WO2024103070A1

WO2024103070A1 - Systems and devices for suspension therapy preparation and/or infusion and methods for use

Info

Publication number: WO2024103070A1
Application number: PCT/US2023/079546
Authority: WO
Inventors: Nikhil S. JOSHI; Marcus Andrew FOLEY; Avnesh Sinh THAKOR; Malik MARLIN
Original assignee: Cellular Vehicles Inc.
Priority date: 2022-11-11
Filing date: 2023-11-13
Publication date: 2024-05-16

Abstract

Systems, devices, and methods disclosed herein may be configured to receive a volume of a first therapeutic suspension comprising a volume of a first media and a plurality of therapeutic agents, separate the plurality of therapeutic agents from the volume of the first media, thereby generating a plurality of separated therapeutic agents, add a volume of a second media to a plurality of separated therapeutic agents, thereby generating a volume of a second therapeutic suspension, and facilitate infusion of the volume of the second therapeutic suspension into a patient.

Description

SYSTEMS AND DEVICES FOR SUSPENSION THERAPY PREPARATION AND/OR INFUSION AND METHODS FOR USE

RELATED APPLICATIONS

[0001 ] This application is an INTERNATIONAL APPLICATION (PCT) claiming priority to U.S. Provisional Patent Application Number 63/424,862 filed on 11 November 2022 and entitled “SYSTEMS AND DEVICES FOR SUSPENSION THERAPY PREPARATION AND INFUSION AND METHODS FOR USE” and U.S. Provisional Patent Application Number 63/463,818 filed on 03 May 2023 and entitled “SYSTEMS AND DEVICES FOR SUSPENSION THERAPY PREPARATION AND INFUSION AND METHODS FOR USE,” and U.S. Provisional Patent Application Number 63/598,046 filed on 10 November 2023 and entitled “SYSTEMS AND DEVICES FOR PREPARATION AND/OR INFUSION OF SUSPENSION THERAPIES, all of which are incorporated by reference, in their respective entireties, herein.

FIELD OF INVENTION

[0002] This invention is directed to medical devices, medical robotic devices, and methods for their use and, in particular is directed to suspension therapy preparation and/or infusion, suspension therapy preparation and/or infusion systems, and methods for using same.

BACKGROUND

[0003] Recent innovations in the treatment of blood-based diseases including cancers such as leukemia and lymphoma utilizing engineered T-cells (CAR T-Cell Therapy) have led to tremendous excitement in the potential of cell-based therapies across a multitude of indications. The challenge with cell-based therapies is that cells are exponentially more difficult to manufacture and deliver when compared to more common molecular therapeutics. Cells are the basic units of life, and because these are living drugs, they’re extremely sensitive to external factors such as mechanical stress, material interactions, temperature changes, and many more. Due to these sensitivities, the manufacturing and delivery process for cell-based therapies must account for and eliminate any potential detrimental factors. Largely, this process is completed via laborious manual process steps, which are often performed by highly skilled technicians and scientists. These process steps are manual, error-prone, lacking in control and standardization, and unsustainable for the cell therapy space to scale. Similarly, in other suspension-based therapies, such as gene therapies with viruses as the modality, or nuclear medicines/radiopharmaceuticals, where radioactive beads are used in radioembolization procedures, challenges of maintaining even suspensions with well-mixed components are important for ensuring therapeutic success. There is an opportunity for innovative automation technologies to solve some of the pain points of suspension-based therapy manufacturing and delivery.

SUMMARY

[0004] System, devices, and methods disclosed herein may be configured to receive a volume of a first therapeutic suspension comprising a volume of a first media and a plurality of therapeutic agents. Exemplary therapeutic agents include one or more of biological agents, cells, DNA, stem cells, radioactive particles, particles of insoluble medication, viruses, and genetic therapy vectors.

[0005] The system may be further configured to separate the plurality of therapeutic agents from the volume of the first media, thereby generating a plurality of separated therapeutic agents, add a volume of a second media to a plurality of separated therapeutic agents, thereby generating a volume of a second therapeutic suspension and facilitate infusion of the volume of the second therapeutic suspension into a patient. The first media may be a cryopreservation media and/or a hydrogel-based media and the second media may be saline, a hydrogel-based media, and/or blood. [0006] In some embodiments, the system may further include a temperature regulation device (e.g., thermal plate or water bath) configured to warm, cool, or maintain a temperature of the volume of therapeutic suspension, warming, by the system, the volume of a first therapeutic suspension prior to the separating.

[0007] In many embodiments, the system may be configured to filter and/or wash the plurality of separated therapeutic agents prior to adding the volume of a second media to a plurality of separated therapeutic agents. The filter may be configured to separate the plurality of therapeutic agents from the volume of the first media and/or second media. The separation may be performed by pumping the volume of the first therapeutic suspension through the filter. The filter may include one or more layers of filtration material and each layer of filtration material may comprise at least one of a metallic sieve layer, a wire mesh layer, a metal sheet with a plurality of small holes positioned therein, a series of linearly oriented posts, and a gelatinous membrane. At times, the filter may include a first layer of filtration material with a first plurality of holes and a second layer of filtration material that includes a second plurality of holes, wherein the second layer of filtration material is arranged in the filter so that the second plurality of holes partially obscures the first plurality of holes. Additionally, or alternatively, the filter may be a microfluidic device that may include an inertial element configured to separate therapeutic agents from waste components of the volume of therapeutic suspension.

[0008] In some embodiments, the plurality of separated therapeutic agents may be a first plurality of separated therapeutic agents and the system further being configured to separate a second plurality of therapeutic agents from the volume of the second media prior to the facilitating, thereby generating a third plurality of separated therapeutic agents and add a volume of a third media to the second plurality of separated therapeutic agents, thereby generating a volume of a third therapeutic suspension, wherein the facilitating step includes facilitating the volume of a third therapeutic suspension into the patient instead of the volume of a second therapeutic suspension.

[0009] In some embodiments, the system may further comprise an activation module configured to hold the volume of the second therapeutic suspension in a container for a duration of time. The duration of time may be responsive to, for example, a characteristic of the volume of therapeutic suspension, a characteristic of the therapeutic agents suspended in the volume of therapeutic suspension, and/or a time period that is sufficient to activate and/or cultivate the therapeutic agents suspended in the volume of therapeutic suspension.

[00010] In some embodiments, the system may further include a source of compressed air or gas configured to move the volume of the first therapeutic suspension, media, wash fluid, waste, and/or the volume of the first therapeutic suspension throughout the system and/or components thereof. Additionally, or alternatively, the system may further include radiation shielding, a backpressure valve, a flow rate modification device, and/or a pneumatic valve.

[00011] Additionally, or alternatively, in some embodiments, the systems, devices, and/or methods disclosed herein may include and/or use an output from a quality control measurement device configured to sample a volume of therapeutic suspension (e.g., the second therapeutic suspension and/or patient-ready therapeutic suspension) and determine a characteristic thereof. Exemplary characteristics include, but are not limited to, a count of a quantity of therapeutic agents included in the volume of therapeutic suspension, viability of therapeutic agents included in the volume of therapeutic suspension, functionality of the therapeutic agents included in the volume of therapeutic suspension, and/or a concentration of therapeutic agents included in the volume of therapeutic suspension. At times, an output and/or determination of the quality control measurement device may be used to determine a dosage of the therapeutic agents to be provided to a patient and/or a volume of the therapeutic suspension to infuse into a patient.

[00012] Additionally, or alternatively, in some embodiments, the system, devices, and/or methods disclosed herein may be configured to deliver payloads intra-cellularly to the plurality of therapeutic agents and/or the plurality of separated therapeutic agents, via, for example, pressurization within the system and/or a component thereof.

[00013] Additionally, or alternatively, in some embodiments, the system, devices, and/or methods disclosed herein may be configured to agitate and/or rotate a container holding the first volume of the therapeutic suspension and/or the second volume of therapeutic suspension. Agitation of the container of the first and/or second volumes of therapeutic suspension may generate a density gradient within the therapeutic suspension. The agitation may be generated using, for example, a motor coupled to an agitation device (e.g., a band or gear) in communication with the container.

[00014] Additionally, or alternatively, in some embodiments, the system, devices, and/or methods disclosed herein may be configured to mix one or more hydrogel precursors and/or solutions in which therapeutic agents may be suspended (e.g., the second media) prior to adding the plurality of separated therapeutic agents to the second media. Once the mix one or more hydrogel precursors and/or solutions are properly mixed to generate the second media, the separated therapeutic agents may be added to the second media.

[00015] At times, the systems, methods, and/or devices disclosed herein may include and/or use a microfluidic device that includes a quality control chamber that may be configured to cooperate with a quality control measurement device to, for example, count a quantity of therapeutic agents included in the second therapeutic suspension, determine a viability of therapeutic agents included in the second therapeutic suspension, determine a functionality of the therapeutic agents included in the second therapeutic suspension, and/or determine a concentration of therapeutic agents included in the second therapeutic suspension. At times, an output (e.g., viability determination, count, etc.) of the quality control measurement device may be used to, for example, determine a dosage of the therapeutic agents to be provided to a patient and a volume of the second therapeutic suspension to infuse into a patient. The second therapeutic suspension may correspond to a patient-ready therapeutic suspension.

[00016] Additionally, or alternatively, the microfluidic device may be configured to be in liquid communication with a flush chamber and/or a volume of flush media that may be introduced into the microfluidic device to, for example, flush, or rinse, therapeutic agents from a channel of the microfluidic device.

BRIEF DESCRIPTION OF DRAWINGS

[00017] The present invention is illustrated by way of example, and not limitation, in the figures of the accompanying drawings in which:

[00018] FIG. 1A provides a side view of an exemplary therapeutic suspension infusion device, in accordance with some embodiments of the present invention.

[00019] Fl G. 1 B provides a diagram of a pneumatic system that includes a therapeutic suspension infusion device similar to the therapeutic suspension infusion device of FIG. 1 A and a source of compressed gas, in accordance with some embodiments of the present invention.

[00020] FIG. 2A is a perspective view of another exemplary therapeutic suspension infusion device with a pressure relief system, in accordance with some embodiments of the present invention.

[00021] FIG. 2B is a close-up cross-section view of a portion of the exemplary therapeutic sOuspension infusion device of FIG. 2A with a pressure relief system a first state, in accordance with some embodiments of the present invention.

[00022] FIG. 2C is a vertical cross-section view of the exemplary therapeutic suspension infusion device with a pressure relief system of FIG. 2A in a first state, in accordance with some embodiments of the present invention. [00023] FIG. 2D is a cross-section view of the exemplary therapeutic suspension infusion device of FIG. 2A with the pressure relief system in a second state, in accordance with some embodiments of the present invention.

[00024] FIG. 2E provides a diagram of a pneumatic system that includes a therapeutic suspension infusion device similar to the therapeutic suspension infusion device of FIG. 2A, in accordance with some embodiments of the present invention.

[00025] FIG. 3 is a block diagram of a system of components that may be included in a suspension therapy preparation and infusion system, in accordance with some embodiments of the present invention.

[00026] FIG. 4A provides a schematic diagram of a first exemplary therapeutic suspension preparation and infusion system, in accordance with some embodiments of the present invention.

[00027] FIG. 4B provides a schematic diagram of a second exemplary therapeutic suspension preparation and infusion system, in accordance with some embodiments of the present invention.

[00028] FIG. 4C provides a schematic diagram of a third exemplary therapeutic suspension preparation and infusion system, in accordance with some embodiments of the present invention.

[00029] FIGs. 5A1 provides a top view of an exemplary system configured as bioreactor and/or a cell culture rescue bioreactor, in accordance with some embodiments of the present invention.

[00030] FIG. 5A2 provides a cut-away side view of the system of FIG. 5A1 , in accordance with some embodiments of the present invention.

[00031] Fl G. 5B is a block diagram of an exemplary container mount lid, in accordance with some embodiments of the present invention.

[00032] FIG. 5C is a block diagram of a container mount housing a cylindrical container with a lid that contains, or holds, a volume of therapeutic suspension.

[00033] FIG. 5D provides a side cutaway schematic diagram of a system that includes a puncturing device configured to puncture a cap positioned on top of a container such as a cryovial, in accordance with some embodiments of the present invention.

[00034] FIG. 5E provides a side cutaway schematic diagram of a system that includes a flask, in accordance with some embodiments of the present invention. [00035] FIG. 5F1 provides a diagram of a container with a cap positioned thereon, in accordance with some embodiments of the present invention.

[00036] Fl G. 5F2 provides a diagram of the container of FIG. 5F1 with cap removed therefrom, in accordance with some embodiments of the present invention. [00037] Fl G. 5F3 provides a diagram of the de-capped container of FIG. 5F2 with a conduit inserted therein, in accordance with some embodiments of the present invention.

[00038] Fl G. 6A is a schematic diagram of a layer of a first type of filtration material that comprises a wire mesh, in accordance with some embodiments of the present invention.

[00039] Fl G. 6B is a schematic diagram of a layer of a second type of filtration material that comprises a metal sheet with a plurality of small holes positioned therein, in accordance with some embodiments of the present invention.

[00040] FIG. 6C is a schematic diagram of a layer of a third type of filtration material that comprises a series of linearly oriented metal wires, strings, or posts, in accordance with some embodiments of the present invention.

[00041] FIG. 6D is a schematic diagram of a layer of a fourth type of filtration material that comprises a metal sheet with a plurality of holes positioned therein, in accordance with some embodiments of the present invention.

[00042] FIG. 6E is a schematic diagram of a layer of a fifth type of filtration material 600E that comprises a gelatinous membrane, in accordance with some embodiments of the present invention.

[00043] FIG. 6F provides a vertical cross section view of a first multi-layer filter, in accordance with some embodiments of the present invention.

[00044] FIG. 6G provides a vertical cross section view of a second multi-layer filter, in accordance with some embodiments of the present invention.

[00045] FIG. 7A provides a vertical cross section view of a first multicomponent filter, in accordance with some embodiments of the present invention. [00046] FIG. 7B provides a vertical cross section view of a second multicomponent filter, in accordance with some embodiments of the present invention. [00047] FIG. 7C is a block diagram of a top view of an exemplary microfluidic device, in accordance with some embodiments of the present invention. [00048] FIG. 7D is a diagram of a top view of an exemplary cover for the microfluidic device of FIG. 7C, in accordance with some embodiments of the present invention.

[00049] FIG. 7E is a diagram of a side view of an assembly of the cover of FIG. 7D and the microfluidic device of FIG. 7C, in accordance with some embodiments of the present invention.

[00050] FIG. 8A is a diagram of a top view of an exemplary base unit, in accordance with some embodiments of the present invention.

[00051] FIG. 8B is a diagram of a front view of the base unit of FIG. 8A, in accordance with some embodiments of the present invention.

[00052] Fl G. 8C is a diagram of a perspective view of the base unit of FIG. 8A, in accordance with some embodiments of the present invention.

[00053] FIG. 8D is a diagram of a perspective view of the system of FIG. 8A, a thaw block, and an automation system in a first state, in accordance with some embodiments of the present invention.

[00054] FIG. 8E is a diagram of a side view of the system of FIG. 8D, in accordance with some embodiments of the present invention.

[00055] FIG. 8F is a diagram of a top view of the system of FIG. 8D, in accordance with some embodiments of the present invention.

[00056] FIG. 8G is a diagram of a perspective view of the system of FIG. 8D with the automation system in a second state, in accordance with some embodiments of the present invention.

[00057] FIG. 8H is a diagram of an exemplary system that includes the base unit of FIG. 8A and a plurality of additional devices, in accordance with some embodiments of the present invention.

[00058] FIG. 9 is a flowchart of a process for preparing a volume of patientready therapeutic suspension and administering the patient-ready therapeutic suspension to the patient, in accordance with some embodiments of the present invention.

[00059] FIG. 10 is a flowchart of a process for preparing a volume of therapeutic suspension including a plurality of therapeutic agents for administration to a patient as part of the process of FIG. 9, in accordance with some embodiments of the present invention. [00060] FIG. 11 is a flowchart illustrating an exemplary process for preparing a volume of therapeutic suspension and facilitating infusion of the prepared volume of therapeutic suspension into the patient, in accordance with some embodiments of the present invention.

[00061] Fl G. 12 is a flowchart illustrating an exemplary process for preparing a volume of therapeutic suspension and facilitating infusion of the prepared volume of therapeutic suspension into the patient, in accordance with some embodiments of the present invention.

[00062] FIG. 13 is a block diagram of an exemplary system including a plurality of therapeutic suspension preparation and infusion systems, in accordance with some embodiments of the present invention.

[00063] Throughout the drawings, the same reference numerals, and characters, unless otherwise stated, are used to denote like features, elements, components, or portions of the illustrated embodiments. Moreover, while the subject invention will now be described in detail with reference to the drawings, the description is done in connection with the illustrative embodiments. It is intended that changes and modifications can be made to the described embodiments without departing from the true scope and spirit of the subject invention as defined by the appended claims.

WRITTEN DESCRIPTION

[00064] As disclosed herein, a therapeutic suspension may include a therapeutic agent (e.g., biological therapeutic agents, cells, genetic therapy vectors, viruses, and/or particles (e.g., insoluble medication and/or radioactive particles)) and media used to suspend the therapeutic agent within the therapeutic suspension. Therapeutic suspensions are often manufactured and/or stored using media (sometimes referred to herein as “original media”) such as cryopreservation media (e.g., dimethyl sulfoxide (DMSO)) and/or media that enables transport of the therapeutic suspension (sometimes referred to herein as “transport media”) that is not therapeutic and, in some cases, may be harmful to a patient. An exemplary material that may be used to suspend therapeutic agents before, during, and after processing (e.g., washing, cultivating, etc.) as described herein, the therapeutic agents may be suspended in a hydrogel-based media, which may be used to create a more viscous suspension that can , for example, act as a protective buffer to the suspended therapeutic agents and/or prevent suspended therapeutic agents from falling out of suspension. Often times, manufactured and/or stored therapeutic suspensions (sometimes referred to herein as a “original therapeutic suspension”) must undergo a multi-step preparation process prior to infusion into a patient to convert a volume of the original therapeutic suspension into a volume of therapeutic suspension that is ready for infusion into a patient (sometimes referred to herein as a “final therapeutic suspension” or (patient-ready therapeutic suspension”). In addition, when a suspension therapy referred to herein is being delivered to and/or infused into a patient, it is, in most cases, patient-ready and/or finalized. This multi- step preparation process may include thawing the therapeutic suspension, filtering and/or washing the therapeutic agents (e.g., separation of therapeutic cells and/or therapeutic particles from their original media), jesuspending the therapeutic agents in new media (e.g., blood, reagents, and/or saline), agitating a suspension of the new media and therapeutic agents to keep them in suspension, sorting the therapeutic agents present in a volume of the original therapeutic suspension, cultivation of cellular therapeutic agents, and/or adding reagents to the new media and/or filtered and/or washed therapeutic agents. Many steps of this process are currently done manually and are therefore laborious and prone to errors. For example, common errors that occur during while preparing therapeutic suspensions for infusion into a patient include overly vigorous agitation of cells, breaking of the temperature chain, resuspension of cells that is done too quickly, introduction of air bubbles into the original, processed, and/or final therapeutic suspensions, and much more. These types of errors directly impact cell viability and functionality and can potentially compromise treatment efficacy.

[00065] In addition, infusion or delivery of a patient-ready, or final, therapeutic suspension to a patient is also susceptible to errors such as uneven delivery of a therapeutic agent to the patient and/or a target region (e.g., organ or body part) thereof and failure to deliver a proper dosage of the therapeutic agent to the patient due to, for example, the therapeutic agent falling out of suspension and/or adherence of the therapeutic agent to a container wall prior to infusion. A tool, system, and/or device to standardize and optimize one or more of these steps may ensure that the highest quality cell product and/or therapeutic suspension is being delivered into the patient and/or a target region (e.g., organ, tumor, bone, etc.) of the patient. [00066] The present invention is directed to, among other things, systems, devices, and methods for atraumatically preparing and delivering volumes of therapeutic suspension under controlled conditions that optimize their efficacy and reduce the laboriousness of the preparation and infusion processes. One or more of the therapeutic suspensions disclosed herein may be delivered to a patient via, for example, direct routes of access (ROA) to target tissue without damaging, altering, or killing therapeutic agents of the therapeutic suspension during the delivery process.

[00067] The present invention achieves these objectives by, for example, maintaining optimized conditions for the therapeutic agents and therapeutic suspension both prior to and during the delivery process. In some cases, when the therapeutic agents are cells and/or living agents (e.g., viruses and/or DNA), conditions for therapeutic agents included in a patient-ready therapeutic suspension may be optimized by minimizing stressors exerted on the therapeutic agents during the administration process by, for example, reducing, or eliminating, shear stress, compressive force, pressure, and/or material interactions (e.g., clumping and/or sticking of the therapeutic agents to an internal surface of a delivery system and/or device) between delivery systems and/or devices and the therapeutic agents during administration to a patient. This minimization of stressors exerted on the therapeutic agents may reduce a likelihood of an alteration in their behavior, viability, and/or concentration, so that, for example, a prescribed dosage and/or type of suspension therapy is properly and/or optimally delivered to the patient tissue.

[00068] In some embodiments, the systems and devices disclosed herein may be configured to infuse volumes of patient-ready therapeutic suspension into a patient’s body (e.g., tissue or blood) over time and, in these embodiments, the systems and devices disclosed herein may have a relatively small (e.g., less than a cubic foot) and light weight (e.g., 3-20kg) form factor to, for example, enable portability and/or use by a patient’s bedside.

[00069] In some embodiments, the therapeutic suspension infusion devices disclosed herein may be associated with (e.g., as a sticker or imprint) an identifier such as an optical, alpha-numeric, and/or binary code that may be matched to, for example, a type of therapeutic suspension being held by the therapeutic suspension infusion device, an instruction for the preparation and/or delivery of the therapeutic suspension being held by the therapeutic suspension infusion device, a patient characteristic, an indication for use of the therapeutic suspension and a system that uses the disposable therapeutic suspension infusion devices (e.g., the systems disclosed herein). The identifier may be configured to be recognizable to, for example, optical and/or RFID scanners.

[00070] Exemplary suspension therapies that do not include biological therapeutic agents include, but are not limited to, suspensions of insoluble pharmacological agents, flocculated suspensions, deflocculated suspensions, and/or suspensions that include a radioactive therapeutic agent and/or radioactive bead therapy, such as suspensions that include radioactive Y90 beads. When a radioactive agent is being processed and/or administered to a patient using one or more of the systems and/or devices disclosed herein, the systems and/or devices may be configured to include and/or cooperate with one or more radiation isolation and/or mitigation mechanisms (e.g., lead shielding) that may prevent unintended exposure of people (e.g., clinicians, hospital staff, etc.) and/or equipment to the radioactive agents. Additionally, or alternatively, the systems and devices disclosed herein may be configured for remote operation so that, for example, a patient receiving the radioactive therapy may be isolated from all other individuals including those administering, controlling, and/or supervising, infusion of the radioactive therapeutic agent and/or beads to the patient and/or target tissue.

[00071] Turning now to the figures, FIG. 1A provides a side view of a first exemplary therapeutic suspension infusion device 100 embodied as a syringe that may be configured, designed, and manufactured to deliver a volume of a therapeutic suspension to a patient in an optimized manner that preserves, for example, initial, and/or prescribed, parameters (e.g., therapeutic agent count, viability, behavior, and/or byproduct production) for the therapeutic suspension and/or therapeutic agents suspended therein. A size, shape, and/or configuration of therapeutic suspension infusion device 100 may be adapted and/or configured to accommodate varying volumes and/or types of therapeutic suspension and/or different delivery modalities for delivery, or infusion, of the therapeutic suspension to a patient. An internal surface of one or more components of therapeutic suspension infusion device 100 may be configured to prevent adhesion of a therapeutic agent thereto. This may be accomplished by use of a friction-resistant material in manufacturing one or more components therapeutic suspension infusion device 100 and/or coating a surface of therapeutic suspension infusion device 100 with a friction-reducing, hydrophobic, non-stick (e.g., polytetrafluoroethylene), lubricious and/or protein-based material configured to reduce interactions between therapeutic suspension infusion device 100 and the therapeutic suspension and/or therapeutic agents suspended in a therapeutic suspension.

[00072] Therapeutic suspension infusion device includes a barrel 110, a plunger 115, and a plunger end 120 and a coupling 140 that may be configured to couple to, for example, a tube and/or catheter (not shown). In some embodiments, infusion device 101 may also include an optional syringe shaft 145 and/or an optional catheter coupling 150. Barrel 110 may be sized and configured to hold a volume of therapeutic suspension and accommodate actuation of plunger 115 into (i.e., depression) and out of (i.e., extraction) barrel 110 to respectively push a volume of therapeutic suspension out of barrel 110 and pull a volume (e.g., , 0.1 mL-50 ml_) of therapeutic suspension out of barrel 110 via translation of plunger 115 down (as oriented in the figure) and up (as oriented in the figure). Exemplary dimensions for barrel 110 are an outer diameter of 10-45mm an inner diameter of 8-43mm, and a length of 60-200mm. Exemplary dimensions for plunger 115 are an outer diameter of 8-43mm and a length of 70-300mm. In many embodiments, a sealing device, such as a gasket, may be present between plunger 115 and barrel 110. The sealing device may be configured to form an air- and/or water-tight seal between plunger 120 and an interior surface of barrel 110.

[00073] FIG. 1 B is a diagram of a pneumatic system 102 that includes therapeutic suspension infusion device 100 (without plunger 120 inserted therein) with a pneumatic coupling 130 positioned over an open end of barrel 110.

Pneumatic coupling 130 may be any cap or stopper configured to create an air-tight seal with barrel 110 and enable communication with a tube 132 that is coupled to a source of compressed gas 135 and pneumatic coupling 130. Source of compressed gas 135 may be any source of compressed gas or air including, but not limited to, a canister or gas compressor that is configured to push gas into barrel 110, which may cause a corresponding volume of therapeutic suspension held within barrel 110 to be pushed therefrom via displacement caused by the introduction of compressed gas into barrel 110. A flow rate and/or degree of compression for gas exiting source of compressed gas 135 may be controlled and/or regulated by, for example, a user interface of source of compressed gas 135 and/or a processor and/or controller such as processor/controller 340 discussed herein according to, for example, one or more sets of instructions.

[00074] Fl Gs. 2A-2D are drawings that provide various views of an exemplary therapeutic suspension infusion device 201 with an inline pressure relief system 250. In particular, FIG. 2A provides a perspective view of therapeutic suspension infusion device 201 ; FIG. 2B provides a close-up cross-section view of a portion therapeutic suspension infusion device 201 with a inline pressure relief system 250 in a first state; FIG. 2C provides a cross-section view of therapeutic suspension infusion device 201 with inline pressure relief system 250 in the first state; and FIG. 2D provides a cross-section view of therapeutic suspension infusion device 201 with inline pressure relief system 250 in a second state.

[00075] Therapeutic suspension infusion device 201 includes a barrel 210 configured to hold a volume of therapeutic suspension, a plunger 215 configured to fit within barrel 210 and a plunger end 220. In some embodiments, plunger 215 may be similar to plunger 115, barrel may be similar to barrel 110, and plunger end 220 may be similar to plunger end 120. Therapeutic suspension infusion device 201 also includes inline pressure relief system 250.

[00076] As shown in the close-up cross-section view of FIG. 2B, inline pressure relief system 250 includes a first channel 230A, a second channel 230B, a third channel 230C, a fourth channel 230D, and a first extension 255 configured to fit within barrel/pressure system coupling 240 and be secured thereto. In some embodiments, barrel 210 may be configured to rotate on a central axis independent of inline pressure relief system 250 via barrel/pressure system coupling 240 so that, for example, barrel 210 rotates around the central axis to, for example, agitate a therapeutic suspension held therein to, keep therapeutic agents suspended in the therapeutic suspension by, for example, preventing adhesion of therapeutic agents to a sidewall of barrel 210 and/or the settling of therapeutic agents that may fall out of suspension in the absence of rotation of barrel 210. Barrel/pressure system coupling 240 may include a lumen 285 that may be configured to be in liquid and/or gaseous communication with first channel 230A of inline pressure relief system 250 as shown. As a volume of therapeutic suspension is pushed from barrel 210 via depression of plunger 215, the volume of therapeutic suspension may travel through lumen 285 to first channel 230A to second channel 230B and then to third channel 230C and finally to fourth channel 230D so that the volume of therapeutic suspension may exit inline pressure relief system 250 via fourth channel 230D of a pressure relief system coupling 260, which may be configured to couple with a patient delivery device, such as a catheter, to enable infusion into a patient. Excess pressure that may be exerted on the therapeutic suspension as it flows through first, second, and/or third channels 230A, 230B, and 230C may be communicated to a circumferential channel 275 and absorbed via expansion of a diaphragm 270 as shown in, for example, FIG. 2D. This expansion of diaphragm 270 when fluid flows into barrel 210 may increase a total volume through which the therapeutic suspension may travel, which may serve to reduce fluid pressure exerted on the therapeutic suspension via, for example, Boyle’s Law. This reduction of fluid pressure may, in turn, reduce shearing stresses exerted on the therapeutic suspension, throughout the entire volume.

[00077] As may be seen in FIGs. 2B and 2C, plunger 210 is configured to have a tight (e.g., liquid tight and/or airtight) fit with an interior surface of barrel 210 and terminates with a plunger tip 280 that is shaped to fit within an angled end of barrel 210 so that therapeutic suspension may be pushed through nearly an entirety of barrel 210.

[00078] Fl G. 2E provides a diagram of a pneumatic system that includes a therapeutic suspension infusion device without plunger 215 positioned within barrel 210 with pneumatic coupling 130 positioned over an open end of barrel 210. Tube 132 is connected to pneumatic coupling 130 and source of compressed gas 135 Source of compressed gas 135 may be configured to push gas into barrel 210, which may cause a corresponding volume of therapeutic suspension held within barrel 210 to be pushed therefrom via displacement caused by the introduction of compressed gas into barrel 210. A flow rate and/or degree of compression for gas exiting source of compressed gas 135 may be controlled and/or regulated by, for example, a user interface of source of compressed gas 135 and/or a processor and/or controller such as processor/controller 340 discussed herein according to, for example, one or more sets of instructions.

[00079] FIG. 3 is a block diagram of components that may be included in a therapeutic suspension preparation and/or infusion system 300. System 300 includes a temperature regulation device 310, an optional fan 312, a power supply 315, a first motor 320, a user interface device 325, a transceiver 330, one or more ports 335, a processor/controller 340, a memory 342, a second motor 345, a thermometer 350, one or more valves 355, and a source of compressed gas 135; all of which may be enclosed in a housing 305. Additionally, or alternatively, one or more components of system 300 may be resident within a separate device (i.e., not resident within housing 305) that is in communication (e.g., electrical, liquid, and/or gaseous communication) with housing 305 and/or another component of system 300. Housing 305 may be configured to house the components of system 300 and may be made from any suitable material (e.g., metal, plastic, etc.). In some embodiments, housing 305 may be configured to attach to one or more components or external devices including, for example, an IV pole, a bed frame, a tray table, furniture, and/or scaffolding. This may enable, for example, convenient and/or safe deployment of system 300 while in use and/or may allow system to be portable and/or used while at a patient’s bedside and/or chair.

[00080] Temperature regulation device 310 may be configured to bring a volume of therapeutic suspension to a desired temperature and/or keep the volume of therapeutic suspension at the desired temperature for a period of time. For example, temperature regulation device 310 may be configured to warm a frozen volume of therapeutic suspension to a desired temperature and/or maintain a desired temperature for a volume of suspension therapies during processing and/or infusion into a patient. Exemplary temperature regulation devices 310 include, but are not limited to, resistance coils, water baths, refrigeration components, and/or warming plates. Often times, temperature regulation device 310 may be configured and/or programmed to bring a volume of therapeutic suspension to one or more preferred temperatures over time according to, for example, 325 where in the preparation process a volume of therapeutic suspension may be and/or one or more instructions that may be received from, for example, processor/controller 340 and/or user interface device. For example, if a volume of therapeutic suspension is going to be filtered through a gelatinous filtration material, then, a temperature of the volume of therapeutic suspension may be held below a dissolving point for the gelatinous filtration material (e.g., 1-5 degrees Celsius) using temperature regulation device 310 until the filtration process using the gelatinous filtration material is complete. In another example, a volume of therapeutic suspension may be warmed to and/or maintained at a temperature of approximately 37 degrees Celsius prior to and/or during infusion into a patient. In some embodiments, temperature regulation device 310 may include and/or be communicatively coupled to thermometer 350, which may be configured to measure a temperature of, for example, a volume of therapeutic suspension, temperature regulation device 310, and/or system 300. Thermometer 350 and may be further configured to provide the temperature to, for example, user interface device 325, transceiver 330, a port 335, and/or processor/controller 340. Fan 312 may be configured to circulate air and/or heat provided by temperature regulation device 310 within housing 305, system 300, and/or components thereof to achieve and/or maintain a desired temperature within system 300. In some cases, temperature regulation device may be, and/or may be coupled to, an infusion device mount like infusion device mount 410 as will be discussed below with regard to FIGs. 4A, 4B, and 4C.

[00081] Power supply 315 may be configured to provide electrical power to one or more components of system 300 and may be, for example, a battery and/or a plug or circuitry configured to couple to an electrical main. First motor 320 and/or second motor 345 may be, for example, a stepper motor. First motor 320 and second motor 345 may be configured to rotate and/or move one or more components of system 300 as will be discussed in greater detail below with regard to FIGs. 4D-4F.

[00082] User interface device 325 may be any device, or combination of devices, that are configured to enable a user to monitor an operation of a component of system 300 and/or provide input and/or instructions (e.g., on/off) to a component of system 300. Exemplary user interface device(s) 325 include, but are not limited to, dials, optical scanners, RFID scanners, buttons, keyboards, display devices, speakers, microphones, and touch screens.

[00083] Transceiver 330 may be configured to transmit and/or receive communication via, for example, wireless or wired (via e.g., a port 335) communication. Exemplary received communications include, but are not limited to, instructions for operation, processes to be executed such as the processes described herein, and/or other parameters for operation (e.g., start/stop times, run time duration, type of therapeutic agents being used, infusion rates, preferred temperature of therapeutic suspensions, preferred temperature within a suspension therapy preparation and infusion system, and/or agitation rates). Exemplary transmitted communications include but are not limited to, parameters of operation (e.g., run time duration, temperature of therapeutic cells over time, and/or error conditions). Ports 335 may be configured as, for example, power, user interface, and/or communication ports and may be coupled to, for example, transceiver 330, controller/processor 340 and/or memory 342. In some embodiments, one or more ports 335 may be configured to cooperate to enable liquid and/or gaseous communication with one or components of a system disclosed herein.

[00084] Thermometer 350 may be configured to measure a temperature within a suspension therapy preparation and infusion system so that it achieves and/or maintains a desired temperature (e.g., 37 degrees Celsius). At times, thermometer 350 may be coupled to processor/controller and/or temperature regulation device 310 and activation of temperature regulation device 310 may be responsive to a temperature measurement from thermometer 350 that is received by processor/controller 340 (which provides an activation instruction to temperature regulation device 310) and/or temperature regulation device 310 directly via, for example, a thermocouple or switch.

[00085] The one or more valves 355 may be configured to open and close according to, for example, instructions received from processor/controller 340 and/or may be manually operated to facilitate movement of therapeutic suspension and other liquids and/or gasses throughout system 300. Exemplary valves include, but are not limited to, bi-directional valves, single direction valves, pinch valves and/or automated manifolds that are configured to open, close, and/or control a flow rate of therapeutic suspension or other liquids therethrough. Additionally, or alternatively, in some embodiments, a valve 355 may be pneumatic valve configured to cooperate with a source of compressed air and/or an air pump (e.g., compressed air source 472) and/or release air or gasses from the system.

[00086] Processor/controller 340 may be programmed and/or configured to control an operation of one or more components of system 300 according to, for example, one or more methods disclosed herein. For example, processor/controller 340 may be configured to set and/or control a rate of rotation of first motor 320, a rate of rotation of second motor 345, a temperature achieved and/or maintained by temperature regulation device 310, and/or communications sent out and/or received by transceiver 330. Instructions for operating the processor/controller and/or executing one or more methods disclosed herein may be stored in memory 342 and/or received from user interface 323 and/or transceiver 330. Additionally, or alternatively, processor/controller 340 may be configured to receive instructions pertaining to an operation of system 300 via, for example, user interface device 325, a port 335, and/or transceiver 330. Additionally, or alternatively, processor/controller 340 may be configured to provide information to a user regarding an operation of system 300 via, for example, user interface device 325, a port 335, and/or transceiver 330. Processor/controller 340 may further be configured to precisely control various parameters for infusing the therapeutic suspension into a patient such as the thaw rate, temperature, agitation rate, type of agitation (e.g., spinning, rotating, shaking, oscillating, rocking and/or random motion), and/or infusion rate (e.g., a rate of motion for a worm gear and/or a headplate) of the therapeutic suspension through therapeutic suspension infusion device 100 and into a patient. At times, these parameters may be default settings. In some cases, one or more of these parameters may be specific to, for example, a type of suspension therapy, a type of media in which the suspension therapy is suspended, a type of filtration used to prepare the volume of therapeutic suspension, whether the therapeutic agents of the volume of therapeutic suspension have been washed, a characteristic of a target tissue for treatment with the suspension therapy, and/or a characteristic of the patient receiving the suspension therapy. In some embodiments, processor/controller 340 may enable a user to override one or more default settings of system 300 via, for example, user interface device 325 and/or a software program running on an external computing device that may be in communication with transceiver 330, a port 335, and/or user interface device 325.

[00087] In some embodiments, temperature regulation device 310, fan 312, processor/controller 340 and thermometer 350 may cooperate as a thermal equilibrium system so that processor/controller 340 controls the operation of temperature regulation device 310 and fan 312 responsively to a temperature (received from thermometer 350) within a suspension therapy preparation and infusion system or components thereof to achieve and/or maintain a desired temperature within the suspension therapy preparation and infusion system or components thereof.

[00088] At times, processor/controller 340 and transceiver 330 may cooperate to communicate with a software application running on, for example, a computer, tablet computer, and/or smart phone. Transceiver 330 may use a wired and/or wireless (e.g., BLUETOOTH) communication protocol to communicate with the software application.

[00089] Fl Gs. 4A, 4B, and 4C provide diagrams of exemplary therapeutic suspension preparation and infusion systems 401 , 402, and 403, respectively, that are configured to receive an original volume of therapeutic suspension that was generated by, for example, a laboratory prior to administration to a patient, prepare the volume of therapeutic suspension for infusion into a patient, and/or infuse a prepared volume of therapeutic suspension into the patient. The original volume of therapeutic suspension may include original media and one or more types of therapeutic agents and may be held in a therapeutic suspension infusion device such as therapeutic suspension infusion device 101 or 201 , a bag, and/or another container. The original volume of therapeutic suspension is typically frozen when received and a first step in preparing the original volume of therapeutic suspension for infusion into a patient may be warming the original volume of therapeutic suspension to a preferred temperature as defined by, for example, one or more instructions or directions for use of the therapeutic suspension being used. The warmed original volume of therapeutic suspension may then be filtered and/or separated to, for example, remove the original media and/or the therapeutic agents may be washed to, for example, remove undesirable components of the original volume of therapeutic suspension (e.g., debris, dead cells, and/or portions of the original media that may remain attached to the therapeutic agents following filtration and/or separation). Following filtration and/or washing, the therapeutic agents may be re-suspended in new media (e.g., blood, saline, etc.) that is biocompatible and, in some cases, may be configured to, for example, provide nutrients to the therapeutic agents (when the therapeutic agents are biological in nature). Therapeutic suspension preparation and infusion systems 401 , 402, and 403, and/or components thereof may be configured to perform all these steps and/or processes to convert an original volume of therapeutic suspension into a patient-ready volume of therapeutic suspension and may be further configured to infuse the patient-ready volume of therapeutic suspension into the patient in a controlled and prescribed manner. [00090] In particular, FIG. 4A provides a diagram of a first exemplary therapeutic suspension preparation and infusion system 401 that includes a first suspension therapy preparation and infusion system housing 305A that houses one or more components for a suspension therapy preparation and infusion system like suspension therapy preparation and infusion system 300. In particular, first suspension therapy preparation and infusion system housing 305A houses an infusion device mount 410 sized, shaped, and configured to accept, mount, hold, and release a therapeutic suspension infusion device such as therapeutic suspension infusion device 101 or 201 while a volume of therapeutic suspension including a plurality (e.g., thousands, millions, or billions) of therapeutic agents is prepared for administration to a patient and/or during administration of a volume of therapeutic suspension to the patient. In some embodiments, infusion device mount 410 may also be a temperature regulation device and/or may be thermally coupled to temperature regulation device 310 that may be configured to, for example, adjust and/or maintain a temperature of a volume of therapeutic suspension during, for example, preparation for infusion and/or infusion into a patient. In some embodiments, first therapeutic suspension preparation and infusion system 401 and/or infusion device mount 410 may be resident within a housing and/or include a cover or other device configured to, for example, thermally isolate the volume of therapeutic suspension included in therapeutic suspension infusion device 101 or 201 from ambient conditions/air.

[00091] In some embodiments, first exemplary therapeutic suspension preparation and infusion system 401 and/or a component thereof (e.g., infusion device mount 410, plunger 115 and/or 215, and/or source of compressed gas 135) may be configured to agitate a volume of therapeutic suspension contained by therapeutic suspension infusion device 101 or 201 during processing and/or infusion into a patient to, for example, prevent therapeutic agents from falling out of suspension by, for example, settling, clumping, and/or adhering to an interior surface of therapeutic suspension infusion device 101 or 201 . This agitation may be achieved via, for example, rotating, spinning, rocking, shaking, and/or vibrating the volume of therapeutic suspension and/or therapeutic suspension infusion device 101 or 201 so that, for example, the therapeutic agents remain in suspension and/or in a state of free fall within the media of the therapeutic suspension. Additionally, or alternatively, agitation of the volume of therapeutic suspension may be achieved via movement of plunger 115 or 215 within barrel 110 or 210, respectively. This movement of plunger 115 or 215 may be achieved via movement of headplate 420 back and forth along track 415. Additionally, or alternatively, agitation of the volume of therapeutic suspension may be achieved via pushing compressed gas into and/or extracting it out of barrel 110 or 210 using source of compressed air 135. A parameter (e.g., type(s), rate, duration, and/or frequency) of the agitation may be responsive to, for example, a type of therapeutic suspension, a type of therapeutic agent present within a volume of therapeutic suspension, a type of media present within a volume of therapeutic suspension, a patient characteristic, a preparation parameter or step being performed, and/or a duration of time during which the volume of therapeutic suspension is prepared for and/or infused into a patient. [00092] In some embodiments, infusion device mount 410 and/or another component of first exemplary therapeutic suspension preparation and infusion system 401 may be configured to thaw a volume of frozen therapeutic suspension (e.g., an original volume of therapeutic suspension) in a linear and/or non-linear fashion to achieve a desired temperature for the volume of therapeutic suspension according to, for example, one or more parameters, protocols, and/or processes described that may be specific to, for example, a characteristic of the volume of therapeutic suspension (e.g., type of therapeutic agent, type of media in the therapeutic suspension, and/or concentration of therapeutic agents in the therapeutic suspension, etc.), a preparation process for the volume of therapeutic media, a time when infusion of the suspension therapy into a patient is expected to occur, and/or other conditions (e.g., ambient environment, number of lab technicians available to administer suspension therapy to patients, etc.). For example, a volume of frozen therapeutic suspension an initial temperature of -100 to -60 degrees Celsius may be placed in first exemplary therapeutic suspension preparation and infusion system 401 and/or temperature regulation device 310 (which may be embodied as and/or coupled to infusion device mount 410) thereof. The frozen volume of therapeutic suspension may then be heated at a rate of, for example, 10-100 degrees Celsius per minute to a temperature of -3 to -5 degrees Celsius. The warmed volume of therapeutic suspension may be held at this temperature until further processing of the volume of therapeutic suspension is desired and, at this time, the temperature may be increased thereby bringing the temperature above 0 degrees Celsius (e.g., 37 degrees Celsius) so that, for example, the therapeutic suspension may flow through one or more of the tubes 450 and/or components of system 401 as, for example, disclosed herein.

[00093] When the frozen volume of therapeutic suspension is non-linearly warmed, a level of heat applied to the frozen volume of therapeutic suspension may decrease as the temperature of the volume of therapeutic suspension approaches 0 degrees Celsius so that the frozen volume of therapeutic suspension transitions from frozen to liquid in a gradual manner, which may be less stressful on the therapeutic agents (oftentimes, cells) contained within the volume of therapeutic suspension. In some embodiments, features of system 401 proximate to the frozen volume of therapeutic suspension may be designed in such a way as to remove moisture that may accumulate when thawing the frozen volume of therapeutic suspension. These features may be, for example, channels that route condensation to travel away from the volume of therapeutic suspension and/or or disposable absorbent (e.g., fabric) pads placed on an interior surface of system 401, or a component thereof, to capture condensed moisture for eventual disposal.

[00094] First exemplary therapeutic suspension preparation and infusion system 401 may also include a headplate 420 configured to articulate on a track 415 back (e.g., away from infusion device mount 410) and forth (e.g., toward infusion device mount 410) via, for example, motion generated via first motor 320 so that, for example, a plunger like plunger 115 or 215, may be articulated within barrel 110 or 210, respectively, to, for example, push a volume of therapeutic suspension out infusion device 101 or 201 and/or create a vacuum within barrel 110 or 210, which may act to, for example, suck a volume of therapeutic suspension or other material (e.g., fresh media and/or washing fluid) into barrel 110 or 210.

[00095] First exemplary therapeutic suspension preparation and infusion system 401 further includes a plurality of valves 355 configured and positioned to control a flow of, for example, therapeutic suspension, media, washing fluid, and/or gas through a plurality of tubes 450 to different components of first exemplary therapeutic suspension preparation and infusion system 401 via, for example, an instruction provided by processor/controller 340.

[00096] First exemplary therapeutic suspension preparation and infusion system 401 includes a therapeutic agent separation device 430 that is coupled to infusion device 101 or 201 via a first tube 450A. First valve 355A is coupled to therapeutic agent separation device 430 via a second tube 450B. Therapeutic agent separation device 430 may be configured to separate therapeutic agents from the media in which they are suspended (e.g., original media, nutrient-providing media, and/or washing media) and/or contaminants (e.g., dead cells and/or debris).

Exemplary therapeutic agent separation device(s) 430 include one or more of a filter, trap, dead cell trap, debris trap, therapeutic agent separation device such as a centrifuge, microfluidic device, and/or a combination thereof. In some embodiments, therapeutic agent separation device 430 may include one or more layers of sieves and/or filtration material configured to, for example, separate therapeutic agents from therapeutic suspension and/or washing solution. At times, when the therapeutic agents are cells, a plurality of sieves/filtration material layers may be used that are, for example, sized, arranged, and/or configured to atraumatically break up clumps of cells and/or remove dead cells, precipitates, undesired material, and/or media from a volume of therapeutic suspension without damaging the cells. Exemplary components of therapeutic agent separation device 430 (e.g., filters) may be made of, for example, non-woven fibers, woven fibers, electro-spun layers of gelatin, metallic mesh, fiber mesh that, in some cases, may include hole sizes that are precisely tuned to particular dimensions that may be advantageous for atraumatic cell capture and/or release.

[00097] In some embodiments, filtration material used in therapeutic agent separation device 430 may include one or more layers of electro-spun gelatin membrane filtration material. Single layers of the electro-spun gelatin membrane filtration material may be manufactured by electro-spinning gelatin in warm liquid. The liquid and electro-spun gelatin may then coagulate into a layer of filtration material as the liquid cools. Two or more of these layers of filtration material may then be stacked on top of one another and compressed together to generate a multilayer membrane with a 0.2-5micron pore size when at, for example, room temperature. The multi-layer membrane may be placed in a housing and used as, for example, a therapeutic agent separation device 430 as disclosed herein.

[00098] Additionally, or alternatively, therapeutic agent separation device 430 may include one or more filter layers and/or sieves with relatively large openings (e.g., are large enough for single cells to pass through, but small enough to capture and/or break up clumps of cells). These filter layers and/or sieves may be used to, for example, break up and eliminate cell clumps. Additionally, or alternatively, therapeutic agent separation device 430 may include relatively smaller filter layers and/or sieves that may be used to capture single cells and/or particles while allowing the suspension media and any cell fragments or other debris to pass through. These large and small filter layers and/or sieves may be deployed in series and/or independently within a particular therapeutic agent separation device 430.

Exemplary layers of filtration material and filters that include one or more layers of filtration material are provided in FIGs. 6A-6E and 6F, and 6G, respectively and discussed below. [00099] In some embodiments, first exemplary therapeutic suspension preparation and infusion system 401 may further include a mechanical disrupter and/or agitator 432 that is resident in and/or coupled to therapeutic agent separation device 430. Agitator 432 may be configured to, for example, vibrate, rock, shake, and/or spin therapeutic agent separation device 430, which may assist with, for example, moving a volume of therapeutic suspension and/or media through a first and/or a second side of therapeutic agent separation device 430, preventing adhesion of therapeutic agents (e.g., cells) to therapeutic agent separation device 430, breaking up cell clumps, assist with lifting trapped cells off filter layers and/or sieves with smaller openings, and/or lifting cells from a surface of therapeutic agent separation device 430 during, for example, a filtration process. Exemplary agitators 432 may be, for example, a vibratory motor, an ultrasonic device, a shaking device, an impact device, and/or a rotational device.

[000100] In some embodiments, therapeutic agents within a volume of therapeutic suspension (e.g., a volume of original suspension therapy) may be washed with one or more solutions (e.g., saline, blood, or plasma) prior to, or after, filtering the therapeutic agents from the volume of therapeutic suspension. This washing may be achieved by, for example, mixing the volume of therapeutic suspension with a washing solution at an optional washing station 470, which may include a plurality of stations and/or tubes along with one or more reservoirs of fresh, or unused, washing solution and/or media. The washing and/or transferring of the volume of therapeutic suspension transfer between various stations and tubes of washing station 470 may be precisely controlled at set flow rates to minimize damage to cells using, for example, one or more valves 355 and/or source of compressed gas 135. For example, a volume of therapeutic suspension resident within infusion device 101 or 201 may be directed to washing station 470 via tenth tube 450J via, for example, a manifold and/or set of valves 442 that are in liquid communication with infusion device 101 or 201 and tubes 450A, 450 F, 450G, 450J. At times, the washing solution may employ a magnetic separation mechanism, such as magnetic microbeads and/or nanoparticles, suspended, or otherwise mixed into, the washing solution. These magnetic microbeads/nanoparticles may be configured to selectively bind to, for example, debris, cell debris, cellular metabolic byproducts, and dead cells that may be present within the volume of therapeutic suspension. Then, a combination of the volume of therapeutic suspension (or therapeutic agents separated from the volume of therapeutic suspension) and the washing solution including the magnetic microbeads/nanoparticles may be passed through ninth tube 4501 and exposed to a magnetic field source 475, which may be, for example, a coil and/or a set of magnets placed on either side of ninth tube 4501. The magnetic field of magnetic field source 475 may attract the magnetic microbeads/nanoparticles and the debris and/or dead cells attached thereto so that they may be removed from the volume of therapeutic suspension. Then, the resulting product containing the volume of therapeutic suspension may be passed through therapeutic agent separation device 430 via ninth tube 4501. In some embodiments, washing station 470 may include a mechanical agitation device like agitator 432, which may be configured to agitate the volume of therapeutic suspension and/or a combination of the volume of therapeutic suspension and washing solution. This agitation may assist with, for example, mixing of the volume of therapeutic suspension and the washing solution, creation of precipitates of waste material that precipitate from the volume of therapeutic suspension, and/or otherwise washing or diluting the volume of therapeutic suspension and/or therapeutic agents included therein. In some cases, washing station 470 may be configured to wash received a volume of therapeutic suspension and/or therapeutic agents included therein one or more times using the same and/or different washing agents and/or processes (e.g., agitation, rotation, etc.).

[000101] Therapeutic agent separation device 430 may be configured to receive volume of therapeutic suspension (e.g., an original volume of therapeutic suspension) from infusion device 101 or 201 via manifold 442 and first tube 450A and/or washing station 470 and separate out therapeutic agents from their suspension media. Waste from this separation (e.g., suspension media and/or debris) may be communicated by second tube 450B to first valve 355A and then a waste reservoir 445 via third tube 450C for eventual disposal.

[000102] In some embodiments, a barrel of infusion device 101 or 201, may be agitated, or spun, to create centrifugal force that may, for example, separate living, verdant therapeutic agents, in this instance, cells from undesired material (e.g., suspension media and/or debris) by pushing the therapeutic agents outward toward the interior surface of the barrel, which may encourage adherence of the verdant cells to the interior surface of the barrel. In this way, the suspension media and less dense debris (collectively referred to herein as “waste”) may be concentrated toward the center (i.e., away from the interior surface) of the barrel and evacuated from the barrel via, for example, the opening of first valve 355A and/or application of negative pressure to the barrel so that the waste flows to waste reservoir 445 and, in some embodiments, flows through therapeutic agent separation device 430, which may act to capture any therapeutic agents not adherent to an interior surface of the barrel. Then, new media and/or suspension agents may be added to the barrel to detach the therapeutic agents (e.g., verdant cells) previously adhered to the interior surface of the barrel and resuspend them. This resuspension process may be aided by a spinning or agitation of the barrel.

[000103] Once the therapeutic agents are collected by therapeutic agent separation device 430, they may be suspended in new media (e.g., blood, water, saline, etc.) that may be configured to, for example, maintain viability of the therapeutic agents and/or aid in the administration of the therapeutic agents to the patient. This resuspension may be facilitated by new media reservoir 440, which may hold a volume of new, or unused, media for the volume of therapeutic agents captured and/or held by therapeutic agent separation device 430, via transfer of media from new media reservoir 440 to therapeutic agent separation device 430 via second valve 355B, fourth tube 450D and fourth tube 450E. On some occasions, resuspension of the therapeutic agents at therapeutic agent separation device 430 may be a reverse of the process used to filter the therapeutic cells from the original volume of therapeutic suspension. Additionally, or alternatively, resuspension may be assisted by vibration (e.g., vibration of therapeutic agent separation device 430) to mix and/or resuspend the therapeutic agents in media.

[000104] In some embodiments, new media reservoir 440 may be configured to adjust and/or establish a particular concentration of therapeutic agents within a volume of therapeutic suspension provided to a patient by, for example adjusting a volume of new media introduced into and/or mixed with the therapeutic agents that have been separated from suspension using, for example, therapeutic agent separation device 430. For example, new media reservoir 440 may be configured to introduce an individualized and/or specified volume of media to the therapeutic agents so that a concentration of therapeutic agents suspended within a volume of new media may be known and/or calculated. This may enable administration of a particular, or known, dosage, or number, of therapeutic agents to a patient. At times, a concentration of therapeutic agents within the new media may be responsive to a 1 patient characteristic such as weight, gender, patient contraindications, age, size, blood volume, expected and/or potential side effects, and/or therapy the patient is receiving and, in some embodiments, may be determined by, for example, processor/controller 340 using one or more of these patient characteristics that may be input into, for example, user interface device 325 by a technician and/or clinician preparing the volume of therapeutic suspension for use.

[000105] A suspension of therapeutic agents in new media (i.e., patient-ready therapeutic suspension) may be extracted from therapeutic agent separation device 430 via application of negative pressure to a first tube 450A coupled to infusion device 101 or 201 via manifold 442. This negative pressure may by achieved via movement of headplate 420 away from infusion device mount 410 so that a vacuum is created within barrel 110 or 210 of infusion device. Additionally, or alternatively, the negative pressure may be achieved via source of compressed gas 135 applying a vacuum to tube 132 that is communicated to infusion device 101 or 201. Once the patient-ready therapeutic suspension is positioned within barrel 110/210, it is ready for administration to the patient and/or a patient delivery device 480 (e.g., catheter) coupled to therapeutic suspension preparation and infusion system 401 via, for example, a patient delivery device coupling 455 coupled to eighth tube 450H.

[000106] When administering the patient-ready therapeutic agents to the patient, third valve 355C may open and the patient-ready may be communicated from infusion device 101 and/or 201 to third valve 355C via seventh tube 450G and then communicated from third valve 355C to eighth tube 450H for eventual communication to a patient-interfacing device 480 coupled to eighth tube 450H via a coupling 455. In some cases, this administration the patient-ready therapeutic agents may be facilitated by headplate 420 moving toward infusion device mount 410, which may act to depress and/or push in plunger 115 or 215 into barrel 110 or 210, respectively, thereby pushing the patient-ready therapeutic agents into seventh tube 450G for communication to third valve 355C and eighth tube 450H.

[000107] Optionally, therapeutic suspension preparation and infusion system 401 may include and/or be cooperative with patient-interfacing device 480, such as a catheter, that has an infusion pressure system 485 attached thereto and/or incorporated therein. Infusion pressure system 485 may be configured to reduce pressure exerted on the patient-ready therapeutic agents as they are infused into the patient and/or reduce pressure exerted on patient anatomy where patient-interfacing device 480 is positioned within, or on, the patient. In some embodiments, infusion pressure system 485 may be a one-way valve that opens to allow therapeutic agents to infuse into the patient (e.g., artery or organ) when the patient’s blood pressure is low (e.g., between heart beats) and closes when the patient’s blood pressure exceeds a certain threshold value. Additionally, or alternatively, infusion pressure system 485 may be a pressure sensor that is coupled to a valve (e.g., a pinch valve) and/or manifold that triggers the opening of the valve/manifold when the patient’s blood pressure is low and the closing of the valve/manifold when the patient’s blood pressure exceeds a certain threshold value. Alternatively, infusion pressure system 485 may be directly and/or indirectly coupled to processor/controller 340, and processor/controller 340 may increase or decrease a speed of the therapeutic agent’s movement through system 401 responsively to feedback from infusion pressure system 485 via, for example, controlling a rotational speed of the motor that is driving motion of headplate 420 and/or an operation of source of compressed gas 135 to, for example, regulate pressure within the system responsively to feedback from the infusion pressure system 485. In some cases, infusion pressure system 485 may also be configured to record and store pressure data and/or communicate same to the processor/controller 340. Additionally, or alternatively, infusion pressure system 485 may be configured to detect and calculate pressure based on information regarding one or more motors and/or controllers driving and/or controlling headplate 420, first valve 355A, second valve 355B, and/or third valve 355C. Exemplary information regarding the one or more motors and/or controllers driving and/or controlling headplate 420 includes, for example, force measurements provided by force transducers at the motor and/or headplate 420 and/or by measuring a draw of electricity and/or motor torques required to move headplate 420 and/or hold a position of headplate 420.

[000108] Optionally, therapeutic suspension preparation and infusion system 401 may include a heating/thermally insulating device 490 that covers all, or a part, of infusion device 101 and/or 201. On some occasions, heating/thermally insulating device 490 may incorporate a water bath to raise and/or maintain a temperature of the therapeutic suspension and therapeutic cells held in infusion device 101 and/or 201.

[000109] Optionally, therapeutic suspension preparation and infusion system 401 may include a viability and/or sterility assessment module 492 configured to assess viability and/or sterility of a volume of therapeutic suspension and/or therapeutic agents included therein following, for example, warming, washing, or otherwise processing of the volume of therapeutic suspension by first exemplary suspension therapy and preparation and infusion system 401 and/or a component thereof. Viability and/or sterility assessment module 492 may be coupled to third valve 355C (which may be a three-way valve) via a tube 450K and may operate by, for example, examining a small sample of the volume of therapeutic suspension received by third valve 355C via tube 450G to determine, for example, a number of living and/or dead therapeutic agents included in the sample. Exemplary viability assessment modules include, but are not limited to, flow cytometers, automated microscopy, etc. Exemplary tests performed by viability and/or sterility assessment module 492 include, but are not limited to, testing, detecting, and/or assessing mechanical integrity, cellular membrane integrity, membrane disruption, metabolic activity (e.g., cellular consumption of nutrients and/or metabolites), byproducts of metabolism (e.g., differentiation potential when stem cells are being tested), multilineage differentiation (e.g., CFU and/or trilineage assays), teratoma formation, cellular attachment, cellular migration, cellular phagocytosis, cellular motility, cellular contractility, cellular aggregation and/or self-assembly, cellular mitotic activity (e.g., proliferation and/or cell cycle analysis), and/or transplantation (e.g., sygenic and/or xenogenic). Viability and/or sterility assessment module 492 may also include a small fluorescence microscope with an optical system (emitter/receiver pair) that may be tightly integrated into the system and able to measure fluorescence of cells that have entered viability and/or sterility assessment module for assessment of various attributes such as viability, functionality, sterility, etc.

[000110] Optionally, therapeutic suspension preparation and infusion system 401 may include an activation module 494 configured to, for example, activate therapeutic agents prior to infusion via, for example, introduction of a catalyst and/or an activation reagent into the processed (e.g., washed, separated, suspended in new media, etc.), or unprocessed, volume of therapeutic suspension that may, for example, flow from infusion device 101 or 201 into third valve 355C via tube 450G and into activation module 494 via tube 450L. Activation module 494 may be configured to, for example, accept a volume of processed volume of therapeutic suspension, introduce one or more activation reagents (e.g. interleukins, accessory cells, antibodies, etc.) into the volume of processed therapeutic suspension, mix (e.g., rotation, agitation, vibration, etc.) the volume of processed therapeutic suspension and the activation reagent for a length of time to sufficiently activate the therapeutic agents, and provide the activated volume of therapeutic suspension to third valve 355C, via tube 450L, for infusion to the patient via tube 450H. At times activation module 494 may be configured to achieve and/or maintain a desired temperature while the volume of processed therapeutic suspension is being mixed with the activation reagents and/or otherwise activated. Exemplary activation modules 494 may include a serene bioreactor. In some embodiments, the activation reagent may be DNAse, which may act to reduce a size and/or volume of clumps of therapeutic agents, or cells, within the activated volume of therapeutic suspension. Additionally, or alternatively, the activation reagent may be one or more enzymes that may activate, or unlink, one or more components of the volume of therapeutic suspension.

[000111] Additionally, or alternatively, in some embodiments, activation module 494 may be embodied as, for example, a modularly configurable tissue printing module, that enables tissue printing using therapeutic suspension preparation and infusion system 401 and/or a component thereof. In these embodiments, activation module 494 may be configured to, for example, store a volume of hydrogel or other matrix solution in which to generate a cell and/or tissue matrix, mix therapeutic agents (e.g., cells) with hydrogel in specific, prescribed, ratios under controlled conditions (e.g., temperature, agitation rates, etc.) to generate a functional tissue (e.g., bioink), a volume of material including hydrogel crosslinks and cells, and/or cell-matrix for infusion to a patient. In some embodiments, activation module 494 may be configured to accept a volume of processed therapeutic cells from third valve 355C via tube 450L, introduce one or more cell-matrix materials (e.g., hydrogel) into the volume of processed therapeutic cells, mix (e.g., rotation, agitation, vibration, etc.) the volume of processed therapeutic cells and the cell-matrix materials for a length of time to form the cell-matrix, and provide the cell-matrix to third valve 355C, via tube 450L, for infusion to the patient via tube 450H.

[000112] Fl G. 4B is a diagram showing a second exemplary therapeutic suspension preparation and infusion system 402 that includes a second suspension therapy preparation and infusion system housing 305B that houses one or more components for a suspension therapy preparation and infusion system like suspension therapy preparation and infusion system 300. Second exemplary therapeutic suspension preparation and infusion system 402 is similar to first exemplary therapeutic suspension preparation and infusion system 401 except that it is configured for cooperation with an original volume of therapeutic suspension that is received in a bag or container (e.g., a cryovial) rather than infusion device 101 and/or 201. Following processing (e.g., after washing and preparation), the volume of therapeutic suspension is transferred to infusion device 101 and/or 201 in a manner similar to that used with first therapeutic suspension preparation and infusion system 401.

[000113] In particular, second suspension therapy preparation and infusion system housing 305B houses infusion device mount 410, infusion device 101 and/or 201, track 415, headplate 420, first valve 355A, second valve 355B, third valve 355C, therapeutic agent separation device 430, waste reservoir 445, new media reservoir 440, coupling 455, and first tube 151 A, tenth tube 451 J, and second-ninth tubes 450B-450I. Second exemplary therapeutic suspension preparation and infusion system 402 also includes a container mount 465 configured to hold, retain, hang, and/or mount a container of therapeutic suspension 460. Container of therapeutic suspension 460 (also referred to herein as “container 460”) may be any container of therapeutic suspension including, but not limited to, a syringe, a barrel configured to be coupled to a syringe, a cartridge, a cassette, a cartridge, a vial, a screw-top vial, a puncture-top vial, a bag, a tube, a conical tube, a flask, a culture flask, a tissue culture dish, a cell culture dish, and/or an Eppendorf tube. Further details regarding exemplary containers 460 and/or container mounts 465 are provided herein with regard to FIGs. 5A1-5G and their associated discussion.

[000114] Container mount 465 may be, for example, a pole or hook and/or a flat surface upon which container of therapeutic suspension 460 may rest. On some occasions, container mount 465 may be configured to warm and/or defrost/thaw a frozen volume of therapeutic suspension held in container of therapeutic suspension 460. Container mount 465 may also be configured to cool a volume of therapeutic suspension and hold the volume at desired temperature in order to, for example, prevent therapeutic agents (e.g., cells) from undergoing apoptosis.

[000115] When the therapeutic suspension is ready (e.g., defrosted/thawed, at a particular temperature, and/or sufficiently agitated) for communication through second exemplary therapeutic suspension preparation and infusion system 402, a volume of therapeutic suspension may flow from container of therapeutic suspension 460 to therapeutic agent separation device 430 and/or washing station 470, which may operate to wash and/or separate therapeutic agents from the volume of therapeutic suspension in a manner similar to manner in which the therapeutic agents were washed and/or separated when first therapeutic suspension preparation and infusion system 401 is used.

[000116] Optionally, container mount 465 may include a heating/thermally insulating device 490 that covers all, or a part, of container 460. On some occasions, heating/thermally insulating device 490 may incorporate a water bath to raise and/or maintain a temperature of the therapeutic suspension and therapeutic cells held in container of therapeutic suspension 460. In various embodiments, container of therapeutic suspension 460 may of different sizes, shapes, and/or configurations (e.g., a small bag, a large bag, a small cryovial, and/or large cryovial) and container mount 465 may be sized, shaped, and/or configured to accept insertion and/or containment of these differently sized and/or shaped containers of therapeutic cells and media 460 via, for example, one or more adapters (not shown) to cooperate with container mount 465 to facilitate acceptance and/or containment of container of therapeutic suspension 460 therein.

[000117] When container of therapeutic suspension 460 does not have an exit port, as may be the case when container of therapeutic suspension 460 is a vial and/or cryovial, container mount 460 may be configured to create an exit port for the volume of therapeutic suspension so that if may be extracted from container 460 and be processed by system 402 as described herein. The exit port may be created by, for example, an extraction device (e.g., a needle or blade) configured to puncture container 460 in a sterile manner and provide a port for extraction of the therapeutic cells and media from the container in a sterile manner via, for example, tubing and/or a needle. For example, in some embodiments, container 460 may be punctured by a needle-like device with a bore or channel and, once container 460 is punctured, negative pressure may be applied to the volume of therapeutic suspension contained within punctured container 460 via, for example, moving a plunger in a barrel attached to the puncturing needle that acts to pull the volume of therapeutic suspension from container 460 into the barrel of the needle in, for example, a sterile manner. The extracted therapeutic cells and media may then be provided to, for example, washing station 470 and/or therapeutic agent separation device 430 by pushing the extracted therapeutic cells and media from the extraction device to tube 451 J and/or 451A, respectively, for further processing as described herein. In some embodiments, the extraction device may be used to flush and/or rinse container 460 to, for example, extract any therapeutic agents that may not have been extracted from container 460 via the initial extraction of therapeutic cells and media from the container. In these embodiments, the material used to flush and/or rinse container 460 may be provided by a reservoir of flushing and/or rinsing fluid housed in container mount 465 and/or washing station 470 (via, e.g., tube 451 J).

[000118] Fl G. 4C is a diagram showing a third exemplary therapeutic suspension preparation and infusion system 403 that is similar to second exemplary therapeutic suspension preparation and infusion system 402 except that third suspension therapy preparation and infusion system housing 305C does not include infusion device mount 410, infusion device 101 and/or 201 , track 415, or headplate 420. Instead, therapeutic agent separation device 430 is directly coupled to third valve 355C via, for example, first tube 450A.

[000119] In some embodiments, one or more interior surfaces of first, second, and/or third exemplary therapeutic suspension preparation and infusion system(s) 401, 402, and/or 403 may be coated with and/or manufactured from, a material that inhibits cellular adhesion or is hydrophilic or hydrophobic. This coating and/or material may, for example, assist with the flow of, for example, suspension therapies, washing solutions, pharmaceuticals, and/or waste materials, through first, second, and/or third exemplary therapeutic suspension preparation and infusion system(s) 401, 402, and/or 403 and/or prevent buildup of these materials within first, second, and/or third exemplary therapeutic suspension preparation and infusion system(s) 401, 402, and/or 403. Additionally or alternatively, this coating and/or material may assist with the quantification and/or control of the number of therapeutic agents delivered to a patient because, for example, they may prevent the inadvertent and/or undesired loss of therapeutic agents that may adhere to and/or settle on one or more surfaces of first, second, and/or third exemplary therapeutic suspension preparation and infusion system(s) 401, 402, and/or 403 thereby decreasing a number of therapeutic agents delivered to a patient by an unknown amount, which may lead to ineffective delivery of the suspension therapy to patients.

[000120] In some instances, infusion device mount 410 and/or container mount 465 may be configured to oxygenate the cells via, for example, breathers and/or gas- permeable membranes including within infusion device mount 410 and/or container mount 465 and/or components thereof and/or attached thereto.

[000121] In some embodiments, one or more components of system(s) 401 , 402, and/or 403 may be configured to deliver a very small volume (e.g., 10 microliters - 1mL) of therapeutic suspension to a patient as may be the case when, for example, infusing a volume of therapeutic suspension into a particularly small/sensitive region of the body (e.g., a retina or gingiva) and/or infusing the therapeutic suspension into a child’s organ or tissue. In these embodiments, one or more tubes 450 may have a relatively small internal diameter (e.g., 1/64”) that may be coated with a friction-reducing material and correspondingly small valves 355 so that a flow rate of the therapeutic suspension into the patient is relatively low, steady, and controlled. In some instances, an inner diameter of tubing 450 may be smaller prior to delivery of the therapeutic suspension to therapeutic agent separation device 430 and when exiting therapeutic agent separation device 430. Pushing a volume of therapeutic suspension through tubes with such a small internal diameter may require application of a relatively high degree of force to components of system(s) 401, 402, and/or 403 such as infusion device 101 or 201 and/or container of therapeutic suspension 430 and processor/controller 340 and/or source of compressed gas 135 (which may be communicatively coupled to processor/controller 340) may control a magnitude of force exerted on the therapeutic suspension so that it is adequately pushed and/or pulled through system

401, 402, and/or 403 without causing damage to therapeutic agents that may be included in the therapeutic suspension.

[000122] When the systems (e.g., 102, 202, 300, 401 , 402, and/or 403) disclosed herein include source of compressed air 135, one or more valves 355 may be configured as an air/gas purge valve configured to purge any gas or air bubbles from a volume of therapeutic suspension prior to infusion into a patient. In some embodiments, use of compressed gas in a system like system 300, 401 , 402, and/or 403 may facilitate the delivery of a volume of therapeutic suspension in a highly controlled (e.g., pressure, velocity, etc.) and steady manner. Additionally, or alternatively, use of compressed gas in a system like system 102, 202, 300, 401 ,

402, and/or 403 may facilitate complete evacuation of the volume of therapeutic suspension from system components (e.g., barrel 110 or 210, coupling 140, syringe shaft 145, catheter coupling 150, inline pressure relief 250, barrel/pressure system coupling 240, first extension 255, pressure relief system coupling 260, tubes 450, valves 355, and/or a catheter or tube coupled thereto) and/or assist with pushing therapeutic suspension through the one or more systems or system components described herein in a consistent, controlled, and/or complete manner. In addition, use of compressed gas within the systems disclosed may also assist with reducing dead space within respective systems and/or components thereof.

[000123] In some embodiments, infusion device mount 410 and/or container mount 465 may be configured as a bioreactor and/or a cell culture rescue bioreactor that may be configured to, for example, facilitate recovery of living therapeutic agents (e.g., cells in culture) to recover from the freezing and/or thawing process by, for example, allowing for the thawed therapeutic agents and media to be held in their original (or a different) container after thawing under preferred conditions (e.g., preferred temperature, agitation rate, etc.) for a particular duration of time that may be responsive to, for example, a recovery rate for the therapeutic agents and/or a reproduction rate for the therapeutic agents. FIGs. 5A1 -5F3 provide diagrams of exemplary bioreactor and/or a cell culture rescue bioreactors that may be included in system 401 , 402, and/or 403 and/or a component thereof such as infusion device mount 410 and/or container mount 465. In particular, FIG. 5A1 provides a top view (without a lid 515) and FIG. 5A2 provides a cut-away side view of an exemplary system 501 configured as bioreactor and/or a cell culture rescue bioreactor that is compatible with one or more systems and/or devices disclosed herein. System 501 includes a first container mount 465A that holds a first container 460A in the form of a cell culture dish or tray that holds a volume of therapeutic suspension 510 that, in this instance, may be media that includes therapeutic cells. Lid 515 is configured to fit over first container mount 465A to, for example, seal and/or thermally isolate an interior of first container mount 465A from the ambient environment. System 501 may be configured to provide an environment configured to, for example, enhance the viability and/or number of therapeutic cells in volume of therapeutic suspension 510 by, for example, providing a temperature conducive to cell reproduction and/or metabolic processes.

[000124] FIG. 5B is a block diagram of an exemplary container mount lid 522 that includes a port, aperture, and/or opening 524 (collectively referred to as “port 524”) therein. Although container mount lid 522 only includes one port 524, this need not necessarily be the case as container mount lid 522 may include any desired number of (e.g., 2-10) ports. Port 524 may be configured to accept insertion of one or more devices (e.g., needle, tube, straw, etc.) configured to, for example, puncture container 460 and/or access a volume of therapeutic suspension 510 that may be held in a container 460. In some instances, container mount lid 522 may be configured to make a thermally, liquid, and/or air-tight seal with a container 465. At times, container mount lid 522 may be transparent so that a technician or clinician may visually observe container 465, a device positioned within port 524 and/or contents of container 465 (e.g., therapeutic suspension). In some embodiments, lid 522 may be configured to deliver compressed gas into a container 460 via a port and/or valve therein. The compressed gas may be provided by compressed gas source 135. When compressed gas is pushed into container 460, it may act to push therapeutic suspension up into, for example, a conduit 530 (see e.g., FIG. 5C and 5E) so that it may exit container 460C.

[000125] FIGs. 5C-5F3 are schematic diagrams of exemplary systems 503-506, respectively, that include various container mounts 465 and containers 460 with volume of therapeutic suspension 510 contained therein. In particular, system 503 of FIG. 5C includes a container mount 465C housing a cylindrical container 460C with a lid 535 that contains, or holds, a volume of therapeutic suspension 510. Lid 535 may be configured to be punctured by, for example, a needle or a therapeutic suspension conduit 530, which may be configured to be in liquid communication with container 460C by, for example, extracting therapeutic suspension 510 from container 460C and/or adding fluid or other material such as therapeutic agents, saline, nutrients, cellular growth media, and/or radioactive beads, to container 460C. In one example, container of therapeutic suspension 460C may contain a frozen volume of therapeutic suspension may be received from, for example, a manufacturing source (e.g., lab or pharmaceutical company) and placed within container mount 465C (with lid 522 off). Lid 522 may then be placed over container 460C, thereby sealing an internal cavity of container mount 465C and one or more processes for controlling and/or optimizing an environment within container mount 465 may be performed and, when therapeutic suspension 510 is ready for extraction and/or decanting from container 460C, conduit 530 may be inserted into port 524 so that some, or all, of therapeutic suspension 510 may be extracted from container 460C via conduit 530 via, for example, application of negative and/or positive pressure to container 460C via conduit 530 according to, for example, one or more processes and/or methods disclosed herein. In some embodiments, therapeutic suspension 510 may be extracted from container 460C, washed and/or filtered using, for example, washing station 470 and/or therapeutic agent separation device 430 and may then be returned to container 460C for storage until infusion into the patient it desired. In some instances, clean therapy media from, for example, new media reservoir may be placed into container 460C before, during, and/or after placing the cleaned and/or processed therapeutic agents back into container 460C and/or a similar new container (e.g., sterile new container like container 460C). [000126] In another example, container 460C and/or lid 522 may be configured for the handling of a volume of therapeutic suspension that includes radioactive therapeutic agents and, in these instances, the sidewalls of container 460C and/or lid 522 may include a layer of radiation shielding and/or may be configured to house and/or provide other radiation mitigation devices and/or systems.

[000127] Fl G. 5D provides a side cutaway schematic diagram of a system 504 that is similar to system 503 with the exception that it includes a puncturing device 545 configured to puncture a cap 537 positioned on top of a container 460D, which may be embodied as, for example, a cryovial. Puncturing device 545 may be inserted into port 524 of lid 522 and/or may be embedded within a lid 540 configured to cover and/or close a container 465D. Once cap 537 is punctured with puncturing device 545, a hollow tube or needle may be inserted into the hole created by puncturing device 545 (e.g., following removal of puncturing device 545 and/or lid 540 with puncturing device included therein) so that volume therapeutic suspension 510 may be extracted therefrom using, for example, negative or positive pressure to respectively pull and/or push therapeutic suspension 510 from container 460D according to one or more processes described herein.

[000128] FIG. 5E provides a side cutaway schematic diagram of a system 505 that is similar to system 503 except that it includes a container 460E in the form of a flask.

[000129] FIGs. 5F1-5F3 provide a time series of schematic diagrams wherein a container 460F with a cap 570 is de-capped and conduit 530 is inserted therein. Cap 570 may be, for example, a screw-on cap and/or a pop-on cap. As may be seen in FIG. 5F1 , capped container 460F is placed within container mount 465F, wherein container 460F is grasped and/or held on both sides by extensions 560 and cap 570 is grasped and/or held on both sides by cap holders 565. In some embodiments, cap holders 565 and extensions 560 may be configured to cooperate with one another so that cap 570 may be removed from container 460F. This may occur when, for example, cap holder 565 holds cap 570 in place and extensions 560 rotate or pull container 460F away from cap 570 as shown in FIG. 5F2. Once cap 570 is removed, it may be discarded and conduit 530 may be inserted into container 460F as shown in FIG. 5F3.

[000130] In some embodiments, filtration material used in in, for example, therapeutic agent separation device 430 may comprise one or more metal (e.g., stainless steel) layers in the form of, for example, mesh, wire, electroplated material and/or sheets with punched holes. Using metal, or stainless steel, filtration material provides advantages over other types of filtration material such as polymer mesh because it is stronger, resists deformation, and is easier to clean. Metallic filtration material may be manufactured using, for example, dies, stamping, laser cutting, etching, and/or electroforming of, for example, holes or openings that may be, for example, round, ovoid, square, and/or rectangular in shape. When the metallic filtration material is electroformed, it may be done so using electrodeposition in a manner that may be, similar to, for example, electroplating and/or electrorefining. The electrodeposition filter media generation process may take place in an electrolytic bath and may involve use of two electrodes (an anode and a cathode) and an electrolytic solution. A mandrel may be placed in the bath and connected to electrodes. The electrodes may stimulate a nickel ion flow through the electrolytic solution by solving nickel ions from the anode and electrodepositing them at the cathode (the mandrel). Accurate current dosing may create the desired filter layer thickness. Compared to other traditional metal forming technologies like casting, forging, stamping, or deep drawing, electroforming may deliver high volumes of filtration material that have superior accuracy and extreme design complexity, due to the fact that it can replicate the shape of the mandrel at extreme accuracy.

[000131] FIGs. 6A-6E are schematic diagrams of metallic filtration material layers 600A, 600B, 600C, 600D, and 600E, respectively, that provide different examples of metallic filtration material layers and/or configurations that may be used in, for example, therapeutic agent separation device 430 to, for example, filter therapeutic agents from a volume of therapeutic suspension as, for example, described herein. In particular FIG. 6A is a schematic diagram of a layer of a first type of filtration material 600A, which comprises a wire (e.g., stainless steel) mesh; FIG. 6B is a schematic diagram of a layer of a second type of filtration material 600B that comprises a metal (e.g., stainless steel) sheet with a plurality of small holes positioned therein; FIG. 60 is a schematic diagram of a layer of a third type of filtration material 600C that comprises a series of linearly-oriented metal (e.g., stainless steel) wires or posts; FIG. 6D is a schematic diagram of a layer of a fourth type of filtration material 600D that comprises a metal sheet with a plurality of holes positioned therein; FIG. 6E is a schematic diagram of a layer of a fifth type of filtration material 600E that comprises an gelatinous membrane such as the electrospun gelatin membranes disclosed herein.

[000132] At times, a filter and/or therapeutic agent separation device 430 may include a plurality of the same and/or different types of filtration material such as filtration material layers 600A, 600B, 600C, 600D, and 600E. Additionally, or alternatively, a filter and/or therapeutic agent separation device 430 may include a plurality of layers of the same and/or different types of filtration material that may be arranged relative to one another to achieve smaller openings through which therapeutic suspension and/or therapeutic agents may be filtered and/or separated into different components (e.g., therapeutic agents, waste media, debris, etc.). For example, a filter and/or therapeutic agent separation device 430 may include a plurality of the same and/or different types of layers of filtration material that include holes or openings that are aligned relative to one another so the holes/openings of each layer of filtration material are slightly offset from each other, which may have a net effect of creating a smaller hole through which therapeutic suspension and/or therapeutic agents may travel. This may allow for smaller effective holes than what can actually be machined and/or manufactured a single layer of filtration material. For example, standard machining and PCB filtration material fabrication techniques typically only produce holes around 75 micrometers in size. However, arranging a plurality of layers of filtration material on top of one another so that the openings or holes in the layers of filtration material are offset from one another in this manner may allow for creation of pathways through the plurality of filtration material pieces or disks that have a size as low as 2-15 (e.g., 5 or 10) microns.

[000133] In some embodiments a plurality of filtration material layers like filtration material layers 600 may be included in a filter and/or therapeutic agent separation device 430 as disclosed herein. In some embodiments, filter and/or therapeutic agent separation device 430 may comprise multiple layers of filtration material resident within a housing that is closed and sealed so that therapeutic suspension and other liquids or solutions only flow through filter and/or therapeutic agent separation device 430 along an axial flow path. In some embodiments, the plurality of layers of filtration material may be the same as or different from one another. For example, a stainless-steel mesh filter may be used in conjunction with a gelatinous, fibrous, and/or membrane polymer filter or a fibrous and/or membrane polymer filter may be used in combination with a glass fiber filtration material layer. Additionally, or alternatively, an orientation of a first filtration material layer within a multi-layer filter may be oriented in a first direction and a subsequent filtration material layer may be oriented in a different direction (e.g., 10-170 degrees off a central axis of the first filtration material layer.

[000134] Two or more of these layers of filtration material may then be stacked on top of one another and compressed together to generate a multi-layer membrane with a 0.2-5micron pore size when at, for example, room temperature. The multilayer membrane may be placed in a housing and used as, for example, a therapeutic agent separation device 430 as disclosed herein.

[000135] In some embodiments, a multi-layer filter and/or therapeutic agent separation device 430 may include a multi-layer stack of filtration material layers (e.g., filtration material layers 600A, 600B, 600C, 600D, and/or 600E) that may be vertically oriented and arranged so that a volume of therapeutic suspension to be filtered and/or processed as, for example, described herein may enter the therapeutic agent separation device 430 from the bottom, travel through therapeutic agent separation device 430 in a direction in opposition to gravity, and exit from a top of therapeutic agent separation device 430. In this way, the volume of therapeutic suspension may fight gravity as it is pumped through therapeutic agent separation device 430, which may allow for lighter components (e.g., cells) within the therapeutic or other media to naturally reach the filter first, before the heavier components (e.g., dead cells, debris, etc.), especially when the infusion rate is kept extremely slow. This may aid in separation of the therapeutic agents from other undesirable components of the volume of therapeutic suspension.

[000136] Exemplary arrangements of a plurality of layers of filtration material such as filtration material layers 600A, 600B, 600C, 600D, and/or 600E that may be housed within a multi-layer filter and/or therapeutic agent separation device 430 are provided by FIGs. 66F-6E, wherein FIG. 6F provides a vertical cross section view of a first multi-layer filter 601 that includes a plurality of layers of filtration material 600 that are separated by a region of empty space 615 within a first housing 610. In some embodiments, region of empty space 615 may be consistent within housing 610 and, in other embodiments, region of empty space 615 may vary between different layers of filtration material 600. An exemplary size of region of empty space 615 is 1 micron -1cm.

[000137] FIG. 6G provides a vertical cross section view of a second multi-layer filter 602 that includes a plurality of layers of filtration material 600 interleaved between a plurality of layers of filtration material 600’ within a second housing 611. The plurality of layers 600 and 600’ are positioned proximate to one another so that, for example, they may create smaller overall sized holes through which therapeutic suspension may pass. This may work to capture therapeutic agents and/or cells while letting all other material flow through the multi-layer filter 602. Multi-layer filters 601 and 602 include two ports 620 that may be configured for as inlet and/or outlet ports that may be configured to couple to, for example, one or more tubes (e.g., tube 450) or other components disclosed herein.

[000138] FIG. 7A provides a vertical cross section view of a multi-component filter 701 that includes two ports 620, a plurality of projections 710 (e.g., columns or microposts) attached to an inside wall of a housing 711, and projecting into a center of third housing 730. Projections 710 may have, for example, a circular, triangular, ovoid, hexagonal, and/or octagonal cross-sectional shape.

[000139] FIG. 7B provides a vertical cross section view of a second multicomponent filter 702 that includes two ports 620, a first plurality (in this case three) of projections of a first type 710A and a second plurality (in this case two) of projections of a second type 710B attached to an inside wall of a housing 722 and projecting into a center of housing 722.

[000140] As therapeutic suspension including cells flow through first and/or second multi-layer and/or multi-component filters 601, 602, 603, and/or 604 and/or microfluidic devices 703, 704, and/or 705 in a first direction, therapeutic agents may adhere to filtration material 600, 600’, and/or projections 710 while a remainder of the therapeutic suspension (e.g., waste media, dead cells, debris, etc.) passes through the multi-layer filter and on to, for example, a waste reservoir like waste reservoir. Then, once the waste removal is complete, fresh media or wash media may be flowed back through first and/or second multi-layer and/or multi-component filters 601 , 602, 603, and/or 604 in a second, or opposite, direction, which may facilitate removal of the therapeutic agents from filtration material 600 or 600’ or columns 710 so that they may be, for example, resuspended in a desired therapeutic suspension for further processing and/or eventual infusion to a patient according to, for example, one or more processes disclosed herein.

[000141] One challenge with using traditional membrane filters for separation of therapeutic agents from unwanted media (e.g., removal of DMSO cryopreservation media) and debris (e.g., dead cells, waste, etc.) and/or washing the therapeutic agents according to, for example, one or more processes disclosed herein is that with high volume/high density therapeutic suspension products the therapeutic agents can quickly obscure holes or openings in the filtration material (i.e., plug the filter) and disallow the passage of the unwanted media and debris therethrough. One way to avoid this issue is to increase the surface area of the filtration material, but as the surface area of the filtration material increases, its overall strength of respective layers of filtration material may decrease (e.g., larger surface area means greater surface that is not supported by a housing) and, consequently, may fail (e.g., tear, perforate, and/or stretch (thereby increasing a size of holes therein to dimensions too large to capture cells)). Another way to prevent filtration material clogging is to create a density gradient within a volume of a therapeutic suspension so that lower density elements of the suspension (e.g., the cryopreservation media) that are unlikely to clog filtration material reach the filter first and the denser elements (e.g., therapeutic agents and/or cells) of the therapeutic suspension reach the filtration material later in time, with the goal of allowing a percentage (e.g., 30-80%) of the lower density elements to pass through the filter prior to a percentage (e.g., 40-90%) of the larger density elements reaching the filtration material. This may act to prevent, or reduce, clogging of the filtration material with larger density elements at initial stages of the filtration process. One way to create this density gradient within a volume of therapeutic suspension is to spin, rotate, agitate, and/or vibrate the volume of therapeutic suspension so that the heavier elements (e.g., therapeutic agents and/or cells) move away from a center axis of rotation and toward a container (e.g., infusion device(s) 101 and/or 201 and/or container 460) wall. In one or more embodiments, infusion device mount, infusion device(s) 101 and/or 201 , infusion device mount 410, container 460, container mount 465, therapeutic agent separation device 430, a multi-component filter like multi-component filters 603 and/or 604 and/or a multi-layer filter like first and/or second multi-layer filters 601 and/or 602 may be configured to move, rotate, and/or be agitated during a filtration process to generate this density gradient.

[000142] Once the density gradient within the therapeutic suspension is sufficient, the therapeutic suspension may be pumped through the filtration material and/or therapeutic agent separation device 430 and this may cause the denser elements to remain within the container (e.g., stay towards an inner wall of the container) while the lighter components of the suspension may pass through the container outlet and reach the filtration material and/or therapeutic agent separation device 430 first. In this way, the lighter components of the suspension (e.g., cryopreservation media, cell debris, dead cells, etc.) may pass through relatively unclogged filtration material of, for example, therapeutic agent separation device 430 while the denser elements pass through and are captured by the filtration material after a majority of the lighter components have already been filtered from the original therapeutic suspension. Density of cells is a very consistent variable across cells of the same type, and we know that DMSO, dead cells, and debris contents are much less dense and smaller, therefore less likely to clog the filter. Having cells reach the filter at the end of the wash step also means they are easier to pull off the filter during the resuspension step in fresh media.

[000143] In some embodiments, systems, devices, and/or filters/cell separation devices disclosed herein may be configured to create conditions that encourage delivery of cargo into therapeutic agents embodied as cells via an intra-cellular pathway. In these embodiments, the systems and/or devices disclosed herein may be configured to pressurize cells in a manner that opens their respective cellular membranes so that may take in cargo and become functionally modified. This may be accomplished by, for example, exerting a desired amount of pressure (e.g., 50- 100 pounds-per-square inch (PSI) upon plunger 110 or 210 and/or pneumatically introducing compressed gas into a container 460 until cells within volume of therapeutic suspension 510 open their cellular membranes at, approximately 50-100 PSI, and take in the cargo that enables functional modification of the cells. A gentle increase and decrease of fluid pressure with high resolution allows cellular membranes to be opened, without the cells incurring any permanent damage. Pressure may be increased in the system (e.g., barrel 110 or 210 and/or container 460) by closing the valves (e.g., valves 355 and/or 835) of the systems and/or devices disclosed herein and applying force to plunger 110 and/or 210 and/or container 460 until the desired pressure is reached. Additionally, or alternatively, pressure in the system may be increased by tuning one or more filters (e.g., therapeutic agent separation device 430) and/or microfluidic devices to achieve a pressure sufficient to achieve delivery of cargo into therapeutic agents embodied as cells via an intra-cellular pathway. The filters and/or microfluidic devices disclosed herein may be tuned so that a set amount of pressure is required to push the volume of therapeutic suspension to pass therethrough. Tuning may be achieved via, for example, adjusting a setting of the filter/microfluidic device and/or selection of a filter and/or microfluidic device from a plurality of filters/microfluidic devices configured to require varying amounts of pressure to push the volume of therapeutic suspension therethrough.

[000144] In some embodiments, therapeutic agent separation device 430 may be and/or include a microfluidic device such as a microfluidic cell filter and/or microfluidic cell separation device configured to, for example, separate therapeutic cells and/or particles from therapeutic suspension. The microfluidic device may be configured to separate therapeutic cells from and/or concentrate therapeutic cells within media in which they are suspended as part of, for example, washing the therapeutic cells as, for example, described herein. In some embodiments, one or more channels within the microfluidic device may be sized, shaped, and/or arranged within the microfluidic device to facilitate hydrodynamic and/or inertial focusing of therapeutic suspension as it flows therethrough. For example, a channel diameter may be sized, shaped, and/or configured for facilitate hydrodynamic focusing so that the liquid portion of the therapeutic suspension flows along a laminar flow path through the channel with therapeutic cells and/or particles within therapeutic suspension concentrated in a center of the channel, which may enable liquid from the therapeutic suspension to be directed into one or more off-channels, thereby separating the liquid from the therapeutic agents so that a concentration of therapeutic agents within the therapeutic suspension increases as it travel along the channel. Additionally, or alternatively, a channel diameter may be sized, shaped, and/or configured with one or more inertial elements (e.g., spirals, curves, etc.) that facilitate inertial focusing of the therapeutic suspension so that as the therapeutic suspension travels along the inertial elements, an inertial gradient may push the therapeutic agents to an edge of the channel so that the therapeutic agents may be separated from the therapeutic suspension by, for example, diverting the therapeutic suspension into to another channel using this inertial gradient. This may also enable filtration of dead cells and debris, given that those elements may be lighter in weight than whole cells, and thus can be directly to flow out of the device along with the bulk of the therapeutic suspension.

[000145] In some embodiments, the microfluidic device may be configured to include a mechanism (e.g., a sealed or unsealed side channel and/or chamber) that is configured to divert a portion of therapeutic suspension flowing therethrough into the mechanism to, for example, count a number of diverted therapeutic agents (e.g., cell counting) and/or perform one or more quality control measurements to, for example, determine a strength or viability, or functionality of the therapeutic agents and/or a component thereof (e.g., cellular membrane). At times, the mechanism may contain and/or be pre-loaded with one or more stains and/or fixatives that may facilitate automatic staining and/or counting of the therapeutic agents by, for example, a cell counter in communication with the mechanism and/or microfluidic device. An outcome of the counting and/or quality control checks may be used to, for example, determine how many viable therapeutic cells may be included in a volume of therapeutic suspension and/or a dosage (i.e., how many therapeutic agents or what volume of therapeutic suspension) is needed to treat a patient using a volume of therapeutic suspension. This calculation may be done by, for example, processor and/or controller 340 according to, for example, one or more instructions received from memory 342 and/or user interface device 325 in, for example, an automated, semi-automated, and/or manual fashion. In some embodiments, the microfluidic device may also include a flush port and chamber configured to accept entry of fresh media into microfluidic device that may be used to, for example, dislodge a number of therapeutic agents captured by the microfluidic device during the filtration process so that they may be, for example, resuspended in a patient-ready therapeutic suspension according to one or more processes described herein. This flush port and chamber may be a bag, a vial, or any type of closed container that can hold the therapeutic volume and enable connection to various inputs and outputs. Additionally, the microfluidic device may incorporate a microfluidic bubble trap device designed to efficiently capture and remove gas bubbles within a flowing liquid. The microfluidic bubble trap device comprises a substrate with integrated channels and features to facilitate the effective trapping and removal of gas bubbles. A core element of the microfluidic bubble trap portion of a microfluidic device may be a bubble-capturing channel strategically embedded within the substrate. This channel is engineered to leverage hydrodynamic and/or inertial principles, directing the liquid portion of a fluid through a laminar flow path within the channel. Simultaneously, gas bubbles may concentrate toward a designated area of the channel, allowing for their separation from the liquid and preventing interference with downstream processes.

[000146] FIG. 7C is a block diagram of an exemplary microfluidic device 703 that may be included in, and/or cooperate with, therapeutic agent separation device 430 and/or one or more of the systems and/or base units disclosed herein. Microfluidic device 703 may include a substrate 750 with an inlet port 705, a waste outlet port 710, a concentrated therapeutic agents port 715, a primary channel 720, a plurality of outlet channels 725, a waste channel 730, a concentrated therapeutic agents channel 735, and a resistive element 740. During use, a volume of therapeutic suspension may enter microfluidic device 703 via inlet port 705 and may travel along primary channel 720 until it reaches a separation point 722. In the embodiment of FIG. 7C, primary channel 720 is spiral shaped so that it creates an inertial gradient in the volume of therapeutic suspension that acts to concentrate the therapeutic agents toward a center of the spiral and waste media in which the therapeutic agents are suspended toward an outer edge of the spiral as the volume of therapeutic suspension moves along the primary channel. Upon reaching separation point 722, an inertially separated portion of the volume of therapeutic suspension (e.g., waste media, debris, etc.) may be split of into one or more side channel 725 for collection in waste channel 730 and, as it travels along waste channel 730, it may exit microfluidic device 703 via waste outlet port 710. As the inertially separated volume of therapeutic suspension arrives at separation point 722 a portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents continues to travel in a spiral path along concentrated therapeutic agents channel 735. As the portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents travels along concentrated therapeutic agents channel 735, it continues to be inertially separated from waste, which is drawn off into outlet channel 725 until the portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents reaches resistor 742, which acts to further separate the therapeutic agents from the volume of therapeutic suspension. Once the portion of the volume of therapeutic suspension with a greater concentration of therapeutic agents (also referred to herein as “volume of concentrated therapeutic suspension”) fully travels through concentrated therapeutic agents channel 735, it may exit microfluidic device 703 via concentrated therapeutic agents port 715. In some embodiments, a portion and/or a surface of side of one or more of primary channel 720, plurality of outlet channels 725, waste channel 730, concentrated therapeutic agents channel 735 may be coated and/or pre-loaded with a stain and/or fixative to assist with, for example, separation of the therapeutic agents from the volume of therapeutic suspension and/or staining of a portion of the therapeutic agents for further processing and/or analysis (e.g., counting, viability measurements, etc.).

[000147] Optionally, in some embodiments, microfluidic device 703 may include a quality control chamber 737 that may be in liquid communication with concentrated therapeutic agents channel 735 via a quality control channel 733. A relatively small sample of the volume of concentrated therapeutic suspension may flow into quality control channel 733 and pool in quality control chamber 737. In some instances, this chamber may be coated with stain, fixative, and/or other substances that may make quality control measurements (e.g., cell count, cell viability, and/or therapeutic agent concentration within the sample) easier. In some embodiments, the quality control measurements and/or determinations using the sample may be made and/or assisted by viability and/or sterility assessment module 492.

[000148] Optionally, in some embodiments, microfluidic device 703 may include a flush inlet 747 coupled to concentrated therapeutic agents channel 735 via a flush channel 743. Flush inlet 747 may be configured to allow for introduction of wash media or other fluid (e.g., saline) to flush therapeutic agents from concentrated therapeutic agents channel 735 into, for example, concentrated therapeutic agents port 715 so that therapeutic agents that may remain within concentrated therapeutic agents channel 735 may be evacuated and/or washed therefrom.

[000149] FIG. 7D is a diagram of an exemplary cover 704 for microfluidic device 703 that includes a cover body 751 with an inlet port connector 706, a waste outlet port connector 711 , a concentrated therapeutic agents port connector 716.

Connectors 706, 711 , and/or 716 may be, for example, luer or other connectors adapted to couple one or more tubes and/or devices disclosed herein to cover body 751 so that volume of therapeutic suspension may be added to microfluidic device 703 via a coupling between inlet port connector 706 and inlet port 705; waste may be extracted from microfluidic device 703 via a coupling between waste port 710 and waste port coupling 711 ; and concentrated therapeutic agents may be extracted from microfluidic device 703 via a coupling between concentrated therapeutic agents outlet port 715 and concentrated therapeutic agents outlet port connector 716. In many cases, cover 704 may fit over and/or cover all and/or a portion of microfluidic device 703 as shown in the assembly 705 of FIG. 7E.

[000150] In some embodiments, for microfluidic device 703 and/or cover 704 may be configured to cooperate with a therapeutic agent collection device and/or container such as therapeutic agent collection device 760, which is also shown in FIG. 7D. When in use, therapeutic agent collection device 706 may be configured to couple to concentrated therapeutic agents outlet port 715 via concentrated therapeutic agents outlet port connector 716 (e.g., screw and/or clamp on) and collect a volume of concentrated therapeutic agents that flows from concentrated therapeutic agents outlet port 715. Once the volume of therapeutic suspension is fully separated by microfluidic device 703 (i.e., there is none left to separate) and/or therapeutic agent collection device 760 is full, the volume of concentrated therapeutic agents may be removed from therapeutic agent collection device 760 and placed, in for example, an infusion device like infusion device 101 and/or 201 for further processing (e.g., washing, cultivation, etc.) according to, for example, one or more processes disclosed herein. Additionally, or alternatively, the volume of concentrated therapeutic agents may be housed in therapeutic agent collection device 760 for a desired length of time. Additionally, or alternatively, the volume of concentrated therapeutic agents may be housed in therapeutic agent collection device 760 and may then be further processed and/or infused into a patient in a manner similar to the volume of therapeutic suspension housed in a container like containers 460 disclosed herein. In some embodiments, therapeutic agent collection device 760 may be embodied as a small distensible bag in communication with concentrated therapeutic agents outlet port connector 716 and, once the distensible bag contains the volume of concentrated therapeutic suspension, it may be transferred to another component of the one or more of the systems (e.g., system 401, 402, 403, and/or 801 ) disclosed herein. This process may be assisted by rinsing and/or washing the therapeutic agent collection device 760 with, for example, wash media, to remove any therapeutic agents that may remain in therapeutic agent collection device 760 and resuspend the therapeutic agents of the volume of concentrated therapeutic suspension in, for example, new media for eventual infusion to a patient as, for example, described herein.

[000151] In some embodiments, cover 704 may include a flush coupling 749 sized, shaped, and/or configured to be flush inlet 747 so that flush media may be introduced to flush inlet 747.

[000152] In some embodiments, cover 704 may include a quality control coupling and/or cover 739 configured to cooperate with quality control chamber 737 and, in some cases, enable imaging and/or processing of therapeutic agents held within quality control chamber 737. This may be accomplished when, for example, quality control coupling and/or cover 739 is transparent and allows for imaging of the therapeutic agents held in quality control chamber 737. In some cases, a lower surface of quality control chamber 737 may also be transparent so that, for example, a light may be positioned beneath quality control chamber 737 and a camera, microscope, or other imaging device may be positioned on top of quality control coupling and/or cover 739 so that it may image the lit therapeutic agents held in quality control chamber 737 and/or perform one or more quality control checks thereon.

[000153] In some embodiments, a result of a quality control checks on therapeutic agents and/or a volume of concentrated therapeutic suspension may be used to control dosing of the therapeutic suspension for a particular patient so that the patient gets a particular number, or dose, of therapeutic agents rather than a particular volume of therapeutic suspension in which therapeutic agent viability and/or concentration may vary. The dosing of the patient may be dependent on, for example, a patient characteristic (e.g., weight, size, age, gender, etc.), a prescription, a clinician protocol or preference, a system constraint, and/or a diagnosis of the patient. In some cases, quality control checks may be performed throughout infusion of the patient and dosing may be dynamically updated and/or adjusted during an infusion session based on outcomes of one or more quality control checks. For example, if a dosage for a particular type of therapeutic agent calls for 10 million therapeutic agents per kilogram of body weight and quality control measurements indicate that there are 4.5 million viable therapeutic agents per milliliter of therapeutic suspension, then dosage for a patient who weighs 50kg may be set to 111 .1 ml_ so that the patient receives the correct dosage of therapeutic agents. In this way, dosing may be more precise than if an entire volume of therapeutic suspension for the patient received from, for example, a lab or manufacturing facility that included 150mL Additionally, or alternatively, if the initial volume of therapeutic suspension were only 100ml_, a result of the quality control output may indicate that an additional volume of therapeutic suspension is needed to achieve optimal therapeutic dose.

[000154] In some embodiments, the systems and/or devices disclosed herein may be configured as one or more modular components that are configured to be coupled to one another via, for example, one or more couplings and/or valves like the valves and/or couplings disclosed herein. For example, the systems and devices disclosed herein may be configured as a base unit to which one or more additional devices and/or components may be added and/or coupled depending on, for example, need and/or circumstances under which a volume of therapeutic suspension is being prepared and/or infused into a patient. FIGs. 8A-8C provides various views of an exemplary base unit 801 , wherein FIG. 8A is a top view, FIG. 8B is a front view, and FIG. 8C is a perspective view of base unit 801 . Base unit 801 includes a housing 805 configured to house one or more components described herein, such as the components of system 300 (e.g., temperature regulation device 310, optional fan 312, power supply 315, first motor 320, user interface device 325, transceiver 330, one or more ports 335, processor/controller 340, memory 342, second motor 345, thermometer 350, and source of compressed gas 135). Base unit 801 includes a plurality of valves, in this case a first valve 835A, a second valve 835B, a third valve 835C, a fourth valve 835D, a fifth valve 835E, and a sixth valve 835G that may be, for example, similar to valve 335 and/or may be omni-directional, bi-directional, pneumatic, and/or pressure-sensitive valves. Valves 835 may be configured to, for example, couple to one or more components as, for example, disclosed herein.

[000155] Base unit 801 also includes an infusion device mount 810 that, in some cases, may be similar to, and/or configured to operate in a manner similar to, infusion device mount 410. Infusion device mount 810 is configured to hold and/or allow an infusion device, such as infusion device 101 and/or 201 , to rest therein. In the embodiment of FIGs. 8A-8C, infusion device mount 810 includes a base 812 on which a portion of an infusion device (e.g., barrel 110 as shown) may rest. Barrel 110 may be held in place by a first and second retaining device 814, which may be embodied as a piece of curved metal or plastic, an elastic band, and/or a strap. Base 812 may further include and/or be proximate to a barrel agitation device 816 that may be embodied as a device configured to engage with barrel 110 via, for example, friction and/or a gear to rotate barrel around an axis within retaining device 814 via, for example, cooperation with, for example, second motor 320 and/or 345. In some cases, barrel agitation device 816 may be elastic and/or deformable (e.g., made from rubber or plastic) so that it may be placed over barrel 110 or barrel 110 may otherwise be coupled thereto. Rotation of barrel 110 may serve to, for example, keep therapeutic agents in suspension, prevent adhesion of therapeutic agents to an internal surface of barrel 110, and/or create a density gradient within a volume of therapeutic suspension held by barrel 110. Base unit 801 also includes a headplate 820 that may be configured and/or function in a manner similar to headplate 420 and may be configured to engage with or otherwise press against plunger 120 and articulate along a track 815 back (e.g., away from coupling 140) and forth (e.g., toward coupling 140) via, for example, motion generated via first motor 320 so that, for example, plunger 115 may be articulated within barrel 110 to, for example, push a volume of therapeutic suspension out infusion device 101 and/or create a vacuum within barrel 110, which may act to, for example, suck a volume of therapeutic suspension or other material (e.g., fresh media and/or washing fluid) into barrel 110 or another component of base unit 801 and/or a tube or device coupled thereto. [000156] As shown in FIGs. 8A-8C, an optional thermal device 840 may be added to and/or attached to base unit 801 . Thermal device 840 may be configured to warm, cool, and/or thermally stabilize a volume of therapeutic suspension according to one or more processes disclosed herein. Thermal device 840 includes a base thermal plate 841 and a top thermal plate 842 (shown in FIG. 8C). When needed (e.g., when a frozen volume of volume of therapeutic suspension needs to be defrosted), thermal device 840 may be attached to base unit 801 via one or more attachment mechanisms 843, which may be embodied as pins or posts sized, positioned, and configured to correspond to openings in top and/or bottom thermal plate 841 and/or 842. In some embodiments, thermal device 840 may be in communication with fan 213, temperature regulation device 310 and/or thermometer 350 via, for example, a communicative, electrical, and/or thermal coupling.

[000157] Base unit 801 also includes an optional filter 856 and filter housing 854 configured to hold filter 856 while enabling coupling of filter 856 to one or more components as, for example, described herein. Filter 856 may be, for example, a housing for one or more layers of filtration material, a multi-layer filter like multi-layer filters 601 , 602, 603, and/or 604, a multi-component filter like multi-component filters 701 and/or 702, and/or a microfluidic device like the microfluidic devices disclosed herein.

[000158] Base unit 801 further includes an optional container holder 850 configured to hold a container 852 (e.g., a tube or bag) configured to hold a volume of therapeutic suspension that, in some cases, may be patient-ready volume of therapeutic suspension. In some embodiments, container 852 may be similar to container 460 and/or therapeutic agent collection device 760.

[000159] At times, an operation of base unit 801 , thermal device 840, one or more valves 835, headplate 820, first motor 320, and/or second motor 345 and/or any device included in and/or coupled to base unit 801 may be controlled and/or operated by processor/controller 340 according to, for example, one or more inputs and/or instructions received from, for example, memory 342, transceiver 330, ports 335, and/or user interface device 325.

[000160] In some embodiments, base unit 801 may be coupled to one or more devices configured to receive containers of volume of therapeutic suspension (e.g., container 460) and/or process the volume of therapeutic suspension held within the containers. For example, FIGs. 8D-8F provide various views of a system 802 that includes base unit 801 , a thaw block 880, and an automation system 881 , wherein FIG. 8D provides a perspective view, FIG.8E provides a side view, and FIG. 8F provides a top view thereof. Thaw block 880 may be configured to accept and hold a plurality (in this case six) containers 460 of volume of therapeutic suspension (not shown) that are covered by a cap 888 that may be, for example, a septum top and may be further configured to warm, cool, and/or stabilize a temperature of the volume of therapeutic suspension held by each respective container 460 according to, for example, one or more methods disclosed herein.

[000161] Automation system 881 may include two articulating extensions 890 configured to articulate up and down relative to base unit 801 and an assembly of a beam 892 from which three arms 884 extend. Each arm 884 includes two puncturing devices 886 that extend down (as oriented in FIG. 8D) and are configured to puncture cap 888 and/or remain in container 460 when articulating extensions 890 move from their up position (seen in FIGs. 8D, 8E, and 8F) to their down position as shown in FIG. 8G. Once within container 460, puncturing devices 886 may be configured to extract the volume of therapeutic suspension from container 460 via, for example, application of negative and/or positive pressure thereto as explained, for example, herein. A volume of therapeutic suspension extracted from a container 460 via a puncturing device 886 may be pulled into one or more tubes like tubes 450 (not shown) for processing (e.g., filtering, washing, culturing, etc.) as, for example, described herein. In some cases, the volume of therapeutic suspension may be transferred to barrel 110 for further processing and/or infusion into a patient as, for example described herein.

[000162] FIG. 8H provides a block diagram of an exemplary system 803 that includes base unit 801 coupled to a plurality of devices including a cell collection chamber 872, a microfluidic device, or microfluidic filter, 875, a filtration device, or strainer, 80, a first reservoir of wash media 862, a second reservoir of wash media 864, a waste reservoir 866, reservoir of cell culture media 868, and an infusion media reservoir 870. In some embodiments, microfluidic device, or microfluidic filter 879 may include and/or be similar to microfluidic devices 703, 704, and/or 705, a filtration device, or strainer, 876 may be similar to the filtration devices disclosed herein, first and/or second reservoir(s) of wash media 862 and/or 864 may be use components of a washing station like washing station 470, waste reservoir 866 may be similar to waste reservoir 445, reservoir of cell culture media 868 may be a component of activation module 494, and infusion media reservoir 870 may be similar to new media reservoir 440. The lines of FIG. 8H may be similar to tubes 450 and may facilitate movement of volume of therapeutic suspension and/or other materials through system 803 as, for example, described herein.

[000163] System 803 may be used in many different ways and/or different components of system 803 may be used at different times and/or in different ways to prepare a volume of therapeutic suspension for infusion into a patient and/or infusion of a patient-ready volume of therapeutic suspension according to, for example, one or more processes disclosed herein. For example, a volume of therapeutic suspension may exit barrel 110 and flow to microfluidic filter 879 to be separated into waste, which is communicated to waste reservoir 866, and a volume of concentrated therapeutic suspension, which may flow to cell chamber 872, which may be embodied as, for example, therapeutic agent collection device 760. When barrel 110 is empty and washing of the therapeutic agents is desired, third valve 835C and/or second valve 835B may be opened to allow wash media from first and/or second wash media reservoirs 862 and/or 864 to flow through cell chamber 872 and into barrel 110, which may act to resuspend the therapeutic agents held in cell chamber 872 in the wash media.

[000164] When infusion of the volume of concentrated therapeutic suspension is desired without washing or other processing, fourth valve 835D may be opened so that the volume of concentrated therapeutic suspension flow from cell chamber 872 to strainer 876 and final output 878 and/or directly to final output 878 (i.e., without traveling through strainer 876). Additionally, or alternatively, the volume of the concentrated therapeutic suspension may flow from microfluidic filter 879 to strainer 876 and final output 878 and/or directly to final output 878 (i.e., without traveling through strainer 876) when fourth valve 835D is opened.

[000165] In some embodiments, one or more of the devices disclosed herein may be configured to mix a hydrogel in which a concentrated volume of therapeutic agents prepared according to one or more processes described herein may be suspended. For example, when a volume (original, or otherwise) of therapeutic suspension is evacuated from barrel 110 and/or 210 and/or container 460, one or more hydrogel precursors may be added to the barrel and/or container and mixed together via, for example, agitation and/or rotation of barrel 110 and/or 210 with, for example, barrel agitation device 816. In some embodiments, the evacuated volume of therapeutic suspension may be washed, concentrated, or otherwise processed as described herein. The precursors may be mixed together according to, for example, one or more sets of instructions while the volume of evacuated and/or concentrated therapeutic suspension is held in another container (e.g., a container like container 460 and/or container 852). When the mixture and/or hydrogel is thoroughly mixed and/or prepared, the volume of therapeutic suspension and/or volume of concentrated therapeutic suspension may be added to the mixed hydrogel material, thereby creating a volume of patient-ready therapeutic suspension and/or a volume of therapeutic suspension that may be further processed according to one or more processes disclosed herein.

[000166] FIG. 9 is a flowchart of a process 900 for preparing a volume of therapeutic suspension including a plurality (e.g., millions or billions) of therapeutic agents for administration to a patient and facilitating administration of the prepared volume of therapeutic suspension to a patient. Process 900 may be executed by one or more systems and/or devices disclosed herein such as a therapeutic suspension infusion device like therapeutic suspension infusion device 101 and/or 201, a therapeutic suspension preparation and infusion system like therapeutic suspension preparation and infusion system 300, 401 , 402, or 403 and/or a processor like processor/controller 340.

[000167] Initially, in step 905, a volume of therapeutic suspension including the plurality (e.g., millions or billions) of therapeutic agents may be received. In some embodiments, the volume of the therapeutic suspension may be frozen and contained within an infusion device like infusion device 101 or 201 and received an infusion device mount like infusion device mount 410 and/or a container like container 460 and received by a container mount like container mount 465.

Following receipt of volume of therapeutic suspension including the plurality of therapeutic agents, a cover or other thermally insulating device may be placed over the frozen therapeutic suspension infusion device, the infusion device mount, and/or suspension therapy preparation and infusion system housing or a portion thereof. [000168] Optionally, in step 910, information about the therapeutic agents, therapeutic suspension, and/or the patient may be received via, for example, a user interface device like user interface device 325, or other device communicatively coupled to a processor and/or controller of a therapeutic suspension preparation and infusion system (e.g., processor/controller 340) and/or a transceiver of a therapeutic suspension preparation and infusion system (e.g., transceiver 330) that may be used to, for example, scan an optical code (e.g., bar code or QR code), a binary or alphanumeric code, a radio-frequency identifier (RFID) and/or receive manual entry of a code (e.g., patient identifier, current procedural terminology (CPT)). The information received in step 910 may be used to, for example, set and/or control one or more actions performed the therapeutic suspension preparation and infusion system and/or control one or more parameters for the preparation (e.g., washing, thawing, temperature, level of agitation, etc.) and/or infusion (e.g., flow rate of therapeutic suspension from a source of therapeutic suspension and/or a magnitude of pressure exerted on the therapeutic suspension) of the therapeutic suspension in to a catheter for distribution to the patient.

[000169] Then, following either step 905 or 910 the therapeutic agents may be prepared for administration to the patient (step 915). The preparation of step 915 may include, for example, thawing the therapeutic suspension and therapeutic agents included therein, washing the therapeutic agents, changing a media in which the therapeutic agents are suspended, agitating the therapeutic suspension to keep the therapeutic agents in suspension and/or prevent adhesion to one another and/or the walls of a container and/or infusion device, and/or filtering the therapeutic suspension to remove debris and/or dead cells. Further details regarding how step 915 may be performed are provided herein with regard to FIGs. 10 and 11 and the associated discussion of processes 1000 and 1100.

[000170] Then, the suspension therapy (i.e., prepared therapeutic agents and media from step 915) may be administered to the patient (step 920) via, for example, a patient delivery device such as a catheter via, for example, coupling a source of the suspension therapy (e.g., infusion device 101 and/or 201 and/or component of therapeutic suspension preparation and infusion systems 401 , 402, and 403 such as catheter coupling 455 or third valve 355C) to a catheter coupled to the patient. On some occasions, step 920 may be executed when headplate 420 moves toward infusion device mount 410 along track 415, thereby depressing plunger 115/215 into barrel 110/210, which acts to push the suspension therapy through barrel 110/210 into one or more tubes 450 as shown in FIGs. 4A, 4B, and 4C and discussed above. [000171] Optionally, in step 925, one or more operational parameter feedback measurements may be taken and, if the feedback indicates that the therapeutic suspension infusion device and/or therapeutic suspension preparation and infusion system is working as expected (e.g., in accordance the information about the therapeutic agents, therapeutic suspension, and/or the patient received in step 910 and/or instructions associated therewith), step 920 may continue until administration of the suspension therapy to the patient is complete (step 935). Exemplary operational parameter feedback measurements include, but are not limited to, pressure within the therapeutic suspension infusion device and/or a component coupled thereto (e.g., a catheter) and/or temperature within the suspension therapy preparation and infusion system.

[000172] When the feedback indicates that the therapeutic suspension infusion device and/or therapeutic suspension preparation and infusion system is not working as expected (step 925), a notice (e.g., alarm and/or message) may be provided to the user and/or an operational parameter (e.g., temperature, flow rate, agitation rate, etc.) may be adjusted (step 930) and step 920 may be repeated. [000173] FIG. 10 is a flowchart of a process 1000 for preparing a volume of therapeutic suspension including a plurality of therapeutic agents for administration to a patient as part of process 900 and, more particularly, step 915 of process 900. Process 1000 may be executed by one or more systems and/or devices disclosed herein such as a therapeutic suspension infusion device like therapeutic suspension infusion device 101 and/or 201 , a therapeutic suspension preparation and infusion system like therapeutic suspension preparation and infusion system 401 , 402, or 403, a suspension therapy preparation and infusion system such as suspension therapy preparation and infusion system 300, and/or a processor included therein such as processor/controller 340. The steps of process 1000 may not necessarily be performed in the order shown in FIG. 10 and discussed below. In addition, some of the steps of process 1000 may not be performed in every instance of executing process 1000.

[000174] When a volume of therapeutic suspension that may be received in, for example, step 905, is frozen and/or not at a preferred temperature, the therapeutic suspension may be heated (or cooled) until a preferred temperature for the volume of therapeutic suspension is achieved (step 1005). The system can also hold the volume of therapeutic suspension at a desired temperature during execution of process 900 and/or 1000. In step 1010, the therapeutic agents may be washed to, for example, remove debris, original media, used media, metabolic byproducts, dead cells, and/or reagents or chemicals (e.g., freezing reagents) included in the therapeutic suspension received in step 905. In some embodiments, step 1010 may be executed by placing the therapeutic suspension received in step 905 in a solution that includes magnetic microbeads configured to bind to debris or dead cells and using a magnetic field source like magnetic field source 475 to separate out the magnetic microbeads and the debris/dead cells bound to the magnetic microbeads from the solution containing the therapeutic agents. Additionally, or alternatively, step 1010 may be executed by adding saline or another solution to the therapeutic suspension received in step 905 to, for example, wash the therapeutic agents to remove unwanted substances therefrom.

[000175] In step 1015, the therapeutic agents may be filtered from the therapeutic suspension received in step 905, the thawed therapeutic suspension of step 1005, and/or the washed therapeutic agents of step 1010 so that, for example, the therapeutic suspension received in step 905 and/or the washing solution for the therapeutic agents (of step 1010) may be removed from the therapeutic agents and placed in, for example, a waste reservoir like waste reservoir 445. Step 1015 may be achieved by, for example, passing the therapeutic suspension from step 905, 1005, and/or 1010 through one or more layers of filtration material and/or a therapeutic agent separation device like therapeutic agent separation device 430 as described herein.

[000176] In step 1020, the cleaned and/or filtered cells of step 1015 may be added to and/or resuspended within a volume of new media configured for compatibility with the patient and/or the therapeutic agents as, for example, described herein. A result of executing step 1020 may be the generation of a volume of patient-ready therapeutic suspension. In step 1025, the new therapeutic suspension including the therapeutic agents may be prepared for infusion into a patient by, for example, placing the patient ready therapeutic suspension in a therapeutic suspension infusion device like therapeutic suspension infusion device 101 or 201 for administration to the patient (step 920) and/or facilitating infusion of the patient-ready therapeutic suspension to the patient via, for example, a catheter. [000177] FIG. 11 is a flowchart illustrating an exemplary process 1100 for preparing a volume of therapeutic suspension and facilitating infusion of the prepared volume of therapeutic suspension into the patient. In some embodiments, the volume of therapeutic suspension may include biological agents (e.g., cells or viruses) and/or insoluble pharmacological agents (e.g., drugs) and/or radioactive particles or beads.

[000178] Initially, a volume of therapeutic suspension may be received and placed within a therapeutic suspension preparation and/or infusion system such as systems 401 , 402, or 403 (step 1105). In some cases, the volume of therapeutic suspension may be placed in container mount 465 and/or infusion device mount 410. When the volume of therapeutic suspension includes radioactive material, the system and/or system component into which it is placed may include radioactive shielding (e.g., lead) or other mechanisms to control or limit emission of radioactivity into the environment.

[000179] Then, instructions regarding the preparation and/or delivery of the volume of therapeutic suspension to a patient may be received (step 1110) and the volume of therapeutic suspension may be prepared accordingly (step 1115) using, for example, one or processes and/or system components described herein. The instructions received in step 1110 may relate to, for example, an incubation time or parameter, an activation time or parameter, a temperature, a flow rate, and/or a degree of agitation and/or rotation needed to keep insoluble agents within the volume of therapeutic suspension suspended therein. Once the volume of therapeutic suspension is prepared (step 1115), infusion into the patient may be facilitated via, for example, delivery of the prepared volume of therapeutic suspension to a catheter or needle inserted into the patient (step 1120). When volume of therapeutic suspension includes radioactive agents, some, or all, of process 1100 may be executed without human intervention and/or without any humans other than the patient being proximate to the volume of therapeutic suspension. This may be accomplished robotically and/or via one or more remotely operated and/or controlled devices and/or routines.

[000180] FIG. 12 is a flowchart illustrating an exemplary process 1200 for preparing a volume of therapeutic suspension and facilitating infusion of the prepared volume of therapeutic suspension into the patient using, for example, one or more devices and/or systems disclosed herein.

[000181] In step 1205, a volume of a first therapeutic suspension may be introduced to, and/or pushed through, a first side of a therapeutic agent separation device like a therapeutic agent separation device 430 and/or filtration material. In some embodiments, the volume of the first therapeutic suspension may be cool (e.g., 5-25 degrees Celsius) as may be the case when the volume of therapeutic suspension has been defrosted and/or thawed. The first volume of therapeutic suspension may include DMSO. At times, step 1205 may be performed by pushing the volume of the first volume of therapeutic suspension through the therapeutic agent separation device and/or filtration material with a syringe. The first side of the therapeutic agent separation device and/or filtration material may capture and hold therapeutic agents, and/or particles included within the volume of the first therapeutic suspension while allowing other waste material (e.g., debris, cryopreservation media, and/or DMSO) to pass therethrough.

[000182] In step 1210, fresh media may be introduced to, and/or pushed through, a second side of the therapeutic agent separation device and/or filtration material. The fresh media may disengage the therapeutic agents from the first side of the therapeutic agent separation device and/or filtration material so that they may be resuspended within the fresh media, thereby forming a volume of a second therapeutic suspension. Step 1210 may be performed when, for example, the entire (or nearly entire) volume of the first volume of therapeutic suspension has been pushed through the cell and or particle separation device and/or filtration material. [000183] Following execution of step 1210, the volume of the second therapeutic suspension may be collected in a container such as the containers disclosed herein (step 1215). In step 1220, the volume of the second volume of therapeutic suspension may be prepared (e.g., washed, separated, heated, agitated, etc.) for infusion into a patient. In some embodiments, step 1220 may be executed in a manner similar to execution of step(s) 915, 1020, and/or 1115 of processes 900, 1000, and/or 1100, respectively. Then, in step 1225, infusion of the prepared volume of the second therapeutic suspension into a patient may be facilitated. At times, execution of step 1225 may be similar to execution of steps 920, 1025, and/or 1120.

[000184] When the therapeutic agent separation device and/or filtration material includes one or more electro-spun gelatin membrane(s) used during execution of process 1200, the volume of the first therapeutic suspension may be of a temperature that will not dissolve and/or disturb a construction of the one or more electro-spun gelatin membrane(s) (e.g., 2-15 degrees Celsius) when, for example, step 1205 is executed so that a first side of the electro-spun gelatin membrane(s) may capture therapeutic agents, and/or particles included within the volume of the first therapeutic suspension. Then, when step 1210 is executed, the fresh media pushed through the one or more electro-spun gelatin membrane(s) may be relatively warm (e.g., 30-45, or 37 degrees Celsius) and the warm fresh media may dissolve the one or more electro-spun gelatin membrane(s) thereby releasing the therapeutic agents and/or particles from the first side of the one or more electro-spun gelatin membrane(s) so that they may be resuspended in the warm fresh media, thereby generating the volume of the second volume of therapeutic suspension that is collected in step 1215. Preparation of the volume of the second volume of therapeutic suspension in step 1220 may, for example, include filtering the volume of the second volume of therapeutic suspension to remove the dissolved gelatin or otherwise washing the therapeutic agents and/or particles according to, for example, one or more processes disclosed herein.

[000185] In some embodiments, the systems, devices, and methods disclosed herein may be used to deliver a suspension therapy matrix of multiple cell types, and/or tissue, and/or tissue (e.g., fragments), and/or hydrogel or other viscous solution to a target within the body such as an organ (e.g., liver or pancreas). For example, the infusion devices and systems disclosed herein may be used to hold a volume of a suspension therapy matrix and/or tissue and dispense that volume of suspension therapy matrix and/or tissue via, for example, a catheter and/or delivery tool that may be inserted into and/or moved along a portion of a subject’s tissue. For example, the infusion devices and systems disclosed herein may be used to deliver a matrix of pancreatic cells to an organ such as a liver and/or pancreas of a subject so that, for example, the pancreatic function of the subject may be revived and/or reactivated.

[000186] Additionally, or alternatively, the infusion devices and systems disclosed herein may be configured to deliver a plurality, or sequence, of different types of therapeutic agents and/or suspension therapy matrixes so that, for example, a different strata or types of tissue and/or cells may be delivered to the subject. This may be facilitated by, for example, using a plurality of infusion devices (each with a different type of therapeutic agent and/or cellular matrix), via a timed introduction of different types of therapeutic agent and/or cellular matrix, and/or via a segmented, collimated, and/or separated set of different types of therapeutic agents and/or cellular matrixes within the same infusion device that may be separated by, for example, density and/or viscosity.

[000187] Additionally, or alternatively the infusion devices and systems disclosed herein may be configured to print tissue and/or multiple types of cells within the body of a subject to, for example, re-grow and/or replace an organ (e.g., liver, pancreas, heart, etc.) or other tissue (e.g., muscle tissue, tendon tissue, ligament tissue, bone, etc.), or restore function of an organ or tissue in a manner that may, in some instances, resemble bioprinting and/or three-dimensional printing of tissue.

[000188] Additionally, or alternatively, the infusion devices and systems disclosed herein may be configured to accept a bag or vial of a therapeutic suspension as an input to a syringe. In this configuration, the systems disclosed herein may be programmed to fill the syringe using the volume of therapeutic suspension extracted from the bag or vial and may then proceed to execute one or more processes described herein (e.g., washing, filtration, separation, resuspension etc.). This may allow for compatibility with existing workflows and allow the systems and devices disclosed herein to automate many of the steps that bagged cell therapy products/therapeutic suspensions need to go through after thawing to prepare them for infusion into a patient.

[000189] In some instances, two or more of therapeutic suspension preparation and infusion systems 401 , 402, and/or 403 may be operated together as a system, or array, that may concurrently, sequentially, or otherwise provide suspension therapy to a single patient and/or to multiple patients. FIG. 13 is a block diagram of an exemplary system 1300 including a plurality of therapeutic suspension preparation and infusion systems (labeled system A, system B, system C, and system N) that may include 401 A, 401 B, 401 C, 402A, 402B, 402B, 403A, 403B, and/or 403C through 401 N, 402N, and/or 403N and hardware components to control and/or provide instructions for the operation of one or more of the systems that may include, but not be limited to, a controller 1310, an optional electronic medical record (EMR) database 1320, and/or an optional treatment facility computer system 1330. Communication between one or more components of system 1300 may be facilitated by, for example, a wired and/or wireless network.

[000190] System 1300 may be set up in, for example, a clinic, hospital, and/or pharmacy to dispense suspension therapy to one or more patients via individual and/or a combination of one or more of systems A, B, C, and/or N. Provision of the suspension therapy to the one or more patients may be controlled and/or facilitated by controller 1310, which may be set up as, for example, a central dashboard that allows one or more overseers (e.g., nurse, technician, pharmacist, and/or doctor) to control an operation of one or more of the plurality of systems A, B, C, and/or N to, for example, prepare suspension therapy for dispensing to a patient, dispense prepared suspension therapy to a patient, and/or conclude dispensing suspension therapy to a patient.

[000191] Controller 1310 may be configured to provide system A, B, C, and/or N with operating instructions for one or more components according to, for example, one or more of the methods disclosed herein. At times, controller 1310 may receive information from EMR database 1320 that pertains to a patient.

[000192] In some instances, EMR database 1320 and/or treatment facility computer system 1330 may be configured to provide information about, for example, a patient characteristic, contraindications for the patient, a routine or set of parameters (e.g., concentration of therapeutic agents and/or a count of therapeutic agents to be delivered), for administration of suspension therapy, and/or one or more instructions for the delivery of suspension therapy to a patient that may be used by controller to administer and/or delivery the suspension therapy to the patient. Additionally, or alternatively, EMR database 1320 and/or treatment facility computer system 1330 may be configured to provide information about, for example, the suspension therapy to the controller to, for example, govern one or more operations of system A, B, C, and/or N. This information may pertain to, for example, suspension therapy characteristics (e.g., type of cell, type of media for the cell, washing instructions, bioreactor instructions, activation instructions, etc.).

[000193] An advantage of system 1300 is that enables operation of a plurality of therapeutic suspension preparation and infusion systems 401 , 402, and/or 403 with a reduced number of technicians, which increases efficiency of dispensing suspension therapy to patients and, in some case, may reduce resource costs (e.g., time, personnel, and/or money) while increasing availability of provision of suspension therapy. At times, a number and/or type of therapeutic suspension preparation and infusion systems 401 , 402, and/or 403 included in system 1300 may include modular components so that it may be configured and/or arranged to meet specific needs (e.g., space, demand, etc.) of a particular facility and/or suspension therapy infusion site. In some embodiments, modular components of system 1300 may be physically and/or communicatively linked together (e.g., daisy chained) in a manner that fits preferences of operators and/or patients and/or configurations of a space in which they operate. For example, in some embodiments, two or more of the plurality of systems A, B, C, and/or N may be vertically and/or horizontally arranged relative to one another.

Claims

CLAIMS We claim:

1 . A system configured to: receive a volume of a first therapeutic suspension comprising a volume of a first media and a plurality of therapeutic agents; separate the plurality of therapeutic agents from the volume of the first media, thereby generating a plurality of separated therapeutic agents; add a volume of a second media to a plurality of separated therapeutic agents, thereby generating a volume of a second therapeutic suspension; and facilitate infusion of the volume of the second therapeutic suspension into a patient.

2. The system of claim 1 , wherein therapeutic agents of the plurality of therapeutic agents are at least one of biological agents, cells, DNA, stem cells, radioactive particles, particles of insoluble medication, viruses, and genetic therapy vectors.

3. The system of claim 1 , further comprising: a temperature regulation device configured to warm, cool, or maintain a temperature of the volume of therapeutic suspension, warming, by the system, the volume of a first therapeutic suspension prior to the separating.

4. The system of claim 1 or 2, wherein the system is further configured to: wash the plurality of separated therapeutic agents prior to adding the volume of a second media to the plurality of separated therapeutic agents.

5. The system of claim 1 , 2 or 3, comprising: a filter configured to separate the plurality of therapeutic agents from the volume of the first media and the separating is performed by pumping the volume of the first therapeutic suspension through the filter.

6. The system of claim 5, wherein the filter includes one or more layers of filtration material, each layer of filtration material comprising at least one of a metallic sieve layer, a wire mesh layer, a metal sheet with a plurality of small holes positioned therein, a series of linearly oriented posts, and a gelatinous membrane.

7. The system of claim 5, wherein the filter includes a first layer of filtration material that includes a first plurality of holes and a second layer of filtration material that includes a second plurality of holes, wherein the second layer of filtration material is arranged in the filter so that the second plurality of holes partially obscures the first plurality of holes. The system of claim 5, wherein the filter is a microfluidic device. The system of claim 8, wherein the microfluidic device comprises an inertial element configured to separate therapeutic agents from waste components of the volume of therapeutic suspension. The system of claim 8, wherein the microfluidic device includes a quality control chamber. The system of claim 10, wherein the system further comprises a quality control measurement device configured to cooperate with the quality control chamber. The system of claim 11 , wherein the quality control measurement device is configured to perform at least one of counting a quantity of therapeutic agents included in the second therapeutic suspension, determining a viability of therapeutic agents included in the second therapeutic suspension, determining a functionality of the therapeutic agents included in the second therapeutic suspension, and determining a concentration of therapeutic agents included in the second therapeutic suspension. The system of any claim 11 or 12, wherein an output of the quality control measurement device is used to determine at least one of a dosage of the therapeutic agents to be provided to a patient and a volume of the second therapeutic suspension to infuse into a patient. The system of any of claims 8-12, wherein the microfluidic device is configured to be in liquid communication with a flush chamber. The system of any of the above claims, wherein the plurality of separated therapeutic agents is a first plurality of separated therapeutic agents, the system further being configured to: separate a second plurality of therapeutic agents from the volume of the second media prior to the facilitating, thereby generating a third plurality of separated therapeutic agents; and add a volume of a third media to the second plurality of separated therapeutic agents, thereby generating a volume of a third therapeutic suspension, wherein the facilitating step includes facilitating the volume of a third therapeutic suspension into the patient instead of the volume of a second therapeutic suspension. The system of any of the above claims, wherein the first media is at least one of a cryopreservation media and a hydrogel-based media. The system of any of the above claims, wherein the second media is at least one of saline, a hydrogel-based media, and blood. The system of any of the above claims, wherein the duration of time is responsive to a characteristic of the volume of therapeutic suspension. The system of any of the above claims, wherein the duration of time is responsive to a characteristic of the therapeutic agents suspended in the volume of therapeutic suspension. The system of any of the above claims, wherein the duration of time is sufficient to activate the therapeutic agents suspended in the volume of therapeutic suspension. The system of any of the above claims, wherein the duration of time is sufficient to cultivate the therapeutic agents suspended in the volume of therapeutic suspension. The system of any of the above claims, wherein the system includes a source of compressed air configured to move the volume of the first therapeutic suspension throughout the system. The system of any of the above claims, wherein the system further includes at least one of a backpressure valve, a flow rate modification device, and a pneumatic valve. The system of any of the above claims, wherein the system includes radiation shielding. The system of any of the above claims, wherein the system further comprises a quality control measurement device configured to sample a volume of the second therapeutic suspension and determine a characteristic thereof. The system of claim 25, wherein the characteristic of the second volume of therapeutic suspension is at least one of a count of a quantity of therapeutic agents included in the second therapeutic suspension, a viability of therapeutic agents included in the second therapeutic suspension, a functionality of the therapeutic agents included in the second therapeutic suspension, and a concentration of therapeutic agents included in the second therapeutic suspension. The system of claim 25 or 26, wherein an output of the quality control measurement device is used to determine at least one of a dosage of the therapeutic agents to be provided to a patient and a volume of the second therapeutic suspension to infuse into a patient. The system of any of the above claims, further comprising: a valve configured to remove at least one of air and gas from the volume of the second therapeutic suspension prior to facilitating infusion of the volume of the second therapeutic suspension into a patient. The system of any of the above claims, further comprising: a bioreactor configured to facilitate growth of biological therapeutic agents. The system of any of the above claims, wherein the volume of first therapeutic suspension is received in a container, system further comprising: a mechanism in communication with the container and configured to spin the container thereby creating a density gradient within the volume of first therapeutic suspension. The system of any of the above claims, wherein the system is further configured to deliver payloads intra-cellularly to at least one of the plurality of therapeutic agents and the plurality of separated therapeutic agents. The system of claim 31 , wherein the payloads are delivered via pressurization within the system. The system of any of the above claims, wherein the first volume of the therapeutic suspension or the second volume of therapeutic suspension is held in a container, the system further comprising a device configured to generate a density gradient within the container. The system of claim 33, wherein the device is a motor coupled to an agitation device in communication with the container. The system of any of the above claims, wherein the second media includes one or more hydrogel precursors, and the hydrogel precursors are mixed in a container into which the second volume of therapeutic suspension will be added prior to adding the plurality of separated therapeutic agents to the second media. A method comprising: receiving, by a system, a volume of a first therapeutic suspension comprising a volume of a first media and a plurality of therapeutic agents; separating, by the system, the plurality of therapeutic agents from the volume of the first media, thereby generating a plurality of separated therapeutic agents; adding, by the system, a volume of a second media to a plurality of separated therapeutic agents, thereby generating a volume of a second therapeutic suspension; and facilitating, by the system infusion of the volume of the second therapeutic suspension into a patient. The method of claim 36, wherein therapeutic agents of the plurality of therapeutic agents are at least one of biological agents, cells, DNA, stem cells, radioactive particles, particles of insoluble medication, viruses, and genetic therapy vectors. The method of claim 36 or 37, further comprising: warming, by the system, the volume of a first therapeutic suspension prior to the separating. The method of any of claims 36-38, further comprising: washing, by the system, the plurality of separated therapeutic agents prior to the adding. The method of any claims 36-39, wherein the system comprises a filter and the separating is performed by pumping the volume of the first therapeutic suspension through the filter. The method of claim 40, wherein the filter includes one or more layers of filtration material, each layer of filtration material comprising at least one of a metallic sieve layer, a wire mesh layer, a metal sheet with a plurality of small holes positioned therein, a series of linearly oriented posts, and a gelatinous membrane. The method of claim 40, wherein the filter includes a first layer of filtration material that includes a first plurality of holes and a second layer of filtration material that includes a second plurality of holes, wherein the second layer of filtration material is arranged in the filter so that the second plurality of holes partially obscures the first plurality of holes. The method of claim 40, wherein the filter is a microfluidic device. The method of any of claims 36-43, wherein the plurality of separated therapeutic agents is a first plurality of separated therapeutic agents, the method further comprising: separating, by the system, a second plurality of therapeutic agents from the volume of the second media prior to the facilitating, thereby generating a third plurality of separated therapeutic agents; and adding, by the system, a volume of a third media to the second plurality of separated therapeutic agents, thereby generating a volume of a third therapeutic suspension, wherein the facilitating step includes facilitating the volume of a third therapeutic suspension into the patient instead of the volume of a second therapeutic suspension. The method of any of claims 36-44, wherein the first media is at least one of a cryopreservation media and a hydrogel-based media. The method of any of claims 36-45, wherein the second media is at least one of saline, hydrogel-based media, and blood. The method of any of claims 36-46, further comprising: holding, by the system, the volume of the second therapeutic suspension in a container for a duration of time. The method of claim 47, wherein the duration of time is responsive to a characteristic of the volume of therapeutic suspension. The method of any of the claims 47 or 48, wherein the duration of time is responsive to a characteristic of the therapeutic agents suspended in the volume of therapeutic suspension. The method of any of claims 36-49, wherein the duration of time is sufficient to activate the therapeutic agents suspended in the volume of therapeutic suspension. The method of any of claims 36-50, wherein the duration of time is sufficient to cultivate the therapeutic agents suspended in the volume of therapeutic suspension. The method of any of claims 36-51 , wherein the system includes a source of compressed air configured to move the volume of the first therapeutic suspension throughout the system. The method of any of claims 36-52, wherein the system further includes at least one of a backpressure valve, a flow rate modification device, and a pneumatic valve. The method of any of claims 36-53, wherein the system includes radiation shielding. The method of any of claims 36-54, further comprising: removing at least one of air and gas from the volume of the second therapeutic suspension prior to facilitating infusion of the volume of the second therapeutic suspension into a patient. The method of any of claims 36-55, wherein the volume of first therapeutic suspension is received in a container, method further comprising: rotating the container thereby creating a density gradient within the volume of first therapeutic suspension.