WO2024108052A1

WO2024108052A1 - Dispenser, system and method of dispensing contents from sealed containers

Info

Publication number: WO2024108052A1
Application number: PCT/US2023/080160
Authority: WO
Inventors: Michael Gordon
Original assignee: Life Technologies Corporation
Priority date: 2022-11-16
Filing date: 2023-11-16
Publication date: 2024-05-23

Abstract

Dispenser for dispensing contents of sealed container(s) and systems and methods employing the same. The dispenser includes: a dispenser body having a first receptacle configured to receive a sealed container; a cover body for covering the first receptacle; an inlet configured to receive a fluid; a fluidic channel formed in or on the cover body; a piercing element extending from a bottom surface of the cover body into the first receptacle, the piercing element having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end; and an outlet fluidically coupled to the inlet via the first receptacle, the fluidic channel, and the piercing element.

Description

DISPENSER, SYSTEM AND METHOD OF DISPENSING CONTENTS FROM

SEALED CONTAINERS

CROSS REFERENCE TO RELATED APPLICATION(S)

[0000] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63/425,750, filed November 16, 2022, the disclosure of which is considered part of, and incorporated in its entirety by reference in the disclosure of this application.

FIELD

[0001] This disclosure relates generally to dispensers, and more particularly to a dispenser for dispensing contents from a sealed container, as well as systems and methods employing the same, e.g., for development and manufacture of cell-based therapies.

BACKGROUND

[0002] Micro-sized particles used for biological assays, such as magnetic beads, dendrimers, carriers and the like, can be suspended in a fluid (e.g., liquid, or liquid/gas suspensions being homogeneous, heterogenous, or otherwise) contained in a vial with a septum. The particles can be used for a variety of processes including cell isolation, separation and activation during the manufacturing of various cell and gene therapies. The liquid contents of these vials are typically removed in one of three ways. The first method is to peel back a protective metal foil tab, pierce the septum with a needle, and then aspirate the contents into a syringe. The second method is to peel back the protective metal foil tab, install a vial adapter (vented or non-vented), and then use a syringe to aspirate the contents. The third commonly used method is to completely remove the metal foil, physically remove the entire rubber septum, and then use a pipette to aspirate the fluid. All of these methods are commonly performed within a biosafety cabinet to maintain sterility.

[0003] Transferring the contents of multiple vials in a workflow is cumbersome, user dependent, and prone to human error. Importantly, it is also a high-risk step for introducing contamination. As such, a platform that can be less cumbersome, user dependent, and prone to human error, while decreasing the risk of introducing contamination, has industrial utility. BRIEF SUMMARY

[0004] In one aspect, the disclosure provides a dispenser for dispensing contents of a sealed container to be used, for example, in a biological assay. In embodiments, the dispenser includes: an inlet configured to receive a fluid; a dispenser body having a top portion, a bottom portion, and a first receptacle configured to receive a sealed container; a first fluidic channel formed in the bottom portion fluidically connected to the first receptacle; a piercing element disposed in the first receptacle, the piercing element having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end, wherein the piercing end is configured to pierce the sealed container and allow contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, and the piercing element in the first receptacle.

|0005] In another aspect, the disclosure provides a dispenser for dispensing contents of a sealed container to be used, for example in a biological assay. In embodiments, the dispenser includes: a dispenser body having a top portion, a bottom portion, and a first receptacle configured to receive a sealed container; a cover body for covering the first receptacle, the cover body having a bottom surface and a top surface; an inlet configured to receive a fluid; a first fluidic channel formed in or on the cover body; a piercing element extending from the bottom surface into the first receptacle, the piercing element having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end, wherein the piercing end is configured to pierce the sealed container and allow contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, and the piercing element.

[0006] In yet another aspect, the disclosure provides a dispenser for dispensing contents of one or more sealed containers to be used, for example, in a biological assay. In embodiments, the dispenser includes: an inlet configured to receive a fluid; a dispenser body having a top portion, a bottom portion, and a plurality of receptacles formed in the top portion extending toward the bottom portion, wherein the plurality of receptacles include at least a first receptacle and a second receptacle, each of the first receptacle and the second receptacle being configured to receive a sealed container; a first fluidic channel formed in the bottom portion and fluidically connecting the first receptacle to the second receptacle; a piercing element disposed in each receptacle of the plurality of receptacles, the piercing element having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end, wherein the piercing end is configured to pierce the sealed container and allow contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, the piercing element in each receptacle of the plurality of receptacles, and the second receptacle, wherein the outlet is configured to fluidically transport the contents of the sealed container.

[0007] In some embodiments, the sealed container(s) includes a reagent used in an assay, such as a biological or chemical assay. In some embodiments, the sealed container(s) includes a reagent in the form of, or containing, a particle, such as a micro-sized particle, configured to conjugate to a cell or portion thereof, such as a bead (e.g., magnetic, paramagnetic or otherwise) or other particle including one or more of a dendrimer, plastic, polymer, carrier, microcarrier, microparticle, liposome, vesicle, extracellular vesicle, microvesicle, amino acid, peptide, nucleic acid, steroid, hormone, ferrous or non-ferrous metal, ion, polysaccharide, organic molecule, non-organic molecule or the like.

[0008] In some embodiments, the sealed container(s) includes a lyophilized, or otherwise dried, reagent that can be reconstituted upon introduction of a liquid into the sealed container(s). Such reagents may be in the form of, for example, a bead, powder and/or coating deposited on an interior surface of the container(s). In various embodiments, the lyophilized or dried reagent is in the form of, or contains, a particle, such as a micro-sized particle, configured to conjugate to a cell or portion thereof, such as a bead (e.g., magnetic, paramagnetic or otherwise) or other particle including one or more of a dendrimer, plastic, polymer, carrier, microcarrier, microparticle, liposome, vesicle, extracellular vesicle, microvesicle, amino acid, peptide, nucleic acid, steroid, hormone, ferrous or non-ferrous metal, ion, polysaccharide, organic molecule, non-organic molecule or the like.

[0009] In some embodiments, the sealed container includes a solid or liquid reagent, including a micro-sized particle composed of a carrier particle conjugated to one or more of a dendrimer, plastic, polymer, amino acid, peptide, nucleic acid, steroid, hormone, ferrous or non-ferrous metal, ion, polysaccharide, organic molecule, non-organic molecule or the like. [0010] In another aspect, the disclosure provides a system including the dispenser of the disclosure in fluid connection with a fluid flow module operable to control the flow of fluid through the dispenser, such as supplying pressurized fluid to the dispenser to move fluid from the inlet to the outlet and transport the particles contained in one or more sealed containers through the outlet and into a closed system. In embodiments, the system includes: a dispenser as described herein; and a fluid flow module fluidically coupled to the inlet and/or the outlet of the dispenser operable to control a flow of fluid into a sealed container causing the contents therein to be forced out of the sealed container and through the outlet of the dispenser via a fluidic channel and a piercing element.

[0011] In related embodiments, the system includes: a dispenser configured to receive a plurality of sealed containers; the dispenser comprising: a plurality of receptacles, each of the plurality of receptacles configured to receive a sealed container of the plurality of sealed containers; a plurality of fluidic channels, each of the fluidic channels fluidically connecting two receptacles of the plurality of receptacles; a plurality of piercing elements, each piercing element disposed in one of the receptacles of the plurality of receptacles such that each receptacle includes at least one piercing element, each of the plurality of piercing elements configured to fluidically couple with a sealed container disposed within the receptacle associated with that piercing element, each piercing element fluidically connected to a fluidic channel of the plurality of fluidic channels; an inlet configured to receive a fluid; and an outlet fluidically coupled to the inlet via the plurality of receptacles, the plurality of fluidic channels and the plurality of piercing elements, the outlet configured to deliver contents of the plurality of sealed containers; and a fluid flow module coupled to the inlet and/or the outlet of the dispenser operable to control a flow of fluid into at least one sealed container causing the contents therein to be forced out of the sealed container and through the outlet of the dispenser via the plurality of fluidic channel and the plurality of piercing elements.

[0012] In various embodiments, the fluid flow module is operable to drive the fluid flow into the inlet and through the outlet by generating a fluid flow force fluidically upstream of the inlet, downstream of the inlet, or downstream of both the inlet and the outlet. In embodiments, the fluid flow module is a pump, such as a positive displacement or dynamic pump operable to drive fluid flow in a downstream manner (e.g., from the inlet to the outlet) either by a positive force being generated in the fluid upstream of the inlet or by a negative force being generated in the fluid downstream of the inlet and/or outlet (e.g., suction/vacuum force).

[0013] In yet another embodiment, the disclosure provides a method of using the dispenser or system of the disclosure to perform an assay, such as a biological assay in a cell processing workflow to produce a cell or gene therapy product. In embodiments, the method uses the dispenser or system of the disclosure and includes: disposing a sealed container into at least one receptacle of the dispenser thereby defining a fluid path between the inlet and the outlet; advancing a fluid along the flow path to transport particles within the sealed container out of the outlet; and optionally contacting a cell, or portion thereof, with the transported reagent, e.g., particles, or depositing the transported reagent into a fluid reservoir, e.g., container or bag. [0014] The forgoing general description of the illustrative implementations and the following detailed description thereof are merely exemplary aspects of the teachings of this disclosure, and are not restrictive.

BRIEF DESCRIPTION OF DRAWINGS

[0015| The accompanying drawings, which are incorporated in and constitute a part of the specification, illustrate one or more embodiments and, together with the description, explain these embodiments. The accompanying drawings have not necessarily been drawn to scale. Any values dimensions illustrated in the accompanying graphs and figures are for illustration purposes only and can or cannot represent actual or preferred values or dimensions. Where applicable, some or all features cannot be illustrated to assist in the description of underlying features. In the drawings:

[0016] Figure 1 is a front perspective view of a dispenser loaded with a plurality of sealed containers (e.g., vials), according to an embodiment;

[0017] Figure 2 is an exploded perspective view showing the dispenser, an alignment jig and a plurality of sealed containers (e.g., vials), according to an embodiment;

[0018] Figure 3 is a bottom perspective view of the dispenser, according to an embodiment;

[0019] Figure 4 is a cross-section view of the dispenser according to an embodiment;

[0020] Figure 5 is a cross-section view of the dispenser with a locking element disposed therein, according to an embodiment;

[0021] Figure 6 is a cross-section view showing the dispenser loaded with a plurality of containers which are held in place with the locking, according to an embodiment;

[0022] Figure 7 illustrates an exemplary piercing element that can be placed in the dispenser, according to an embodiment;

[0023] Figure 8 is a perspective view of an exemplary locking element that can be placed in the dispenser, according to an embodiment;

[0024] Figure 9A is a bottom view of the dispenser illustrating a series flow path through the dispenser, according to an embodiment;

[0025] Figure 9B is a bottom view of the dispenser illustrating a parallel flow path through the dispenser, according to an embodiment; [0026] Figure 10 illustrates a dispenser connected between a desired system and a sterile air source, according to an embodiment;

[0027] Figure 11 illustrates a dispenser connected between the desired system and a wash before, according to an embodiment;

[0028] Figure 12 illustrates a dispenser connected between the desired system, a wash buffer and a sterile air source delivered via a common pump, according to an embodiment;

[0029] Figure 13 illustrates a dispenser connected between the desired system, a wash buffer and sterile air source delivered via different pumps according to an embodiment;

[0030] Figure 14 illustrates a dispenser having receptacles oriented in a linear manner, according to an embodiment;

[0031] Figure 15 illustrates a dispenser having receptacles oriented in a linear manner, wherein the sealed containers are retained by the receptacles, according to an embodiment;

[0032] Figure 16 is a front perspective view of a dispenser, according to an embodiment;

[0033] Figure 17 is a cross-section perspective view of the dispenser depicted in Figure 16 illustrating attachment elements;

[0034] Figure 18 is a cross-section perspective view of the dispenser depicted in Figure 16 along the length of the dispenser without sealed containers loaded;

[0035] Figure 19 is a cross-section perspective view of the dispenser depicted in Figure 16 along the length of the dispenser loaded with a plurality of sealed containers (e.g., vials), according to an embodiment;

[0036] Figure 20 is a front cross-section view of the dispenser depicted in Figure 16 along the length of the dispenser loaded with a plurality of sealed containers (e.g., vials), according to an embodiment;

[0037] Figure 21 is a front cross-section view of the dispenser depicted in Figure 16 along the length of the dispenser without sealed containers loaded;

[0038] Figure 22 is a front cross-section view of the dispenser depicted in Figure 16 along the length of the dispenser loaded with a plurality of sealed containers (e.g., vials), according to an embodiment;

[0039] Figure 23 is a cross-section perspective view of the dispenser depicted in Figure 16 along the length of the dispenser loaded with a plurality of sealed containers (e.g., vials), according to an embodiment; [0040] Figure 24 is a cross-section top perspective view of the dispenser depicted in Figure 16 along the length of the dispenser loaded with a plurality of sealed containers (e.g., vials), according to an embodiment;

[0041] Figure 25 is an exploded perspective view of a dispenser according to an embodiment;

[0042] Figure 26 is an exploded front view of the dispenser depicted in Figure 25;

[0043] Figure 27 is an exploded perspective view of the dispenser depicted in Figure 25; [0044] Figure 28 is an exploded cross-section perspective view of the dispenser depicted in Figure 25;

[0045] Figure 29 is an exploded cross-section perspective view of the dispenser depicted in Figure 25;

[0046] Figure 30 is an exploded cross-section perspective view of the dispenser depicted in Figure 25;

[0047] Figure 31 is an exploded perspective view of the dispenser depicted in Figure 25; [0048] Figure 32 is a cross-section front view of the dispenser depicted in Figure 25; [0049] Figure 33 is a cross-section perspective view of the dispenser depicted in Figure 25;

[0050] Figure 34 is a cross-section perspective view of the dispenser depicted in Figure 25;

[0051] Figure 35 is a cross-section perspective view of the dispenser depicted in Figure 25.

DETAILED DESCRIPTION

[0052] The description set forth below in connection with the appended drawings is intended as a description of various embodiments of the disclosed subject matter and is not necessarily intended to represent the only embodiment(s). In certain instances, the description includes specific details for the purpose of providing an understanding of the disclosed embodiment(s). However, it will be apparent to those skilled in the art that the disclosed embodiment(s) can be practiced without those specific details. In some instances, well-known structures and components can be shown in block diagram form in order to avoid obscuring the concepts of the disclosed subject matter. [0053] Reference throughout the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment of the subject matter disclosed. Thus, the appearance of the phrases “in one embodiment” or “in an embodiment” in various places throughout the specification is not necessarily referring to the same embodiment. Further, the particular features, structures or characteristics can be combined in any suitable manner in one or more embodiments. Further, it is intended that embodiments of the disclosed subject matter cover modifications and variations thereof.

[0054] It is to be understood that terms such as “distal,” “proximal,” “top,” “bottom,” “front,” “side,” “length,” “lower,” “interior,” “inner,” “outer,” and the like that can be used herein merely describe points of reference and do not necessarily limit embodiments of the present disclosure to any particular orientation or configuration. Furthermore, terms such as “first,” “second,” “third,” etc., merely identify one of a number of portions, components, steps, operations, functions, and/or points of reference as disclosed herein, and likewise do not necessarily limit embodiments of the present disclosure to any particular configuration or orientation.

|0055] The terms “longitudinal,” “axial” or “axially” are generally longitudinal as used herein to describe the relative position related to a syringe, a delivery mechanism, and components of the system herein. 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 the axis “A”.

[0056] Current systems and devices for transferring contents of one or more containers, such as vessels or vials within a closed system (e.g., transfer of vessels or vials containing a reagent including particles, such as beads, have several undesirable shortcomings. These include that their use is highly manual. For example, their use may include a user operating a syringe pump and multiple pinch valves, in the correct sequence, in order to transfer the contents of the vessels or vials into a more usable format, such as a bag. In addition, when transferring solutions or suspensions of particles, the particles can settle out of suspension relatively quickly, sometimes in minutes. Therefore, it is up to the user to not only keep the particles in suspension but to hold the vessels or vials in a position (up- side-down) such that the contents are adequately extracted. [0057] The present disclosure provides a dispenser that reduces the risk of contamination of the contents/particles to be transferred, reduces variabilities in the number of particles transferred, and minimizes waste of costly contents that are left behind. The system provided herein also increases ease of use, repeatability, and robustness of the transfer process. [0058] In various embodiments, the dispenser disclosed herein is used as a consumable. [0059] In embodiments, the dispenser includes a first portion configured to receive a sealed container (e.g., vessel or vial) and a second portion configured to convey contents of the sealed container. In some embodiments, the first portion includes a plurality of receptacles configured to receive a sealed container in each of the receptacles. The receptacles can be separated from each other by a wall and fluidically connected to each other via fluidic channels in the second portion. In some embodiments, the dispenser also includes one or more receptacles that cannot receive a sealed container and act as a fluidic bypass. For example, in some embodiments, the one or more receptacles has at least one receptacle having a flow path functionally configured as a fluidic bypass such that the receptacle need not include a sealed container to allow fluid flow through the receptacle. As such, in some embodiments, one or more receptacles include a fluidic bypass in which lumens of the piercing element are directly fluidically coupled thereby allowing fluid flow through the receptable without having a container retained within the receptacle. It will be appreciated that such receptacles are also connected via fluidic channels and still convey contents of the sealed containers retained in other receptacles.

[0060] In some embodiments, the dispenser includes an inlet channel, also referred as an inlet, and an outlet channel, also referred as an outlet. In some embodiments, the inlet is configured to receive a fluid that is caused to flow through the dispenser by a fluid flow module fluidically coupled to the inlet. In some embodiments, the inlet receives a pressurized fluid (e.g., liquid, gas, or combination thereof), wherein the fluid is pressurized by a source arranged upstream of the inlet and configured to cause fluid flow into the inlet and out of the outlet. In some embodiments, the inlet receives a pressurized fluid (e.g., liquid, gas, or combination thereof), wherein the fluid is pressurized by a source arranged downstream of the inlet and configured to cause fluid flow into the inlet and out of the outlet. In some embodiments, the inlet receives a pressurized fluid (e.g., liquid, gas, or combination thereof), wherein the fluid is pressurized by a source arranged downstream of the inlet and the outlet and configured to cause fluid flow into the inlet and out of the outlet. In various embodiments, the fluid flow module is a pump, pressurized fluid source, and/or vacuum source that controls flow of fluid into the inlet and out of the outlet.

[0061] In various embodiments, the outlet is configured to deliver the contents of the sealed container within the fluid flow passing from the inlet to the outlet. In some embodiments, the inlet is coupled to an inlet connector and the outlet is coupled to an outlet connector. The inlet connector and the outlet connector are further operable to be fluidically coupled to one or several tubes, pipes and/or conduits, respectively, to establish a fluid connection with other components of a system in which the dispenser is deployed.

[0062] In some embodiments, a sealed container includes a fluid, such as a liquid, gas (e.g., sterilized air, inert gas, or the like), or combination thereof. By way of example only, in some embodiments, the sealed container includes a liquid containing particles (such as a suspension of beads dispersed in a solution, be it homogeneous and/or heterogeneous), a buffer solution (e.g., washing buffer for washing particles, such as beads). In some embodiments, the sealed containers deployed in the receptacles of the dispenser include the same contents. In some embodiments, the sealed containers deployed in the receptacles of the dispenser include different contents. In some embodiments, all of the sealed containers include particles, such as beads, and a fluid, wherein the particles are optionally in suspension. In some embodiments, all of the sealed containers include particles, such as beads, and a buffer, wherein the particles are optionally in suspension. In some embodiments, all of the sealed containers include particles, such as beads, suspended in a buffer solution.

[0063] In some embodiments, a sealed container includes gas (e.g., sterilized air, inert gas, or the like) and does not include a liquid. By way of example only, in some embodiments, the sealed container includes a lyophilized, or otherwise dried, reagent that is reconstituted by fluid, such as a buffer solution, introduced into the sealed container through the inlet and/or outlet. The reconstituted reagent includes particles in suspension which are then transferred out of the dispenser via the outlet.

[0064] In various embodiments, the systems and methods provided herein are used, for example, in cell therapy applications in which particles, such as magnetic beads are desired to be inserted into a reservoir containing cells, e.g., a LEUKOPAK™ or the like. In some embodiments, sealed containers including particles, such as beads (e.g., beads used to activate or isolate desired cells), dendrimers (e.g., dendrimers used to activate or isolate desired cells), and combinations thereof are used. The ordinarily skilled artisan will readily appreciate that any number of sealed containers can be used in the embodiments described herein, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more sealed containers. In some embodiments, one or more sealed containers includes particles, such as magnetic beads, while one or more sealed containers do not include particles. In some embodiments, the one or more sealed containers that do not include particles are dummy, empty containers, or are containers including a fluid without particles. In some embodiments, this includes two sealed containers having particles (e.g., magnetic beads), and two sealed containers without particles. In some embodiments, such containers without particles are used when use of a smaller total number of particles is desired, such as, for example, when a small number of particles such as magnetic beads are injected into a small amount of sample containing cells (e.g., LEUKOPAK™ or the like).

[0065] In some embodiments, the sealed container is a vessel or vial, such as a test tube, a conical shaped bottle, a rectangular shaped bottle, or other container configured to store fluid. In some embodiments, the sealed container is sealed by, for example, a septum made of compliant material such as, for example, an elastic material, e.g., rubber, silicone, polymer, plastic, or other sealing material that can be easily pierced by a needle, for example. In some embodiments, the sealed container is fluidically sealed by a pierceable membrane, such as a thin film composed of a polymer, plastic, metal or combination thereof.

[0066] The dispenser herein provides several advantages over conventional methods and systems. For example, the system provided herein is adaptable for automation. As such, contents of a sealed container of the system can be automatically delivered at a desired time and rate, and in a sterile manner by controlling any number of sealed containers within the system via pressure of the fluid used to drive the contents of the sealed container from the inlet to the outlet. Additionally, the dispenser of the disclosure facilitates automation of manual tasks related to extracting contents from a sealed container. For example, in some embodiments, the dispenser is connected to a system configured to deliver particles, such as magnetic beads with bioactive molecules attached thereto (e.g., to activate T cells, and/or to selectively label or isolate certain cell types or subpopulations) to cells, thereby enabling automation of cell activation, and/or isolation, and/or separation, and/or labeling within a cell workflow process.

[0067] The dispenser described herein eliminates several manual operations of workflows that include cell labeling, isolation and/or activation processes. For example, in some embodiments, the dispenser eliminates a manual process that includes use of a syringe to extract particles, e.g., magnetic beads, from a vial in a biosafety cabinet. Undesirably, the extracted particles are often further manually transported to a system to wash the particles which is tedious and introduces additional risks of contamination. Such manual processes are automated using the dispenser disclosed herein.

[0068] Yet another advantage of the dispenser of the disclosure, is that the dispenser is configured to be loaded with the sealed containers and deployed in a mixer to keep the contents (e.g., suspensions of particles, such as magnetic beads) suspended in the fluid. This ensures that the contents can be thoroughly extracted, thereby minimizing waste and increasing throughput of a given workflow. It will be appreciated that the reagent contents may be mixed and/or suspended in the fluid using any number of conventional techniques, such as, by application of an energy source (e.g., magnetic, sound, and the like) or by mechanical mixing using, for example, vibration, vortex, stir bar, propeller, bubbles and the like.

[0069] Figures 1-3 illustrate perspective views of a dispenser 100 for delivering contents of sealed containers, according to some embodiments. The dispenser 100 includes a plurality of receptacles for receiving sealed containers, a plurality of piercing elements for piercing the sealed containers and at least one fluidic channel to convey contents of the sealed containers from one receptacle to another receptacle. The dispenser 100 also includes an inlet and an outlet each fluidically coupled to a receptacle of the plurality of receptacles so that contents of the sealed containers can be dispensed via the outlet to a desired system. [0070] An exemplary configuration of the dispenser 100 is further discussed below. The parts or elements of the dispenser 100 discussed herein are only provided to illustrate the concepts of the present disclosure. In embodiments, the dispenser 100 allows extracting contents of the sealed container(s) in a functionally closed loop system and thereby facilitates automation of various processes of downstream workflows, such as cell isolation, activation, labeling, and/or other processes for generation of cell and gene therapy products. [0071] A person of ordinary skill in the art can contemplate several variations in dispenser structure without deviating from the scope of the present disclosure. For example, variations in the dispenser can be in a number, or shape and size of receptacles, the fluidic channels, piercing elements, or other element discussed herein. For example, in some embodiments, the dispenser includes one, two, three, four, five, six, seven, eight, nine, ten, twenty or more receptacles, and one or more fluidic channels. As another example, in some embodiments, each receptacle of the invention has the same shape and/or size, a different shape and/or size, or a combination thereof.

[0072] In some embodiments, the dispenser 100 includes a dispenser body 101 having a first portion 10 It, also referred as a top portion 10 It, and a second portion, also referred as a bottom portion 101b. It will also be appreciated that in some embodiments, a plurality of receptacles are formed in the top portion 10 It of the dispenser body 101. In some embodiments, the plurality of receptacles includes at least a first receptacle and a second receptacle. Each receptacle extends toward the bottom portion 101b of the dispenser body 101. As shown in Figure 2, each receptacle can have an opening large enough to receive a sealed container, an interior surface I l ls extending in an axial direction, and a base surface 111b (see Figure 4) at the bottom portion 101b.

[0073] In one embodiment, as shown in Figures 1-3, the plurality of receptacles includes four receptacles - a first receptacle 111, a second receptacle 112, a third receptacle 113, and a fourth receptacle 114. In one embodiment, the receptacles 111-114 are configured to receive a plurality of sealed containers 201, 202, 203 and 204. For example, the first receptacle 111 and the second receptacle 112 of the plurality of receptacles are each structured to receive a sealed container such as vials 201 and 202. In some embodiments, the first receptacle 111 and second 112 are separated by a wall 115, as shown in cross-section view of Figure 4, and are fluidically coupled via a fluidic channel in the bottom portion 101b.

[0074] In one embodiment, the receptacles 111-114 have same shape and sizes and receive sealed containers of complementary or non-complementary shapes and sizes. In one embodiment, shown in Figure 2, the plurality of receptacles 111- 114 are cylindrical in shape and configured to receive the plurality of sealed containers (e.g., sealed vessels or vials) having a corresponding cylindrical shape. In some embodiments, the plurality of receptacles are configured to receive sealed containers of different shapes and/or sizes. For example, in some embodiments, the receptacles and the sealed containers have any of a conical shape, a rectangular prism shape, a cube shaped or other geometric shape. In some embodiments, at least one receptacle of the plurality of receptacles has a shape conforming to a shape of the sealed container. In some embodiments, the receptacle has a different shape than the sealed container but sized to freely receive the sealed container. For example, in some embodiments, the receptacle has a cylindrical shape and the sealed container has a rectangular shape, where the cylindrical receptacle is larger in size than the rectangular sealed container.

[0075] Referring to Figure 2, for loading the sealed containers 201-204, an alignment jig 300 can be provided. The alignment jig 300 includes a plurality of holes 311-314 sized to receive the sealed containers 201-204. In embodiments, the alignment jig 300 has a shape corresponding to an outer periphery of the top portion 10 It of the dispenser body 101 and the holes 311-314 are formed along the axis of the receptacles 111-114, respectively, so that the holes 311-314 and the receptacles 111-114 are axial aligned when assembled. The alignment jig 300 can be assembled on the top surface 102 of the dispenser body 101. In one embodiment, the receptacles 111-114 are tall enough to keep the sealed containers axially aligned with the piercing elements after installation. In some embodiments, the alignment jig 300 is used to obtain an initial axial alignment of the sealed containers 201-204 with the receptacles 111-114, respectively. In some embodiments, the alignment jig 300 is configured to facilitate axial alignment, particularly when the sealed containers 201-204 have small sizes and directly inserting such sealed containers 201-204 can cause misalignment with piercing elements. Accordingly, the holes 311-314 are sized to that of the sealed containers without adjusting sizes of the receptacles 111-114 of the dispenser 100. [0076] In some embodiments, the dispenser body 101 has a cube shaped body that includes a first surface 102 (see Figures 1 and 2) defining a first side (e.g., a top side), an opposite second surface 120 (see Figure 3) defining a second side (e.g., a bottom side) of the dispenser body 101 and side surfaces such as surfaces 103 and 104 extending perpendicular to the plane of the first surface 102 and the second surface 120. In some embodiments, depending on an outer shape of the dispenser body 101, the surfaces 102, 103, 104, and 120 are shaped and oriented differently. In some embodiments, as shown in Figures 1-3, the first surface 102 is also referred as a top surface 102 and the second surface 120 is referred as the bottom surface 120. Correspondingly, the alignment jig 300 is shaped to facilitate assembly over the body of the dispenser.

[0077| In some embodiments, referring to Figures 1-2, the dispenser body 101 includes slots along one or more side faces to view the sealed container and a level of the contents therein during a dispensing operation. For example, in some embodiments, slots 101s are formed on side faces 103 and 104 to view a level of contents in the sealed containers 201, 203 and 204.

[0078] In some embodiments, the slots 101s also provide physical access to the sealed containers to manipulate orientation of a sealed container in a receptacle or remove the sealed container when stuck. In some embodiments, the slots 101s are provided with level indicia (not illustrated) indicating an amount of contents being dispensed. Based on an amount of contents being dispensed per time unit (e.g., minutes or seconds), the level indicia also assists with determining a rate at which the contents are being dispensed. In some embodiments, the rate of dispensing of the contents further facilitates controlling of the amount of the contents to a system when connected in an automated system. For example, based on a desired rate of dispensing, a pump (or vacuum) pressure or flow rate of fluid is controlled such that the automated system receives the desired amount of contents from the sealed container. It will be understood that the present disclosure is not limited to determining rate of dispensing of the contents based on visual indicators. A person of ordinary skill in the art can employ other techniques for determining a rate of dispensing. For example, a correlation table between a rate of dispensing and control parameters of a system (e.g., pressure or flow rate) can be established by testing, or a flow rate sensor can be deployed at the outlet of the dispenser. Add dosing disclosure re known volume of reagent [0079] In some embodiments, at least one fluidic channel is formed at the bottom portion 101b to convey contents of the sealed containers from one receptacle to another. For example, as shown in Figures 3-4, a first fluidic channel 121 fluidically connects the first receptacle 111 to the second receptacle 112 that are separated by the wall 115. The dispenser 100 can also include a second fluidic channel 122 and a third fluidic channel 123. In one embodiment, the second and third fluidic channels 122 and 123 are similar in size and shape as the first fluidic channel 121. In some embodiments, a fluidic channel is large enough to allow the fluid to pass through the channels without restriction. In embodiments, the fluidic channels are linear, e.g., straight, non-linear, e.g., include an acute angle or arcuate portion, such as a serpentine or coil shape, or include both linear and non-linear portions. In some embodiments, the fluidic channel has a circular cross-section with a diameter or width in a range of about 0.1 mm to about 5 mm, including about 0.25 mm to about 7 mm, or about 0.2 mm to about 5 mm, about 0.25 mm to about 4 mm, about 0.25 mm to about 3 mm, about 0.5 mm to about 3 mm, or the like. It will be understood that the fluidic channel need not have a circular cross-section to allow fluid and/or particles in suspension to flow through the fluidic channel. For example, in embodiments, the fluidic channel has any number of cross- sectional geometries, such as, triangular, rectangular, square, oval, elliptical, or other cross- sectional shape. In some embodiments, the fluidic channel has a non-circular cross-sectional shape having a channel width of about 0.1 mm to about 5 mm, including about 0.25 mm to about 7 mm, or about 0.2 mm to about 5 mm, about 0.25 mm to about 4 mm, about 0.25 mm to about 3 mm, about 0.5 mm to about 3 mm, or the like. In some embodiments, the fluidic channel has a rectangular or square cross-sectional shape having a channel width of about 0.1 mm to about 5 mm, including about 0.25 mm to about 7 mm, or about 0.2 mm to about 5 mm, about 0.25 mm to about 4 mm, about 0.25 mm to about 3 mm, about 0.5 mm to about 3 mm, or the like.

[0080] In one embodiment, as shown in Figures 4-6, the fluidic channels 121-123 are formed on the bottom surface 120 and have a specified depth in the bottom portion 101b to allow fluid and/or particles to flow through the fluidic channels 121-123. In one embodiment, the bottom surface 120 can be at least partially coated with a coating 125 (see Figure 3), for example, a polycarbonate film 125 using a pressure sensitive adhesive to seal at least the fluidic channel from surrounding environment. In some embodiments, the entire bottom surface 120 of the dispenser body can be coated with a polycarbonate film or other adhesive seals without blocking the fluidic channels. Furthermore, as shown in Figures 1-2 and Figures 4-6, a bottom plate 150 can be attached to the bottom surface 120 over the coating 125. For example, the bottom plate 150 can be screwed to the bottom surface 120. The screw holes can be located away from the fluidic channels, for example, at the corners of the cube shaped dispenser. The bottom plate 150 can provide a resting surface for the dispenser 100 and also prevent damaging (e.g., wear and tear) of the coating 125 during use. [0081] In embodiments, a surface is coated, or otherwise functionalized. A surface may be referred to as “functionalized” when it includes a linker, a scaffold, a building block, or other reactive moiety attached thereto, whereas a surface may be “nonfunctionalized” when it lacks such a reactive moiety attached thereto.

[0082] A functionalized surface may refer to a surface having a functional group. A functional group may be a group capable of forming an attachment with another functional group. For example, a functional group may be biotin, which may form an attachment with streptavidin, another functional group. Illustrative functional groups may include, but are not limited to, aldehydes, ketones, carboxy groups, amino groups, biotin, streptavidin, nucleic acids, small molecules (e.g., for click chemistry), homo- and hetero-bifunctional reagents (e.g., N-succinimidyl(4-iodoacetyl) aminobenzoate (STAB), dimaleimide, dithio- bis- nitrobenzoic acid (DTNB), N-succinimidyl-S-acetyl-thioacetate (SATA), N- succinimidyl- 3-(2-pyridyldithio) propionate (SPDP), succinimidyl 4-(N-mafeimidomethyl)- cyclohexane- 1-carboxylate (SMCC) and 6-hydrazinonicotimide (HYNIC), and antibodies. In some instances, the functional group is a carboxy group (e.g., COOH).

[0083] Fluidic channels with optionally functionalized surfaces, fluidically couple the inlet to the first receptacle, the first receptacle to the second receptacle, the second receptacle to the third receptacle, and so on, and the last receptacle to the outlet. The inlet and outlet are coupled to inlet and outlet pipes or tubes. For example, in the embodiment shown in Figure 4, fluidic channels 121-123 facilitate fluidic connection between the receptacles 111-114. In some embodiments, as shown in cross-section view of Figures 4-6, the first receptacle 111 is fluidically connected to the inlet 160, which can be further coupled to a pipe 161, also referred to herein as tube 161. The first receptacle 111 and second receptacle 112 are fluidically connected via the first fluidic channel 121. Similarly, the second receptacle 112 and the third receptacle 113 can be fluidically connected via the second fluidic channel 122. The third receptacle 113 and fourth receptacle 114 can be fluidically connected via the third fluidic channel 123. In the embodiment shown in Figures 4-6, the fourth and final receptacle 114 can be fluidically connected to the outlet 170, which can be further coupled to second pipe 171, also referred to herein as a second tube 171. [0084] In some embodiments, a piercing element can be disposed in each receptacle of the plurality of receptacles to pierce a seal of a sealed container so that contents of the sealed container can be extracted. In some embodiment, the piercing element includes a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end. The piercing end pierces the sealed container and allows contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel. In some embodiments, the lumen portion of the piercing element includes a first lumen to receive an input and a second lumen to deliver contents of the sealed container. [0085] In some embodiments, the piercing element can be integrally formed with the bottom portion of the dispenser body. Referring to Figures 4-6, piercing elements 131, 132, 133, and 134 are formed in the bottom portion 101b of the dispenser body 101. In some embodiments, the piercing element is formed as a separate element configured to be assembled in a receptacle of the plurality of receptacles of the dispenser body. For example, the piercing elements 131-134 can be hollow needles that can be inserted in the bottom portion 101b and sealed in place via, for example, injection molding, thermosetting, adhesive or fastening mechanism, to create a sealed fluidic connection through the lumen portion to the fluidic channel. In some embodiments, the bottom portion 101b of the dispenser body 101 includes a hole (not illustrated) to mount the piercing element in a receptacle such that the piercing end is disposed in the receptacle of the plurality of receptacles and the bottom end is fluidically connecting to the fluidic channel. For example, the hole can be formed from the bottom surface 120 extending into the receptacle 111, and another hole can be formed at another location of the bottom surface 120 and extend into the second receptacle 112, and so on.

[0086] Referring to Figure 5, the piercing element includes a first needle 131 having a piercing end 13 Ip, a base end 131b, and the first lumen 13 IL (see Figure 5) extending between the piercing end 13 Ip and the base end 131b. The piercing element also includes a second needle 132 having a piercing end 132p, a base end 132b, and the second lumen 132L extending between the piercing end 132p and the base end 132b. In this embodiment, the first needle 131 is being spaced from the second needle 132 in the first receptacle 111. Similarly, the second receptacle 112 includes a first needle 133 having ends 133p, 133e and a lumen 133L and a second needle 134 having ends 134p, 133e and a lumen 134L. Similarly, the other receptacles 113 and 114 can each include a pair of needles as piercing element. In some embodiments, the first needle (e.g., 131 and 133 in Figures 4-6) has a first length LI larger than a second length L2 of the second needle (e.g., 132 and 134 in Figures 4-6). Accordingly, the first lumen (e.g., 13 IL and 133L) has a first length larger than a second length of the second lumen (e.g., 132L and 134L). In some embodiments, the first needle has a length that is the same as a length of the second needle. In such embodiments, the length of the first lumen and the second lumen are the same.

[0087] In various embodiments, a “needle” as referred to herein has a membrane piercing tip optionally having a beveled and/or angled tip to facilitate piercing of the membrane. [0088] In some embodiments, as shown in Figures 4-6, the piercing element 131 can be disposed in the first receptacle 111 and configured to receive the pressurized fluid or air from the inlet 160. The pressurized fluid or air can be conveyed to the sealed container 201 via the first lumen 13 IL. The other piercing element 132 can be disposed in the same receptacle 111 and deliver the contents from the sealed container to the first fluidic channel 121 via the second lumen 132L. Similarly, the outlet 170 can be fluidically connected to a bottom end of another piercing element disposed in the second receptacle or subsequent receptacle.

[0089] In operation, referring to Figures 1, 6 and 9A, upon loading each receptacle of the plurality of the receptacles 111-114 with the sealed container 201-204, the piercing elements (e.g., 131-134 in Figure 6) pierce a seal (e.g., 201s, 202s in Figure 6) of the sealed containers 201-204. This creates a continuous flow path from the inlet 160 to the outlet 170 via the fluidic channels 121-123, the piercing elements 131-134, and sealed containers 201- 204 while connecting the sealed containers in series along the continuous flow path. The continuous flow path can, in some embodiments, be a closed path such that contents (e.g., 211 and 212) of the sealed containers (e.g., 201 and 202) do not spill into the receptacle 111- 114, thereby advantageously allowing for the maintenance of a functionally closed system which maintains the sterility of the contents of the receptacles. In some embodiments, including in the embodiment shown in Figure 9A, the continuous flow path is marked by arrows labeled 901, 902, 903, 904, 905, 906, 907, 908 and 909. As shown, a first path portion 901-903 starts from the inlet 160 passing through the first lumen 13 IL of the first piercing element (e.g., the first needle 131) into the first sealed container 201 located in the first receptacle 111 and from the first sealed container 201 to the second lumen 132L of the first piercing element (e.g., the second needle 132) into the first fluidic channel 121. A second path portion 904-905 from the first fluidic channel 121 to the first lumen 133L of the second piercing element (e.g., the first needle 133) into the second sealed container 202 located in the second receptacle 112 and from the second sealed container 202 to the second lumen 134L of the second piercing element (e.g., the second needle 134) into the second fluidic channel 122. A third path portion 906-907 from the second fluidic channel 122 to a first lumen 135L of a third piercing element (e.g., a first needle 135) into the third sealed container 203 located in the third receptacle 113 and from the third sealed container 203 to a second lumen 136L of the third piercing element (e.g., a second needle 136) into the third fluidic channel 123. A fourth path portion 908-909 from the third fluidic channel 123 to a first lumen 137L of the fourth piercing element (e.g., a first needle 137) into a fourth sealed container 204 located in the fourth receptacle 114 and from the fourth sealed container 204 to a second lumen 138L of the fourth piercing element (e.g., a second needle 138) leading to the outlet 170.

[0090] In some embodiments, upon loading each receptacle of the plurality of the receptacles with a sealed container, the dispenser creates a continuous flow path from the inlet 160 to the outlet 170 via the sealed containers and while connecting one or more sealed containers in parallel along the continuous flow path. An example parallel flow path is illustrated in Figure 9B, where the arrow 901 corresponds to an inlet that leads to fluidic channels corresponding to arrows 912 and 922, which are in parallel. The flow path further passes though sealed containers corresponding to arrows 913 and 923. The contents from the sealed containers are simultaneously passed through channels corresponding to arrows 914 and 924 leading to the outlet marked by arrow 910. It can be understood that the dispenser can be configured to include receptacles and fluidic channels corresponding to the flow path in Figure 9B. The detailed construction of this dispenser is omitted herein for brevity as the elements or parts (e.g., receptacles, fluidic channels, piercing elements, inlet, outlet, etc.) are similar to the dispenser 100 discussed herein.

[0091| It will be understood that the piercing elements discussed above do not limit the scope of the present disclosure to one or two separate needles. The ordinarily skilled artisan will readily appreciate that in some embodiments, a piercing element is formed as a single unit with the first lumen and the second lumen being formed adjacent to each other separated by a wall. In one embodiment, as shown in Figure 7, a piercing element 500 is formed as a single unit where a first lumen 512 and a second lumen 514 are separated by a wall 513. The piercing element 500 has a piercing end 502 and a base end 504, also referred as a top piercing end 502 and a bottom end 504, respectively, depending on an orientation of the piercing element 500. The base end 504 can be fluidically coupled to a fluidic channel to receive and deliver contents of the sealed containers. In one embodiment, as shown in Figure 7, the first lumen 512 is fluidically connected to the inlet channel 160, for example, to receive pressured fluid, such as a liquid or gas, to drive the contents out of a sealed container. The second lumen 514 is fluidically connected to the first fluidic channel 121 to convey the contents of the sealed container to the first fluidic channel 121. Thus, a closed fluidic path is created from the inlet 160 via the sealed container and piercing element 500 to the first fluidic channel 121. In some embodiments, the first lumen 512 can have a first length the same, or larger than a second length of the second lumen 514. In some embodiments, the piercing element 500 can be formed as a separate element and inserted from the bottom surface 120 (see Figure 3) of the dispenser body 101.

|0092] In some embodiments, referring to Figures 4-6, an inlet of the dispenser 100 includes an inlet port or an inlet channel 164 that fluidically couples with a lumen portion of a piercing element. In some embodiments, as shown in cross-section views of Figures 4-6, the inlet 160 includes an inlet channel 164 configured to receive an inlet connector 160 having a lumen 162 that fluidically couples with a lumen portion of the piercing element. As used herein, the inlet connector 160, the inlet lumen 162 of the inlet connector or the inlet channel 164 of the dispenser can be used interchangeably and generally referred as the inlet 160.

[0093] Similar to the inlet 160, the outlet 170 includes an outlet portion or an outlet channel (not illustrated but similar to 164) that fluidically couples with a lumen portion of a piercing element. In some embodiments, the outlet 170 includes an outlet channel (similar to 164) configured to receive an outlet connector 170 having a lumen (similar to 162) that fluidically couples with a lumen portion of the piercing element. As used herein, the outlet connector 170, the outlet lumen of the outlet connector or the outlet channel of the dispenser can be used interchangeably and generally referred as the outlet 170. [0094] The outlet 170 is fluidically coupled to the inlet 160 via the first receptacle, the fluidic channel(s) connecting the piercing elements to one or more receptacles (whether in a serial or in parallel path configuration), the piercing element in each receptacle of the one or more (e.g., plurality) receptacles, and the optional multitude of additional receptacles, wherein the outlet is configured to deliver the contents of the sealed container(s).

[0095| In some embodiments, the dispenser 100 includes a locking element disposed in a receptacle of the plurality of receptacles for holding the sealed container in place. In some embodiments, such as for example, the embodiment shown in Figure 8, the locking element 400 is configured as a latch mechanism that includes a plurality of cantilevered arms 411- 414, each cantilevered arm having a proximal end and a distal end 401-404. In some embodiments, the proximal end can be disposed at the bottom portion 101b of the dispenser body and the distal end 401-404 being located in a receptacle of the plurality of receptacles, each cantilevered arm 411-414 being deflectable at the distal end 401-404, respectively. In one embodiment, the distal end is shaped to hold the sealed container in place.

[0096] In some embodiments, referring to Figures 6 and 8, the distal end (e.g., 401) of the cantilevered arm (e.g., 411) of the plurality of cantilevered arms 411-414 includes an engagement member shaped to engage with the sealed container (e.g., 201) and hold the sealed container (e.g., 201) in the respective receptacle (e.g., 111). In one embodiment, the engagement member 401 is a protrusion extending from each cantilevered arm of the plurality of cantilevered arms. For example, the cantilevered arm 411 includes a protruding surface 431 protruding from a surface 432 of the cantilevered arm 411.

[0097] In one embodiment, the locking element 400 includes a base portion 415 attached to proximal ends of the plurality of cantilevered arms 411-414 such that the plurality of cantilevered arms extend perpendicularly from the base portion 415. In one embodiment, the base portion 415 includes a hole 416 to assemble the locking element 400 into the bottom portion 101b and fix it to the dispenser 100 by a fastener (not illustrated) passing through the hole 416. For example, a screw can be passed through the hole 416 and screwed into the bottom portion 101b.

[0098] The skilled artisan will readily appreciate that the locking element having cantilevered arms is merely an exemplary type locking element configured for use with the embodiments provided herein, and that any conventional locking element(s) can be employed. By way of example only, the locking elements is mechanically actuated, such as by a spring.

[0099] Figures 16-35 illustrate views of a dispenser 100 for delivering contents of sealed containers, according to some embodiments. The dispenser 100 includes a plurality of receptacles for receiving sealed containers, a plurality of piercing elements for piercing the sealed containers and at least one fluidic channel to convey contents of the sealed containers from one receptacle to another receptacle. The dispenser 100 further includes a cover body disposed over the plurality of receptacles for securing the sealed containers. The dispenser 100 also includes an inlet and an outlet each fluidically coupled to a receptacle of the plurality of receptacles so that contents of the sealed containers can be dispensed via the outlet to a desired system.

[0100] With reference to Figures 16-35, in embodiments, the dispenser 100 includes a dispenser body 1001 having a top portion 1005, and a bottom portion 1006. It will also be appreciated that in some embodiments, a plurality of receptacles are formed in the top portion 1005 of the dispenser body 1001. In some embodiments, the plurality of receptacles includes at least a first receptacle and a second receptacle. Each receptacle extends toward the bottom portion 1006 of the dispenser body 1001. As shown in the Figures, each receptacle can have an opening large enough to receive a sealed container, an interior surface extending in an axial direction, and a base surface at the bottom portion 1006.

[0101] In one embodiment, as shown in Figures 16-35, the plurality of receptacles includes four receptacles - a first receptacle 1020, a second receptacle 1021, a third receptacle 1022, and a fourth receptacle 1023. In one embodiment, the receptacles 1020- 1023 are configured to receive a plurality of sealed containers 1025, 1026, 1027 and 1028. For example, the first receptacle 1020 and the second receptacle 1021 of the plurality of receptacles are each structured to receive a sealed container such as vials 1025 and 1026. In some embodiments, the first receptacle 1020 and second 1021 are separated by a wall 1018, as shown in cross-section view of Figure 18 (sealed containers not shown), and are fluidically coupled via a fluidic channel formed via the cover body.

[0102] In some embodiments, at least one fluidic channel is formed in or on the cover body 1010 to convey contents of the sealed containers 1025-1028 from one receptacle to another. For example, as shown in Figures 20 and 21, a first fluidic channel 1040 fluidically connects the first receptacle 1020 to the second receptacle 1021 that are separated by the wall 1018. The dispenser 100 can also include a second fluidic channel 1041 and a third fluidic channel 1042. In one embodiment, the second and third fluidic channels 1041 and 1042 are similar in size and shape as the first fluidic channel 1040.

[0103] In one embodiment, the fluidic channels 1040-1042 are formed in or on the cover body 1010 and have a specified depth to allow fluid and/or particles to flow through the fluidic channels 1040-1042. In one embodiment, fluidic channels are formed by a top portion of the cover body and a bottom portion of the cover body, but may also be formed through a unitary cover body by conventional manufacturing techniques.

[0104] As shown in throughout various Figures 16-35, a piercing element 1016 can be disposed in each receptacle of the plurality of receptacles to pierce a seal of a sealed container so that contents of the sealed container can be extracted. In some embodiments, the piercing element is integrally formed with the cover body as shown in the Figures.

[0105] In operation, referring to Figures 16-35, each receptacle 1020-1024 of the plurality of the receptacles is loaded with sealed containers 1025-1028 while the cover body 1010 is separated from the dispenser body 1001. Once the sealed containers are loaded, the cover body is lowered over the dispenser body to assembly the loaded dispenser. As the cover body is lowered over the dispenser body, the piercing elements (e.g., 1016 in Figure 6) pierce a seal of each of the sealed containers 1025-1028. This creates a continuous flow path from the inlet 1012 to the outlet 1014 via the fluidic channels 1040-1042, the piercing elements 1016, and sealed containers 1025-1028 while connecting the sealed containers in series along the continuous flow path. Additionally, as the cover body is lowered over the dispenser body, one or more attachment elements 1030 disposed on the cover body engage one or more attachments elements 1032 disposed on the dispenser body (see Figure 17) to couple the cover body to the dispenser body and secure the sealed containers within the receptacles as depicted in the Figures.

[0106] The continuous flow path can, in some embodiments, be a closed path such that contents of the sealed containers do not spill into the receptacles, thereby advantageously allowing for the maintenance of a functionally closed system which maintains the sterility of the contents of the receptacles. Additionally, a sealing member, such as a gasket or o-ring may be disposed between the cover body and the sealed container(s) to prevent leakage and ingress of contaminants into the fluid flow.

[0107] In embodiments where the dispenser includes 2 or more receptacles, it will be appreciated that sealed containers may be utilized as blanks (e.g., empty or buffer only) to complete the continuous flow path through the dispenser. For example, in some embodiments, the dispenser includes at least one or more reagent containing sealed containers and one or more non-reagent or empty sealed containers. For example, Figure 22 shows an embodiment in which sealed container 1025 is a reduced volume container which can include a reagent for use in a biological assay or workflow, such as a fluid containing magnetic beads, and one or more of sealed containers 1026-1028 are empty or contain buffer. In some embodiments, the dispenser includes 1, 2, 3 or more sealed containers that are blanks (e.g., empty) and solely used to complete the continuous flow path through the dispenser. It will be appreciated that the number of blanks that may be utilized will depend on the number of receptacles included in the dispenser body.

[0108] In operation, once the sealed containers are loaded, the cover body is attached to the dispenser body and the sealed containers are pierces by the piercing members, the contents of the sealed containers can be agitated to suspend and mix particles contained in the containers to ensure the entire contents of reagent is fully dispensed during the dispensing procedure. Additionally, in the embodiments shown in Figures 16-35, once loaded with sealed containers and optionally mixed, the dispenser may be inverted such that fluid contained in the sealed containers to facilitate flow of fluid through the piercing elements through the flow path of the dispenser.

[0109] In some embodiments, the contents of the sealed containers are dispensed through the outlet into a container, such as a bag, and subsequently flowed into a workflow. It will be appreciated that in one embodiment, dosing of the reagent may include determining the volume of reagent dispensed from the sealed containers and the resulting concentration and/or volume of reagent in solution dispensed into the container.

[0110] Figures 10-13 illustrate exemplary implementation of the dispenser 100 delivering contents of one or more sealed containers to a system 600. The system 600 can be a medical application or a chemical application that prefers the contents of the sealed containers be delivered in a closed path to avoid contamination of the contents. By way of example only, the system 600 can be used in the production of cell therapy or related products, e.g., for facilitating cell activation, and/or cell isolation, and/or labeling processes.

[0111] Referring to Figure 10, the dispenser 100 is loaded with sealed containers 201-204 in respective receptacles, according to one embodiment. The sealed containers 201-204 can include fluid as liquid, a liquid/gas, or gas, as including suspended particles, e.g., magnetic beads, non-magnetic beads, dendrimers, or the like. The input 160 is connected to a pump 750 that provides pressurized sterile air to the first sealed container 201 via the piercing element (not shown in Figure 10) located in the first receptacle 111. The sterilized air can be obtained by passing air through a filter 700. In one embodiment, as discussed with respect to Figure 9A, the dispenser 100 connects the sealed containers 201-204 in series and conveys the contents of the sealed containers through the piercing elements and fluidic channels to the outlet 170. The pump 750 pushes the sterilized fluid, e.g., ambient air, or fluid from a concentrated source (e.g., nitrogen, carbon, argon, oxygen and the like) in the first sealed container 201 that sequentially drives out contents from the containers 202, 203, and 204 to the outlet 170. From the outlet 170, the system 600 can receive the contents (e.g., magnetic beads) at desired time and rate.

[0112] Referring to Figure 11, the dispenser 100 is loaded with sealed containers 201-204 and connected to a vessel 800 containing solution 802, according to one embodiment. A pump 850 receives the solution 802 and pumps the solution 802 into the sealed container 201. Similar to the discussion above, the pressured solution 802 sequentially drives out contents from the containers 201, 202, 203 and 204 to the outlet 170. By way of example only, the sealed containers can contain a suspension of particles (e.g., magnetic beads, nonmagnetic beads, dendrimers, and the like), and the solution can be a wash solution for washing the particles and also washing the emptied containers to ensure maximal delivery of particles from the suspension thereby minimizing waste. As such, in some embodiments, the dispenser 100 facilitates washing of the particles, as well as the containers to remove the particles from the containers such that processing proceeds without human intervention. [0113] Referring to Figures 12 and 13, in certain embodiments, the dispenser 100 is connected to both a sterilized gas source (e.g., air) and a wash buffer 800. For example, in Figure 12, the dispenser 100 receives the sterilized gas source passed through the filter 700 and the buffer solution 802 via a single pump 850. In such embodiments, one or more valves 1 is utilized to coordinate the flow path of the gas source and/or was buffer 800 though the system. In Figure 13, the dispenser 100 can receive the air passed through the filter 700 via the pump 750 and receive the buffer solution 802 via another pump 850. Accordingly, by controlling individual pumps 750 and 850 the amount of buffer and sterilized air delivered to the dispenser 100 can be controlled.

[0114] Depending on how the system is configured, an automation system having one or more processors in electronic communication with components of the system is operable to control movement of the particles in a suspension of fluid by controlling a speed of a mixer designed to maintain particles in suspension, such as a Vortex mixer, a position of the valves, and a direction/speed of one or several pumps such as, for example, one or more peristaltic pump(s). In some embodiments, sterile fluid, such as liquid, gas or air, can be used to first empty the contents of the sealed containers. Then, wash buffer can be flushed through the dispenser to facilitate washing of the sealed containers. Sterile fluid, such as liquid, gas or air, can then be used again to transfer remaining particles into an output vessel. [0115] While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the present disclosures. Indeed, the novel methods, apparatuses and systems described herein can be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the methods, apparatuses and systems described herein can be made without departing from the spirit of the present disclosures. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the present disclosure.

Claims

WHAT IS CLAIMED IS:

1. A dispenser comprising: an inlet configured to receive a fluid; a dispenser body having a top portion, a bottom portion, and a first receptacle configured to receive a sealed container; a first fluidic channel formed in the bottom portion fluidically connected to the first receptacle; a piercing element disposed in the first receptacle, the piercing element having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end, wherein the piercing end is configured to pierce the sealed container and allow contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, and the piercing element in the first receptacle.

2. The dispenser of claim 1, further comprising: a plurality of receptacles formed in the top portion extending toward the bottom portion, the plurality of receptacles including at least the first receptacle and a second receptacle, each of the plurality of receptacles being configured to receive a sealed container; wherein the first fluidic channel formed in the bottom portion fluidically connects the first receptacle to the second receptacle; a piercing element disposed in each receptacle of the plurality of receptacles, each of the piercing elements having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end, wherein the piercing end is configured to pierce the sealed container and allow contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, the piercing element in each receptacle of the plurality of receptacles, and the second receptacle.

3. The dispenser of claim 2, further comprising a sealed container received by the first receptacle and defining a continuous flow path from the inlet to the outlet via the sealed container.

4. The dispenser of claim 3, further comprising a sealed container received by each of the plurality of the receptacles and defining a continuous flow path from the inlet to the outlet via the sealed containers, wherein the sealed containers are fluidically connected in series along the continuous flow path.

5. The dispenser of claim 4, wherein the dispenser comprises at least 3 receptacles receiving sealed containers defining a continuous flow path from the inlet to the outlet.

6. The dispenser of claim 5, wherein the sealed containers are fluidically connected in series along the continuous flow path.

7. The dispenser of claim 5, wherein 2 of the sealed containers are fluidically connected in parallel along the continuous flow path.

8. The dispenser of claim 4, wherein the dispenser comprises at least 4 receptacles receiving sealed containers defining a continuous flow path from the inlet to the outlet.

9. The dispenser of claim 8, wherein the sealed containers are fluidically connected in series along the continuous flow path.

10. The dispenser of claim 8, wherein 2 or 3 of the sealed containers are fluidically connected in parallel along the continuous flow path.

11. The dispenser of claim 2, further comprising a sealed container received by each of the plurality of the receptacles and defining a continuous flow path from the inlet to the outlet via the sealed containers, wherein the sealed containers are fluidically connected in parallel along the continuous flow path.

12. The dispenser of any one of claims 1-11, wherein the piercing element is integrally formed with the bottom portion of the dispenser body.

13. The dispenser of any one of claims 1-11, wherein the piercing element is formed as a separate element configured to be assembled in a receptacle of the plurality of receptacles of the dispenser body.

14. The dispenser of any one of claims 1-11, wherein the lumen portion of the piercing element comprises: a first lumen configured to receive the pressurized fluid from the inlet and convey the pressurized fluid to the sealed container; and a second lumen configured to deliver the contents from the sealed container to the first fluidic channel.

15. The dispenser of claim 14, wherein the first lumen and the second lumen are formed adjacent each other in a unitary structure separated by a surface extending along the first and second lumens.

16. The dispenser of claim 14, wherein the piercing element comprises: a first needle having the first lumen; and a second needle having the second lumen, the first needle being non-unitary with the second needle.

17. The dispenser of claim 16, wherein the first needle and the second needle are separated by a distance of from less than about 1 mm to about 3 cm.

18. The dispenser of any one of claims 12-17, wherein the first needle and/or the second needle has one or more side holes disposed along a length of the needle.

19. The dispenser of any one of claims 12-18, wherein the first needle has a first length larger than a second length of the second needle.

20. The dispenser of any one of claims 12-18, wherein the first lumen has a first length larger than a second length of the second lumen.

21. The dispenser of any one of claims 2 or 4- 11 , wherein: the plurality of receptacles further comprises: a third receptacle and a fourth receptacle; and the bottom portion further comprises a second fluidic channel and a third fluidic channel, wherein the first fluidic channel, the second fluidic channel and the third fluidic channel are configured to fluidically connect the plurality of receptacles in series.

22. The dispenser of claim 21 , wherein: the first receptacle is fluidically connected to the inlet; the second receptacle is fluidically connected to the first receptacle via the first fluidic channel; the third receptacle is fluidically connected to the second receptacle via the second fluidic channel; and the fourth receptacle is fluidically connected to the third receptacle via the third fluidic channel and the fourth receptacle is fluidically connected to the outlet.

23. The dispenser of claim 21, wherein, when each of the plurality of the receptacles contains a sealed container, the dispenser creates a continuous flow path comprising: a first path portion starting from the inlet through a first lumen of a first piercing element into a first sealed container located in the first receptacle and from the first sealed container to a second lumen of the first piercing element into the first fluidic channel; a second path portion from the first fluidic channel to a first lumen of the second piercing element into a second sealed container located in the second receptacle and from the second sealed container to a second lumen of the second piercing element into the second fluidic channel; a third path portion from the second fluidic channel to a first lumen of a third piercing element into a third sealed container located in the third receptacle and from the third sealed container to a second lumen of the third piercing element into the third fluidic channel; and a fourth path portion from the third fluidic channel to a first lumen of the fourth piercing element into a fourth sealed container located in the fourth receptacle and from the fourth sealed container to a second lumen of the fourth piercing element leading to the outlet.

24. The dispenser of any one of claims 1-23, wherein the bottom portion of the dispenser body has a bottom surface at least partially covered with a planar substrate to seal at least the fluidic channel from surrounding environment.

25. The dispenser of claim 2, wherein the inlet is fluidically connected to the bottom end of the piercing element disposed in the first receptacle; and the outlet is fluidically connected a bottom end of another piercing element disposed in the second receptacle.

26. The dispenser of claim 1, wherein the bottom portion of the dispenser body comprises a hole configured to receive the piercing element and dispose the piercing end into the first receptacle and the bottom end fluidically connecting to the fluidic channel.

27. The dispenser of any one of claims 5-11, wherein the plurality of receptacles are oriented in a non-linear pattern within the dispenser body.

28. The dispenser of any one of claims 5-11, wherein the plurality of receptacles are oriented in a linear geometry within the dispenser body.

29. The dispenser of claim 2, wherein at least one receptacle of the plurality of receptacles has a shape conforming to a shape of the sealed container.

30. The dispenser of claim 2, the at least one receptacle of the plurality of receptacles defines a cylinder, a rectangular prism, a cubical prism, or a cone.

31. The dispenser of claim 1, wherein the fluidic channel has a diameter in a range of between about 0.1 cm to about 0.75 cm and operable to allow micro-sized particles to flow through the fluidic channel.

32. The dispenser of claim 1, further comprising: a locking element disposed in the first receptacle for holding the sealed container in place.

33. The dispenser of claim 32, wherein the locking element comprises: a plurality of cantilevered arms, each cantilevered arm having a proximal end and a distal end, the proximal end being disposed at the bottom portion of the dispenser body and the distal end being located in the first receptacle, each cantilevered arm being deflectable at the distal end and configured to hold the sealed container in place.

34. The dispenser of claim 33, wherein the distal end of each cantilevered arm of the plurality of cantilevered arms comprises an engagement member configured to engage with the sealed container and hold the sealed container in the first receptacle.

35. The dispenser of claim 34, wherein the engagement member is a protrusion extending from each cantilevered arm of the plurality of cantilevered arms.

36. The dispenser of any one of claims 33-35, wherein the locking element further comprises a base portion attached to proximal ends of the plurality of cantilevered arms such that the plurality of cantilevered arms extend perpendicularly from the base portion.

37. The dispenser of claim 1, wherein the sealed container comprises particles dispersed in the fluid.

38. The dispenser of claim 2, wherein each of the plurality of receptacles comprises a sealed container.

39. The dispenser of claim 38, wherein at least one of the sealed containers comprises a liquid reagent and at least one of the sealed containers is empty.

40. The dispenser of claim 1, further comprising: a cover disposed over the top portion of the dispenser body.

41. The dispenser of claim 40, wherein the cover comprises one or more attachment elements for attaching the cover to the dispenser body for securing the sealed container within the first receptacle.

42. The dispenser of claim 1, wherein the one or more attachment elements engage one or more attachments disposed on the dispenser body to attach the cover to the dispenser body.

43. A dispenser comprising: a dispenser body having a top portion, a bottom portion, and a first receptacle configured to receive a sealed container; a cover body for covering the first receptacle, the cover body having a bottom surface and a top surface; an inlet configured to receive a fluid; a first fluidic channel formed in or on the cover body; a piercing element extending from the bottom surface into the first receptacle, the piercing element having a top piercing end, a bottom end, and a lumen portion extending from the top piercing end to the bottom end, wherein the piercing end is configured to pierce the sealed container and allow contents of the sealed container to flow through the lumen portion toward the bottom end into the first fluidic channel; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, and the piercing element.

44. The dispenser of claim 43, further comprising: wherein the dispenser body has a plurality of receptacles formed in the top portion extending toward the bottom portion, the plurality of receptacles including at least the first receptacle and a second receptacle, each of the first receptacle and the second receptacle being configured to receive sealed containers; wherein the first fluidic channel formed in the cover body fluidically connects the first receptacle to the second receptacle; a piercing element extending from the bottom surface into each of the plurality of receptacles; and an outlet fluidically coupled to the inlet via the first receptacle, the first fluidic channel, the piercing element in each receptacle of the plurality of receptacles, and the second receptacle.

45. The dispenser of claim 44, further comprising a sealed container received by the first receptacle and defining a continuous flow path from the inlet to the outlet via the sealed container.

46. The dispenser of claim 45, further comprising a sealed container received by each of the plurality of the receptacles and defining a continuous flow path from the inlet to the outlet via the sealed containers, wherein the sealed containers are fluidically connected in series along the continuous flow path.

47. The dispenser of claim 46, wherein the dispenser comprises at least 3 receptacles receiving sealed containers defining a continuous flow path from the inlet to the outlet.

48. The dispenser of claim 47, wherein the sealed containers are fluidically connected in series along the continuous flow path.

49. The dispenser of claim 47, wherein 2 of the sealed containers are fluidically connected in parallel along the continuous flow path.

50. The dispenser of claim 46, wherein the dispenser comprises at least 4 receptacles receiving sealed containers defining a continuous flow path from the inlet to the outlet.

51. The dispenser of claim 50, wherein the sealed containers are fluidically connected in series along the continuous flow path.

52. The dispenser of claim 50, wherein 2 or 3 of the sealed containers are fluidically connected in parallel along the continuous flow path.

53. The dispenser of claim 44, further comprising a sealed container received by each of the plurality of the receptacles and defining a continuous flow path from the inlet to the outlet via the sealed containers, wherein the sealed containers are fluidically connected in parallel along the continuous flow path.

54. The dispenser of any one of claims 43-53, wherein the piercing element is integrally formed with the bottom surface of the cover body.

55. The dispenser of any one of claims 43-53, wherein the piercing element is formed as a separate element configured to be assembled in a receptacle of the plurality of receptacles of the dispenser body.

56. The dispenser of any one of claims 43-53, wherein the lumen portion of the piercing element comprises: a first lumen configured to receive the pressurized fluid from the inlet and convey the pressurized fluid to the sealed container; and a second lumen configured to deliver the contents from the sealed container to the first fluidic channel.

57. The dispenser of claim 56, wherein the first lumen and the second lumen are formed adjacent each other in a unitary structure separated by a surface extending along the first and second lumens.

58. The dispenser of claim 56, wherein the piercing element comprises: a first needle having the first lumen; and a second needle having the second lumen, the first needle being non-unitary with the second needle.

59. The dispenser of claim 58, wherein the first needle and the second needle are separated by a distance of from less than about 1 mm to about 3 cm.

60. The dispenser of any one of claims 54-59, wherein the first needle and/or the second needle has one or more side holes disposed along a length of the needle.

61. The dispenser of any one of claims 54-60, wherein the first needle has a first length larger than a second length of the second needle.

62. The dispenser of any one of claims 54-60, wherein the first lumen has a first length larger than a second length of the second lumen.

63. The dispenser of any one of claims 44 or 46-53, wherein: the plurality of receptacles further comprises: a third receptacle and a fourth receptacle; and the bottom portion further comprises a second fluidic channel and a third fluidic channel, wherein the first fluidic channel, the second fluidic channel and the third fluidic channel are configured to fluidically connect the plurality of receptacles in series.

64. The dispenser of claim 63, wherein: the first receptacle is fluidically connected to the inlet; the second receptacle is fluidically connected to the first receptacle via the first fluidic channel; the third receptacle is fluidically connected to the second receptacle via the second fluidic channel; and the fourth receptacle is fluidically connected to the third receptacle via the third fluidic channel and the fourth receptacle is fluidically connected to the outlet.

65. The dispenser of claim 63, wherein, when each of the plurality of the receptacles contains a sealed container, the dispenser creates a continuous flow path comprising: a first path portion starting from the inlet through a first lumen of a first piercing element into a first sealed container located in the first receptacle and from the first sealed container to a second lumen of the first piercing element into the first fluidic channel; a second path portion from the first fluidic channel to a first lumen of the second piercing element into a second sealed container located in the second receptacle and from the second sealed container to a second lumen of the second piercing element into the second fluidic channel; a third path portion from the second fluidic channel to a first lumen of a third piercing element into a third sealed container located in the third receptacle and from the third sealed container to a second lumen of the third piercing element into the third fluidic channel; and a fourth path portion from the third fluidic channel to a first lumen of the fourth piercing element into a fourth sealed container located in the fourth receptacle and from the fourth sealed container to a second lumen of the fourth piercing element leading to the outlet.

66. The dispenser of any one of claims 43-65, wherein the top surface of the cover body has at least partially covered with a planar substrate to seal at least the fluidic channel from surrounding environment.

67. The dispenser of claim 44, wherein the inlet is fluidically connected to the bottom end of the piercing element disposed in the first receptacle; and the outlet is fluidically connected a bottom end of another piercing element disposed in the second receptacle.

68. The dispenser of claim 45, wherein each of the plurality of receptacles comprises a sealed container.

69. The dispenser of claim 68, wherein at least one of the sealed containers comprises a liquid reagent and at least one of the sealed containers is empty.

70. The dispenser of claim 68, further comprising: a sealing member disposed between the bottom surface of the cover body and at least one of the sealed containers.

71. The dispenser of claim 28, wherein the sealing member is a gasket or o-ring.

72. The dispenser of any one of claim 43-71, wherein the cover body comprises one or more attachment elements for attaching the cover to the dispenser body for securing the sealed container within the first receptacle.

73. The dispenser of claim 72, wherein the one or more attachment elements engage one or more attachment elements disposed on the dispenser body to attach the cover body to the dispenser body.

74. The dispenser of claim 73, wherein the one or more attachment elements are disposed on a sidewall extending from the bottom surface of the cover body.

75. The dispenser of any one of claims 47-53, wherein the plurality of receptacles are oriented in a non-linear pattern within the dispenser body.

76. The dispenser of any one of claims 47-53, wherein the plurality of receptacles are oriented in a linear geometry within the dispenser body.

77. The dispenser of claim 44, wherein at least one receptacle of the plurality of receptacles has a shape conforming to a shape of the sealed container.

78. The dispenser of claim 44, the at least one receptacle of the plurality of receptacles defines a cylinder, a rectangular prism, a cubical prism, or a cone.

79. The dispenser of claim 43, wherein the fluidic channel has a diameter in a range of between about 0.1 cm to about 0.75 cm and operable to allow micro-sized particles to flow through the fluidic channel.

80. A system comprising: a dispenser according to any one of claims 1-79; and a fluid flow module fluidically coupled to the inlet and/or the outlet of the dispenser operable to control a flow of fluid into a sealed container causing the contents therein to be forced out of the sealed container through the outlet of the dispenser via a fluidic channel and a piercing element.

81. The system of claim 80, wherein the fluid flow module is operable to drive the fluid flow into the inlet and through the outlet by generating a fluid flow force fluidically upstream of the inlet or downstream of the outlet.

82. The system of claim 81, wherein the fluid flow module is a pump.

83. The system of claim 82, wherein the pump is arranged fluidically upstream of the inlet.

84. The system of claim 82, wherein the pump is arranged fluidically downstream of the outlet.

85. A system comprising: a dispenser configured to receive a plurality of sealed containers; the dispenser comprising: a plurality of receptacles, each of the plurality of receptacles configured to receive a sealed container of the plurality of sealed containers; a plurality of fluidic channels, each of the fluidic channels fluidically connecting two receptacles of the plurality of receptacles; a plurality of piercing elements, each piercing element disposed in one of the receptacles of the plurality of receptacles such that each receptacle includes at least one piercing element, each of the plurality of piercing elements configured to fluidically couple with a sealed container disposed within the receptacle associated with that piercing element, each piercing element fluidically connected to a fluidic channel of the plurality of fluidic channels; an inlet configured to receive a fluid; an outlet fluidically coupled to the inlet via the plurality of receptacles, the plurality of fluidic channels and the plurality of piercing elements, the outlet configured to deliver contents of the plurality of sealed containers; and a fluid flow module coupled to the inlet and/or the outlet of the dispenser operable to control a flow of fluid into at least one sealed container causing the contents therein to be forced out of the sealed container and through the outlet of the dispenser via the plurality of fluidic channel and the plurality of piercing elements.

86. The system of claim 85, wherein the fluid flow module is operable to drive the fluid flow into the inlet and through the outlet by generating a fluid flow force fluidically upstream of the inlet or downstream of the outlet.

87. The system of claim 86, wherein the fluid flow module is a pump.

88. The system of claim 87, wherein the pump is arranged fluidically upstream of the inlet.

89. The system of claim 87, wherein the pump is arranged fluidically downstream of the outlet.

90. The system of claim 85, further comprising: the plurality of sealed containers configured to be received in the plurality of receptacles.

91. The system of claim 85, wherein the pressurized fluid is a sterile gas or air to move the contents of the plurality of sealed containers in a sterile manner.

92. The system of claim 85, wherein the pressurized fluid is a wash fluid for washing contents of the plurality of sealed containers.

93. The system of claim 85, wherein the inlet is configured to receive a mixture of gas and fluid.

94. The system of claim 85, wherein the plurality of sealed containers includes at least one sealed container comprising particles.

95. The system of claim 94, wherein the pressurized fluid comprises a wash fluid for washing of the particles in the at least one sealed container of the plurality of sealed containers.

96. The system of claim 95, wherein the wash fluid is introduced into a first sealed container located in a first receptacle of the plurality of receptacles causing the wash fluid to push out the contents of the first sealed container into a first fluidic channel of the plurality of fluidic channels, further conveying the contents into a second sealed container located in a second receptacle of the plurality of receptacles, and dispensing the washed particles through the outlet of the dispenser, wherein at least one of the first sealed container or the second sealed container includes the particles.

97. The system of claim 87, wherein the pump is configured to pump air or fluid at a specified pressure into the inlet, the specified pressure being associated with a specified amount of content to be dispensed.

98. The system of claim 85, further comprises an alignment jig comprising holes corresponding to each receptacle of the plurality of receptacles, and is configured to axially align a sealed container in the respective receptacle.

99. The system of any one of claims 85-98, wherein at least one of the piercing elements is integrally formed with a bottom portion of the dispenser body or a cover disposed over the plurality of receptacles.

100. The system of any one of claims 85-98, wherein at least one of the piercing elements is formed as a separate element configured to be assembled in a receptacle of the plurality of receptacles of the dispenser body.

101. The system of any one of claims 85-98, wherein the lumen portion of at least one of the piercing elements comprises: a first lumen configured to receive the fluid from the inlet and convey the fluid to the sealed container; and a second lumen configured to deliver the contents from the sealed container to the first fluidic channel.

102. The system of claim 101, wherein the first lumen and the second lumen are formed adjacent each other in a unitary structure separated by a surface extending along the first and second lumens.

103. The system of claim 101, wherein at least one of the piercing elements comprises: a first needle having the first lumen; and a second needle having the second lumen, the first needle being non-unitary with the second needle.

104. The system of claim 103, wherein the first needle and the second needle are separated by a distance of from less than about 1 mm to about 3 cm.

105. The system of any one of claims 103-104, wherein the first needle and/or the second needle has one or more side holes disposed along a length of the needle.

106. The system of any one of claims 103-105, wherein the first needle has a first length larger than a second length of the second needle.

107. The system of any one of claims 103-105, wherein the first lumen has a first length larger than a second length of the second lumen.

108. The system of any one of claims 85-107, wherein at least one of the piercing elements includes one or more side holes disposed along a length of the piercing element.

109. The system of claim 99, wherein: the plurality of receptacles comprises: a first receptacle, a second receptacle, a third receptacle and a fourth receptacle; and the plurality of fluidic channels comprises a first fluidic channel, a second fluidic channel and a third fluidic channel, wherein the first fluidic channel, the second fluidic channel and the third fluidic channel being configured to fluidically connect the plurality of receptacles in series.

110. The system of claim 109, wherein: the first receptacle is fluidically connected to the inlet; the second receptacle is fluidically connected to the first receptacle via the first fluidic channel; the third receptacle is fluidically connected to the second receptacle via the second fluidic channel; and the fourth receptacle is fluidically connected to the third receptacle via the third fluidic channel and the fourth receptacle is fluidically connected to the outlet.

111. The system of claim 109, wherein, upon loading each receptacle of the plurality of the receptacles with a sealed container, the dispenser creates a continuous flow path comprising: a first path portion starting from the inlet through a first lumen of a first piercing element into a first sealed container located in the first receptacle and from the first sealed container to a second lumen of the first piercing element into the first fluidic channel; a second path portion from the first fluidic channel to a first lumen of the second piercing element into a second sealed container located in the second receptacle and from the second sealed container to a second lumen of the second piercing element into the second fluidic channel; a third path portion from the second fluidic channel to a first lumen of a third piercing element into a third sealed container located in the third receptacle and from the third sealed container to a second lumen of the third piercing element into the third fluidic channel; and a fourth path portion from the third fluidic channel to a first lumen of the fourth piercing element into a fourth sealed container located in the fourth receptacle and from the fourth sealed container to a second lumen of the fourth piercing element leading to the outlet.

112. A method of using the dispenser of any one of claims 1-79 or the system of any one of claims 85-112 comprising: disposing a sealed container into at least one of the plurality of receptacles thereby defining a fluid path between the inlet and the outlet; advancing a fluid along the flow path to transport particles within the sealed container out of the outlet; and contacting a cell, or portion thereof, with the transported particles.

113. The method of claim 112, further comprising processing the cell, or portion thereof, wherein the cell, or portion thereof comprises one or more particles bound thereto.

114. The method of claim 113, wherein processing comprises activating, isolating, separating, imaging, labeling, and/or culturing the cell, or portion thereof.