Assembly and system for controlled dispensing of fluids

Abstract

The present disclosure provides assemblies, methods, and systems for delivering a fluid into a fluid flow. An assembly includes a dispenser body having an inner wall defining a lumen, the lumen having a longitudinal axis and a diameter; a cap configured to span the diameter of the lumen, the cap having an upper surface and a lower surface; a piston disposed within the lumen, the piston having a top surface and a bottom surface, the top surface defining a working volume of the lumen together with the inner wall and the lower surface of the cover, where the piston is movable along the longitudinal axis to vary the working volume; an outlet in fluid connection with the working volume; and a fluid conduit extending between a first portion of the fluid conduit and a second portion of the fluid conduit, the fluid conduit being in fluid connection with the working volume via the outlet between the first portion and the second portion of the fluid conduit.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 523,331, filed June 26, 2023, the disclosure of which is considered part of the disclosure of this application and is incorporated herein by reference. background Technical Field

[0003] This disclosure relates generally to fluid transport, and more specifically to components and systems for controlled fluid distribution, and methods of use for distributing fluid into fluid conduits to perform processing in a fluid workflow. Background Technology

[0004] Syringes are widely used for sample manipulation in research, medical, and diagnostic settings. A syringe typically consists of a needle attached to one end of a hollow syringe and a plunger connected to a sliding piston. By pulling the plunger, fluid is drawn from the needle into the hollow syringe. By pushing the plunger, the piston pushes the fluid out of the needle, allowing fluid to be injected or dispensed from the hollow syringe. Syringes can be filled with the desired sample before use, or they can be pre-filled with the desired sample.

[0005] In several applications, pre-filled syringes transport samples from one location to another (e.g., within a laboratory or from one geographic location to another). Such pre-filled syringes have a plunger attached to a piston, which typically extends far beyond the top of the hollow syringe. A disadvantage of using syringes is that fluid may be dispensed at unexpected times and / or locations if the plunger is accidentally pushed or struck.

[0006] Another drawback of using syringes is the risk of accidental needle pricks to technicians. This is a particular concern in applications involving the risk of exposure to biological samples (such as patient samples) due to needle pricks by technicians.

[0007] Therefore, there is a need for an improved device for controlled fluid dispensing that enables the delivery of fluid contained in the device without posing a risk to technicians of accidental needle pricks or accidental fluid leakage from the device during delivery. Summary of the Invention

[0008] One aspect of this disclosure provides a component for dispensing fluid. In an embodiment, the component includes:

[0009] A distributor body having an inner wall defining a cavity having a longitudinal axis and a diameter;

[0010] A cover, configured to span the diameter of the lumen, having an upper surface and a lower surface;

[0011] A piston disposed within a cavity, the piston having a top surface and a bottom surface, the top surface together with the lower surface of the inner wall and the cover defining the working volume of the cavity, wherein the piston is movable along a longitudinal axis to change the working volume;

[0012] An outlet, which is fluidly connected to the working volume; and

[0013] A fluid conduit extending between a first portion and a second portion of a fluid conduit, the fluid conduit being fluidly connected to the working volume via an outlet between the first and second portions of the fluid conduit.

[0014] In embodiments, the assembly has a first configuration and a second configuration, in which the cap does not span the diameter of the lumen and the lumen is fluid-open, and in the second configuration, the cap spans the diameter of the lumen and the lumen is fluid-sealed. In some embodiments, when the assembly is in the second configuration where the lumen is fluid-sealed, movement of the piston along the longitudinal axis causes fluid to flow through the outlet.

[0015] In some embodiments, the dispenser body includes one or more additional inner walls defining individual additional lumens, each additional lumen having a longitudinal axis and a diameter. In some embodiments, each additional lumen includes a piston defining a working volume, and each piston is movable along a respective longitudinal axis to change the corresponding working volume of each lumen. In some embodiments, a fluid conduit is fluidly connected to the working volume of each lumen between an inlet port and an outlet port of the fluid conduit. In one embodiment, the assembly includes two to ten lumens formed in the dispenser body, each lumen having a working volume that is fluidly connected to the fluid conduit between an inlet port and an outlet port of the fluid conduit.

[0016] On the other hand, this disclosure provides a system for dispensing fluid, the system including the components of this disclosure. In an embodiment, the system includes:

[0017] The components disclosed herein; and

[0018] An actuator operatively coupled to a lumen of a distributor body configured to move a piston defining a working volume of the lumen along the longitudinal axis of the lumen, in order to reduce the working volume and allow fluid to flow from the working volume into a fluid conduit when the assembly is in a second configuration in which the lumen is fluid-sealed.

[0019] On the other hand, this disclosure provides a system for dispensing fluid, the system including the components of this disclosure. In an embodiment, the system includes:

[0020] One or more components of this disclosure, the one or more components having one or more dispenser bodies, each dispenser body having one or more lumens with a working volume; and

[0021] One or more actuators operatively coupled to each lumen of one or more distributor bodies configured to move a piston defining a working volume along the longitudinal axis of the lumen to reduce the working volume and allow fluid to flow from the working volume into a fluid conduit when the assembly is in a second configuration in which the lumen is fluid-sealed.

[0022] In some embodiments, the system includes: a first feed line fluidly coupled to an input port of a fluid conduit located upstream of one or more dispenser bodies; and a second feed line fluidly coupled to an output port fluidly coupled to a fluid conduit located downstream of one or more dispenser bodies, to form a sterile and functionally closed system. In some embodiments, the system includes a cell processing system fluidly coupled to the first and second feed lines.

[0023] In another aspect, this disclosure provides a method for dispensing fluid from components of this disclosure. The method includes:

[0024] Provides the components disclosed herein;

[0025] When the component is in the first configuration and the working volume of the lumen is opened by fluid, fluid is loaded into the working volume of the lumen of the distributor body;

[0026] The component is converted to a second configuration in which the working volume of the lumen is fluid-sealed; and

[0027] A piston positioned within the lumen is advanced along the longitudinal axis of the lumen to allow fluid to flow from the working volume into the fluid conduit.

[0028] In another aspect, this disclosure provides a method for performing a fluid workflow using the components or systems of this disclosure. The method includes:

[0029] Transporting fluid from the working volume of a component or system of this disclosure to a fluid flow contained within a functionally enclosed system; and

[0030] Execute fluid workflows.

[0031] In some embodiments, the fluid includes gene editing reagents, and the fluid flow includes cells or components thereof. In some embodiments, the fluid workflow includes cell processing protocols, such as protocols that include transformation, transfection, transduction, activation, isolation, sorting, imaging, labeling, and / or culture of cells or portions thereof.

[0032] The foregoing general description of the illustrative embodiments and the following detailed description are merely exemplary aspects of the teachings of this disclosure and are not limiting. Attached Figure Description

[0033] The accompanying drawings are incorporated in and form part of this specification. The drawings illustrate one or more embodiments and, together with the description, explain these embodiments. The drawings are not necessarily drawn to scale. Any values ​​or dimensions shown in the accompanying tables and figures are for illustrative purposes only and may or may not represent actual or preferred values ​​or dimensions. Where applicable, some or all features cannot be illustrated to help describe essential characteristics.

[0034] Figure 1 is an elevation perspective view showing the components in an embodiment of the present disclosure.

[0035] Figure 2 is a bottom perspective view of the component shown in Figure 1.

[0036] Figure 3 is a cross-sectional front view of the component shown in Figure 1.

[0037] Figure 4 is a cross-sectional elevation front view of the component shown in Figure 1.

[0038] Figure 5 is a cross-sectional front view of the component shown in Figure 1.

[0039] Figure 6 is an exploded view of the cap and fluid conduit of the component shown in Figure 1.

[0040] Figure 7 is an exploded view of the cap and fluid conduit of the component shown in Figure 1.

[0041] Figure 8 is a cross-sectional elevation side view of the component shown in Figure 1.

[0042] Figure 9 is a bottom perspective view of the component shown in Figure 1.

[0043] Figure 10 is an exploded view of the components shown in Figure 1.

[0044] Figure 11 is a perspective view of the components shown in Figure 1 before the cover is coupled to the dispenser body.

[0045] Figure 12 is a side view of the component shown in Figure 11.

[0046] Figure 13 is a side view of the component shown in Figure 11, in which the cover contacts the dispenser body and the attachment member is not coupled to the dispenser body.

[0047] Figure 14 is a side view of the assembly shown in Figure 13, in which the cover contacts the dispenser body and the attachment member is moved to couple with the dispenser body.

[0048] Figure 15 is a side view of the assembly shown in Figure 13, in which the cover contacts the dispenser body and the attachment member is moved to couple with the dispenser body.

[0049] Figure 16 is a side view of the assembly shown in Figure 13, in which the cover contacts the dispenser body and the attachment member is moved to couple with the dispenser body.

[0050] Figure 17 is a side view of the assembly shown in Figure 13, wherein the cover contacts the dispenser body and the attachment member is coupled to the dispenser body to prepare the assembly for dispensing fluid.

[0051] Figure 18 is a cross-sectional front view of the assembly shown in Figure 1, in which the piston is moved away from the cover, thereby defining a positive working volume in each cavity.

[0052] Figure 19 is a cross-sectional front view of the assembly shown in Figure 1, in which the pistons disposed in the cavities move toward the cover, such that the working volume in each cavity is zero.

[0053] Figure 20 is an elevation perspective view showing the components in an embodiment of the present disclosure.

[0054] Figure 21 is a side view of the component shown in Figure 20.

[0055] Figure 22 is a perspective view of the component shown in Figure 20, in which the cover is moved to cover the lumen of the dispenser body.

[0056] Figure 23 is a side view of the component shown in Figure 21.

[0057] Figure 24 is a perspective view of the component shown in Figure 20, in which the cover is moved to contact the dispenser body.

[0058] Figure 25 is a side view of the component shown in Figure 24.

[0059] Figure 26 is a perspective view of the assembly shown in Figure 20, wherein the cap and the dispenser body have a liquid-tight seal.

[0060] Figure 27 is a side view of the component shown in Figure 26. Detailed Implementation

[0061] The description set forth below with reference to the accompanying drawings is intended as a description of various embodiments of the disclosed subject matter and is not necessarily intended to represent the only embodiment. In certain cases, the description includes specific details intended to provide an understanding of the disclosed embodiments. However, it will be apparent to those skilled in the art that the disclosed embodiments can be practiced without specific details. In some cases, well-known structures and components may be shown in the form of block diagrams in order to avoid obscuring the concepts of the disclosed subject matter.

[0062] Throughout this specification, references to "an embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the disclosed subject matter. Therefore, the phrases "in one embodiment" or "in an embodiment" appearing throughout this specification do not necessarily refer to the same embodiment. Furthermore, in one or more embodiments, a particular feature, structure, or characteristic may be combined in any suitable manner. Moreover, it is intended that embodiments of the disclosed subject matter encompass modifications and variations thereof.

[0063] It should be understood that terms such as “far end,” “proximal end,” “top,” “bottom,” “front,” “side,” “length,” “lower,” “inner,” “internal,” and “outer” used herein describe reference points only and do not necessarily limit the embodiments of this disclosure to any particular orientation or configuration. Furthermore, terms such as “first,” “second,” and “third” identify only one of the parts, components, steps, operations, functions, and / or reference points disclosed herein, and likewise do not necessarily limit the embodiments of this disclosure to any particular configuration or orientation.

[0064] The terms “longitudinal,” “axial,” or “axially” as used herein generally refer to the longitudinal direction and are used to describe the relative positions of components in relation to the syringe, delivery mechanism, and system. The term “radial” generally refers to a direction perpendicular to the “axial” direction. For example, the term “radial” generally refers to a direction perpendicular to axis “A.”

[0065] The term "fluid" primarily refers to a liquid, but also includes solid suspensions diffused in or dissolved in a liquid, or gases coexisting in a liquid within the fluid-containing portion of a syringe. In this disclosure, fluids are used as example substances aspirated into a syringe to explain the concept. In many embodiments, samples may be dispensed (e.g., aspirated) without departing from the scope of this disclosure.

[0066] As used herein, the term “sample” refers to a liquid, such as a biomolecule, that may include one or more reagents.

[0067] The term “biological molecule” or “biomolecule” is intended to generally refer to any organic or biochemical molecule present in a biological system, including whole cells, cellular components, substrates, or any part thereof.

[0068] As used herein, “cellular component” is intended to include any component of a cell that can be at least partially separated upon cell lysis. Cellular components include recombinant or synthetically produced components that may be functionally and / or structurally modified to include synthetically (e.g., chemically synthesized) derived components. Cellular components can be organelles such as the nucleus, perinuclear region, nuclear membrane, mitochondria, chloroplasts, or cell membrane; polymers or molecular complexes such as lipids, polysaccharides, proteins (membrane proteins, transmembrane proteins, or cytoplasmic proteins); nucleic acids, viral particles, or ribosomes; or other molecules such as hormones, ions, cofactors, or drugs.

[0069] In various embodiments, the sample includes cells (e.g., mammalian or non-mammalian cells), cellular components, biomolecules, or other reagents (e.g., reagents for the research or manufacture of cell and gene therapies). In some embodiments, the sample may be a fluid and loaded into the components of this disclosure via a needle, test tube, vial, or other container. In some embodiments, the test tube, vial, or other container is for single use and is made of materials suitable for preparing, mixing, centrifuging, transporting, and / or storing solid and liquid samples and reagents, such as quartz, glass, metal, or polymers (e.g., polypropylene, polyethylene, polyurethane, polycarbonate, etc.).

[0070] Systems used in cell-based or gene-based therapies (such as T-cell therapy or CAR T-cell therapy) involve a large number of devices performing multiple processes and adding large amounts of reagents / cell culture components in various devices, typically in a specified sequence known as a workflow or fluid workflow.

[0071] In the fields of cell and gene therapy, functionally closed sterile systems are in high demand. "Open" steps (e.g., those involving human intervention) should be minimized to reduce the risk of biocontamination.

[0072] Currently, when electroporation (a technique commonly used in gene editing) is used to deliver payloads (e.g., biomolecules such as nucleic acids or proteins, or other reagents), cells are concentrated and resuspended in an electroporation buffer (e.g., a conductive fluid) within a bag or rigid container. After resuspension, additional reagents can be added to the cells in a specific sequence. Currently, this is performed within a biosafety cabinet and is considered an open procedure with a certain risk of contamination. Ideally, this step would be performed outside the biosafety cabinet and within an automated closed system; however, current solutions for automating the injection of different fluids are insufficient, especially for small amounts of fluid (e.g., <1 ml). After adding the payload and necessary additional reagents, a bag containing cells or other storage media is coupled to an electroporation platform for electroporation of the cells.

[0073] The arrangement of syringes and automated injection devices used to deliver fluids (e.g., fluids including payloads) into fluid workflows may be associated with problems such as dead volume, perfusion problems, needle punctures, or accidental injection of liquids, such as when the plunger is impacted or unintentionally depressed. This disclosure addresses several of the problems listed above and provides novel components, systems, and methods for delivering fluid samples (e.g., liquids, suspensions, etc.).

[0074] As further discussed herein, the component 10 of this disclosure typically includes a cap and a dispenser body. After fluid is added to one or more lumens of the dispenser body, the cap and dispenser body are assembled by forming a fully liquid-tight seal between the cap and the dispenser body to contain the added fluid within the working volume of the lumen. Therefore, component 10 has a first unassembled configuration and a second assembled configuration. In the first unassembled configuration, the cap is not sealingly engaged with the dispenser body, and fluid can be added to the dispenser body. In the second assembled configuration, the cap is disposed on one or more lumens of the dispenser body, and a fluid seal is created between the cap (and optionally an intermediate sealing member) and the dispenser body to fully seal the fluid contained within the lumen of the dispenser body.

[0075] As discussed herein, component 10 of this disclosure can be configured to dispense a single fluid from an assembly having a lumen containing a single fluid, or to dispense multiple fluids from an assembly having multiple (e.g., 1, 2, 3, 4, 5, 6 or more) fluid-containing lumens. The accompanying drawings illustrate an embodiment of component 10 configured to dispense multiple fluid samples (i.e., 6) into a fluid flow path (e.g., fluid within a fluid conduit that can be operatively coupled to a fluid workflow). It should be understood that while the assembly shown in the drawings is configured with a dispenser body having 6 lumens, this disclosure covers assemblies in which the dispenser body is configured to have any number of lumens (e.g., a single lumen, or 2, 3, 4, 5, 6, 7, 8, 9, 10 or more lumens).

[0076] Figures 1 through 19 illustrate embodiments of component 10, which includes a dispenser body 15, a cap 30, a piston 45, and a fluid conduit 65. Figures 11 through 16 show example illustrations of component 10 in a first unassembled configuration, and Figures 1, 2, and 17 show example illustrations of component 10 in a second assembled configuration.

[0077] In one embodiment, the dispenser body 15 has an inner wall 20 defining a lumen 25 having a longitudinal axis (A-A') and a diameter (D). A cap 30 is configured to span the diameter of the lumen 25 and includes an upper surface 35 and a lower surface 40. A piston 45 is disposed within the lumen and includes a top surface 50 and a bottom surface 55. The top surface 50, together with the inner wall 20 and the lower surface 40 of the cap, optionally together with an intermediate sealing member 95 (e.g., a gasket), defines the working volume (LQ) of the lumen (see Figure 5).

[0078] As shown in Figure 5, the assembly may further include an outlet 60 in fluid connection with the working volume (LQ). The outlet provides a fluid passage to a fluid conduit 65 extending between a first portion 70 and a second portion 75 of the fluid conduit, such that the fluid conduit is in fluid connection with the working volume via the outlet between the first and second portions of the fluid conduit.

[0079] In the assembly 10 shown in Figures 1 through 19, the region of the fluid conduit 65 disposed between the first portion 70 and the second portion 75 of the fluid conduit is defined by a channel 90 formed within the upper surface 35 of the cap and a cap member 100 disposed on the channel 90. It should be understood that the cap 30 and the cap member 100 may be formed of two or more discrete portions coupled together to form a regional fluid conduit, wherein the channel 90 is formed in the cap member 100, the upper surface 35 of the cap, or a combination thereof. Alternatively, the cap 30 and the cap member 100 may be formed as a single integral component. In some embodiments, the channel 90 is formed entirely within the volume of the cap 30, such that the inner surface of the fluid conduit 65 disposed between the first portion 70 and the second portion 75 of the fluid conduit is disposed within the volume of the cap material (e.g., the channel traversing the cap).

[0080] As discussed herein, component 10 has a first unassembled configuration and a second assembled configuration. In the first unassembled configuration, the cap may or may not span the diameter D of the lumen 25, and the lumen is fluid-open (see Figures 11 to 16). In the second assembled configuration, the cap spans the diameter D of the lumen 25, and the lumen is fluid-sealed (see Figures 11 to 16). Figure 1 (Figures 2 and 17).

[0081] In an embodiment, component 10 further includes one or more attachment members 105 configured to engage the dispenser body 15 and secure the cap 30 to the dispenser body when the component is in a second assembled configuration. For example, component 10 shown in Figures 1 through 19 includes two attachment members hinged to the cap 30. Each attachment member 105 includes features that engage features of the dispenser body 15 to facilitate securing the cap to the dispenser body. In some embodiments, each attachment member may include one or more engagement elements that interact with one or more engagement surfaces of the dispenser body.

[0082] Figures 11 through 16 illustrate the transition of the assembly from a first unassembled configuration to a second assembled configuration. During assembly, the cap 30 is positioned on the lumen of the dispenser body 15, and the attachment member 105 is subsequently moved downward to contact the side of the dispenser body. As the attachment member 105 moves downward, the engagement element 110 contacts the engagement surface 115, which presses the central portion of the cap positioned on the lumen downward against the dispenser body, thereby forming a fully liquid-tight seal (see Figures 13 through 16). During the final step of assembly, one or more distal tip surfaces 120 of each attachment member 105 are received by one or more corresponding slots 125 provided on the dispenser body 15 to secure the cap 30 to the dispenser body and form the complete assembly 10 (see Figure 1).

[0083] It should be understood that while Figures 1 through 19 show an embodiment of component 10, which includes a specific element configuration to facilitate attachment of the cap to the dispenser body, many different connectors can be used to achieve attachment. For example, fasteners, latches, snap-fit ​​connections, threaded engagements, etc., can be used for attachment. Similarly, it should be understood that the cap and dispenser body can be constructed in various ways to achieve a fully liquid-tight seal between the cap and the dispenser body to form a complete assembly.

[0084] For example, Figures 20 through 27 illustrate an embodiment of component 10, which includes a single attachment member hinged to both the dispenser body and the cap. As shown in Figures 20 through 27, in this embodiment, component 10 includes a dispenser body 15, a cap 30, and an attachment member 105 hinged to both the dispenser body and the cap. Figures 20 through 25 show component 10 in a first unassembled configuration, where the attachment member 105 is not engaged with the dispenser body 15, creating a fully liquid-tight seal between the cap 30 and the dispenser body 15. During assembly, the attachment member 105 rotates about the hinge, such that the cap 30 covers the lumen of the dispenser body 15 (see Figure 20). Figure 24 Then, the attachment member 105 moves downward to contact and engage the side of the dispenser body 15. As the attachment member 105 moves downward, the engagement element 110 contacts the engagement surface 115, which presses the central portion of the cap disposed on the lumen down onto the dispenser body, thereby forming a fully liquid-tight seal. During the final step of assembly, one or more distal tip surfaces 120 of the attachment member 105 are received by one or more corresponding slots 125 disposed on the dispenser body 15 to secure the cap 30 to the dispenser body and form the complete assembly 10 (see FIG. 26).

[0085] In various embodiments, the piston is movable along the longitudinal axis of the cavity to change the working volume. For example, in Figure 1 In the embodiment shown in Figure 19, the piston 45 is moved along the length of the lumen 25 to increase the distance between the upper surface 50 of the piston and the cap 30, thereby increasing the working volume (LQ). Alternatively, the piston 45 is moved along the lumen 25 to decrease the distance between the upper surface 50 of the piston and the cap 30, thereby decreasing the working volume (LQ), for example, to distribute fluid contained within the working volume into a fluid conduit.

[0086] During use, fluid is added to one or more lumens while the component is in a first unassembled configuration, with the lumens oriented toward the bottom portion of the dispenser body to provide a working volume. The component is then transformed from the first configuration to a second assembled configuration to complete assembly. These steps can be performed in a sterile environment, such as a biosafety cabinet or laminar flow hood, to avoid contamination. The component is then fluidly connected to the fluid workflow by fluidly coupling the inlet and outlet ports to a feed line fluidly connected to the fluid workflow (e.g., a closed-loop electroporation component). Furthermore, the component is operatively coupled to one or more actuators configured to automatically control the movement of individual pistons within their respective lumens, for example, to advance the pistons along the length of the lumen toward the outlet to reduce the working volume and dispense fluid into the fluid conduit. Fluid is then dispensed from the respective lumens into the fluid conduit via the controlled movement of the individual pistons. Dispensing from different lumens can be performed independently or uniformly at a controlled rate via manual or automatic operation of one or more actuators.

[0087] Therefore, this disclosure further provides a system for distributing fluid, the system including the components of this disclosure. In an embodiment, the system includes the components of this disclosure; and an actuator operatively coupled to a lumen of a dispenser body configured to move a piston defining a working volume of the lumen along a longitudinal axis of the lumen to reduce the working volume and allow fluid to flow from the working volume into a fluid conduit when the assembly is in a second configuration in which the lumen is fluid-sealed.

[0088] In another aspect, this disclosure provides a system for distributing fluid, the system including one or more components of this disclosure. In an embodiment, the system includes one or more components of this disclosure having one or more dispenser bodies, each dispenser body having one or more lumens with a working volume; and one or more actuators operatively coupled to each lumen of the one or more dispenser bodies, the one or more dispenser bodies being configured to move a piston defining a working volume along a longitudinal axis of the lumen to reduce the working volume and allow fluid to flow from the working volume into a fluid conduit when the assembly is in a second configuration in which the lumen is fluid-sealed.

[0089] In some embodiments, the system includes: a first feed line fluidly coupled to an inlet port of a fluid conduit located upstream of one or more dispenser bodies; and a second feed line fluidly coupled to an outlet port fluidly coupled to a fluid conduit located downstream of one or more dispenser bodies, to form a sterile and functionally closed system. In some embodiments, the system includes a cell processing system, such as a transfection assembly, fluidly coupled to the first and second feed lines.

[0090] In various embodiments, the actuator for controlling the movement of the piston may include a pneumatic mechanism, a lead screw mechanism, a load spring mechanism, or other drive mechanism.

[0091] In some embodiments, the dispenser body 15 is made of a material that enables visual detection of the contents within the lumen, such as transparent plastic, transparent glass, etc. The dispenser body may be marked with a measuring scale to allow visualization of the amount of contents contained in the lumen. For example, the measuring scale may be configured to measure the volume of contents in the aspirated lumen in milliliters (ml), microliters (μl), ounces (oz), or other units of measurement. In some embodiments, the dispenser body is composed of any known material commonly used for dispensing fluids containing biomolecules, such as non-bioreactive plastics, glass, or other materials that do not react with the contents to be dispensed. In some embodiments, the dispenser body is composed of or includes a bioreactive material that preserves or otherwise stabilizes the contents of the lumen to maintain an extended lifespan.

[0092] In various embodiments, the piston can be made of a compliant material, such as an elastic material, like rubber or silicone or other elastically deformable materials. The terms "elastic" and "elastic material" primarily refer to cross-linked thermosetting polymers, such as silicone or rubber-like polymers, that are more easily deformed than plastics. Such materials, for example, are biologically and chemically inert / non-reactive and are therefore suitable for use with reactive or biological fluids, and are not easily affected by leaching or gas movement at ambient temperatures and pressures.

[0093] Once the desired amount of contents (e.g., fluids, samples, etc.) is loaded into one or more lumens, the assembly can be used for various applications, such as preparing for gene editing steps in T-cell therapy workflows. Therefore, it should be understood that, depending on the specific application, multiple lumens can be filled with different types of contents, such as biomolecules (e.g., Cas9 protein, guide RNA, and donor DNA, respectively, for gene editing applications). Advantageously, the assembly can be easily transported and handled without accidental spillage or mixing of fluids. Furthermore, the inlet and outlet ports of the fluid conduit can be fully sealed, ensuring that the fluid contents of the assembly are not exposed to contamination risks when transported out of a sterile environment.

[0094] In some embodiments, the output port (e.g., in a closed, sterile manner) is connected to a system or culture system such as electroporation or other transfection systems (e.g., as described in International Patent Application No. PCT / US2020 / 05713, which is incorporated herein by reference in its entirety). Therefore, the systems described herein can be used to generate cell therapies or treatments using genetically modified cells, T cells, CAR T cells, NK cells, stem cells, etc.

[0095] While specific embodiments have been described, these embodiments are presented by way of example only and are not intended to limit the scope of this disclosure. In fact, the novel methods, components, and systems described herein can be embodied in various other forms; furthermore, various omissions, substitutions, and changes may be made to the form of the methods, apparatus, and systems described herein without departing from the spirit of this disclosure. The appended claims and their equivalents are intended to cover such forms or modifications falling within the scope and spirit of this disclosure.

[0096] Exemplary subject matter of the present invention is indicated by the following terms:

[0097] Clause 1: An assembly comprising: a dispenser body having an inner wall defining a lumen having a longitudinal axis and a diameter; a cap configured to span the diameter of the lumen, the cap having an upper surface and a lower surface; a piston disposed within the lumen, the piston having a top surface and a bottom surface, the top surface together with the inner wall and the lower surface of the cap defining a working volume of the lumen, wherein the piston is movable along the longitudinal axis to change the working volume; an outlet fluidly connected to the working volume; and a fluid conduit extending between a first portion and a second portion of the fluid conduit, the fluid conduit being fluidly connected to the working volume via the outlet between the first and second portions of the fluid conduit, wherein the assembly has a first configuration and a second configuration, in the first configuration the cap does not span the diameter of the lumen and the lumen is fluidly open, in the second configuration the cap spans the diameter of the lumen and the lumen is fluidly sealed, and wherein when the assembly is in the second configuration, movement of the piston along the longitudinal axis causes fluid to flow through the outlet.

[0098] Clause 2: The assembly according to Clause 1, wherein the fluid conduit has an inlet port adjacent to a first portion of the fluid conduit and an outlet port adjacent to a second portion of the fluid conduit, and wherein when the assembly is in the second configuration, movement of the piston toward the cover along the longitudinal axis causes fluid to flow from the working volume through the outlet into the fluid conduit.

[0099] Clause 3: The component as described in Clause 2, wherein the input and output ports are fully sealed.

[0100] Clause 4: The component according to Clause 1, wherein the inner surface of the fluid conduit is defined by a channel formed between a first portion of the fluid conduit and a second portion of the fluid conduit within the volume of the cap or on the upper surface of the cap.

[0101] Clause 5: The component according to Clause 1, wherein at least one region of the fluid conduit between a first portion and a second portion of the fluid conduit is defined by a channel formed by the upper surface of a cap and a cap member disposed above the channel.

[0102] Clause 6: The component according to Clause 1, wherein the cover includes a channel formed by the cover, defining a portion of the fluid conduit between a first portion and a second portion of the fluid conduit.

[0103] Clause 7: The component as described in Clause 1 further includes a sealing member disposed between the lower surface of the cap and the dispenser body.

[0104] Clause 8: The component as described in Clause 1, wherein the cover is hingedly attached to the dispenser body.

[0105] Clause 9: The component according to Clause 8, wherein the cover includes a first attachment member configured to reversibly engage the dispenser body, and wherein the first attachment member engages the dispenser body when the component is in the second configuration.

[0106] Clause 10: The component according to Clause 1, wherein the cover includes a first attachment member and a second attachment member configured to reversibly engage the dispenser body, and wherein the first attachment member and the second attachment member engage the dispenser body when the component is in the second configuration.

[0107] Clause 11: The component according to Clause 10, wherein the first attachment member and the second attachment member are hinged to the central portion of the cover.

[0108] Clause 12: Components as described in Clause 1, wherein the outlet includes a valve.

[0109] Clause 13: The component according to Clause 12, wherein the valve is configured to allow fluid to flow from the working volume through the outlet and into the fluid conduit, and to prevent fluid from flowing from the fluid conduit through the outlet and into the working volume.

[0110] Clause 14: The component according to Clause 1, wherein the dispenser body includes a second inner wall defining a second lumen having a longitudinal axis and a diameter.

[0111] Clause 15: The assembly according to Clause 14, wherein the second lumen includes a second piston defining a working volume of the second lumen, and wherein the second piston is movable along a longitudinal axis to change the working volume.

[0112] Clause 16: The component according to Clause 15, wherein the fluid passage is fluidly connected to the working volume of the lumen and the working volume of the second lumen.

[0113] Clause 17: The component according to Clause 1, wherein the dispenser body comprises at least four to six lumens, each lumen being defined by a different inner wall of the dispenser body and having a longitudinal axis and a diameter.

[0114] Clause 18: The assembly as described in Clause 17, wherein each lumen has the same or different diameters and each lumen has the same or different lengths.

[0115] Clause 19: The assembly according to Clause 17, wherein each lumen includes a piston defining a working volume of each lumen, and wherein each piston is movable along the longitudinal axis of each lumen to change the working volume.

[0116] Clause 20: The component as described in Clause 19, wherein each lumen includes an outlet.

[0117] Clause 21: The component according to Clause 20, wherein the fluid passage is fluidly connected to each working volume in the working volume via an outlet of each lumen, and wherein each outlet is disposed between a first portion and a second portion of the fluid conduit.

[0118] Clause 22: A system comprising: an assembly according to any one of Clauses 1 to 21; and an actuator operable to move a piston along a longitudinal axis, thereby reducing the working volume of a lumen and allowing fluid to flow from the working volume into a fluid conduit when the assembly is in a second configuration.

[0119] Clause 23: A system pursuant to Clause 22, wherein the actuator is operable to allocate all or any portion of the working volume in a single operation.

[0120] Clause 24: A system pursuant to Clause 23, wherein the actuator is configured to allocate a portion of the working volume at one or more time intervals.

[0121] Clause 25: The system according to Clause 22, wherein the component includes a plurality of lumens, and wherein the working volume of each of the plurality of lumens is independently controlled by a separate actuator.

[0122] Clause 26: A system pursuant to Clause 25, wherein individual actuators are operable to allocate all or any portion of their respective working volumes independently or simultaneously in a single operation.

[0123] Clause 27: A system pursuant to Clause 26, wherein individual actuators are configured to allocate a portion of their respective working volumes at one or more time intervals.

[0124] Clause 28: The system according to Clause 22, wherein a first feed line is fluidly coupled to an input port and a second feed line is fluidly coupled to an output port, forming a sterile and functionally closed system.

[0125] Clause 29: The system according to Clause 28 further includes a cell processing system fluidly coupled to a first feed line and a second feed line.

[0126] Clause 30: The system described in Clause 22, wherein the input port is fluidly coupled to a fluid source.

[0127] Clause 31: The system described in Clause 30, wherein the fluid source is a liquid.

[0128] Clause 32: The system described in Clause 30, wherein the fluid source is a gas.

[0129] Clause 33: The system described in Clause 32, wherein the gas is pressurized.

[0130] Clause 34: The system described in Clause 33, wherein the gas is pressurized via a line pump.

[0131] Clause 35: The system described in Clause 33, wherein the gas originates from a container containing pressurized gas.

[0132] Clause 36: A method of distributing fluid, the method comprising: a component according to any one of Clauses 1 to 21 or a system according to any one of Clauses 22 to 35; loading fluid into a working volume of a lumen when the component is in a first configuration; changing the component to a second configuration; and advancing a piston along the longitudinal axis of the lumen to allow fluid to flow from the working volume into a fluid conduit.

[0133] Clause 37: The method according to Clause 36, wherein the loading of the fluid is performed under aseptic conditions.

[0134] Clause 38: The method according to Clause 36 further includes fluidly coupling a first portion and a second portion of a fluid conduit to one or more fluid lines prior to advancing the piston.

[0135] Clause 39: The method according to Clause 38, wherein a first portion and a second portion of a fluid conduit are fluidly coupled to one or more fluid lines to form a sterile and functionally closed system.

[0136] Clause 40: A method of performing a fluid workflow, the method comprising: conveying fluid from the working volume of a component according to any one of Clauses 1 to 21 or a system according to any one of Clauses 22 to 35 into a fluid flow contained within a functionally enclosed system; and performing the fluid workflow.

[0137] Clause 41: The method according to Clause 40, wherein the fluid comprises gene editing reagents and the fluid flow comprises cells.

[0138] Clause 42: The method described in accordance with Clause 41, wherein the fluid workflow includes a cell treatment protocol.

[0139] Clause 43: The method described in accordance with Clause 42, wherein the cell treatment protocol includes transformation, transfection, transduction, activation, isolation, sorting, imaging, labeling and / or culture of cells or portions thereof.

[0140] Clause 44: Use of a component pursuant to any one of Clauses 1 to 21 or a system pursuant to any one of Clauses 22 to 35 to distribute fluid into a fluid workflow.

[0141] Clause 45: Use in a workflow to produce genetically modified cells using any of the components pursuant to any of Clauses 1 to 21 or any of the systems pursuant to any of Clauses 22 to 35.

[0142] Clause 46: Use in a workflow to produce cell or gene therapy using any of the components pursuant to any of Clauses 1 to 21 or any of the systems pursuant to any of Clauses 22 to 35.

Claims

1. A component, the component comprising: A dispenser body having an inner wall defining a cavity having a longitudinal axis and a diameter; A cover, configured to span the diameter of the lumen, the cover having an upper surface and a lower surface; A piston disposed within the cavity, the piston having a top surface and a bottom surface, the top surface together with the lower surface of the inner wall and the cover defining a working volume of the cavity, wherein the piston is movable along the longitudinal axis to change the working volume; An outlet, which is fluidly connected to the working volume; as well as A fluid conduit extending between a first portion and a second portion of the fluid conduit, the fluid conduit being fluidly connected to the working volume via an outlet between the first and second portions of the fluid conduit. The component has a first configuration and a second configuration. In the first configuration, the cap does not span the diameter of the lumen, and the lumen is fluid-open. In the second configuration, the cap spans the diameter of the lumen, and the lumen is fluid-sealed. When the component is in the second configuration, the movement of the piston along the longitudinal axis causes fluid to flow through the outlet.

2. The assembly of claim 1, wherein the fluid conduit has an input port adjacent to the first portion of the fluid conduit and an output port adjacent to the second portion of the fluid conduit, and wherein when the assembly is in the second configuration, movement of the piston toward the cap along the longitudinal axis causes fluid to flow from the working volume through the outlet into the fluid conduit.

3. The component of claim 2, wherein the input port and the output port are fully sealed.

4. The component of claim 1, wherein the inner surface of the fluid conduit is defined by a channel between the first portion of the fluid conduit and the second portion of the fluid conduit, the channel being formed within the volume of the cap or on the upper surface of the cap.

5. The assembly of claim 1, wherein at least one region of the fluid conduit between the first portion and the second portion of the fluid conduit is defined by a channel formed by the upper surface of the cap and a cap member disposed above the channel.

6. The component of claim 1, wherein the cover includes a channel formed through the cover, defining a portion of the fluid conduit between the first portion and the second portion of the fluid conduit.

7. The component of claim 1, further comprising a sealing member disposed between the lower surface of the cover and the dispenser body.

8. The component of claim 1, wherein the cover is hinged to the dispenser body.

9. The component of claim 8, wherein the cover includes a first attachment member configured to reversibly engage the dispenser body, and wherein the first attachment member engages the dispenser body when the component is in the second configuration.

10. The component of claim 1, wherein the cover includes a first attachment member and a second attachment member configured to reversibly engage the dispenser body, and wherein when the component is in the second configuration, the first attachment member and the second attachment member engage the dispenser body.

11. The component of claim 10, wherein the first attachment member and the second attachment member are hinged to the central portion of the cover.

12. The component of claim 1, wherein the outlet comprises a valve.

13. The component of claim 12, wherein the valve is configured to allow fluid to flow from the working volume through the outlet and into the fluid conduit, and to prevent fluid from flowing from the fluid conduit through the outlet and into the working volume.

14. The assembly of claim 1, wherein the dispenser body includes a second inner wall defining a second lumen having a longitudinal axis and a diameter.

15. The assembly of claim 14, wherein the second lumen includes a second piston defining a working volume of the second lumen, and wherein the second piston is movable along the longitudinal axis to change the working volume.

16. The component of claim 15, wherein the fluid passage is fluidly connected to the working volume of the lumen and the working volume of the second lumen.

17. The assembly of claim 1, wherein the dispenser body comprises at least four to six lumens, each lumen being defined by a different inner wall of the dispenser body and having a longitudinal axis and a diameter.

18. The assembly of claim 17, wherein each lumen has the same or different diameters and each lumen has the same or different lengths.

19. The assembly of claim 17, wherein each lumen includes a piston defining a working volume for each lumen, and wherein each piston is movable along the longitudinal axis of each lumen to change the working volume.

20. The component of claim 19, wherein each lumen includes an outlet.

21. The assembly of claim 20, wherein the fluid passage is fluidly connected to each working volume in the working volume via the outlet of each lumen, and wherein each outlet is disposed between the first portion and the second portion of the fluid conduit.

22. A system comprising: The component according to any one of claims 1 to 21; as well as An actuator operable to move the piston along the longitudinal axis, thereby reducing the working volume of the lumen and allowing fluid to flow from the working volume into the fluid conduit when the assembly is in the second configuration.

23. The system of claim 22, wherein the actuator is operable to allocate all or any portion of the working volume in a single operation.

24. The system of claim 23, wherein the actuator is configured to allocate a portion of the working volume at one or more time intervals.

25. The system of claim 22, wherein the component comprises a plurality of lumens, and wherein the working volume of each of the plurality of lumens is independently controlled by a separate actuator.

26. The system of claim 25, wherein the individual actuator is operable to allocate all or any portion of its respective working volume independently or simultaneously in a single operation.

27. The system of claim 26, wherein the individual actuator is configured to allocate a portion of its respective working volume at one or more time intervals.

28. The system of claim 22, wherein a first feed line is fluidly coupled to the input port and a second feed line is fluidly coupled to the output port, forming a sterile and functionally closed system.

29. The system of claim 28, further comprising a cell processing system fluidly coupled to the first feed line and the second feed line.

30. The system of claim 22, wherein the input port is fluidly coupled to a fluid source.

31. The system of claim 30, wherein the fluid source is a liquid.

32. The system of claim 30, wherein the fluid source is a gas.

33. The system of claim 32, wherein the gas is pressurized.

34. The system of claim 33, wherein the gas is pressurized via a line pump.

35. The system of claim 33, wherein the gas originates from a container containing pressurized gas.

36. A method for distributing fluid, the method comprising: The component according to any one of claims 1 to 21; When the component is in the first configuration, fluid is loaded into the working volume of the lumen; Transform the component into the second configuration; as well as The piston is advanced along the longitudinal axis of the lumen to allow fluid to flow from the working volume into the fluid conduit.

37. The method of claim 36, wherein the loading of the fluid is performed under aseptic conditions.

38. The method of claim 36, further comprising fluidly coupling the first portion of the fluid conduit and the second portion of the fluid conduit to one or more fluid lines prior to advancing the piston.

39. The method of claim 38, wherein the first portion of the fluid conduit and the second portion of the fluid conduit are fluidly coupled to the one or more fluid lines to form a sterile and functionally closed system.

40. A method for performing a fluid workflow, the method comprising: The fluid is delivered from the working volume of the component according to any one of claims 1 to 21 into a fluid flow contained within a functionally closed system; as well as Execute fluid workflows.

41. The method of claim 40, wherein the fluid comprises a gene editing reagent and the fluid flow comprises cells.

42. The method of claim 41, wherein the fluid workflow includes a cell treatment protocol.

43. The method of claim 42, wherein the cell treatment protocol includes transformation, transfection, transduction, activation, isolation, sorting, imaging, labeling and / or culture of the cells or portions thereof.

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