduits, a sterilization fluid transfer port, and an air treatment port, wherein the sterilization fluid transfer port and the air treatment port are in fluid communication with the multiple conduits, respectively. The robot connects the inverted sterilization liquid transfer port of the fluid device to the corresponding sterilization liquid transfer port of the cartridge. At least a portion of the fluid is pumped from the inverted fluid device to the cartridge via the plurality of conduits and the sterilization fluid transfer port, A method comprising purging the plurality of conduits after pressurizing using compressed air through the air treatment port.
35. A method for automatic fluid transfer, wherein the method is A robot inverts a fluid device comprising a general-purpose collar having a container, a robot engagement mechanism, multiple conduits, a sterilization liquid transfer port, and multiple sterilization processing ports, wherein each of the sterilization liquid transfer ports and the multiple sterilization processing ports is in fluid communication with the multiple conduits. The robot connects the inverted sterilization liquid transfer port of the fluid device to the corresponding sterilization liquid transfer port of the cartridge. The sterilizing agent is flowed through the sterilizing liquid transfer port via one or more sterilization processing ports, A method comprising pressurizing at least a portion of the fluid from the inverted fluid device to the cartridge through the plurality of conduits and the sterile fluid transfer port.
36. A method for automatic fluid transfer, wherein the method is When the fluid device is in an upright position, the fluid device is filled, which comprises a container, a robot engagement mechanism, a plurality of conduits, and a general-purpose collar equipped with a sterile liquid transfer port. The robot reverses the fluid device via the robot engagement mechanism, The robot connects the inverted sterilization liquid transfer port of the fluid device to the corresponding sterilization liquid transfer port of the cartridge. A method comprising pressurizing at least a portion of the fluid from the fluid device to the cartridge via the plurality of conduits and the sterilization fluid transfer device.
37. The method according to claim 36, further comprising purging the plurality of conduits in the collar via the air treatment port of the collar.
38. The method according to claim 36, wherein the filling is carried out via the fluid access port of the collar.
39. The aforementioned pumping is, A sensor positioned in close proximity to the aforementioned color viewing window, configured to detect the presence of liquid in the compartments of the plurality of conduits, receives data from the sensor, Based on the received data, the fluid transition from air to liquid is detected, Based on the detection of the presence of the fluid transition from air to liquid, the fluid pump is operated. Based on the received data, the fluid transition from liquid to air is detected, The method according to claim 36, further comprising stopping the operation of the fluid pump when a fluid transition from the liquid to air is detected.
40. The aforementioned pumping is, Receiving data regarding a specified amount of fluid to be transferred to the cartridge, A sensor positioned in close proximity to the aforementioned color viewing window, configured to detect the presence of liquid in the compartments of the plurality of conduits, receives data from the sensor, Based on the received data, the fluid transition from air to liquid is detected, Based on the received data regarding the presence of the detected fluid transition from air to liquid and the specified amount of fluid, the fluid pump is operated. The method according to claim 36, further comprising stopping the operation of the fluid pump when the specified amount of fluid has been transferred.
41. A system for automatic fluid transfer, Fluid pump and A fluid device, A container for a certain amount of fluid, A general-purpose collar that can be attached to the aforementioned container, wherein the collar is Multiple conduits, A sterilization liquid transfer port that is in fluid communication with the aforementioned plurality of conduits, A fluid pump module comprising a compressible fluid tube coupled between an inlet port and an outlet port, wherein each of the inlet port and the outlet port is in fluid communication with a plurality of conduits, and the compressible fluid tube is configured to be compressed by the fluid pump to control the movement of fluid out of the container, A fluid device comprising a general-purpose color having one or more viewing windows, A system comprising one or more sensors configured to detect the presence of liquid in the compartments of the plurality of conduits through one or more viewing windows.
42. It is a processor, Receiving data from one or more of the aforementioned sensors, Based on the received data, the fluid transition from air to liquid is detected. Start the fluid pump, Detecting fluid transitions from liquid to air, The system according to claim 41, further comprising a processor configured to stop the fluid pump when it detects a fluid transition from the liquid to air.
43. A system for automatic fluid transfer, Fluid pump and Robots and, A fluid device, A container for a certain amount of fluid, A general-purpose collar that can be attached to the aforementioned container, wherein the collar is A robot engagement mechanism that can be engaged by the robot, Multiple conduits, A sterilization liquid transfer port that is in fluid communication with the aforementioned plurality of conduits, A fluid pump module comprising a fluid pump module having a compressible fluid tube coupled 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, and the compressible fluid tube being compressed by the fluid pump to control the movement of fluid out of the container, comprising a general-purpose collar, and a fluid device, comprising: a fluid pump module;
44. A method for automatic fluid transfer, wherein the method is The robot connects the sterilization fluid transfer port of the fluid device to the corresponding sterilization fluid transfer port of the cartridge, The fluid device pumps at least a portion of the fluid to the cartridge through multiple conduits and the sterile liquid transfer port of the fluid device, A method comprising purging the plurality of conduits after the pressurization using compressed air via the air processing port of the fluid device.
45. A fluid device for automatic fluid transfer, A container for a certain amount of fluid, A general-purpose collar that can be attached to the aforementioned container, wherein the collar is Multiple conduits, A sterilization liquid transfer port that is in fluid communication with the aforementioned plurality of conduits, A fluid pump module comprising a compressible fluid tube coupled between an inlet port and an outlet port, wherein each of the inlet port and the outlet port is in fluid communication with a plurality of conduits, and the compressible fluid tube is configured to be compressed by the fluid pump to control the movement of fluid out of the container, Air treatment port, A fluid device comprising a ball valve coupled to the air processing port, wherein the fluid device is configured to be positioned in an upright orientation and an inverted orientation, and the ball valve is configured so that the fluid in the container does not flow through the air processing port when the fluid device is in the inverted orientation; and a general-purpose collar.