WO2024020344A1 - Aseptic liquid connector - Google Patents

Aseptic liquid connector Download PDF

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Publication number
WO2024020344A1
WO2024020344A1 PCT/US2023/070331 US2023070331W WO2024020344A1 WO 2024020344 A1 WO2024020344 A1 WO 2024020344A1 US 2023070331 W US2023070331 W US 2023070331W WO 2024020344 A1 WO2024020344 A1 WO 2024020344A1
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WO
WIPO (PCT)
Prior art keywords
barrier
hollow tube
processing system
septum
cell processing
Prior art date
Application number
PCT/US2023/070331
Other languages
French (fr)
Inventor
Brandon WHITNEY
Dan SLOMSKI
Jeff Smith
Myo THU
Ivan RAZINKOV
Aaron MALDONADO
Original Assignee
Synthego Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Synthego Corporation filed Critical Synthego Corporation
Publication of WO2024020344A1 publication Critical patent/WO2024020344A1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/04Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus by injection or suction, e.g. using pipettes, syringes, needles
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00Constructional details, e.g. recesses, hinges
    • C12M23/40Manifolds; Distribution pieces
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12MAPPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M37/00Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • C12M37/04Seals

Definitions

  • Ex-vivo cell culturing allows cells to be grown externally in a nutrient rich solution, which can be used for many applications including experiments on certain cell types, production of biological products (e.g., those produced by the cells), production of cells to be used to treat certain diseases, etc.
  • a cell processing system including: a liquid patch panel (LPP) including a flow coupler and a first flow path at least partially defined by the flow coupler.
  • the flow coupler may include: a lumen; a hollow tube (e.g. a needle or cannula) positioned within the lumen; and a first barrier (e.g. a septum such as an engageable septum) that isolates the lumen from the ambient environment.
  • the cell processing system may further include a container (e.g. a consumable) including a second barrier (e.g. a septum) that seals an internal volume of the container from the ambient environment.
  • the flow coupler may be configured to move the first barrier into contact with the second barrier of the container while the hollow tube is positioned within the lumen and to move the hollow tube towards the first barrier until the hollow tube opens the first barrier (e.g. by an end of the hollow tube penetrating and/or emerging through a face of the first barrier), opens the second barrier, and enters into the internal volume of the container.
  • the hollow tube may be presterilized.
  • the first barrier may be a first septum that is configured to be pierced by the hollow tube and the second barrier may be a second septum that is configured to be pierced by the hollow tube;
  • the flow coupler may be configured to move the hollow tube towards the first barrier until the hollow tube pierces the first septum, pierces the second septum, and enters into the internal volume of the container and to retract the hollow tube back through the second barrier, back through the first barrier, and into the lumen of the flow coupler; further, when the hollow tube exits the second septum, the second septum may be resealed to isolate the internal volume of the container from the ambient environment, and when the hollow tube exits the first septum and enters into the lumen, the first septum may be resealed to isolate the lumen from the ambient environment.
  • the flow coupler may include a sleeve that defines the lumen, and the sleeve may be coupled to the first barrier, where the sleeve may be configured to move towards the second barrier, thereby moving the first barrier towards the second barrier.
  • Various embodiments of the cell processing system may further include a sterilant system which includes a housing that includes a channel or opening passing through the housing, where the channel or opening may be configured to be positioned between the first barrier and the second barrier; the first barrier may be configured to be positioned within the channel and the second barrier may also be configured to be positioned within the channel, while the first barrier is positioned within the channel.
  • a sterilant system which includes a housing that includes a channel or opening passing through the housing, where the channel or opening may be configured to be positioned between the first barrier and the second barrier; the first barrier may be configured to be positioned within the channel and the second barrier may also be configured to be positioned within the channel, while the first barrier is positioned within the channel.
  • the flow coupler may include a first seal (e g. a gasket) that surrounds the first barrier, the seal being coaxial with the first barrier and the container may include a second seal (e.g. a gasket) that surrounds the second barrier, the second seal being coaxial with the second barrier;
  • the first seal may be configured to contact a first side of the housing of the sterilant system and the second seal may be configured to contact a second side of the housing of the sterilant system that is opposite the first side, such that when the first seal contacts the first side of the housing and when the second seal contacts the second side of the housing, the first and second barriers are isolated from the ambient environment.
  • the channel may be a first channel
  • the sterilant system may further include: a second channel or opening in fluid communication with the first channel and a pump that is configured to drive a sterilant through the second channel and into the first channel, thereby contacting an exterior surface of the first and second barriers to sterilize the exterior surfaces of the first and second barriers.
  • the sterilant may be at least one of a vapor, a gas, or a liquid and in particular the sterilant may be at least one of a peroxide, hydrogen peroxide, steam, chlorine dioxide, heated gas, dry heated gas, ethylene oxide, an alcohol, ethanol, isopropyl alcohol, or 70% v/v isopropyl alcohol.
  • the flow coupler may include a return spring (e.g. a sheath return spring) and may further include an actuator, where the actuator may be configured to extend to move the hollow tube into the first and second barriers, which loads the return spring, and when the actuator retracts, the return spring unloads to retract the hollow tube out through the first barrier, out through the second barrier, and into the lumen of the flow coupler.
  • a return spring e.g. a sheath return spring
  • the actuator may be configured to extend to move the hollow tube into the first and second barriers, which loads the return spring, and when the actuator retracts, the return spring unloads to retract the hollow tube out through the first barrier, out through the second barrier, and into the lumen of the flow coupler.
  • the actuator may be a first actuator, and the system may include a second actuator and a gas source, where the first actuator may be configured to selectively bring the first flow path into fluid communication with the first internal volume of the first processing module by opening the first barrier, and the second actuator may be configured to selectively bring the second flow path into fluid communication with the second internal volume of the second processing module by opening the second barrier, and the gas source may be configured to drive liquid from the first internal volume of the first processing module, through the first flow path of the LPP, and into the second internal volume of the second processing module.
  • Particular embodiments of the cell processing system may further include a computing device (e.g. a controller) which is configured to: cause the actuator to extend to fluidly couple the LPP to the first processing module; cause the second actuator to extend to fluidly couple the LPP to the second processing module; and cause the gas source to drive liquid from the first processing module and into the second processing module, via the LPP.
  • a computing device e.g. a controller
  • the cell processing system may be sterilized before use.
  • the cell processing system may be configured for use in an automated manufacturing system, which includes the disclosed procedures of connecting and disconnecting components and/or sterilizing components being performed without manual intervention and in a completely automated manner.
  • FIG. 1 shows a single manifold unit of a liquid patch panel (LPP) which depicts an example of how an aseptic liquid connector may be used to couple the LPP and a consumable.
  • FIG. 2 shows vapor sterilized Aseptic Liquid Connector components in a pre-mated configuration, with the male side of the connector (top) including a needle or cannula, which may be housed within the LPP as in FIG. 1, and the container or processing consumable female aseptic connector components including the liquid input/output port and vapor sterilization manifold which may be housed within or connected to the consumable.
  • LPP liquid patch panel
  • FIG. 3 shows a cross-sectional view of FIG. 2 depicting vapor sterilized Aseptic Liquid Connector components in a pre-mated configuration, where the male and female connector portions are initially detached and unsealed from the vapor sterilization manifold.
  • FIG. 4 shows vapor sterilized Aseptic Liquid Connector components in a mated position. The male and female connectors are sealed against the vapor sterilization manifold. Once mated, vaporized sterilant may be pumped into the chamber formed by the two connectors and manifold such that all surfaces within the chamber can be made free of biological contaminants.
  • FIG. 5 shows a cross-section of view of FIG. 4 depicting vapor sterilized Aseptic Liquid Connector components in a mated position.
  • the male and female connectors are sealed against the vapor sterilization manifold.
  • vaporized sterilant may be pumped into the chamber formed by the two connectors and manifold such that all surfaces within the chamber may be made free of biological contaminants.
  • FIG. 6 shows vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath lowered to engage with the septum of the consumable.
  • FTG. 7 shows a cross-sectional view of FIG. 6 depicting vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath lowered to engage with the septum of the consumable.
  • FIG. 8 shows vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath and the needle or cannula lowered.
  • FIG 9 shows a cross-sectional view of FIG. 8 depicting vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath and the needle or cannula lowered.
  • the cannula pierces the engageable septum of the flow coupler as well as the septum of the liquid input/output port of the consumable, allowing liquid to be transferred from the Liquid Patch Panel to the mated consumable.
  • FIG. 10 shows an alternative version of the Aseptic Liquid Connector which does not include a sterilization manifold, where the tip of the needle or cannula is disposed within a septum and does not require disinfection prior to use.
  • an aseptic liquid connector 300 which can be used, for example, in an automated system to connect components to one another, e.g. using a robotic system, in order to move fluids through the system, which includes the disclosed procedures of connecting and disconnecting components and/or sterilizing components being performed without manual intervention and in a completely automated manner.
  • the components may include a liquid patch panel (LPP) 100 as well as one or more consumable 130 containers, as shown in FIG. 1.
  • LPP liquid patch panel
  • FIG. 1 Embodiments of the LPP 100 and consumables 130 which can be used with the disclosed embodiments of the aseptic liquid connector 300 are disclosed in U.S. provisional patent application no. 63/390,786, filed July 20, 2022, entitled “Liquid Patch Panel,” which is incorporated herein by reference in its entirety.
  • an LPP 100 may be fluidly coupled to a consumable 130 by one or more aseptic liquid connectors 300, as shown in FIG. 1
  • FIG. 1 is focused on a single manifold unit of the LPP 100, which may include a pair of liquid connectors 104 and a pair of actuator-controlled liquid routing valves 110 disposed within a rigid, robot-handleable frame; the LPP 100 may have two, three, four, or more manifold units such as that shown in FIG. 1;
  • FIG. 1 shows complete details for a single complete manifold unit and also shows portions of two adjacent manifold units of the LPP 100 and consumables 130 for context.
  • Each of the liquid connectors 104 may include a flow coupler 160 disposed therein, where each flow coupler 160 may include a needle or cannula 162 and a sealed flexible rubber sheath or engageable septum 164, where the needle or cannula includes an opening at or near one or both ends.
  • the consumable 130 (which may include a compartment for storing and/or processing liquid such as reagents, media, and/or cells) may include a pair of liquid input/output ports 132, each of which may include a rubber barrier or septum 133, as shown in FIG. 1.
  • the consumable 130 may also include a pair of air input/output ports 136 that are coupled to a gas source 180 (e.g.
  • the liquid routing valves 110 are fluidly coupled to one another and to the liquid connectors as well as to other fluid connections leading to other manifold units of the LPP 100.
  • the actuators of the liquid routing valves 110 as well as actuators 140 and gas source 180 are connected (e.g.
  • a controller 200 which, in various embodiments, controls the fluid connections to establish at least one flow path through the LPP 100 and consumable(s) 130 and drives the movement of fluid through the established flow path.
  • the positions of the liquid routing valves 110 and the flow couplers 160 may be set to produce a flow path so that, when positive pressure is applied by the gas source 180 to at least one of the air input/output ports 136, fluid is removed from the consumable 130 and is transferred to a second consumable that is coupled to the LPP 100. While many of the components (e.g.
  • the LPP 100 and/or consumables 130 may include any number of these items (e.g. 1, 2, 3, 4, 5, etc.) as is suitable for the particular application to which the components are being put to use. [0029] When the LPP 100 and consumable 130 are brought into proximity to one another (e.g.
  • aseptic liquid connections may be made between the LPP 100 and the consumable 130 using the aseptic liquid connectors 300, which include the flow couplers 160 of the LPP 100 and the liquid input/output ports 132 of the consumable 130; as discussed further below, the liquid input/output ports 132 may also include a sterilization manifold which can be used to sterilize outer surfaces of the septum 133 and/or the engageable septum 164 in an automated manner.
  • actuators 140 e.g.
  • the engageable septum 164 may help drive movement of the engageable septum 164 into position to be sterilized within the sterilization manifold and also drive the needle or cannula 162 through the engageable septum 164 and the rubber barrier or septum 133, which results in fluid flow in one or both directions through the needle or cannula 162 (as indicated by the double arrow in FIG. 1).
  • a connector on the LPP 100 side may be formed by a piercing needle or cannula 162 contained in a sealed flexible rubber sheath or engageable septum 164, which may be part of the flow coupler 160 and which may be sterilized prior to use.
  • the needle or cannula 162 probe is configured to pierce through the sheath on the flow coupler 160 and a rubber barrier or septum 133 on the mating connector (e.g.
  • the engageable septum 164 may be brought near or in contact with the septum 133 for sterilization prior to the point at which the needle or cannula 162 probe pierces through each of the septa 164, 133 (FIG. 1, left), after which the needle or cannula 162 can pierce the septa 164, 133 to transfer fluid into or out of the consumable 130 as part of a transfer operation (FIG. 1, right).
  • the needle or cannula 162 may be withdrawn and each of the septa 164, 133 may reseal to isolate the respective compartments from the ambient environment.
  • a liquid connection may be completed in a way that is aseptic or free of biological contamination using a number of approaches, including: sealing the connector halves (i.e. the portions associated with the LPP 100 and the consumable 130, respectively) to a chamber where gaseous, liquid, or vaporous (e.g.
  • hydrogen peroxide such as vaporous hydrogen peroxide, steam, chlorine dioxide, heated gas, dry heated gas, ethylene oxide, an alcohol, ethanol, isopropyl alcohol, or 70% v/v isopropyl alcohol
  • decontamination agents may be introduced, followed by flushing agents for removing the sterilant.
  • Sterilant may be introduced to the closed chamber using vacuum or positive pressures; spraying the surfaces of the connectors with a liquid sterilant; irradiating the surfaces of the connectors with UV-C light; and/or removing a barrier which forms a closed and pre-sterilized chamber around the otherwise exposed faces of the liquid connectors immediately prior to mating them.
  • Particular embodiments of the aseptic liquid connector 300 are shown in FIGS. 2- 10 and described below.
  • each of the flow coupler 160 and the liquid input/output ports 132 may be sterilized prior to connection by means of vapor sterilant such as vaporized hydrogen peroxide.
  • the sterilization may be accomplished using the flow coupler 160 of the LPP 100 in which the needle or cannula 162 is disposed within and coupled to a tube or housing 166, as shown in FIGS. 2-9, such that the free end of the tube or housing 166 can be fluidically connected by tubing to a liquid media or reagent source or may be connected via the LPP 100 to one or more other consumables 130.
  • the opposite end of the needle or cannula 162 may have a tapered or sharpened end to facilitate piercing the septa 164, 133 and may include an opening at or near an end thereof to facilitate fluid flow therethrough.
  • FIGS. 2-9 show embodiments of an aseptic liquid connector 300 which includes components of the flow coupler 160 (which may be associated with the LPP 100) and the liquid input/output ports 132, which may each include a sterilization manifold 135, and are associated with the consumables 130.
  • the opening at the end of the needle or cannula 162 is initially held within a sealed chamber formed by a body 165 (e.g. which may be made of hard plastic) and two septa 163, 164, above and below the tip of the needle or cannula 162, respectively.
  • the assembly is held in this position by springs 167 A, 167B when not acted on by the instrument, e.g. by an actuator 140.
  • When brought into the instrument e.g.
  • the body of the flow coupler 160 may include a sheath 168 with a cap 168 A and an upper flange 169 as well as shielding 168B surrounded by outer spring 167B.
  • the liquid input/output port 132 may include a lower flange 134.
  • the sterilization manifold 135 may be integrated into the liquid input/output port 132, and in other embodiments the sterilization manifold 135 may be a separate component from the liquid input/output port 132.
  • the sterilization manifold 135 may have an annular shape with an opening 135A therethrough, where the upper flange 169 of the flow coupler 160 and/or the lower flange 134 of the liquid input/output port 132 may abut and make a seal with the opening of the sterilization manifold 135.
  • the abutting surfaces of the sterilization manifold 135, the upper flange 169, and/or the lower flange 134 may include gaskets or other means of promoting a tight seal.
  • the sterilization manifold 135 may also include one or more side openings 135B which permit entry and/or exit of sterilant (e.g. from a vapor sterilant source) into the opening 135A.
  • the liquid input/output port 132 may be raised or otherwise moved towards the sterilization manifold 135 to form a seal between the lower flange 134 and the sterilization manifold 135; in some embodiments this connection between the liquid input/output port 132 and the sterilization manifold 135 may be made prior to deployment of the consumable 130 (i.e.
  • the sterilization manifold 135 may be part of the consumable 130 and in some embodiments may be integrated with the liquid input/output port 132) and in other embodiments the liquid input/output port 132 may be brought into contact with the sterilization manifold 135 at approximately the same time that the upper flange 169 of the flow coupler 160 is brought into contact with the sterilization manifold 135 (see FIGS. 2 and 3, with arrows in FIG. 3 indicating movement of flanges 134, 169 towards manifold 135).
  • the chamber i.e. space within the opening 135A
  • the two connectors i.e. flanges 134, 169
  • the sterilization manifold 135 may be sterilized using a vaporized sterilant then flushed with sterile air to remove the sterilant (see FIGS. 4 and 5).
  • the sheath 168 containing the needle or cannula 162 may be lowered by compressing (e g. using actuator 140) the sheath return spring 167B, creating a seal of the engageable septum 164 against the septum 133 of the mating consumable 130 (FIGS. 6 and 7).
  • the needle or cannula 162 may then be lowered, piercing the septum 133 of the mating consumable 130 and the engageable septum 164 of the LPP 100, creating an aseptic fluidic connection between the liquid source connected to the LPP 100 and the interior of the mating consumable 130 (FIGS. 8 and 9). While only the tip of the needle or cannula 162 is shown extending out of the lower end of the liquid input/output port 132, in various embodiments the needle or cannula 162 may extend further out of the lower end of the liquid input/output port 132 to reach further into the consumable 130.
  • the tip of the needle or cannula 162 may initially be disposed within an engageable septum 164' which fills the entire space between where the septa 163, 164 are initially located in the flow coupler 160 of the previous embodiment (see FIG. 5).
  • the tip of the needle or cannula is maintained in a sterilized state by being encased within the material (e.g. rubber) of the engageable septum 164' up until the time of use and as a result it is not necessary to provide the sterilization manifold 135.
  • the flow coupler 160 has fewer components, with the outer spring 167B, the shielding 168B, the cap 168A, and the upper 169 and lower 134 flanges and any associated gaskets being omitted.
  • the modified engageable septum 164' may be lowered into contact with the septum 133 of the liquid input/output port 132 (as indicated by downward arrow in FIG. 10), followed by advancement of the needle or cannula 162 as it moves through and/or emerges from a face to open the septa 164', 133 into the compartment of the consumable 130.
  • the needle or cannula 162 may extend completely through and out the top end of the tube or housing 166.
  • the free end of the needle or cannula 162 can be fluidically connected by tubing to a liquid media or reagent source or may be connected via the LPP 100 to one or more other consumables 130 (FIG. 10), a feature which may be combined with any of the embodiments of FIGS. 2-9 independently of the use of the modified engageable septum 164'.
  • top As used herein, unless otherwise limited or defined, discussion of particular directions is provided by example only, with regard to particular claims or relevant illustrations. For example, discussion of “top,” “front,” or “back” features is generally intended as a description only of the orientation of such features relative to a reference frame of a particular example or illustration. Correspondingly, for example, a “top” feature may sometimes be disposed below a “bottom” feature (and so on), in some arrangements or claims. Further, references to particular rotational or other movements (e.g., counterclockwise rotation) is generally intended as a description only of movement relative a reference frame of a particular example of illustration.
  • aspects of the disclosure can be implemented as a system, method, apparatus, or article of manufacture using standard programming or engineering techniques to produce software, firmware, hardware, or any combination thereof to control a processor device (e.g., a serial or parallel general purpose or specialized processor chip, a single- or multi-core chip, a microprocessor, a field programmable gate array, any variety of combinations of a control unit, arithmetic logic unit, and processor register, and so on), a computer (e.g., a processor device operatively coupled to a memory), or another electronically operated controller to implement aspects detailed herein.
  • a processor device e.g., a serial or parallel general purpose or specialized processor chip, a single- or multi-core chip, a microprocessor, a field programmable gate array, any variety of combinations of a control unit, arithmetic logic unit, and processor register, and so on
  • a computer e.g., a processor device operatively coupled to a memory
  • another electronically operated controller to implement
  • claims of the disclosure can be implemented as a set of instructions, tangibly embodied on a non-transitory computer-readable media, such that a processor device can implement the instructions based upon reading the instructions from the computer-readable media.
  • Some claims of the disclosure can include (or utilize) a control device such as an automation device, a special purpose or general purpose computer including various computer hardware, software, firmware, and so on, consistent with the discussion below.
  • a control device can include a processor, a microcontroller, a field- programmable gate array, a programmable logic controller, logic gates etc., and other typical components that are known in the art for configuration of appropriate functionality (e.g., memory, communication systems, power sources, user interfaces and other inputs, etc.).
  • article of manufacture as used herein is intended to encompass a computer program accessible from any computer-readable device, carrier (e.g., non-transitory signals), or media (e.g., non-transitory media).
  • computer-readable media can include but are not limited to magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips, and so on), optical disks (e.g., compact disk (CD), digital versatile disk (DVD), and so on), smart cards, and flash memory devices (e.g., card, stick, and so on).
  • a carrier wave can be employed to carry computer-readable electronic data such as those used in transmitting and receiving electronic mail or in accessing a network such as the Internet or a local area network (LAN).
  • LAN local area network
  • FIGS. Certain operations of methods according to the disclosure, or of systems executing those methods, may be represented schematically in the FIGS, or otherwise discussed herein. Unless otherwise specified or limited, representation in the FIGS, of particular operations in particular spatial order may not necessarily require those operations to be executed in a particular sequence corresponding to the particular spatial order. Correspondingly, certain operations represented in the FIGS., or otherwise disclosed herein, can be executed in different orders than are expressly illustrated or described, as appropriate for particular claims of the disclosure. Further, in some claims, certain operations can be executed in parallel, including by dedicated parallel processing devices, or separate computing devices configured to interoperate as part of a large system.
  • a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer.
  • a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer.
  • an application running on a computer and the computer can be a component.
  • One or more components may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on).
  • devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure.
  • description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities.
  • discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system is intended to inherently include disclosure, as claims of the disclosure, of the utilized features and implemented capabilities of such device or system.
  • ordinal numbers are used herein for convenience of reference based generally on the order in which particular components are presented for the relevant part of the disclosure.
  • designations such as “first,” “second,” etc. generally indicate only the order in which the relevant component is introduced for discussion and generally do not indicate or require a particular spatial arrangement, functional or structural primacy or order.
  • the term “or” as used herein is intended to indicate exclusive alternatives only when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.”
  • a list of “one of A, B, or C” indicates options of: A, but not B and C; B, but not A and C; and C, but not A and B.
  • a list preceded by “one or more” (and variations thereon) and including “or” to separate listed elements indicates options of one or more of any or all of the listed elements.
  • the phrases “one or more of A, B, or C” and “at least one of A, B, or C” indicate options of: one or more A; one or more B; one or more C; one or more A and one or more B; one or more B and one or more C; one or more A and one or more C; and one or more of A, one or more of B, and one or more of C.
  • a list preceded by “a plurality of’ (and variations thereon) and including “or” to separate listed elements indicates options of multiple instances of any or all of the listed elements.
  • the phrases “a plurality of A, B, or C” and “two or more of A, B, or C” indicate options of: A and B; B and C; A and C; and A, B, and C.

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  • Organic Chemistry (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
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  • Wood Science & Technology (AREA)
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  • Apparatus For Disinfection Or Sterilisation (AREA)

Abstract

Various embodiments of the disclosure provide a cell processing system including: a liquid patch panel (LPP) including a flow coupler and a first flow path at least partially defined by the flow coupler. The flow coupler may include: a lumen; a hollow tube (e.g. a needle or cannula) positioned within the lumen; and a first barrier (e.g. a septum such as an engageable septum) that isolates the lumen from the ambient environment. The cell processing system may further include a container (e.g. a consumable) including a second barrier (e.g. a septum) that seals an internal volume of the container from the ambient environment. The flow coupler may be configured to move the first barrier into contact with the second barrier of the container while the hollow tube is positioned within the lumen and to move the hollow tube towards the first barrier until the hollow tube opens the first barrier, opens the second barrier, and enters into the internal volume of the container. In various embodiments of the cell processing system, the hollow tube may be presterilized.

Description

ASEPTIC LIQUID CONNECTOR
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 63/390,795, as filed July 20, 2022, the contents of which are incorporated herein by reference in its entirety.
BACKGROUND
[0002] Ex-vivo cell culturing allows cells to be grown externally in a nutrient rich solution, which can be used for many applications including experiments on certain cell types, production of biological products (e.g., those produced by the cells), production of cells to be used to treat certain diseases, etc.
[0003] While cell culturing has numerous applications, it is important to keep groups of cells from cross-contaminating one another and from being contaminated by bacteria or other materials. Thus, it would be desirable to have improved systems and methods for processing cells in a manner that does not introduce contamination.
SUMMARY OF THE DISCLOSURE
[0004] Various embodiments of the disclosure provide a cell processing system including: a liquid patch panel (LPP) including a flow coupler and a first flow path at least partially defined by the flow coupler. The flow coupler may include: a lumen; a hollow tube (e.g. a needle or cannula) positioned within the lumen; and a first barrier (e.g. a septum such as an engageable septum) that isolates the lumen from the ambient environment. The cell processing system may further include a container (e.g. a consumable) including a second barrier (e.g. a septum) that seals an internal volume of the container from the ambient environment. The flow coupler may be configured to move the first barrier into contact with the second barrier of the container while the hollow tube is positioned within the lumen and to move the hollow tube towards the first barrier until the hollow tube opens the first barrier (e.g. by an end of the hollow tube penetrating and/or emerging through a face of the first barrier), opens the second barrier, and enters into the internal volume of the container. In various embodiments of the cell processing system, the hollow tube may be presterilized. [0005] In some embodiments of the cell processing system, the first barrier may be a first septum that is configured to be pierced by the hollow tube and the second barrier may be a second septum that is configured to be pierced by the hollow tube; the flow coupler may be configured to move the hollow tube towards the first barrier until the hollow tube pierces the first septum, pierces the second septum, and enters into the internal volume of the container and to retract the hollow tube back through the second barrier, back through the first barrier, and into the lumen of the flow coupler; further, when the hollow tube exits the second septum, the second septum may be resealed to isolate the internal volume of the container from the ambient environment, and when the hollow tube exits the first septum and enters into the lumen, the first septum may be resealed to isolate the lumen from the ambient environment.
[0006] In other embodiments of the cell processing system, the flow coupler may include a sleeve that defines the lumen, and the sleeve may be coupled to the first barrier, where the sleeve may be configured to move towards the second barrier, thereby moving the first barrier towards the second barrier.
[0007] Various embodiments of the cell processing system may further include a sterilant system which includes a housing that includes a channel or opening passing through the housing, where the channel or opening may be configured to be positioned between the first barrier and the second barrier; the first barrier may be configured to be positioned within the channel and the second barrier may also be configured to be positioned within the channel, while the first barrier is positioned within the channel.
[0008] In some embodiments of the cell processing system, the flow coupler may include a first seal (e g. a gasket) that surrounds the first barrier, the seal being coaxial with the first barrier and the container may include a second seal (e.g. a gasket) that surrounds the second barrier, the second seal being coaxial with the second barrier; the first seal may be configured to contact a first side of the housing of the sterilant system and the second seal may be configured to contact a second side of the housing of the sterilant system that is opposite the first side, such that when the first seal contacts the first side of the housing and when the second seal contacts the second side of the housing, the first and second barriers are isolated from the ambient environment.
[0009] In particular embodiments of the cell processing system, the channel may be a first channel, and the sterilant system may further include: a second channel or opening in fluid communication with the first channel and a pump that is configured to drive a sterilant through the second channel and into the first channel, thereby contacting an exterior surface of the first and second barriers to sterilize the exterior surfaces of the first and second barriers.
[0010] In various embodiments of the cell processing system, the sterilant may be at least one of a vapor, a gas, or a liquid and in particular the sterilant may be at least one of a peroxide, hydrogen peroxide, steam, chlorine dioxide, heated gas, dry heated gas, ethylene oxide, an alcohol, ethanol, isopropyl alcohol, or 70% v/v isopropyl alcohol.
[0011] In some embodiments of the cell processing system, the flow coupler may include a return spring (e.g. a sheath return spring) and may further include an actuator, where the actuator may be configured to extend to move the hollow tube into the first and second barriers, which loads the return spring, and when the actuator retracts, the return spring unloads to retract the hollow tube out through the first barrier, out through the second barrier, and into the lumen of the flow coupler.
[0012] In other embodiments of the cell processing system, the actuator may be a first actuator, and the system may include a second actuator and a gas source, where the first actuator may be configured to selectively bring the first flow path into fluid communication with the first internal volume of the first processing module by opening the first barrier, and the second actuator may be configured to selectively bring the second flow path into fluid communication with the second internal volume of the second processing module by opening the second barrier, and the gas source may be configured to drive liquid from the first internal volume of the first processing module, through the first flow path of the LPP, and into the second internal volume of the second processing module.
[0013] Particular embodiments of the cell processing system may further include a computing device (e.g. a controller) which is configured to: cause the actuator to extend to fluidly couple the LPP to the first processing module; cause the second actuator to extend to fluidly couple the LPP to the second processing module; and cause the gas source to drive liquid from the first processing module and into the second processing module, via the LPP.
[0014] In various embodiments, the cell processing system may be sterilized before use. In certain embodiments, the cell processing system may be configured for use in an automated manufacturing system, which includes the disclosed procedures of connecting and disconnecting components and/or sterilizing components being performed without manual intervention and in a completely automated manner. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The following drawings are provided to help illustrate various features of embodiments of the disclosure and are not intended to limit the scope of the disclosure or exclude alternative configurations.
[0016] FIG. 1 shows a single manifold unit of a liquid patch panel (LPP) which depicts an example of how an aseptic liquid connector may be used to couple the LPP and a consumable. [0017] FIG. 2 shows vapor sterilized Aseptic Liquid Connector components in a pre-mated configuration, with the male side of the connector (top) including a needle or cannula, which may be housed within the LPP as in FIG. 1, and the container or processing consumable female aseptic connector components including the liquid input/output port and vapor sterilization manifold which may be housed within or connected to the consumable.
[0018] FIG. 3 shows a cross-sectional view of FIG. 2 depicting vapor sterilized Aseptic Liquid Connector components in a pre-mated configuration, where the male and female connector portions are initially detached and unsealed from the vapor sterilization manifold. [0019] FIG. 4 shows vapor sterilized Aseptic Liquid Connector components in a mated position. The male and female connectors are sealed against the vapor sterilization manifold. Once mated, vaporized sterilant may be pumped into the chamber formed by the two connectors and manifold such that all surfaces within the chamber can be made free of biological contaminants.
[0020] FIG. 5 shows a cross-section of view of FIG. 4 depicting vapor sterilized Aseptic Liquid Connector components in a mated position. The male and female connectors are sealed against the vapor sterilization manifold. Once mated, vaporized sterilant may be pumped into the chamber formed by the two connectors and manifold such that all surfaces within the chamber may be made free of biological contaminants.
[0021] FIG. 6 shows vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath lowered to engage with the septum of the consumable. [0022] FTG. 7 shows a cross-sectional view of FIG. 6 depicting vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath lowered to engage with the septum of the consumable.
[0023] FIG. 8 shows vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath and the needle or cannula lowered. [0024] FIG 9 shows a cross-sectional view of FIG. 8 depicting vapor sterilized Aseptic Liquid Connector components sealed to the sterilization manifold with the engageable septum and sheath and the needle or cannula lowered. The cannula pierces the engageable septum of the flow coupler as well as the septum of the liquid input/output port of the consumable, allowing liquid to be transferred from the Liquid Patch Panel to the mated consumable.
[0025] FIG. 10 shows an alternative version of the Aseptic Liquid Connector which does not include a sterilization manifold, where the tip of the needle or cannula is disposed within a septum and does not require disinfection prior to use.
DETAILED DESCRIPTION OF THE PRESENT DISCLOSURE
[0026] The foregoing and other aspects and advantages of the present disclosure will appear from the following description. In the description, reference is made to the accompanying drawings that form a part hereof, and in which there is shown by way of illustration one or more exemplary versions. These versions do not necessarily represent the full scope of the disclosure. [0027] Various embodiments of the present disclosure provide an aseptic liquid connector 300 which can be used, for example, in an automated system to connect components to one another, e.g. using a robotic system, in order to move fluids through the system, which includes the disclosed procedures of connecting and disconnecting components and/or sterilizing components being performed without manual intervention and in a completely automated manner. The components may include a liquid patch panel (LPP) 100 as well as one or more consumable 130 containers, as shown in FIG. 1. Embodiments of the LPP 100 and consumables 130 which can be used with the disclosed embodiments of the aseptic liquid connector 300 are disclosed in U.S. provisional patent application no. 63/390,786, filed July 20, 2022, entitled "Liquid Patch Panel," which is incorporated herein by reference in its entirety.
[0028] In some embodiments, an LPP 100 may be fluidly coupled to a consumable 130 by one or more aseptic liquid connectors 300, as shown in FIG. 1 FIG. 1 is focused on a single manifold unit of the LPP 100, which may include a pair of liquid connectors 104 and a pair of actuator-controlled liquid routing valves 110 disposed within a rigid, robot-handleable frame; the LPP 100 may have two, three, four, or more manifold units such as that shown in FIG. 1; FIG. 1 shows complete details for a single complete manifold unit and also shows portions of two adjacent manifold units of the LPP 100 and consumables 130 for context. Each of the liquid connectors 104 may include a flow coupler 160 disposed therein, where each flow coupler 160 may include a needle or cannula 162 and a sealed flexible rubber sheath or engageable septum 164, where the needle or cannula includes an opening at or near one or both ends. The consumable 130 (which may include a compartment for storing and/or processing liquid such as reagents, media, and/or cells) may include a pair of liquid input/output ports 132, each of which may include a rubber barrier or septum 133, as shown in FIG. 1. The consumable 130 may also include a pair of air input/output ports 136 that are coupled to a gas source 180 (e.g. an air compressor, pump, or tank configured to deliver a gas or mix of gases such as oxygen, nitrogen, argon, carbon dioxide, or ambient air). The gas source 180 is configured to apply positive or negative pressure to the air input/output ports 136 (or to simply permit the release of air instead of applying negative pressure). The liquid routing valves 110 are fluidly coupled to one another and to the liquid connectors as well as to other fluid connections leading to other manifold units of the LPP 100. The actuators of the liquid routing valves 110 as well as actuators 140 and gas source 180 are connected (e.g. in a wired or wireless manner) to a controller 200 which, in various embodiments, controls the fluid connections to establish at least one flow path through the LPP 100 and consumable(s) 130 and drives the movement of fluid through the established flow path. As one example, the positions of the liquid routing valves 110 and the flow couplers 160 may be set to produce a flow path so that, when positive pressure is applied by the gas source 180 to at least one of the air input/output ports 136, fluid is removed from the consumable 130 and is transferred to a second consumable that is coupled to the LPP 100. While many of the components (e.g. including without limitation the liquid connectors 104, the liquid routing valves 110, the liquid input/output ports 132, the air input/output ports 136, septa or barriers 133, 164) are disclosed as occurring in a particular number such as two (i.e. a pair of each), in various embodiments the LPP 100 and/or consumables 130 may include any number of these items (e.g. 1, 2, 3, 4, 5, etc.) as is suitable for the particular application to which the components are being put to use. [0029] When the LPP 100 and consumable 130 are brought into proximity to one another (e.g. using an automated device such as a robotic handler), aseptic liquid connections may be made between the LPP 100 and the consumable 130 using the aseptic liquid connectors 300, which include the flow couplers 160 of the LPP 100 and the liquid input/output ports 132 of the consumable 130; as discussed further below, the liquid input/output ports 132 may also include a sterilization manifold which can be used to sterilize outer surfaces of the septum 133 and/or the engageable septum 164 in an automated manner. After the LPP 100 and consumable 130 have been brought into proximity to one another, actuators 140 (e.g. coupled to the flow couplers 160 via pistons 150) may help drive movement of the engageable septum 164 into position to be sterilized within the sterilization manifold and also drive the needle or cannula 162 through the engageable septum 164 and the rubber barrier or septum 133, which results in fluid flow in one or both directions through the needle or cannula 162 (as indicated by the double arrow in FIG. 1).
[0030] Although there are various ways to implement an aseptic liquid connection, in one embodiment a connector on the LPP 100 side may be formed by a piercing needle or cannula 162 contained in a sealed flexible rubber sheath or engageable septum 164, which may be part of the flow coupler 160 and which may be sterilized prior to use. When the LPP 100 and consumables 130 are assembled into a single structure, the needle or cannula 162 probe is configured to pierce through the sheath on the flow coupler 160 and a rubber barrier or septum 133 on the mating connector (e.g. a rubber barrier that is part of the liquid input/output ports 132) such that a fluidic connection is established between the region inside the needle or cannula 162 probe on the one hand and inside of the mating consumable on the other (represented by two-way arrow in FIG. 1). In some embodiments, the engageable septum 164 may be brought near or in contact with the septum 133 for sterilization prior to the point at which the needle or cannula 162 probe pierces through each of the septa 164, 133 (FIG. 1, left), after which the needle or cannula 162 can pierce the septa 164, 133 to transfer fluid into or out of the consumable 130 as part of a transfer operation (FIG. 1, right). Upon completion of the operation, the needle or cannula 162 may be withdrawn and each of the septa 164, 133 may reseal to isolate the respective compartments from the ambient environment.
[0031] Prior to or during use, it may be necessary (or at least advisable as a precaution) to sterilize the needle or cannula 162 probe prior to initial use or before one or more re-uses. As discussed further below, mechanisms are provided in some embodiments for sterilizing the needle or cannula 162 probe in a manner that is automated and does not require operator intervention. Accordingly, in various embodiments, a liquid connection may be completed in a way that is aseptic or free of biological contamination using a number of approaches, including: sealing the connector halves (i.e. the portions associated with the LPP 100 and the consumable 130, respectively) to a chamber where gaseous, liquid, or vaporous (e.g. peroxide, hydrogen peroxide such as vaporous hydrogen peroxide, steam, chlorine dioxide, heated gas, dry heated gas, ethylene oxide, an alcohol, ethanol, isopropyl alcohol, or 70% v/v isopropyl alcohol) decontamination agents may be introduced, followed by flushing agents for removing the sterilant. Sterilant may be introduced to the closed chamber using vacuum or positive pressures; spraying the surfaces of the connectors with a liquid sterilant; irradiating the surfaces of the connectors with UV-C light; and/or removing a barrier which forms a closed and pre-sterilized chamber around the otherwise exposed faces of the liquid connectors immediately prior to mating them. Particular embodiments of the aseptic liquid connector 300 are shown in FIGS. 2- 10 and described below.
[0032] In certain embodiments of the aseptic liquid connector 300, each of the flow coupler 160 and the liquid input/output ports 132 may be sterilized prior to connection by means of vapor sterilant such as vaporized hydrogen peroxide. In various embodiments, the sterilization may be accomplished using the flow coupler 160 of the LPP 100 in which the needle or cannula 162 is disposed within and coupled to a tube or housing 166, as shown in FIGS. 2-9, such that the free end of the tube or housing 166 can be fluidically connected by tubing to a liquid media or reagent source or may be connected via the LPP 100 to one or more other consumables 130. The opposite end of the needle or cannula 162 may have a tapered or sharpened end to facilitate piercing the septa 164, 133 and may include an opening at or near an end thereof to facilitate fluid flow therethrough.
[0033] FIGS. 2-9 show embodiments of an aseptic liquid connector 300 which includes components of the flow coupler 160 (which may be associated with the LPP 100) and the liquid input/output ports 132, which may each include a sterilization manifold 135, and are associated with the consumables 130. The opening at the end of the needle or cannula 162 is initially held within a sealed chamber formed by a body 165 (e.g. which may be made of hard plastic) and two septa 163, 164, above and below the tip of the needle or cannula 162, respectively. The assembly is held in this position by springs 167 A, 167B when not acted on by the instrument, e.g. by an actuator 140. When brought into the instrument, e.g. when operated on as part of an LPP 100, this assembly may be lowered and sealed against the sterilization manifold 135, which may contain internal fluidic connections to a vapor sterilant source, as discussed further below. [0034] The body of the flow coupler 160 may include a sheath 168 with a cap 168 A and an upper flange 169 as well as shielding 168B surrounded by outer spring 167B. The liquid input/output port 132 may include a lower flange 134. In some embodiments, the sterilization manifold 135 may be integrated into the liquid input/output port 132, and in other embodiments the sterilization manifold 135 may be a separate component from the liquid input/output port 132. The sterilization manifold 135 may have an annular shape with an opening 135A therethrough, where the upper flange 169 of the flow coupler 160 and/or the lower flange 134 of the liquid input/output port 132 may abut and make a seal with the opening of the sterilization manifold 135. In various embodiments the abutting surfaces of the sterilization manifold 135, the upper flange 169, and/or the lower flange 134 may include gaskets or other means of promoting a tight seal. The sterilization manifold 135 may also include one or more side openings 135B which permit entry and/or exit of sterilant (e.g. from a vapor sterilant source) into the opening 135A.
[0035] In use, the liquid input/output port 132 may be raised or otherwise moved towards the sterilization manifold 135 to form a seal between the lower flange 134 and the sterilization manifold 135; in some embodiments this connection between the liquid input/output port 132 and the sterilization manifold 135 may be made prior to deployment of the consumable 130 (i.e. the sterilization manifold 135 may be part of the consumable 130 and in some embodiments may be integrated with the liquid input/output port 132) and in other embodiments the liquid input/output port 132 may be brought into contact with the sterilization manifold 135 at approximately the same time that the upper flange 169 of the flow coupler 160 is brought into contact with the sterilization manifold 135 (see FIGS. 2 and 3, with arrows in FIG. 3 indicating movement of flanges 134, 169 towards manifold 135).
[0036] Once sealed, the chamber (i.e. space within the opening 135A) formed by the two connectors (i.e. flanges 134, 169) and the sterilization manifold 135 may be sterilized using a vaporized sterilant then flushed with sterile air to remove the sterilant (see FIGS. 4 and 5). Once clear of sterilant, the sheath 168 containing the needle or cannula 162 may be lowered by compressing (e g. using actuator 140) the sheath return spring 167B, creating a seal of the engageable septum 164 against the septum 133 of the mating consumable 130 (FIGS. 6 and 7). The needle or cannula 162 may then be lowered, piercing the septum 133 of the mating consumable 130 and the engageable septum 164 of the LPP 100, creating an aseptic fluidic connection between the liquid source connected to the LPP 100 and the interior of the mating consumable 130 (FIGS. 8 and 9). While only the tip of the needle or cannula 162 is shown extending out of the lower end of the liquid input/output port 132, in various embodiments the needle or cannula 162 may extend further out of the lower end of the liquid input/output port 132 to reach further into the consumable 130.
[0037] In an alternative embodiment of the flow coupler 160 which is shown in FIG. 10, the tip of the needle or cannula 162 may initially be disposed within an engageable septum 164' which fills the entire space between where the septa 163, 164 are initially located in the flow coupler 160 of the previous embodiment (see FIG. 5). In this embodiment, the tip of the needle or cannula is maintained in a sterilized state by being encased within the material (e.g. rubber) of the engageable septum 164' up until the time of use and as a result it is not necessary to provide the sterilization manifold 135. In this particular embodiment, the flow coupler 160 has fewer components, with the outer spring 167B, the shielding 168B, the cap 168A, and the upper 169 and lower 134 flanges and any associated gaskets being omitted. In this embodiment, the modified engageable septum 164' may be lowered into contact with the septum 133 of the liquid input/output port 132 (as indicated by downward arrow in FIG. 10), followed by advancement of the needle or cannula 162 as it moves through and/or emerges from a face to open the septa 164', 133 into the compartment of the consumable 130.
[0038] In another embodiment, the needle or cannula 162 may extend completely through and out the top end of the tube or housing 166. In this embodiment, the free end of the needle or cannula 162 can be fluidically connected by tubing to a liquid media or reagent source or may be connected via the LPP 100 to one or more other consumables 130 (FIG. 10), a feature which may be combined with any of the embodiments of FIGS. 2-9 independently of the use of the modified engageable septum 164'.
[0039] The present disclosure has described one or more preferred claims, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention. [0040] It is to be understood that the disclosure is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The disclosure is capable of other claims and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings.
[0041] As used herein, unless otherwise limited or defined, discussion of particular directions is provided by example only, with regard to particular claims or relevant illustrations. For example, discussion of “top,” “front,” or “back” features is generally intended as a description only of the orientation of such features relative to a reference frame of a particular example or illustration. Correspondingly, for example, a “top” feature may sometimes be disposed below a “bottom” feature (and so on), in some arrangements or claims. Further, references to particular rotational or other movements (e.g., counterclockwise rotation) is generally intended as a description only of movement relative a reference frame of a particular example of illustration.
[0042] In some claims, aspects of the disclosure, including computerized configurations of methods according to the disclosure, can be implemented as a system, method, apparatus, or article of manufacture using standard programming or engineering techniques to produce software, firmware, hardware, or any combination thereof to control a processor device (e.g., a serial or parallel general purpose or specialized processor chip, a single- or multi-core chip, a microprocessor, a field programmable gate array, any variety of combinations of a control unit, arithmetic logic unit, and processor register, and so on), a computer (e.g., a processor device operatively coupled to a memory), or another electronically operated controller to implement aspects detailed herein. Accordingly, for example, claims of the disclosure can be implemented as a set of instructions, tangibly embodied on a non-transitory computer-readable media, such that a processor device can implement the instructions based upon reading the instructions from the computer-readable media. Some claims of the disclosure can include (or utilize) a control device such as an automation device, a special purpose or general purpose computer including various computer hardware, software, firmware, and so on, consistent with the discussion below. As specific examples, a control device can include a processor, a microcontroller, a field- programmable gate array, a programmable logic controller, logic gates etc., and other typical components that are known in the art for configuration of appropriate functionality (e.g., memory, communication systems, power sources, user interfaces and other inputs, etc.).
[0043] The term “article of manufacture” as used herein is intended to encompass a computer program accessible from any computer-readable device, carrier (e.g., non-transitory signals), or media (e.g., non-transitory media). For example, computer-readable media can include but are not limited to magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips, and so on), optical disks (e.g., compact disk (CD), digital versatile disk (DVD), and so on), smart cards, and flash memory devices (e.g., card, stick, and so on). Additionally it should be appreciated that a carrier wave can be employed to carry computer-readable electronic data such as those used in transmitting and receiving electronic mail or in accessing a network such as the Internet or a local area network (LAN). Those skilled in the art will recognize that many modifications may be made to these configurations without departing from the scope or spirit of the claimed subject matter.
[0044] Certain operations of methods according to the disclosure, or of systems executing those methods, may be represented schematically in the FIGS, or otherwise discussed herein. Unless otherwise specified or limited, representation in the FIGS, of particular operations in particular spatial order may not necessarily require those operations to be executed in a particular sequence corresponding to the particular spatial order. Correspondingly, certain operations represented in the FIGS., or otherwise disclosed herein, can be executed in different orders than are expressly illustrated or described, as appropriate for particular claims of the disclosure. Further, in some claims, certain operations can be executed in parallel, including by dedicated parallel processing devices, or separate computing devices configured to interoperate as part of a large system.
[0045] As used herein in the context of computer configuration, unless otherwise specified or limited, the terms “component,” “system,” “module,” and the like are intended to encompass part or all of computer-related systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on).
[0046] In some configurations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as claims of the disclosure, of the utilized features and implemented capabilities of such device or system.
[0047] As used herein, unless otherwise defined or limited, ordinal numbers are used herein for convenience of reference based generally on the order in which particular components are presented for the relevant part of the disclosure. In this regard, for example, designations such as “first,” “second,” etc., generally indicate only the order in which the relevant component is introduced for discussion and generally do not indicate or require a particular spatial arrangement, functional or structural primacy or order.
[0048] As used herein, unless otherwise defined or limited, directional terms are used for convenience of reference for discussion of particular figures or examples. For example, references to downward (or other) directions or top (or other) positions may be used to discuss aspects of a particular example or figure, but do not necessarily require similar orientation or geometry in all installations or configurations.
[0049] Also as used herein, unless otherwise limited or defined, “or” indicates a nonexclusive list of components or operations that can be present in any variety of combinations, rather than an exclusive list of components that can be present only as alternatives to each other. For example, a list of “A, B, or C” indicates options of: A; B; C; A and B; A and C; B and C; and A, B, and C. Correspondingly, the term “or” as used herein is intended to indicate exclusive alternatives only when preceded by terms of exclusivity, such as “either,” “one of,” “only one of,” or “exactly one of.” For example, a list of “one of A, B, or C” indicates options of: A, but not B and C; B, but not A and C; and C, but not A and B. A list preceded by “one or more” (and variations thereon) and including “or” to separate listed elements indicates options of one or more of any or all of the listed elements. For example, the phrases “one or more of A, B, or C” and “at least one of A, B, or C” indicate options of: one or more A; one or more B; one or more C; one or more A and one or more B; one or more B and one or more C; one or more A and one or more C; and one or more of A, one or more of B, and one or more of C. Similarly, a list preceded by “a plurality of’ (and variations thereon) and including “or” to separate listed elements indicates options of multiple instances of any or all of the listed elements. For example, the phrases “a plurality of A, B, or C” and “two or more of A, B, or C” indicate options of: A and B; B and C; A and C; and A, B, and C.
[0050] Furthermore, in those instances where a convention analogous to “at least one of A, B and C, etc.” is used, in general such a construction is intended in the sense of one having ordinary skill in the art would understand the convention (e.g., “a system having at least one of A, B and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together ). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description or figures, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or ‘B or “A and B.”
[0051] This discussion is presented to enable a person skilled in the art to make and use claims of the disclosure. Various modifications to the illustrated examples will be readily apparent to those skilled in the art, and the generic principles herein can be applied to other examples and applications without departing from the principles disclosed herein. Thus, claims of the disclosure are not intended to be limited to claims shown, but are to be accorded the widest scope consistent with the principles and features disclosed herein and the claims below. The following detailed description is to be read with reference to the figures, in which like elements in different figures have like reference numerals. The figures, which are not necessarily to scale, depict selected examples and are not intended to limit the scope of the disclosure. Skilled artisans will recognize the examples provided herein have many useful alternatives and fall within the scope of the disclosure.
[0052] Various features and advantages of the disclosure are set forth in the following claims.

Claims

CLAIMS What is claimed is:
1. A cell processing system comprising: a liquid patch panel (LPP) including a flow coupler, and a first flow path at least partially defined by the flow coupler, the flow coupler comprising: a lumen; a hollow tube positioned within the lumen; and a first barrier that isolates the lumen from the ambient environment; and a container including a second barrier that seals an internal volume of the container from the ambient environment, and wherein the flow coupler is configured to move the first barrier into contact with the second barrier of the container while the hollow tube is positioned within the lumen, and wherein the flow coupler is configured to move the hollow tube towards the first barrier until the hollow tube opens the first barrier, opens the second barrier, and enters into the internal volume of the container.
2. The cell processing system of claim 1, wherein the hollow tube is presterilized.
3. The cell processing system of claim 1, wherein the first barrier is a first septum that is configured to be pierced by the hollow tube, and wherein the second barrier is a second septum that is configured to be pierced by the hollow tube, and wherein the flow coupler is configured to move the hollow tube towards the first barrier until the hollow tube pierces the first septum, pierces the second septum, and enters into the internal volume of the container, and wherein the flow coupler is configured to retract the hollow tube back through the second barrier, back through the first barrier, and into the lumen of the flow coupler, and wherein when the hollow tube exits the second septum, the second septum reseals to isolate the internal volume of the container from the ambient environment, and wherein when the hollow tube exits the first septum and enters into the lumen, the first septum reseals to isolate the lumen from the ambient environment.
4. The cell processing system of claim 1, wherein the flow coupler includes a sleeve that defines the lumen, and wherein the sleeve is coupled to the first barrier, and wherein the sleeve is configured to move towards the second barrier, thereby moving the first barrier towards the second barrier.
5. The cell processing system of claim 1, further comprising a sterilant system comprising a housing that includes a channel passing through the housing, wherein the channel is configured to be positioned between the first barrier and the second barrier, wherein the first barrier is configured to be positioned within the first channel, and wherein the second barrier is configured to be positioned within the first channel, while the first barrier is positioned within the first channel.
6. The cell processing system of claim 5, wherein the flow coupler includes a first seal that surrounds the first barrier, the seal being coaxial with the first barrier, wherein the container includes a second seal that surrounds the second barrier, the second seal being coaxial with the second barrier, wherein the first seal is configured to contact a first side of the housing of the sterilant system, wherein the second seal is configured to contact a second side of the housing of the sterilant system that is opposite the first side, and wherein when the first seal contacts the first side of the housing and when the second seal contacts the second side of the housing, the first and second barriers are isolated from the ambient environment.
7. The cell processing system of claim 5, wherein the channel is a first channel, and wherein the sterilant system includes: a second channel in fluid communication with the first channel; a pump that is configured to drive a sterilant through the second channel and into the first channel, thereby contacting an exterior surface of the first and second barriers to sterilize the exterior surfaces of the first and second barriers.
8. The cell processing system of claim 7, wherein the sterilant is at least one of a vapor, a gas, or a liquid; and wherein the sterilant is at least one of a peroxide, hydrogen peroxide, steam, chlorine dioxide, heated gas, dry heated gas, ethylene oxide, an alcohol, ethanol, isopropyl alcohol, or 70% v/v isopropyl alcohol.
9. The cell processing system of claim 1, wherein the flow coupler includes a return spring, and further comprising an actuator, wherein the actuator is configured to extend to move the hollow tube into the first and second barriers, which loads the return spring, and wherein when the actuator retracts, the return spring unloads to retract the hollow tube out through the first barrier, out through the second barrier, and into the lumen of the flow coupler.
10. The cell processing system of claim 9, wherein the actuator is a first actuator, and further comprising a second actuator and a gas source; wherein the first actuator is configured to selectively bring the first flow path into fluid communication with the first internal volume of the first processing module by opening the first barrier; wherein the second actuator is configured to selectively bring the second flow path into fluid communication with the second internal volume of the second processing module by opening the second barrier, and wherein the gas source is configured to drive liquid from the first internal volume of the first processing module, through the first flow path of the LPP, and into the second internal volume of the second processing module.
11. The cell processing system of claim 10, further comprising a computing device being configured to: cause the actuator to extend to fluidly couple the LPP to the first processing module; cause the second actuator to extend to fluidly couple the LPP to the second processing module; and cause the gas source to drive liquid from the first processing module and into the second processing module, via the LPP.
12. The cell processing system of any of the preceding claims, wherein the cell processing system is sterilized before use.
13. The cell processing system of any of the preceding claims, wherein the cell processing system is configured for use in an automated manufacturing system.
PCT/US2023/070331 2022-07-20 2023-07-17 Aseptic liquid connector WO2024020344A1 (en)

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US63/390,795 2022-07-20

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020023409A1 (en) * 2000-02-11 2002-02-28 Daniel Py Medicament vial having a heat-sealable cap, and apparatus and method for filling the vial
US20110236962A1 (en) * 2010-02-10 2011-09-29 Hamilton Bonaduz Ag Calibratable sensor unit for reaction vessels
US20170035964A1 (en) * 2010-03-30 2017-02-09 Unomedical A/S Medical device
US20170106135A1 (en) * 2014-04-03 2017-04-20 Novo Nordisk A/S A Needle Arrangement
WO2021123760A1 (en) * 2019-12-17 2021-06-24 Oribiotech Ltd A connector

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020023409A1 (en) * 2000-02-11 2002-02-28 Daniel Py Medicament vial having a heat-sealable cap, and apparatus and method for filling the vial
US20110236962A1 (en) * 2010-02-10 2011-09-29 Hamilton Bonaduz Ag Calibratable sensor unit for reaction vessels
US20170035964A1 (en) * 2010-03-30 2017-02-09 Unomedical A/S Medical device
US20170106135A1 (en) * 2014-04-03 2017-04-20 Novo Nordisk A/S A Needle Arrangement
WO2021123760A1 (en) * 2019-12-17 2021-06-24 Oribiotech Ltd A connector

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